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5. Substantiate your answer. A 56-year-old kidney transplant patient presented to you in the clinic 6 months after ABOI transplantation with severe headache and blurring of vision. He has excellent kidney function and currently on Tacrolimus-based triple immunosuppression. T1 MRI picture is shown below.
- Explain the image finding
- What is the difference between T1 and T2-weighted images?
- What is your differential diagnosis?
- How would you manage this case?
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Primary CNS PTLD is uncommon, difficult to diagnose, and requires a high index of suspicion
PTLD should be suspected in any post-transplant recipient exhibiting a new onset of neurological deficit or disturbance of consciousness.
Typically, the diagnosis is determined by
MRI with gadolinium reveals irregular, iso- or hypointense lesions on T1-weighted images with homogeneous contrast enhancement after gadolinium administration; in immunocompromised patients (including those with HIV and transplant), lymphoma may present as multiple ring-enhancing lesions.
Diagnostic for CSF analysis, cytology, and flow cytometry, the presence of malignant lymphocytes
Evaluation of EBV in both blood and CSF (suggestive)
Sometimes, if the above tests are inconclusive, the definitive diagnosis is determined by obtaining a lesion biopsy (diagnostic).
Radiologic and histopathologic diagnostic evaluations may be altered by steroid use, thereby making the diagnosis even more challenging.
Primary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD) represents a spectrum of diseases characterized by abnormal proliferation of lymphoid tissues encountered in patients who have received solid organ or bone marrow transplants. It can be thought of as one of the immunodeficiency-associated CNS lymphomas 3.
https://radiopaedia.org/articles/primary-central-nervous-system-posttransplant-lymphoproliferative-disorder
● Explain the image finding
Multiple well heterogeneous enhanced irregular ring lesions
● What is the difference between T1 and T2-weighted images?
T1-weighted MRI enhances the signal of the fatty tissue and suppresses the signal of the water. T2-weighted MRI enhances the signal of the water
● What is your differential diagnosis?
The differential diagnosis is:
** CNS-PTLD
** PCNS Lymphoma
** Glioblastoma
** Abscess ( Infectious, Tuberculoma )
** Metastatic disease
● How would you manage this case?
☆ Cerebral spinal fluid (CSF) sampling .
☆ PCR for EBV in blood and CSF .
☆ CSF PCR for EBV can be positive even when PCR on the peripheral blood is negative .
☆ CSF cytological analysis is usually positive in fewer cases but in some small series, a majority of patients have positive CSF cytology .
☆ Flow cytometric analysis can assist in making the diagnosis of PTLD in the CSF. Biopsy is almost always required for a definitive diagnosis
◇ Treatment:
☆ Decreasing or withdrawal of immunosuppressive therapy in the first instance . This must be balanced with not causing rejection of the transplanted organ.
☆ Corticosteroids are used routinely.
☆ Treatment with chemotherapy or radiotherapy should be strongly considered and the therapies utilized have been rather heterogeneous .
☆ Methotrexate has more commonly been used intravenously with less common utilization intrathecally . There have also been promising results utilizing rituximab with cranial radiation.
☆ There is a trend for improved progression-free survival in patients receiving rituximab and/or cytarabine .
☆ More patients are being treated with antiviral therapies with mixed results.
● This is a ring-enhanced lesion. Could it be a PTLD of the brain?
Yes . It can be a PTLD of the brain for these reasons:
PTLD is most common in the first year of transplantation
Multifocal lesions are more common than unifocal lesion
Ring enhancement pattern
Rnhancement heterogeneous
Irregular margin of enhancement
References:
1) Frank Gaillar . Primary central nervous system posttransplant lymphoproliferative disorder . Radiopeadia .15 Mar 2023
2) Matthew L. White, Drew W. Moore, Yan Zhang, Keiper D. Mark, Timothy C. Greiner, and Philip J. Bierman.
Primary central nervous system post-transplant lymphoproliferative disorders: the spectrum of imaging appearances and differential . Insights Imaging. 2019 Dec; 10: 46.
Explain the image finding
The image in the above scenario revealed multiple ring enhancing lesions
What is the difference between T1 and T2-weighted images?
The main difference between T1 and T2 depends on the type of signal –In T1 –water signal is suppressed and appears darker and grey in color, however, it is enhanced in T2 image(appears whiter and brighter).
What is your differential diagnosis?
A lot of differentials can be considered, however, in the above scenario tuberculoma, PTLD, metastasis and nocardiosis are likely.
How would you manage this case?
First, diagnosis should be confirmed by routine labs including CBC, C reactive protein, LFTs, Rfts , ESR and serum LDH, urine analysis. Special investigations include: CMV DNA PCR, beta d glucan, Serum galactomannan, IGRAs,erum Tacrolimus level, sputum and blood cultures, followed by CT chest, abdomen and pelvis.Lumbar puncture can be done and sample sent for RE,ADA, Genexpert-RIF ,AFB ,and culture. Gold standard is the biopsy which can be done by neurosurgery team. Treatment will depend on the cause-Immunosuppression will be reduced i.e., antimetabolite( mmf) will be stopped and tacrolimus target trough level between 5-7ng/ml.Standard ATT (renal adjusted ) with steroids-4 drugs regimen include two months of daily INH, rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB), followed by 7–10 months of INH and RIF with ethambutol (developing endemic country like ours)for tuberculosis. Close monitoring for the side effects and graft function is must due to drug drug interaction. PTLD needs chemotherapy with or without radiotherapy
REFERENCES:
1- Krishnamoorthy S, Kumaresan N, Zumla A. Latent tuberculosis infection and renal transplantation – Diagnosis and management. Int J Infect Dis. 2019 Mar;80S:S73-S76. doi: 10.1016/j.ijid.2019.01.049. Epub 2019 Feb 6. PMID: 30738187.
Explain the image finding
The T1 weighted MRI brain image showing multiple ring-enhancing lesions which are associated with ventricular compression.
What is the difference between T1 and T2-weighted images?
T1 weighted image enhances fatty tissue signals and suppresses the water signal, so, CSF appears dark. T2 weighted MRI image enhances the water signal, so CSF is seen bright on a T2 image.So, in simple:T1 images: 1 tissue type is bright (fat)T2 images: 2 tissue types are bright (fat and water)What is your differential diagnosis?
Immunosuppressed patient presenting WITH headache and blurred vision and MRI images reveals ring-enhancing lesions include for DD Infectious causes: TB, brain abscess, CMV, Aspergillus, Toxoplasma, Nocardia, and Listeria Non-infectious causes: glioblastoma, metastatic disease Primary CNS lymphoma, PTLD, How would you manage this case?
MDT approach including neurologist, neurosurgeon, IR, ID and oncologistDetailed history (including history of TB contact, weight loss, night fever) and full physical examination including neurological examination and checking for LNs Laboratory investigations: FBC, U&E, liver function tests, LDH, CRP, TAC trough level, EBV viral loadChest X ray CT chest and abdomen for metastasis, disseminated tuberculosis or PTLDTissue diagnosis from the lesion in the brainFurther management depends on the cause, in case of PTLD, we need to reduce immunosuppression and consider Rituximab and chemotherapy. On the other hand, if this a tuberculoma, we need to initiate ant-TB treatment. Consider giving steroid with raise ICPReferences:
Moscato M, Boon-Unge K, Restrepo L. Enhancing brain lesions in a renal transplant patient. Neurohospitalist. 2013 Jan; 3(1):15-9. Moscato M, Boon-Unge K, Restrepo L. Enhancing brain lesions in a renal transplant patient. Neurohospitalist. 2013 Jan;3(1):15-9.Shetty G, Avabratha KS, Rai BS. Ring-enhancing lesions in the brain: a diagnostic dilemma. Iran J Child Neurol. 2014 summer; 8(3):61-4. PMID: 25143776; PMCID: PMC4135283.
Explain the image finding
MRI picture showing- 2 ring enhancing lesion in brain
What is the difference between T1 and T2-weighted images?
T1-weighted MRI enhances the signal of the fatty tissue and suppresses the signal of the water. T2-weighted MRI enhances the signal of the water. Consideration of all the information provided by these modalities is conducive to MRI image analysis and diagnosis.
What is your differential diagnosis?
Key organisms to consider in renal transplant patients with enhancing brain lesions include
Aspergillus,
Nocardia asteroides,
Toxoplasma gondii,
Listeria monocytogenes,
Mucorales,
Tuberculosis, and
less commonly Cryptococcus.
.
The major noninfectious causes of enhancing brain lesions in renal transplant patients are
PCNS lymphomas,
PCNS-PTLD,
and metastatic disease.
How would you manage this case?
Good clinical history along with csf examination is needed.Also there are Difference in Ring enhancement between different pathology on MRI. In some case we need to do biopsy the lesion. Treatment according to pathology discovered.
Q1: this is a cerebral ring lesion and edema around it.
Q2: T1 weighted MRI shows brain anatomy. Fatty tissue has
an enhanced signal but water has a low signal. Hence, fat, edema, or infections
(high water content) are dark.
T2 weighted MRI: water has an enhanced signal. Therefore,
it appears white in tissue with high water content tissues and reverses.
Q3:
ΔΔ: malignancies: PTLD, Lymphoma Infections: Tuberculoma, toxoplasmosis, brain abscess, aspergillosis, Nocardia, listeria
Q4: -comprehensive history and physical exam CSF analysis
and smear and culture, cryptococcal AG and fungal examination
Viral PCR (CMV, EBV, HSV, HIV)
If possible → biopsy
In the case of infection, reduce immunosuppression and then
monitor to avoid rejection.
For PTLD: stop MMF and switch to mTORi, reduce CNI, and rituximab if CD-20 positive.
In advanced cases, chemotherapy, even radiotherapy.
For TB: standard four-drug TB treatment but for a long time (7 to 10 months).
Presence of two oval-shaped lesions with presence of halo and little vasogenic edema, with midline shift, but without signs of intracranial hypertension
T1-weighted MRI enhances the signal of the fatty tissue and suppresses the signal of the water. T2-weighted MRI enhances the signal of the water.
The differential diagnoses would be between:
1 – Malignancy
– Primary CNS lymphoma?
– Metastasis?
2 – Infectious diseases:
– Neurotoxoplasmosis
– Nocardiosis
– Tuberculosis
– Criptococosis
– Brain abscess
1 – I would carry out investigation as follows:
EBV A-PCR for evaluation of major cause of PTLD;
B – I would perform a lumbar puncture to study the CSF, because despite the midline deviation and blurring of vision, there are no reports of alterations in the cranial nerves.:
– Tuberculosis PCR + BAAR + ADA
– China ink + Cryptolatest
– Cyto-oncological study
– Culture of pyogenic germs
C- Depending on the findings, if any positive would institute specific therapy.
2 – In parallel, I would start treatment for Neurotoxoplasmosis and reduce the patient’s immunosuppression;
3 – If there was no satisfactory result with the actions above, I would request an opinion from NCR to perform a biopsy
REFERENCE:
– Kawahara D, Nagata Y. T1-weighted and T2-weighted MRI image synthesis with convolutional generative adversarial networks. Rep Pract Oncol Radiother. 2021 Feb 25;26(1):35-42. doi: 10.5603/RPOR.a2021.0005. PMID: 33948300; PMCID: PMC8086713.
MRI brain with contrast showing multiple ring enhancing lesions,peri-lesional edema
– obliteration of the ventricles on the left, slight midline shift.
T1-weighted MRI enhances the signal of the fatty tissue and suppresses the signal of the water. T2-weighted MRI enhances the signal of the water
PTLD is the diagnosis
Any post-transplant recipient presenting with new onset of neurological deficit or disturbance of the level of consciousness should be suspected to have PTLD
The diagnosis is usually settled by
MRI with gadolinium (suggestive not diagnostic) , typically it shows irregular, iso- or hypointense lesions on T1-weighted images lesions with homogeneous contrast enhancement after gadolinium administration, in immunocompromised patients (including those with HIV and transplant), lymphoma could presents with multiple ring enhanced lesions.
CSF analysis, cytology and flow cytometry, presence of malignant lymphocytes in CSF is diagnostic
BIOPSY; from the lesion (diagnostic)
Management; in case of PTLD chemotheraphy
in case infection treat accordingly
T1 weighted MRI showing multiple thick walled ring enhancing shadow, one compressing the corpus callosum.
T1 weighted MRI suppresses the signal of fluid (CSF-black) while enhances the signal of fatty tissue.
T2 weighted MRI enhances the signal of CSF (CSF – white), fluid and grey matter.
1. CNS PTLD
2. Primary CNS lymphoma
3. TB
4. Glioblastoma
5. Toxoplasmosis
6. Pyogenic brain abscess
– Detail history & clinical examination( Fever, anorexia, weight loss, cough, haemoptysis, focal neurological features, lymphadenopathy, hepatosplenomegaly)
Investigations
– CBC, CRP
– S.uric acid, LDH
– CXR P/A view
– Sputum for AFB, Gene Xpert, culture
– EBV, CMV serology
– Blood for C/S
– Toxoplasma serology
– Lymph node biopsy if lymphadenopathy
– CT of chest, abdomen
– Bone marrow study
Treatment
Depends on confirmatory diagnosi( strong probability of CNS PTLD because of intense immunosuppression)
PTLD:
– Stop either CNI or anti metabolite and reduce the other.
– switch to mTORi.
– Radiotherapy for localised disease
– Chemotherapy:
i)I/V rituximab monotherapy (375 mg/ m2) in low risk patient who respond well to rituximab.
ii) Poor response to rituximab then 4 cycle of CHOP therapy
– If conventional therapy fail adaptive immunotherapy
Explain the image finding
T1 W MRI scan showing 2 SOL, with peripheral ring -like enhancement post gadolinium contrast, with some perilesional oedema; slight midline shift to the left.
What is the difference between T1 and T2-weighted images?
T1 enhances the signal of fat and suppresses the signal of water, while T2 enhances the signal of water.
T1 and T2 images may be differentiated by looking at the CSF, where it will be black in T1 and white in T2.
What is your differential diagnosis?
– Cerebral abscess
o due to Tuberculosis (mostly)
o pyogenic bacterial infection
– Lymphoma
– PTLD
– Infections – Aspergillus, Cryptococcus, Nocardia, Toxoplasma
– Brain Metastasis
– Primary brain tumor – Glioblastoma
How would you manage this case?
· Strong immunosuppression could have received in view of ABOi, that increases the risk of PTLD, activation of LTBI and fungal infections.
· The approach should be confirmation of diagnosis, and tailor treatment according to diagnosis.
o Exclude TB, viral, fungal, bacterial infections.
o CBC with PBF, LFT, RFT, LDH, BD-Glucan,
o Viral assays – including EBV, CMV
o TB test (TST and IGRA assays), sputum for C/S and AFB,
o Blood culture for bacteria and fungus
· whole body PET-CT – look for PTLD / lymphoma / TB / fungal lesion / Primary tumor
· The cornerstone of management of IS reduction
o discontinue antimetabolite, reduce CNI by 50% (keep trough level minimal), and maintain on steroids.
– Two third of PTLD respond to RIS.
· IV antibiotics, antifungal and ATT can be started empirically, in view of dissemination (CNS involvement) mean while working up for diagnosis
· Neurologist / neurosurgeon opinion
o LP for CSF analysis could be harmful
o Brain Biopsy is useful to clinch diagnosis
· Mass effect may require craniotomy, excision of abscess / SOL
– can be diagnostic as well as therapeutic for TB, Fungal lesion and Tumor.
· Treatment of cause
· If TB test positive: ATT should be given for 12-24 months as for disseminated TB.
· If fungal or bacterial – IV antibiotics / antifungal
· Lymphoma: Chemotherapy (CHOP regimen)
· PTLD – Retuximab, R-CHOP
o Plasma Cell Neoplasia (30% EBV negative) responds to Retuxi + antiviral + Bortezomib
· Primary Brain tumor: Surgical Excision / RT
· brain metastasis: RT to brain, Surgical excision / chemoradiation to primary lesion
References
1. KY Chan, JCW Siu. Magnetic Resonance Imaging Features of Cerebral Ring-Enhancing Lesions with Different Aetiologies: a Pictorial Essay. Hong Kong J Radiol 2021 Mar;24(1): 62-74. https://doi.org/10.12809/hkjr2117070
2. Mycobacterium Tuberculosis Infection after Kidney Transplantation: Comprehensive Review. https://pubmed.ncbi.nlm.nih.gov / 36145473
3. Handbook of Kidney Transplantation. SIXTH EDITION
4. KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipients: (Special issue) Posttransplant Lymphoproliferative Disorder Following Kidney Transplantation: A Review by Ben Sprangers, Leonardo V. Riella, Daan Dierickx
Response to Prof Ahmed Halawa Question
This is a ring-enhanced lesion. Could it be a PTLD of the brain?
– Yes Prof, it could be PTLD; although isolated CNS involvement is not so common.
– Most of the PTLD occurs within the first-year post-transplant
– may present like opportunistic infections
– MRI may show multi focal lesions – necrotic centre and enhanced peripheral ring (highly cellular surrounded by vasogenic edema) similar to primary CNS lymphoma
– CNS lymphoma represent 10 to 20% of PTLD – typically monomorphic, high grade lymphoma B – cell lymphoma & EBV +ve
– Biopsy is diagnostic – always recommended
Reference:
1. Cavaliere R, Petroni G, Lopes MB, et al. Primary central nervous system post-transplantation lymphoproliferative disorder: an International Primary Central Nervous System Lymphoma Collaborative Group Report. Cancer 2010; 116: 863.
2. Daniel J Bell. Primary central nervous system posttransplant lymphoproliferative disorder. Radiopedia 2022 Dec 12.
Explain the image finding:
There are 2 ring-enhancing cerebral lesions with surrounding edema resulting in mass effect.
What is the difference between T1 and T2-weighted images?
What is your differential diagnosis?
· Toxoplamosis
· Tuberculosis
· Cryptococcomas
· Lymphoma
· Progressive multifocal leucoencephalopathy
· Cerebral abscess
· PTLD
· Aspirgillosis
· Nocardia asteroids
· Brain Metastasis
How would you manage this case?
· Since there was ABOI, strong immunosuppressives could be given, which increases the risk of PTLD, activation of LTBI, and fungal infections.
· The approach should be directed toward excluding all viral, fungal, bacterial, and TB infections.
· CBC, Full chemistry, Virology, TB test (TST and IGRA assays), sputum for C/S and AFB, Blood culture.
· Chest X.R, Total spine MRI, Echocardiography, CAP CT.
· LP should be discussed with the neurologist and neurosurgeon as it could be harmful.
· Mostly Immunosuppressives will be reduced and modulated according to the final diagnosis.
· If the TB test was positive, treatment should be given for 12 months as disseminated TB.
· If fungal or bacterial treat accordingly.
Lymphoma and brain metastasis also can be managed according to the result.
1) https://pubmed.ncbi.nlm.nih.gov/36145473/#:~:text=Mycobacterium%20Tuberculosis%20Infection%20after%20Kidney%20Transplantation%3A%20A%20Comprehensive%20Review
2) https://www.hkjr.org/article/v24n1/62#:~:text=Magnetic%20Resonance%20Imaging%20Features%20of%20Cerebral%20Ring%2DEnhancing%20Lesions%20with%20Different%20Aetiologies%3A%20a%20Pictorial%20Essay
3) Handbook of Kidney Transplantation. SIXTH EDITION
The given image shows multiple (two) ring like enhancing lesions in the brain….There is some perilesional edema with one lesion causing a midline shift….
The appearance of T1 MRI images is that T1 the gray matter appears dark than white matter, in T2 the white matter is darker than the gray matter…CSF fluid appears dark in T1 and bright in T2….
T1 MRI is used for anatomical details, vascular changes delineation while T2 MRI is useful for anatomical details especially CSF…
Differential diagnosis in a patient who has had an ABOi renal transplant and presents in 6 months with headache and blurring of vision include the following
Few other details like induction agent used in transplant, EBV serological status of the recipient and donor if available may be helpful….exposure to pigeons and cats maybe useful in diagnosis of Cryptococcus and Toxoplasmosis respectively
The investigations of this patient include Complete blood count, renal function test, Liver function test, Tacrolimus level, USG transplant kidney, urine culture, blood culture, procalcitonin…Patient has normal renal function at this time…. Patient needs IV broad spectrum antibiotics…. CSF analysis after ruling out raised ICT is needed to rule of bacterial meningitis and TB which maybe positive by Gene XPert MTB or positive CSF culture ..
CSF PCR for toxoplasmosis, EBV PCR maybe done in the CSF fluid itself
Brain biopsy is dangerous but it will clinch the diagnosis
Treatment depends on the underlying disease
PTLD may present as multiple ring enhanced lesions in 10 – 20% of all the PTLD cases …It is EBV + in nature and presents as either single or multiple ring enhanced lesions of the brain….Brain biopsy is diagnostic but it is very invasive….CSF fluid will demonstrate exudative in nature with malignant cells
Two ring enhancing lesions with peri-lesion edema on MRI brain.
T1 weighted MRI enhances the signal of the fatty tissue and suppresses the signal of water.
T2 weighted images enhance the signal of water.
CSF will appear darker in T1 with the grey matter darker than the white matter.
Differentials:
PTLD
TB
Toxoplasma
Nocardia
Bacterial abscesses
Metastatic disease
Management:
Detailed history: onset and duration of symptoms, constitutional symptoms like fever, weight loss, night sweats, history of TB exposure.
Detailed examination specifically palpable lymph nodes.
CSF examination after ruling out raised ICP
CT scan chest and abdomen
Tissue diagnosis from brain lesion.
MDT approach including Neurologist and ID.
Specific management would depend upon diagnosis, if PTLD then reduction of immunosuppression and IV methylprednisolone. ATT for TB.
· Explain the image finding.
There are several well enhanced well margined and with central clarity.
· What is your differential diagnosis?
· Could metastatic brain tumor,
· post-transplant lymphoproliferative disorder,
· pyogenic infection,
· fungal infection,
· tuberculosis.
·
· How would you manage this case?
· Need to confirm and exclude the diagnosis.
· Baseline investigation, radiological investigation.
· Immunosuppression modification,
· Neurologist/ neurosurgeon involvement,
· If responding, otherwise cidofovir, rituximab, IVIG, autologous T-cell adaptive therapy.
· Radiotherapy,
· Surgery.
Explain the image finding
There are 2 ring-enhancing cerebral lesions with surrounding edema resulting in mass effect.
What is the difference between T1 and T2-weighted images?
What is your differential diagnosis?
· Toxoplamosis
· Tuberculosis
· Cryptococcomas
· Lymphoma
· Progressive multifocal leucoencephalopathy
· Cerebral abscess
· PTLD
· Aspirgillosis
· Nocardia asteroids
· Brain Metastasis
How would you manage this case?
· Since there was ABOI, strong immunosuppressives could be given, which increases the risk of PTLD, activation of LTBI, and fungal infections.
· The approach should be directed toward excluding all viral, fungal, bacterial, and TB infections.
· CBC, Full chemistry, Virology, TB test (TST and IGRA assays), sputum for C/S and AFB, Blood culture.
· Chest X.R, Total spine MRI, Echocardiography, CAP CT.
· LP should be discussed with the neurologist and neurosurgeon as it could be harmful.
· Mostly Immunosuppressives will be reduced and modulated according to the final diagnosis.
· If the TB test was positive, treatment should be given for 12 months as disseminated TB.
· If fungal or bacterial treat accordingly.
Lymphoma and brain metastasis also can be managed according to the result.
1) https://pubmed.ncbi.nlm.nih.gov/36145473/#:~:text=Mycobacterium%20Tuberculosis%20Infection%20after%20Kidney%20Transplantation%3A%20A%20Comprehensive%20Review
2) https://www.hkjr.org/article/v24n1/62#:~:text=Magnetic%20Resonance%20Imaging%20Features%20of%20Cerebral%20Ring%2DEnhancing%20Lesions%20with%20Different%20Aetiologies%3A%20a%20Pictorial%20Essay
3) Handbook of Kidney Transplantation. SIXTH EDITION
Explain the image finding
Two ring enhancing session with slight midline shift to the left with some peri-lesional edema.
What is the difference between T1 and T2-weighted images?
T1 enhances the signal of fat and suppresses the signal of water while T2 enhances the signal of water.
Thus T1 and T2 images may be differentiated by looking at the CSF, where it will be black in T1 and white in T2.
What is your differential diagnosis?
Primary CNS lymphoma-PTLD
Glioblastoma
Metastatic disease
Infectious cause: abscess,toxoplasma gondii, tuberculosis Cryptococcus.
How would you manage this case?
The cornerstone of management of PLTD is RIS- reduce CNI trough level by 50%, discontinue antimetabolite and maintain on steroids.
Two third of patients respond to RIS.
Use of antiviral have been controversial
CD20 positive PTLD RIS should be followed with rituximab.
Patient who fail to respond on RIS there is a role of: chemotherapy, radiation and surgery.
References
Special Issue: KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipients
Posttransplant Lymphoproliferative Disorder Following Kidney Transplantation: A Review
Ben Sprangers Leonardo V. Riella Daan Dierickx
right hemispherical multiple cerebral ring enhanced lesions
the difference between T1 and T2-weighted images?
T1-weighted image suppresses water but enhances fats thus helpful for brain structure details
T2- enhances water thus helpful in the detection of brain oedema
What is your differential diagnosis?
CNS tuberculosis
PTLD
metastasis
aspergillosis,
Toxoplasmosis
abscess
WORK UP
routine labs; LFT, KFT, LDH, cni level
neurosurgical consultation
CT chest, abdomen for occult malignancy
septic screen for distant infection
TST, IGRA
serology for aspergillosis
CMV PCR
tissue biopsy
Image findings:
Difference between T1 and T2-weighted images:
Differential diagnosis:
· Tuberculosis
Management:
Detailed History, clinical examination
Investigations :
CBC, ESR – to check for leucocytosis, neutrophilia.
CRP, LDH
Viral Serology: EBV PCR, CMV PCR, JC PCR
Bacterial and fungal blood cultures
Serum Toxoplasma antibodies – very high toxoplasma antibodies could suggest toxoplasmosis.
Serum cryptococcal antigen, Beta D-glucan, Serum galactomannanCXR – To check for any lung lesions to suggest TB, primary lung malignancy.
Sputum for AFBs smear, culture, Gene-Xpert.
Fundoscopy
CSF if possible, for; cell count, glucose, protein, cultures, smear, PCR TB, if no raise in ICP
PET-CT
To confirm, biopsy and histopathology
Treatment:
According to confirm diagnosis. In case of infection, it would require decrease of immunosuppression and starting of specific treatment as per etiology.
In case of PTLD chemotherapy.
References:
(i) UpToDate
(ii) Radiologic Differentiation of Primary CNS Posttransplant Lymphoproliferative Disorder From Brain Metastasis, Matthew L. White, Yan Zhang, Justin Cramer, Fang Yu, Philip J. Bierman, and Timothy C.
T1 weighted MRI film showing multiple irregular ring-enhanced lesion with ventricular compression.
T1 weighted enhancing fatty tissue signals.
T2 weighted enhancing fat and water signals.
DDx :
Tuberculosis
Lymphoma
PTLD
Abscess
Metastasis
Toxoplasmosis
Creptococosis
Norcardia
Management:
Complete history if any travel to endemic are of TB , any exposure to index case ,
Complete examination
Investigations include: CBC, ESR , CRP, RFT, LFT, drug level , EBV PCR , CMV PCR,CSF cytology, flocytometry , and PCR for EBV , CT scan for chest, abdomen and pelvis.
Treatment:
Specific treatment for specific infectious cause, ATT , for PTLD specific treatment by chemotherapy and local radiation.
T1 MRI shows cavity lesion with peripheral enhcement
can be fungal abscess, PTLD ,reactivation of old lesion
involve neurosurgeon
biopsy will help us to diagnose PTLD
If so, reduction of IS is must
T1- water is black/grey fat is white
T2- water is white and fat is black and grey
This is not applicable if gadolinium is given which is a contrast
Multiple cerebral irregular outline ring enhanced lesions one peri ventricular and the second lt temporo parietal with surrounding edema
T1-weighted MRI enhances the signal of the fatty tissue and suppresses the signal of the water. T2-weighted MRI enhances the signal of the water.
CNS tuberculoma
posttransplant lymphoproliferative disorder PTLP
Toxoplasmosis
Metastatic lesions
Abscess
Aspergillosis
History and clinical examination
Labs including CBC,KFT,LFT ,LDH ,CRP,ESR
Viral profile EBV ,CMV
Chest neck abdomen pelvis CT with and without contrast
Diagnosis of TB
TISSUE biopsy
Decrease immunosuppressive therapy
Reference
T1-weighted and T2-weighted MRI image synthesis with convolutional generative adversarial networks
Daisuke Kawahara and Yasushi Nagata
Explain the image finding
T1 MRI head showing 3 ring enhancing lesions with thick nodular wall which favor malignant surrounded with peri-lesional oedema. However, thin walled ring lesions can point to abscess. There is midline shift which indicates increased intra-cranial pressure.
What is the difference between T1 and T2-weighted images?
Appearance of structure in T1 and T2 MRI images:
T1: Gray matter appears darker than white matter.
T2: Gray matter appears lighter than white matter.
CSF /fluids appear dark in T1 and bright in T2. T2 Flair shows dark CSF.
Fat appears white in T1 and less white in T2.
Cortical bones, Tendon, ligaments, calcifications and flowing blood appear dark in both T1 and T2 MRI.
T1 MRI is useful for:
1- Anatomic details
2- Vascular changes (with contrast).
3- Disruption of blood brain barrier (with contrast).
T2 MRI is useful for:
1- Anatomic detail especially CSF spaces.
2- Most lesions.
3- Can’t distinguish lesions from CSF.
FLAIR: Fluid Attenuation Inversion Recovery =T2 +dark free flowing water (CSF) and bright non-free flowing fluid.
FLAIR is useful in delineating lesions near the ventricles and edema and it can improve grey white differentiation.
GRE: Gradient Echo (SWI, T2*)
SWI: Susceptibility weighted images.
Para-magnetic substances are dark like blood, calcium, other metals like cupper in Wilson’s disease.
Useful for: early hemorrhage and old hemorrhage.
DWI= Diffusion weighted image. Useful for detection of early ischemia and detection of abscess and seizures.
Recognized by bright edema of ischemia. Most correlate with ADC.
· What is your differential diagnosis?
DD includes:
1- CNS Lymphoma, part of PTLD.
2- Brain Tumors either primary or metastasis.
3- TB.
4- Neuro-cysti-cericosis.
5- Cryptococci.
6- Toxoplasmosis.
7- Brain abscess.
8- Aspergillosis, Nocardia
The most common cause in this scenario is PTLD, metastasis, tuberculosis, aspergillosis.
· How would you manage this case?
1- Hospitalization.
2- Neurosurgery referral to advice for further investigations and possible need for craniotomy and brain biopsy and further management of hydrocephalus.
3- Steroids (Dexamethasone) to reduce brain edema.
4- Lumbar puncture and CSF analysis: presence of malignant lymphocytes is diagnostic of PTLD (requires flow cytometry), Gene-Expert test for TB and culture for TB. CSF culture and sensitivity and tests for EBV, CMV.
5- Routine bloods: FBC, CRP, LFT, RFT, ESR, LDH, Bone profile, urine analysis, monitor level of immunosuppression medications.
6- Rule out fungal infection by culture for fungi, beta D-glucan, galactomannan test, Serum aspergillus IgG.
7- CT-chest, abdomen and pelvis to evaluate for metastasis.
8- Multi-disciplinary treatment once final diagnosis is achieved.
9- Treatment options according to potential diagnosis:
A- If diagnosis is PTLD: Reduction of immunosuppression, use of rituximab (anti-CD20), +/- radiotherapy.
B- If diagnosis is TB: First 2 months (4 drug regimen including INH+ Rifapentine+Pyrazinamide+Ethambutol) then continue with 2 drugs (INH+Rifapentine) for 4-6 months. Monitor for side effects of anti-TB medications.
Monitor for drug interactions with Rifapentine and immune-suppressive medications especially CNI and m-TOR inhibitors.
C- Reduction of immunosuppression.
D- Treatment of other causes accordingly.
References
· Yadegarynia D, Merza MA, Sali S, Seghatoleslami ZS. Multiple intracranial tuberculomas in a post-kidney transplant patient. Saudi J Kidney Dis Transpl 2016;27:135-8
· Magnetic Resonance Imaging (MRI) of the Brain and Spine: Basics
· Cavaliere R, Petroni G, Lopes MB, et al. Primary central nervous system post-transplantation lymphoproliferative disorder: an International Primary Central Nervous System Lymphoma Collaborative Group Report. Cancer 2010; 116:863.
Explain the image finding
The T1 weighted MRI brain image showing ring-enhancing lesions with ventricular compression.
· What is the difference between T1 and T2-weighted images?
T1 weighted image enhances fatty tissue signals while suppressing signal of water (cerebrospinal fluid (CSF will be dark). On the other hand, T2 weighted MRI image enhances water signal (CSF will be bright).
· What is your differential diagnosis?
Infectious etiology: Tuberculosis, Cytomegalovirus (CMV) and Toxoplasma.
Maliganacy: CNS PTLD, glioblastoma or metastatic disease.
· How would you manage this case?
· Detailed history and examination searching for any clue for infection like travel history to TB endemic area, night sweeting, weight loss, contact to non-vaccinated animals and diarrhea.
· Laboratory investigations: a complete blood count, Tacrolimus trough levels, CMV PCR, toxoplasmosis screening AFB, NAA, TST, IGRA and CSF examination.
· Radiological examination: including PAN-CT.
· Histopathological examination by tissue biopsy maybe needed.
Management would depend on the etiology.
If the lesion is infection, it would require decrease of immunosuppression and starting of specific treatment as per organism.
In case of PTLD chemotherapy would be required.
References:
OUR CASE;
IMAGE FINDINGS;
T1 VS T2 WEIGHTED IMAGES;
DDX;
MGT;
REF;
contrast enhanced MRI.
T1 v T2 images
It’s all about FAT and WATER
The two basic types of MRI images are T1-weighted and T2-weighted images, often
referred to as T1 and T2 images.
The timing of radiofrequency pulse sequences used to make T1 images results in images
which highlight fat tissue within the body.
The timing of radiofrequency pulse sequences used to make T2 images results in images
which highlight fat AND water within the body.
So, this makes things easy to remember.
T1 images – 1 tissue type is bright – FAT
T2 images – 2 tissue types are bright – FAT and WATER.
Management:
Investigation:
CBC.
ESR.
LFT.
RFT.
CSF cytology, flow cytometry, and for EBV genes by
PCR).
EBV load in plasma or white blood cells.
Contrast CT of the chest, abdomen, and pelvis should be performed in patients suspected of having PTLD.
echocardiogram, plus minus BM biopsy.
Cerebral biopsy: because supplementary assessments, including CSF and neuro-
ophthalmologic evaluations, usually are non-diagnostic
is a poor prognostic factor, median survival was 47 month.
MDT consultation with neuro-oncology, transplantation, and haemato-oncology and
neurosurgery is needed.
PTLD primary lymphoma is radiosensitive.
Patients with CNS-PTLD should be offered treatment with RIS followed by combination
chemotherapy with.
Local radiotherapy +/- corticosteroids with RIS where fitness and comorbidity are limiting
factors may be offered in CNS-PTLD.
Infectious cause antituberclous treatment and antifungal depend on the cause.
References:
Phan TG, O’Neill BP, Kurtin PJ. Post-transplant primary CNS lymphoma. Neuro Oncol. 2000; 2:229–238
Brain magnetic resonance imaging showed a multifocal, irregular, and round enhancing mass Posttransplant lymphoproliferative disorder (PTLD) is one of the life-threatening complications of organ transplantation. The incidence ranges from 1% after kidney transplantation to as high as 20% in small bowel recipients, and it is higher in children than adults Few studies refer to the incidence of central nervous system (CNS) involvement in PTLD. prognosis of primary CNS lymphoma is poor as compared to systemic PTLD
PTLD is the second most common malignancy after skin cancer among adult solid organ transplantation recipients. CNS involvement is rare, especially in isolation. Einollahi et al. noted that the incidence of PTLD was significantly increased in patients receiving azathioprine when compared to patients receiving mycophenolate mofetil
References :
1-Taylor AL, Marcus R, Bradley JA. Post-transplant lymphoproliferative
disorders (PTLD) after solid organ transplantation.
Crit Rev Oncol Hematol 2005;56:155-67.
2- Saadat A, Einollahi B, Ahmadzad-Asl MA, Moradi M,
Nafar M, Pourfarziani V, et al. Posttransplantation lymphoproliferative
disorders in renal transplant recipients:
report of over 20 years of experience. Transplant Proc
2007;39:1071-3.
3- Martinez AJ. The neuropathology of organ transplantation:
comparison and contrast in 500 patients. Pathol Res
Pract 1998;194:473-86.
4- Gerstner ER, Batchelor TT. Primary central nervous system
lymphoma. Arch Neurol 2010;67:291-7.
Explain the image finding
T1 weight MR showing multiple ring enhancing lesions with ventricular compression.
Difference between T1 and T2 weighted Images?
T1 weight image enhance fatty tissue signal while suppressing water signals and T2 weight would enhance water signals.
Differential Diagnosis
· Tuberculosis
· Nocardia
· Brain abscess
· Neurocysticercosis
· PTLD
Management
Patient would need thorough evaluation before commencing any particular treatment;
History and exam; Exposure history of TB or travel to endemic area, constitutional symptoms weight loss fever etc.
Labs evidence; baseline workup, CXR, LDH, EBV DNA, Tac level, CSF examination , CT Chest and abdomen and if needed tissue biopsy.
In case of TB routine IS along with ATT and close monitoring of CNI level.
In case of other infectious etiology targeted therapy along with Infectious disease specialist input.
In case of PTLD reduction in immunosuppressant’s and consideration of specific therapies for PTLD.
References
1. Moscato M, Boon-Unge K, Restrepo L. Enhancing brain lesions in a renal transplant patient. Neurohospitalist. 2013 Jan;3(1):15-9. doi: 10.1177/1941874412459333. PMID: 23983883; PMCID: PMC3726124.
2. Ginat DT, Purakal A, Pytel P. Susceptibility-weighted imaging and diffusion-weighted imaging findings in central nervous system monomorphic B cell post-transplant lymphoproliferative disorder before and after treatment and comparison with primary B cell central nervous system lymphoma. J Neurooncol. 2015 Nov;125(2):297-305. doi: 10.1007/s11060-015-1903-1. Epub 2015 Sep 4. PMID: 26341369.
3. UpToDate
The image is showing two ring enhancing leisons almost pressing the ventricles.
These type of leisons could be due to infectious or non infectious etiology.
Brain tumors like glioblastoma , primary CNS lymphoma, Tuberculoma , Brain abscess, CNS PTLD all can present this way .
Ti weighted images enhance fat tissue
T2 images enhance water
Management would depend upon confirmation of diagnosis which at times would require a biopsy
A multidisciplinary team would be needed in that case
Addendum
It’s all about FAT and WATERThe two basic types of MRI images are T1-weighted and T2-weighted images, often referred to as T1 and T2 images.
The timing of radiofrequency pulse sequences used to make T1 images results in images which highlight fat tissue within the body.
The timing of radiofrequency pulse sequences used to make T2 images results in images which highlight fat AND water within the body.
So, this makes things easy to remember.
T1 images – 1 tissue type is bright – FAT
T2 images – 2 tissue types are bright – FAT and WATER
Substantiate your answer. A 56-year-old kidney transplant patient presented to you in the clinic 6 months after ABOI transplantation with severe headache and blurring of vision. He has excellent kidney function and is currently on Tacrolimus-based triple immunosuppression. THE T1 MRI picture is shown below.
Explain the image finding
This is an MRI brain with ring-enhancing multiple lesions, with surrounding heterogeneous hypodense vasogenic edema in T1 weighted MRI,
What is your differential diagnosis?
Infection (abscess, Toxoplasmosis, Nocardia, Mycobacterium tuberculosis including extrapulmonary TB like Mycobacterium avium complex MAC, infection )
Malignancy including CNS -PTLP.PTLD has a heterogenous form with predominant B cell disorder, with extranodal involvement, variable clinical presentation, and complex pathogens (1). The epidemiology of PTLD has been changed with more late presentations of EBV -ve, and decreased prevalence of early PTLD rate primary EBV infection, often from donor-transmitted infection to seronegative recipient( D+VE /R-VE is an important risk factor for EBV syndromes and early EBV + PTLD.
The PTLD lesions usually have homogenous in more than 40%, heterogenous> 56, and ring enhancement patterns in about 26%
How would you manage this case?
Need further workup including an infectious panel for toxoplasmosis, viral, bacterial, fungal, and MBT, including atypical infection MAC, EBV PCR, and rapid plasma test. Toxoplasma IgM and IgG, CSF analysis for MBT gen expert and culture of AFB Staining, Nocardia species, And the viral screen, culture, peripheral blood culture, Fundoscopic eye examination by an ophthalmologist, Toxoplasma IgM, IgG, Toxoplasma by polymerase chain reaction and staining, acid-fast bacilli (AFB) stain, cryptococcal antigen. Further images including MRI with contrast, T1, and T2 weighted images, MRI is superior to CT in distinguishing suspected brain abscess, but the culture of the specimen is the gold standard for accurate diagnosis, and the tissue biopsy Histology and staining Gram’s stain, aerobic, anaerobic, mycobacterial, and fungal cultures including histopathology.The oncogenic Epstein-Barr virus (EBV) contributes to the pathogenesis of post-transplant lymphoproliferative disease (PTLD) in more than 70% of cases and even higher pediatric age groups. The median time from transplant to PTLD diagnosis was 4.3 years the prognosis of PTLD after SOT has improved in the past decades. The early PTLD has better overall survival (0S) than late presentation and shows a significant relationship between EBV status and OS in post-transplant DLBCL in one report (3)
Biopsy remains the gold standard for PTLD diagnosis and identification of histological subtypes of PTLD
Pet CT – SCAN, Flow cytometry, and IHC staining
CT chest in case of MAC with pre-existing primary pulmonary TB
The main treatment options for PTLD include
1. Reduction of immunosuppression.
2. Chemotherapy including anti-CD20 Basliximab, R- chop chemotherapy, as per oncology-hematology team recommendation
3. Radiation therapy
Infectious etiology the treatment will be directed according to the infection source after discussion with the Infectious team and neurosurgical team as might need invasive tissue biopsy or aspiration
4. Modification of immunosuppression to sirolimus-based IS and minimization of CNI with high dose steroid, and close follow up with repeated images, and close observation for the risk of rejection
5. In case of MAC infection, the confirmation by tissue biopsy culture and AFB staining, treatment of MAC includes clarithromycin, ethambutol, rifampin, rifabutin, aminoglycosides such as amikacin, and fluoroquinolone like moxifloxacin. The penetration of anti-NTM drugs to CNS infections is further complicated by the relatively impermeable blood-brain barrier (BBB). Ethambutol and the macrolides only reach adequate CSF concentrations in the presence of meningeal inflammation. As per the infectious disease guidelines (ATS/IDSA guidelines the treatment of disseminated MAC can be extended to 12 months (5). And clarithromycin is preferred first line with ethambutol as the second line along with rifampicin plus amikacin.
References:
1. Allen UD, Preiksaitis JK; AST Infectious Diseases Community of Practice. Post-transplant lymphoproliferative disorders, Epstein-Barr virus infection, and disease in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13652. doi: 10.1111/ctr.13652. Epub 2019 Jul 23. PMID: 31230381.
2. San-Juan R, Comoli P, Caillard S, Moulin B, Hirsch HH, Meylan P; ESCMID Study Group of Infection in Compromised Hosts. Epstein-Barr virus-related post-transplant lymphoproliferative disorder in solid organ transplant recipients. Clin Microbiol Infect. 2014 Sep;20 Suppl 7:109-18. doi: 10.1111/1469-0691.12534. PMID: 24475976.
3. Vergote VKJ, Deroose CM, Fieuws S, Laleman W, Sprangers B, Uyttebroeck A, Van Cleemput J, Verhoef G, Vos R, Tousseyn T, Dierickx D. Characteristics and Outcome of Post-Transplant Lymphoproliferative Disorders After Solid Organ Transplantation: A Single Center Experience of 196 Patients Over 30 Years. Transpl Int. 2022 Dec 14;35:10707. doi: 10.3389/ti.2022.10707. PMID: 36589262; PMCID: PMC9794588.
4. Verma R, Dhamija R. Disseminated Mycobacterium avium-intracellulare infection presenting as multiple ring-enhancing lesions on brain MRI. Mayo Clin Proc. 2009 May;84(5):394.
5. Chowdhary M, Narsinghani U, Kumar RA. Intracranial abscess due to Mycobacterium avium complex in an immunocompetent host: a case report. BMC Infect Dis. 2015 Jul 23;15:281.
1- Image finding:
T1 weighted image of the brain, axial cut shows two ring enhancing brain lesions, obliteration of the third ventricle, brain oedema.
2- Difference between T1 and T2:
T1: suppress the water signals and enhance fat signals
T2: enhance water signals, this fluid appear hyper-intense (bright)
3- DD:
4- Mangement:
-History: infection, contact with TB patients, travelling to endemic areas, previous infection, fever, loss of weight.
-Examination: for other lymphadenopathy, chest examination, neulogical manifestations
-Lab: CBC, DLC, liver function and lytes, CRP, LDH
TB: IGRA,
CSF aspiration for culture and serology
EBV PCR, CMV PCR, HIV PCR, Toxoplasmosis PCR, cryptococcus antigen
-Radiology: CT chest, abdomen and pelvis, graft us
1- Reduction of IS: dcrease or stop MMf and maintain steroid
2- primary CNS lymphoma: chemotherapy
3- PTLD:
combined rituximab and chemotherapy
other options: local RT+ ster0id
where available: EBV-specific CTL in case of EBV positive lesion
4- TB: 6-9 month regimen of 4- drug regimen anti-tuberculous drugs according to the ID recommendations
I dont know anything about this.
Except, It is a ring enhancing lesion with perilesional edema. Its compressing lateral ventricle with some midline shift.
Looks like neurocysticercosis.
Didnt come across this in pediatric renal transplants.
I preferred reading replies of colleagues and mentors to enhance my knowledge
5. Substantiate your answer. A 56-year-old kidney transplant patient presented to you in the clinic 6 months after ABOI transplantation with severe headache and blurring of vision. He has excellent kidney function and currently on Tacrolimus-based triple immunosuppression. T1 MRI picture is shown below.
Issues/ concerns
– 56yo kidney transplant patient, 6months post-transplant
– ABOi transplantation, excellent kidney function, tacrolimus-based regimen
– severe headache, blurring of vision
Explain the image findings
– two ring enhancing lesions, peri-lesional edema
– obliteration of the ventricles on the left, slight midline shift
What is the difference between T1 and T2-weighted images? (1)
– T1-weighted MRI images enhance the fatty tissue signal and suppress the signal of the water
– T2 weighted MRI images on the other hand enhance the signal of the water
What is your differential diagnosis? (2, 3)
– causes of enhancing brain lesions in kidney transplant recipients can be infectious or noninfectious
– Infectious causes include: –
– Noninfectious causes include: –
How would you manage this case? (4, 5)
– multidisciplinary approach: – involve a neurologist, infectious disease specialist
– detailed history: – drenching night sweats, cough, fevers, weight loss, altered mental status, focal neurological symptoms, TB contact, INH prophylaxis, induction therapy, maintenance immunosuppressive therapy, previous TB infection, EBV serostatus
– thorough physical examination
– baseline investigations: – CBC, ESR, CRP, Procalcitonin, blood culture, UECs, LFTs, coagulation profile, CNI trough level, uric acid, LDH, HIV PCR, CMV PCR, EBV PCR, toxoplasmosis PCR, cryptococcal antigen
– CSF analysis – m/c/s, biochemistry, gene xpert, cryptococcal antigen, flow cytometry, cytology
– imaging: – chest radiograph/ CT scan, abdominopelvic ultrasound/ CT scan
– stereotactic biopsy, histology, immunohistochemistry
– treatment: –
References
1. Kawahara D, Nagata Y. T1-weighted and T2-weighted MRI image synthesis with convolutional generative adversarial networks. Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology. 2021;26(1):35-42. PubMed PMID: 33948300. Pubmed Central PMCID: PMC8086713. Epub 2021/05/06. eng.
2. Moscato M, Boon-Unge K, Restrepo L. Enhancing brain lesions in a renal transplant patient. The Neurohospitalist. 2013 Jan;3(1):15-9. PubMed PMID: 23983883. Pubmed Central PMCID: PMC3726124. Epub 2013/08/29. eng.
3. Patchell RA. Neurological complications of organ transplantation. Annals of neurology. 1994 Nov;36(5):688-703. PubMed PMID: 7979215. Epub 1994/11/01. eng.
4. Nabors LB, Palmer CA, Julian BA, Przekwas AM, Kew CE. Isolated central nervous system posttransplant lymphoproliferative disorder treated with high-dose intravenous methotrexate. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2009 May;9(5):1243-8. PubMed PMID: 19422350. Epub 2009/05/09. eng.
5. Cavaliere R, Petroni G, Lopes MB, Schiff D. Primary central nervous system post-transplantation lymphoproliferative disorder: an International Primary Central Nervous System Lymphoma Collaborative Group Report. Cancer. 2010 Feb 15;116(4):863-70. PubMed PMID: 20052713. Pubmed Central PMCID: PMC4113953. Epub 2010/01/07. eng.
MRI brain with contrast showing multiple ring enhancing lesions.
There are different contrast images done by MRI. Knowing these is essential for interpreting the images and help in making the diagnosis.
T1-weighted MRI enhances the signal of the fatty tissue and suppresses the signal of the water. T2-weighted MRI enhances the signal of the water.
Infections:
Tuberculomas
Fungal infection
Toxoplasma
Abscesses
Malignancy:
PTLD
Metastasis
Glioblastoma
Multidisciplinary team approach, including oncologist, infectious disease consultant and radiologist.
To differentiate between the different diagnoses above, we need detailed history of presentation, duration of headache and blurred vision, any associated constitutional symptoms (fever, weight loss, sweating etc), any history of cough, hemoptysis, symptoms of primary tumour anywhere, history of latent TB in recipient or donor and any TB prophylaxis was given or not. Also, the type of induction therapy, any rejection, and any previous infection.
Routine investigation: CBC differential, CRP, renal and liver function, serum glucose, coagulation profile.
Specific investigation: for tuberculosis, specific confirmatory tests include sputum, if any, for AFB, culture, TB PCR, TB culture, and if needed biopsy from the lesion.
If confirmed TB, this is one of the extra pulmonary TB, then treatment should include:
MDT approach, including infectious disease and neurosurgeon or intervention radiologist for biopsy.
Immunosuppression reduction: 50% reduction of MMF, lower target FK level, keep steroid same or increase it if there is brain oedema.
Anti TB medications: 4 medications for 4months, INF, rifampicin, Pyrizinamide and ethambutol, then continuation phase of 6-8months of INH and rifampicin.
Close monitoring of FK level with dose increment at start of treatment and reduction when rifampicin stopped. This needs to be informed clearly to the patient and ID team as timing of changing medications should be known. I have experience with one case of TB of the spine post kidney transplant in my current institute. His FK level was low despite increasing his FK more than 5times, then he developed ACR, fortunately, he responded to IV methyl prednisone.
References:
1- Reports of Practical Oncology and Radiotherapy 2021, Volume 26, no. 1, pages: 35–42,
2- Sorohan, B.M.; Ismail, G.; Tacu, D.; Obris, c ˘a, B.; Ciolan, G.; Gîngu, C.; Sinescu, I.; Baston, C. Mycobacterium Tuberculosis Infection after Kidney Transplantation: A Comprehensive Review. Pathogens 2022, 11, 1041. https://doi.org/10.3390/ pathogens11091041.
3- World J Transplant, 2020 Feb 28;10(2):29-46. doi: 10.5500/wjt.v10.i2.29. Post-transplantation lymphoproliferative disorders: Current concepts and future therapeutic approaches Fedaey Abbas , Mohsen El Kossi , Ihab Sakr Shaheen , Ajay Sharma , Ahmed Halawa
· Explain the image finding
The T1 weighted MRI brain image of the index patient reveals multiple ring-enhancing lesions which are thick-walled, irregular, and associated with ventricular compression.
· What is the difference between T1 and T2-weighted images?
MRI (Magnetic resonance imaging) has different protocols. A T1 weighted image enhances fatty tissue signals while suppressing signal of water. On the other hand, T2 weighted MRI image enhances water signal (1). Hence cerebrospinal fluid (CSF) would be seen dark on T1 image while it would be seen bright on a T2 image.
· What is your differential diagnosis?
The differential diagnosis in a transplant recipient (immunosuppressed patient) presenting with neurological symptoms (headache and blurred vision) with MRI images revealing ring -enhancing lesions include (2-4):
a) Infectious etiology: Brain abscess, Tuberculosis, Cytomegalovirus (CMV), Cryptococcus, Aspergillus, Nocardia, Toxoplasma, Listeria, neurocysticercosis.
b) Non-infectious causes: Primary central nervous system (CNS) lymphoma, Primary CNS PTLD, glioblastoma, metastatic disease.
· How would you manage this case?
The index patient is a recent (6 months back) ABO incompatible renal transplant recipient, on Tacrolimus based triple immunosuppression with excellent kidney function, presenting with neurological symptoms (headache and blurred vision).
The evaluation in this scenario would include
a) Detailed history: Regarding the onset of symptoms, prior history of exposure to tuberculosis (past history of tuberculosis or contact with a positive patient), presence of other symptoms like weight loss, night sweats etc.
b) Physical examination: Especially look for any palpable lymph nodes.
c) Laboratory investigations: a complete blood count, renal function tests, serum electrolytes (sodium, potassium, chloride, calcium, magnesium), liver function tests, LDH, CRP, EBV viral load, chest x ray, and Tacrolimus trough levels.
d) Imaging: CT or MRI brain
e) CSF examination
f) CT chest and abdomen (in pursuit of disseminated tuberculosis/ PTLD).
g) Tissue diagnosis from the brain lesion
A multidisciplinary approach involving transplant specialist, neurologist, neurosurgeon, intervention radiologist, infectious disease specialist, and oncologist would be required.
Further management would depend on the etiology.
If the lesion is a tuberculoma, it would require anti-tubercular treatment (5). In case of PTLD, immunosuppression reduction with chemotherapy would be required (6).
References:
Explain the image finding
MRI is the investigation of choice for assessing patients with suspected neurological disease in the setting of transplant. The appearance of PCNS-PTLD is variable but is generally recognized as a highly cellular tumor, with distribution throughout all parts of the brain, similar to non-transplant related lymphoma. In the majority of cases, patients will present with multiple masses, often with central necrosis, surrounded by vasogenic edema, which is similar to the pattern seen in PCNS lymphoma in patients who have immunodeficiency-associated CNS lymphomas .
There are two ring lesion on left side which are enhancing. appears to be slight midline shift in this cut section. Slight obliteration of lateral ventricle
What is the difference between T1 and T2-weighted images?
T1 and T2 are technical terms applied to different MRI methods used to generate magnetic resonance images. Specifically, T1 and T2 refers to the time taken between magnetic pulses and the image is taken. These different methods are used to detect different structures or chemicals in the central nervous system
T1 weighted MRI enhances the signal of the fatty tissue and suppresses the signal of the water.
T2 weighted images enhance the signal of water.
CSF will appear darker in T1 with the gray mattering darker than the white matter.
What is your differential diagnosis?
The differential diagnosis of ring enhanced lesion in brain in immune compromised patient :
Primary CNS lymphoma.
Brain abscess.
Toxoplasmosis.
Progressive multi focal leukoencephalopathy.
Tuberculoma .
Cryptococcoma
How would you manage this case?
We need multidisciplinary team of neurosurgery and infectious .
First history and examination .
Investigation towards differential diagnosis
CSF examination by LP for :protein ,sugar ,cytology ,chemistry ,culture ,cryptococcal and fungal testing.PCR for CMV,EBV and HIV.
Toxoplasmosis serology .
Consider to reduce immune suppressions.
If we establish a diagnosis of PTLD:
Reduction of immune suppressions
Stop MMF
Decrease CNI by 50 %
Change to Sirolimus .
If we establish the Tuberculoma
A four-drug regimen containing rifamycin used both in severe and non-severe cases. Rifamycin is recommended for its sterilization capacity and efficiency but also to reduce the risk of resistance.
Consider the rifampicin inter action with immune suppressions and adverse effects of anti tuberculous.
References
1 . Castellano-Sanchez AA, Li S, Qian J et-al. Primary central nervous system posttransplant lymphoproliferative disorders. Am. J. Clin. Pathol. 2004;121 (2): 246-53. doi:10.1309/N82C-TQ1J-0XEV-EFQB – Pubmed citation
2 .Subramanian, A.K.; Theodoropoulos, N.M. Mycobacterium Tuberculosis Infections in Solid Organ Transplantation: Guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation. Clin. Transplant. 2019, 33, e13513. [CrossRef]
Explain the image finding
MRI is the investigation of choice for assessing patients with suspected neurological disease in the setting of transplant. The appearance of PCNS-PTLD is variable but is generally recognized as a highly cellular tumor, with distribution throughout all parts of the brain, similar to non-transplant related lymphoma. In the majority of cases, patients will present with multiple masses, often with central necrosis, surrounded by vasogenic edema, which is similar to the pattern seen in PCNS lymphoma in patients who have immunodeficiency-associated CNS lymphomas .
There are two ring lesion on left side which are enhancing. appears to be slight midline shift in this cut section. Slight obliteration of lateral ventricle
What is the difference between T1 and T2-weighted images?
T1 and T2 are technical terms applied to different MRI methods used to generate magnetic resonance images. Specifically, T1 and T2 refers to the time taken between magnetic pulses and the image is taken. These different methods are used to detect different structures or chemicals in the central nervous system
T1 weighted MRI enhances the signal of the fatty tissue and suppresses the signal of the water.
T2 weighted images enhance the signal of water.
CSF will appear darker in T1 with the gray mattering darker than the white matter.
What is your differential diagnosis?
The differential diagnosis of ring enhanced lesion in brain in immune compromised patient :
Primary CNS lymphoma.
Brain abscess.
Toxoplasmosis.
Progressive multi focal leukoencephalopathy.
Tuberculoma .
Cryptococcoma
How would you manage this case?
We need multidisciplinary team of neurosurgery and infectious .
First history and examination .
Investigation towards differential diagnosis
CSF examination by LP for :protein ,sugar ,cytology ,chemistry ,culture ,cryptococcal and fungal testing.PCR for CMV,EBV and HIV.
Toxoplasmosis serology .
Consider to reduce immune suppressions.
If we establish a diagnosis of PTLD:
Reduction of immune suppressions
Stop MMF
Decrease CNI by 50 %
Change to Sirolimus .
If we establish the Tuberculoma
A four-drug regimen containing rifamycin used both in severe and non-severe cases. Rifamycin is recommended for its sterilization capacity and efficiency but also to reduce the risk of resistance.
Consider the rifampicin inter action with immune suppressions and adverse effects of anti tuberculous.
References
1 . Castellano-Sanchez AA, Li S, Qian J et-al. Primary central nervous system posttransplant lymphoproliferative disorders. Am. J. Clin. Pathol. 2004;121 (2): 246-53. doi:10.1309/N82C-TQ1J-0XEV-EFQB – Pubmed citation
2 .Subramanian, A.K.; Theodoropoulos, N.M. Mycobacterium Tuberculosis Infections in Solid Organ Transplantation: Guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation. Clin. Transplant. 2019, 33, e13513. [CrossRef]
A 56-year-old kidney transplant patient presented to you in the clinic 6 months after ABOI transplantation.
C/O: severe headache and blurring of vision.
Has excellent kidney function and currently on Tacrolimus-based triple immunosuppression.
Explain the image finding
T1 weighted Gadolinium based MRI brain: shown two cerebral ring-enhanced lesions with effacement of ipsilateral lateral ventricle and perilesional edema.
What is the difference between T1 and T2-weighted images?
T1 and T2 refers to the time taken between magnetic pulses and the image is taken. These different methods are used to detect different structures or chemicals in the central nervous system.
T1 weighted MRI enhances the signal of the fatty tissue and T2 weighted images enhance the signal of water.
What is your differential diagnosis?
PTLD of the brain.
Tuberculoma of CNS.
Toxoplasmosis.
Cryptococcomas
Neurocysticercosis
Metastatic lesions
Cerebral abscess
How would you manage this case?
Full history (weight loss, cough, chronic diarrhea, night fever , night sweat , past history of TB, etc. ).
Full clinical examination (to exclude organomegaly, chest examination , Lymph nodes examination, etc. ) .
Laboratory investigations:
–Basic investigations such as (CBC, KFT, LFT, Blood and urine culture, LDH, and coagulation profile).
-CSF analysis and sputum, blood cultures, PCR for TB,
-Quanteferone test.
-PCR for (EBV, CMV, HIV, Toxoplasma) and Cryptococci antigen.
-Gold standard is lesional excisional pathology.
-CT abdomen-pelvis and chest to exclude other lesions, and looking for tissue biopsy.
Treatment:
-MDT management.
-Supportive measurements (anticonvulsant in need, dexamethasone to decrease edema).
-Reduction of the immunosuppression.
-Treatment cause of the infection such as TB, Toxoplasma, and Cryptococci.
PTLD treatment:
-Reduction or cessation of immunosuppression medications and the use of rituximab.
-Systemic and intrathecal chemotherapy, radiation, and surgery may be used adjunctively according to the stage of malignancy.
References:
1- Meena, Priti; Bhargava, Vinant; Rana, Devinder; Bhalla, Anil; Gupta, Ashwani. An Approach to Neurological Disorders in a Kidney Transplant Recipient. Kidney360 1(8):p 837-844, August 2020. | DOI: 10.34067/KID.0002052020.
2- Besenski N, Rumboldt Z, Emovon O, et al. Brain MR imaging abnormalities in kidney transplant recipients. AJNR Am J Neuroradiol. 2005;26(9):2282-2289.
3- Radiologic Differentiation of Primary CNS Posttransplant Lymphoproliferative Disorder From Brain Metastasis, Matthew L. White, Yan Zhang, Justin Cramer, Fang Yu, Philip J. Bierman, and Timothy C. Greiner, American Journal of Roentgenology 2020 215:1, 184-191
Ring enhancement lesions in post-RTX have a list of differential diagnoses if we suspect PTLD could be, but sometimes confirmation of the diagnosis is difficult.
This patient with ABOi RTX means she was heavily immunosuppressed, which is an important risk factor for developing PTLD, which can present in 10 to 20 %. (CNS) post RTX .
I do agree with Dr Sherief that every patient post-SOR with neurological symptoms should suspect PTLD until proven otherwise.
These T1 MRI images showed multiple homogeneous ring enhancements, which looks like the PTLD, but confirmation needs to have tissue biopsy.
We will need to send blood and CSF for EBV Virus P CR .
The other causes that may have the same appearance is could be the CNS tuberculoma which is having ring enhancement lesion.
So have to have a high index of suspicion and to start to work him up through the non-invasive approach first.
One of the important approaches is to reduce the IS medications.
references
BSH guidelines
Explain the image finding
There are two ring lesion on left side which are enhancing. There appears to be slight midline shift in this cut section. Slight obliteration of lateral ventricle.
What is the difference between T1 and T2-weighted images?
T1-weighted images
T1-weighted images are produced by using short TE (Time to Echo) and TR times (Repetition Time). The contrast and brightness of the image are predominately determined by T1 properties of tissue. Fat is bright on T 1 Images
T2-weighted images
T2-weighted images are produced by using longer TE and TR times. Both fat and water are bright on T2
Fluid Attenuated Inversion Recovery (Flair) Sequence
It is similar to a T2-weighted image except that the TE and TR times are very long. By doing so, abnormalities remain bright but normal CSF fluid is attenuated and made dark. It can differentiate between CSF and an abnormality much easier
Diffusion weighted imaging (DWI)
It is designed to detect the random movements of water protons. Water molecules movement is significantly restricted in the intracellular space. Spontaneous movements, referred to as diffusion, rapidly become restricted in ischemic brain tissue. The water movement becomes restricted intracellularly, resulting in an extremely bright signal on DWI. Thus, DWI is an extremely sensitive method for detecting Ischemia.
What is your differential diagnosis?
· PTLD
· Tuberculoma
· Aspergilloma
· Cryptococcal infection
· Cerebral toxoplasmosis
How would you manage this case?
Investigation will be required including basic blood tests, EBV PCR, LP and CSF analysis, Imaging like CT chest , abdomen and pelvis with contrast.
A multimodality approach involving radiologist, oncologist and neurosurgeon should be adopted
For PTLD-
Reduction and modification of immune suppression. this will include stoping CNI and reducing MMF. Switching to mTORi can be helpful.
Rituximab
Chemotherapy and Local Radiation therapy can be considered.
For CNS tuberculosis treatment up to 12 months will be required
All treatment will requires frequent monitoring and serial imaging.
Said-Conti V, Amrolia PJ, Gaze MN, Stoneham S, Sebire N, Shroff R, Marks SD. Successful treatment of central nervous system PTLD with rituximab and cranial radiotherapy. Pediatr Nephrol. 2013 Oct;28(10):2053-6
Xu H, Rewerska J, Aardsma N, Slavin K, Valyi-Nagy T, Ni H. EBV-positive post-transplant lymphoproliferative disorder presenting as primary diffuse large B-cell lymphoma of the central nervous system. Folia Neuropathol. 2017;55(3):221-226.
A 56-year-old kidney transplant patient presented to you in the clinic 6 months after ABOI transplantation with severe headache and blurring of vision. He has excellent kidney function and currently on Tacrolimus-based triple immunosuppression. T1 MRI picture is shown below.
Explain the image finding?
What is the difference between T1 and T2-weighted images?
What is your differential diagnosis?
How would you manage this case?
The image finding:
The MRI of the brain; axial-T1 image showed 2 ring enhanced lesions, there are a ring enhanced lesions in the left temporo-parietal area, and one lesion periventricular surrounded by vasogenic edema causing compression on left ventricle and midline shift by T1 weighted MRI.
The enhanced lesions indicate inflammation and breakdown of blood brain barrier (BBP),
Diffuse ring enhancement with surrounding edema and mass effect, and multiple lesions are typical for Toxoplasmosis.
What is the difference between T1 and T2-weighted images?
T1 MRI images highlights fat tissue, produced by using short TE (time to echo) and TR (repetition time)- times- dark CSF.
T2 MRI images highlights fat and water, produced by long TE and TR times- bright CSF.
What is your differential diagnosis?
Toxoplasmosis
Progressive multifocal leukoencephalopathy
Tuberculosis
Primary CNS Lymphoma
Primary CNS PTLD
Cryptococcoses
Neurocysticercosis
Metastatic lesions
Cerebral abscess
Aspergillus
Nocardia asteroids
Listeria monocytogenes
Mucorales
MRI Findings in Favour Of PTLD:
Multicentric Disease
Heterogenous Lesion Enhancement
Lack Of Leptomeningeal and Ependymal Enhancement
There are no highly sensitive or specific serum and CSF tests to help make the
diagnosis of PCNS-PTLD.
Management:
Full Detailed History => Cough, Fevers, Weight Loss
Investigations :
CBC – to check for leucocytosis, neutrophilia.
ESR
CRP, LDH
Viral Serology: EBV PCR, CMV PCR, JC PCR
Bacterial and fungal blood cultures
Serum Toxoplasma antibodies – very high toxoplasma antibodies could suggest toxoplasmosis.
Serum cryptococcal antigen, Beta D-glucan, Serum galactomannanCXR – To check for any lung lesions to suggest TB, primary lung malignancy.
Sputum for AFBs smear, culture, genXpert.
Fundoscopy
CSF if possible, for; cell count, glucose, protein, cultures, smear, PCR TB, if no raise in ICP
PET-CT
Pan-CT to look for any primary tumor with distant CNS-metastasis.
Management:
PTLD – CNS:
Monomorphic, high-grade B-cell lymphoma and all are EBV-positive.
Usually multifocal and detectable by MRI but tissue biopsy is recommended given that opportunistic infections may present with similar radiological findings.
Prognosis is generally poor.
Reduction of IS; Stopping azathioprine and MMF, Reduction of CNIs by 30–50%, maintain corticosteroids
Intrathecal chemotherapy with rituximab, CHOP
Whole-brain radiotherapy.
Local radiotherapy +/- corticosteroids with RIS where fitness and comorbidity are limiting factors may be offered in CNS-PTLD
Where available EBV-specific CTL can be considered for EBV-positive CNS-PTLD.
CNS Tuberculoma:
TB- CNS is the most severe extra-pulmonary presentation.
Forms meningoencephalitis, tuberculoma or abscess formation and may cause pressure effects.
Incidence of CNS TB approximately 1%.
Anti-TB therapy: quadruple of anti-TB drugs for 2 months, then to continue the duration of therapy in CNS-TB 9-12 months with INH and rifapentine.
Paradoxical expansion of the tuberculomas in early phase of treatment is expected and leads to deterioration in the status.
Might be complicated by obstructive hydrocephalus, surgical intervention is indicated, especially when the patient’s vision is threatened by severe intracranial hypertension.
Monitor IS level as anti- TB interact with IS and decrease drug exposure and therapeutic level.
CNS – Toxoplasmosis:
Parasitic infection, affecting brain in immunocompromised patients.
Transmitted through soil, cat litter contaminated with feces, undercooked meat of infected animals.
Prevalence of infection ranges11-80% according to the area endemics.
The initial drug regimen is:
Adjunctive therapies:
Dexamethasone 4 mg x4
Anticonvulsants – drug levels and interactions should be overlocked
References:
*UpToDate- Toxoplasmosis in immunocompromised patients.
*Miller RF, Hall-Craggs MA, Costa DC, Brink NS, Scaravilli F, Lucas SB, Wilkinson ID, Ell PJ, Kendall BE, Harrison MJ. Magnetic resonance imaging, thallium-201 SPET scanning, and laboratory analyses for discrimination of cerebral lymphoma and toxoplasmosis in AIDS. Sex Transm Infect. 1998 Aug;74(4):258-64. doi: 10.1136/sti.74.4.258. PMID: 9924465; PMCID: PMC1758132.
* Radiology masterclass- Dr Graham Lloyd-Jones BA MBBS MRCP FRCR – Consultant Radiologist – Salisbury NHS Foundation Trust UK- 2017.
*Sorohan BM, Ismail G, Tacu D, Obrișcă B, Ciolan G, Gîngu C, Sinescu I, Baston C. Mycobacterium Tuberculosis Infection after Kidney Transplantation: A Comprehensive Review. Pathogens. 2022 Sep 13;11(9):1041. doi: 10.3390/pathogens11091041. PMID: 36145473; PMCID: PMC9505385.
*Shah N, Eyre TA, Tucker D, Kassam S, Parmar J, Featherstone C, Andrews P, Asgari E, Chaganti S, Menne TF, Fox CP, Pettit S, Suddle A, Bowles KM; Haemato-Oncology Task Force of the British Society for Haematology and the British Transplantation Society. Front-line management of post-transplantation lymphoproliferative disorder in adult solid organ recipient patients – A British Society for Haematology Guideline. Br J Haematol. 2021 May;193(4):727-740. doi: 10.1111/bjh.17421. Epub 2021 Apr 20. PMID: 33877688.
*Moscato M, Boon-Unge K, Restrepo L. Enhancing brain lesions in a renal transplant patient. Neurohospitalist. 2013 Jan;3(1):15-9. doi: 10.1177/1941874412459333. PMID: 23983883; PMCID: PMC3726124.
Explain the image finding.
MRI of the brain; axial-T1 image showed 2 ring enhanced lesions, in the left hemisphere surrounded by vasogenic edema causing compression on left ventricle and midline shift.
What is the difference between T1 and T2-weighted images?
MRI depend on mapping of proton energy, the timing of radiofrequency pulse sequences used to make :
T1 images results in images which highlight fat tissue within the body, including; SC fat and bone marrow.
T2 images results in images which highlight fat AND water within the body.
Anything that is bright on the T2 images but dark on the T1 images is fluid-based tissue
What is your differential diagnosis?
KTR with high immunological risk ABOi on Triple IS ( heavy IS) who has acute neurological symptoms with ring enhanced lesions on MRI. Differential diagnosis include:
Opportunistic infections including:
Fungal (Aspergillus, Cryptococcus).
Mycobacterium tuberculosis.
Atypical organisms (Listeria, Nocardia)
Abscess
Toxoplasmosis
Malignancy: PTLD, metastatic tumor or primary CNS tumor.
Multifocal, heterogenous enhanced lesion make the suspicious of CNS-PTLD is high.
How would you manage this case?
Work up:
CBC , ESR, CRP,LDH
Cultures; Bacterial and fungal
Viral serology: EBV PCR, CMV PCR, JC PCR
Serum cryptococcal antigen
Serum Toxoplasma antibodies
CXR – To check for any lung lesions to suggest TB, primary lung malignancy
Sputum for AFBs smear, culture, genXpert.
Beta D-glucan, Serum galactomannan
IS drug level.
PET-CT
CSF if possible for ; cell count, glucose, protein, cultures, smear, PCR TB, if no raise in ICP
Pan-CT to look for any primary tumor with distant CNS-metastasis.
IF possible biopsy to establish a diagnosis.
Management:
– Admission to HDU.
– Close neuro-vital observation.
– Control the pain.
– MDT; oncologist, neurosurgery, neurologist, Transplant team and ID team.
– Management will be guided by the result of the work up.
-Steroids can be consider for brain edema.
PTLD affecting the CNS.
· Typically monomorphic, high grade B-cell lymphoma and all are EBV-positive.
· Usually multifocal and detectable by MRI but tissue biopsy is recommended given that opportunistic infections may present with similar radiological findings.
· The overall prognosis is generally considered poor.
· Reduction of IS; Stopping azathioprine and MMF, Reduction of CNIs by 30–50% , maintain corticosteroids
· Intrathecal chemotherapy with rituximab , CHOP
· Whole-brain radiotherapy.
· Local radiotherapy +/- corticosteroids with RIS where fitness and comorbidity are limiting factors may be offered in CNS-PTLD
· Where available EBV-specific CTL can be considered for EBV-positive CNS-PTLD.
Cerebral tuberculoma
· TB- CNS is the most severe extrapulmonary presentation.
· Forms meningoencephalitis, tuberculoma or abscess formation and may cause pressure effects
· Incidence of CNS TB approximately 1%.
· Anti-TB therapy; quadruple of anti-TB drugs for 2 months, then to continue the duration of therapy in CNS-TB 9-12 months with INH and rifapentine.
· Paradoxical expansion of the tuberculomas in early phase of treatment is expected and leads to deterioration in the status.
· Might be complicated by obstructive hydrocephalus, surgical intervention is indicated, especially when the patient’s vision is threatened by severe intracranial hypertension.
· Monitor IS level as anti- TB interact with IS and decrease drug exposure and therapeutic level.
If fungal infection: treat according to the organism.
References:
Sorohan BM, Ismail G, Tacu D, Obrișcă B, Ciolan G, Gîngu C, Sinescu I, Baston C. Mycobacterium Tuberculosis Infection after Kidney Transplantation: A Comprehensive Review. Pathogens. 2022 Sep 13;11(9):1041. doi: 10.3390/pathogens11091041. PMID: 36145473; PMCID: PMC9505385.
Shah N, Eyre TA, Tucker D, Kassam S, Parmar J, Featherstone C, Andrews P, Asgari E, Chaganti S, Menne TF, Fox CP, Pettit S, Suddle A, Bowles KM; Haemato-Oncology Task Force of the British Society for Haematology and the British Transplantation Society. Front-line management of post-transplantation lymphoproliferative disorder in adult solid organ recipient patients – A British Society for Haematology Guideline. Br J Haematol. 2021 May;193(4):727-740. doi: 10.1111/bjh.17421. Epub 2021 Apr 20. PMID: 33877688.
https://www.radiologymasterclass.co.uk/tutorials/mri/t1_and_t2_images
Describe the image:
There are two ring enhancing lesions on the left with significant perilesional edema and mass effect with compression of the left lateral ventricle
Difference between T1 and T2 weighted images:
T1 weighted MRI enhances the signal of the fatty tissue and suppresses the signal of the water. T2 weighted images enhance the signal of water. CSF will appear darker in T1 with the gray mattering darker than the white matter
The differential diagnosis is:
Management:
Treatment
Whenever the ISS is reduced it is important to discuss with the patient – especially in this high risk case – about the risk of rejection and to monitor the kidney function closely
Explain the image finding
There are a ring enhanced lesions in the left temporo-parietal area, and one lesion periventricular with surrounding edema, by T1 weighted MRI.
The enhanced lesions indicates inflammation and breakdown of blood brain parrier (BBP).
Diffuse ring enhancement with surrounding edema and mass effect, and multiple lesions are typical for Toxoplasmosis.
What is the difference between T1 and T2-weighted images?
T1 MRI images highlights fat tissue, produced by using short TE (time to echo) and TR (repetition time)- times- dark CSF.
T2 MRI images highlights fat and water, produced by long TE and TR times- bright CSF.
What is your differential diagnosis?
Toxoplasmosis.
Primary CNS lymphoma.
Bacterial abscesses.
Tuberculoma.
Cryptococcoma, syphilitic gumma, neurocysticercosis.
Multifocal leukoencephalopathy.
How would you manage this case?
History and physical examination, including ophthalmic exam (Chorioretinitis/ posterior Uveitis).
Laboratory: CBC, KFT, LFT, Blood and urine culture, LDH, and coagulation profile.
CSF analysis and culture (in indexed case I would not do it because of the increased risk of herniation), and serology for the following:
– T. gondii PCR – specific 96-100%, less sensitive 50%.
– JC virus PCR- sensitivity of 74-93%, and specificity of 92-100%
– EBV PCR- is supportive of PCNSL but not diagnostic.
– Cryptococcal antigen- highly sensitive and specific and make the diagnosis.
– CMV PCR- sensitivity of 80% and specificity of 90%.
– Acid fast bacilli (AFB) and culture- low sensitivity
– Cytology and flow cytometry- neither specific nor sensitive.
Toxoplasma IgG serology if negative excludes diagnosis, if positive support the diagnosis.
Serum cryptococcal antigen.
Syphilis IgG serology and rapid plasma reagin.
CXR- pneumonitis.
Single-photon emission computerized tomography (SPECT) scan– high uptake supports diagnosis with (PCNSL).
Brain biopsy- should be performed in patients who are already undergoing surgical decompression for elevated intracranial pressure, and as soon as possible after steroid treatment to an increased intracranial pressure and edema.
I would start empiric treatment for toxoplasmosis – TMX/SMX, or Atovaquone, if clinical improvement and radiological improvement occurs within 2 weeks this supports the diagnosis and treatment then continued.
Toxoplasmosis:
Protozoan parasitic infection, affecting brain in immunocompromised patients.
Transmitted through soil, cat litter contaminated with feline feces, undercooked meat of infected animals
Prevalence of infection ranges11-80% according to the area endemics.
The initial drug regimen is:
(1) Sulfadiazine 1000 mg x4/day.
(2) Pyrimethamine (200 mg loading dose followed by 50 mg daily among patients <60 kg or 75 mg daily among patients ≥60 kg).
(3) Lecovorin (10 to 25 mg daily). This agent should be administered to prevent pyrimethamine-induced hematologic toxicity.
(4) Parentral TMP/SMX.
Adjunctive therapies–
– Dexamethasone 4 mg x4
– Anticonvulsants – drug levels and interactions should be overlocked
References:
(1) Miller RF, Hall-Craggs MA, Costa DC, Brink NS, Scaravilli F, Lucas SB, Wilkinson ID, Ell PJ, Kendall BE, Harrison MJ. Magnetic resonance imaging, thallium-201 SPET scanning, and laboratory analyses for discrimination of cerebral lymphoma and toxoplasmosis in AIDS. Sex Transm Infect. 1998 Aug;74(4):258-64. doi: 10.1136/sti.74.4.258. PMID: 9924465; PMCID: PMC1758132.
(2) Radiology masterclass- Dr Graham Lloyd-Jones BA MBBS MRCP FRCR – Consultant Radiologist – Salisbury NHS Foundation Trust UK- 2017.
(3) UpToDate- Toxoplasmosis in immunocompromised patients.
Explain the image finding
This is CT brain, with 2 ring-enhancing lesions. There is obliteration to left side of lateral ventricle by the lesion and nearby edema.
What is the difference between T1 and T2-weighted images?
· The two basic types of MRI images are T1-weighted and T2-weighted images.
often referred to as T1 and T2 images.
· The timing of radiofrequency pulse sequences used to make T1 images results in images which highlight fat tissue within the body.
· The timing of radiofrequency pulse sequences used to make T2 images results in images which highlight fat AND water within the body.
· T1 images – 1 tissue type is bright – FAT.
· T2 images – 2 tissue types are bright – FAT and WATER.(2)
What is your differential diagnosis?
· PTLD & Lymphoma.
· MB tuberculomas.
· Toxoplasma infection.
· Cryptococcus infection.
· Aspergilloma Metastatic lesion.
How would you manage this case?
PTLD is more likely.
Adjustment of immunosuppression: the treatment of PTLD: the goal is to cure and the mainstay is IS reduction(1):
a. Prior work reported the use of rituximab and chemotherapy (doxorubicin, cyclophosphamide, vincristine, prednisone) have improved overall survival, with 5-year survival at around 60%.
b. The risk of death among recipients of kidney transplants who have PTLD is 14- fold higher than recipients without PTLD. Rituximab and other novel therapies have shown an improvement in overall survival.
References
1. Al-Adra D, Al-Qaoud T, Fowler K, Wong G. De Novo Malignancies after Kidney Transplantation. Clin J Am Soc Nephrol. 2022 Mar;17(3):434-443. doi: 10.2215/CJN.14570920. Epub 2021 Mar 29. PMID: 33782034; PMCID: PMC8975024.
2. Radiology masterclass; https://www.radiologymasterclass.co.uk/
basic laboratories include blood count, chemistry, liver function, PCR for EBV
CSF analysis
definite diagnosis by biopsy and histological examination.
CXR.CT for the chest, abdomen, and pelvis
no standardized regimen for PTLD it generally reduces immunosuppression and reassesses after several weeks.
treatment anti-B cell therapy methotrexate, and radiation therapy.
References
1-. Han X. MR-based synthetic CT generation using a deep convolutional neural network method. Med Phys. 2017;44(4):1408–1419. doi: 10.1002/mp.12155. [PubMed] [CrossRef] [Google Scholar]
2-. Cavaliere R, Petroni G, Lopes MB, Schiff D. Primary central nervous system post-transplantation lymphoproliferative disorder: an International Primary Central Nervous System Lymphoma Collaborative Group Report. Cancer. 2010;116(4):863–870 [PMC free article] [PubMed] [Google Scholar]
3- Pickhardt P, Wippold F. Neuroimaging in posttransplantation lympoproliferative disorder. AJR Am J Roentgneol. 1999;172(4):1117–1121 [PubMed] [Google Scholar]
The image shows two ring-enhancing lesions with surrounding edema.
By boosting the signal from fatty tissue and lowering the signal from water, T1 makes the CSF look very dark, the gray matter look dark, and the white matter look light.
T2 makes the signal from water stronger, so CSF looks very white, grey matter looks light, and white matter looks black.
T1 images show fat tissue, while T2 images show both fat and water.
Differential diagnosis includes infectious and non-infectious causes of brain lesions. These include the following:
CNS toxoplasma, CNS lymphoma (PTLD), CNS tuberculoma, Brain abscess, and fungal CNS infections.
The management depends on the etiology of the lesions. In this case, management should involve neurosurgeon and infectious diseases consultant.
Patient should be screened for Tb infection, EBV infection, and optimally biopsy of the lesion should be obtained.
If the screening confirmed Tb infection, then treat accordingly. This is an active TB infection with symptoms, hence the patient should be treated immediately with quadruple therapy, in accordance with international guidelines.
According to the clinical response, the treatment time can go up to 24 months, however it is suggested to last at least 9 to 12 months.
If the clinical picture is in favor of PTLD , then the treatment is different. PTLD typically occurs in the first year following transplantation. PTLD can manifest similarly to opportunistic infections. Ten to twenty percent of PTLD are CNS lymphomas. single or multiple lesions may be visible on MRI. Biopsy is the gold standard of diagnosis. Hence, it is always advised to have a biopsy; the typical conditions are monomorphic, high grade B cell lymphoma, and positive EBV.
Treatment of PTLD consists initially of reduction in immunosuppression with followup on brain imaging. If initial step fails, consider treatment with Rituximab.
Other infectious causes should be treated with antibiotics or antifungal accordingly .
1-Explain the image finding;
T1 weighted MRI brain —- showed two cerebral ring-enhanced lesions with effacement of ipsilateral lateral ventricle and perilesional edema.
2-What is the difference between T1 and T2-weighted images?
In T1-weighted MRI image; (good for the anatomy (brain structures)).
-The signal of water is suppressed and the signal of fatty tissue is enhanced; so that
Tissue with high water content will appear dark and grey (edema, fat, infection),
Tissue with low water contents will appear whiter, and brighter.
In T2-weighted MRI image; (good for pathology (edema))
-The signal of water is enhanced; so that
Tissue with high water content will appear whiter and brighter,
Tissue with low water content will appear darker and greyer.
3-What is your differential diagnosis?
Neoplastic causes;
-PTLD
-CNS primary lymphoma
-Glioblastoma
-Metastasis
Infectious causes;
-CNS tuberculosis (Tuberculoma)
-CNS toxoplasmosis
-Aspirgillosis
-Brain abscess
-Nocardia asteroides,
-Listeria monocytogenes
4-How would you manage this case?
–Complete History & Examination.
–Further investigations; will be tailored towards specific diagnosis;
(Lumbar puncture & CSF microscopy, protein, glucose, atypical cells, cryptococcal antigen, culture and fungal studies),
(EBV PCR – CMV PCR – HIV PCR),
(Serology for toxoplasmosis).
-Neurosurgery referral; for possible;.
(Craniotomy vs Image guided biopsy for histopathological diagnosis).
-Adequate analgesia.
-Consider reducing immunosuppression depending on the cause.
-Close monitoring graft function to avoid rejection.
If PTLD is confirmed
-The main options for initial treatment are reduction of immunosuppression (RIS).
-Stop CNI, Reduce MMF (adjustment low troughs).
-Switch to mTOR Inhibitors (some studies have shown successful PTLD regression with sirolimus).
-Rituximab is an anti-CD-20 monoclonal antibody with efficacy against CD-20 positive PTLD; it has been postulated to cause destruction of malignant cells by several mechanisms.
-Chemotherapy, Radiotherapy, or a combination of these,
-Adoptive immunotherapy : indicated for patient who showed relapse after other modalities.
-Surgical treatment; for localized disease or emergency situation.
If CNS TB is confirmed
-Combination of (INH + Rifampicin+ Ethambutol + Pyrazinamide) for 2 month,
-Then (Rifampicin + INH) for 7-10 months
-Considering steroid with raise ICP.
References;
-Christina A. Nelson, Joseph R. Zunt, Tuberculosis of the Central Nervous System in Immunocompromised Patients: HIV Infection and Solid Organ Transplant Recipients, Clinical Infectious Diseases, Volume 53, Issue 9, 1 November 2011, Pages 915–926.
-Yadegarynia D, Merza MA, Sali S, Seghatoleslami ZS. Multiple intracranial tuberculomas in a post-kidney transplant patient. Saudi J Kidney Dis Transpl 2016;27:135-8.
-Magnetic Resonance Imaging (MRI) of the Brain and Spine: Basics, Revised 07/04/16 Copyrighted 2006, David C Preston, MD.
-Gaillard F, Bell D, Hacking C, et al. Primary central nervous system posttransplant lymphoproliferative disorder, Radiopaedia.org 2022.
New onset neurological deficit or disturbance of the level of consciousness following transplantation, should raise suspicion of PTLD.
Diagnosis:
MRI with gadolinium; suggestive only: usually showing irregular, iso or hypointense lesions on T1-weighted images. The lesions appear with homogeneous contrast enhancement with gadolinium. I immunocompromised patients, lymphoma can present with multiple ring enhanced lesions.
Presence of malignant lymphocytes in CSF is diagnostic
Assessment of blood and CSF for EBV is suggestive of diagnosis.
If needed, definitive diagnosis can be made by biopsy from the lesion.
References:
Cavaliere R, Petroni G, Lopes MB, et al. Primary central nervous system post-transplantation lymphoproliferative disorder: an International Primary Central Nervous System Lymphoma Collaborative Group Report. Cancer 2010; 116:863.
.👉Description:
Post contrast MRI brain, axial cut, T1 image shows ring enhanced lesions in left parietal lobe, with surrounding vasogenic tissue edema in addition to pressure on lateral ventricle and midline shift.
👉Differenced between T1 and T2 is that, CSF is hypointense in T2 and hyperintense in T2.
👉 Differential diagnosis of complete ring enhancement in MRI;
_ Metastasis as from lymphoma.
_CNS PTLD.
_ Cerebral abscess mainly presented with fever.
_Glioblastoma.
_Subacute infarction.
_Contusion can be excluded from history of trauma.
_Tuberculoma.
_Toxoplasmosis.
_Radiation necrosis can be excluded from history.
_post operative changes.
👉 Management:
⭐ Investigations to confirm diagnosis
_Investigations as CSF analysis (for cytology, geneXpert) but it is contraindicated in presence of brain edema.
_sputum for AFB and culture on BACTEC system.
_EBV PCR (for PTLD).
_basal investigations as liver function, kidney function and CBC.
_LDH level.
⭐ Treatment:
_Treatment is to admit to ICU with close monitoring of vital signs and to treat brain edema by IV dexamethasone.
-Managemnt needs MDT as neurosurgeon, oncologist, chemotherapiest, radiologist.
_After confirmation of the diagnosis as PTLD …treatment is by reduction of immunosupressives medications as decrease CNI to 50% and stop MMF, shift to mTORi…additional rituximab in EBV postive cases and chemotherapy in resistant cases as CHOP protocol.
-If case of tuberculoma, start anti tuberculous therapy as rifampin, INH, ethambutol and pyrazinamide for 2 months then use INH and rifampin.
-Take care of the drug-drug interaction between anti tuberculous and IS medications.
-There is 2 ring enhancing lesions surrounding with edema and mild mid line shift and compression to ventricles.
-T1-weighted MRI enhances the signal of the fatty tissue and suppresses the signal of the water. T2-weighted MRI enhances the signal of the water.
Infection:
Malignancy :
This patient needs a MDT approach including ( neurologist ,neurosurgeon and oncologist or ID according to the specific diagnosis .)
-Full history and thorough clinical examination looking for any mass or lymph nodes , then full blood count ,graft function and liver function test .
-CSF analysis culture , PCR for TB and cytology .
– PCR for TB
-Toxoplasma IgG and IgM
-CXR US or CT abdomen
*If proved TB :
Anti-TB treatment combines initially isoniazid (10mg/kg), rifampicin (15 mg/kg), pyrazinamide (35 mg/kg), and ethambutol (20mg/kg) for two months, followed by dual therapy (isoniazid, rifampicin). More than 85% of cases can be cured by early administration of anti-TB treatment .
-The recommended duration of antituberculous is 9 to 12 months.
Steroid (1mg/kg/d) therapy is indicated in case of extensive cerebral edema or associated meningeal involvement.
-Rifampicin is a potent enzyme inducer; doses of CNI and mTORi should be adjusted
.
*If PTLD :
-Often the first line, the cornerstone of treatment in PTLD, is to reduce or completely stop the immunosuppression .
-Other treatment strategies may include:
*If toxoplasmosis ;
The first choice of treatment comprises pyrimethamine 200 mg PO once, followed by 50–75 mg PO QD depending on the body weight plus sulfadiazine 4–6 g/day in four divided doses plus folinic acid 10 mg PO QD. The duration of treatment is up to 6 weeks till the time of resolution of symptoms.
Reference :
Explain the image finding.T1 image of MRI Brain with gadolinium, the lesion shows ring enhancement.
These lesions press on the left lateral ventricle and causing midline shift.
What is the difference between T1 and T2-weighted images?T1 and T2 are technical terms applied to different MRI methods used to generate magnetic resonance images. Specifically, T1 and T2 refers to the time taken between magnetic pulses and the image is taken.
There are different contrast images in magnetic resonance MRI types. T1-weighted MRI enhances the signal of the fatty tissue and suppresses the signal of the water. T2-weighted MRI enhances the signal of the water.
What is your differential diagnosis?1.Cerebral PTLD
2.Tuberculoma of CNS (Would put first in epidemic area of TB)
3.Cerebral abscess
4.Toxoplasmosis of CNS
5.Brain metastasis
How would you manage this case?Multidisciplinary team meeting involving hematologist, oncologist, neurosurgeon and transplantation team.
Investigations
Through history and examination
Histopathological diagnosis and staging (lympnodes)
PET CT /CT
MRI brain Spetrocopy
EBV viral load evaluation, pretransplant status
CBC, RFT, LDH, Uric acid
Cd20 expression
CSF examination- tlc, dlc, sugar protein, ADA, PCR EBV, PCR MTB
Treatment
Reduction of immunosuppression
Reducing CNI dose (targeting 50% reduction of trough levels)
Stopping antimetabolites
Intravenous steroid for brain edema
Aggressive immunochemotherapy combined with rituximab if CD20 expression is noted.
Cranial radiotherapy
Sprangers B, Riella LV, Dierickx D. Posttransplant Lymphoproliferative Disorder Following Kidney Transplantation: A Review. Am J Kidney Dis. 2021 Aug;78(2):272-281. doi: 10.1053/j.ajkd.2021.01.015. Epub 2021 Mar 25. PMID: 33774079.
1- it is ring enhancing brain lesions
2- The most common MRI sequences are T1-weighted and T2-weighted scans. T1-weighted images are produced by using short TE and TR times. The contrast and brightness of the image are predominately determined by T1 properties of tissue. Conversely, T2-weighted images are produced by using longer TE and TR times.
T1- and T2-weighted images can be easily differentiated by looking the CSF. CSF is dark on T1-weighted imaging and bright on T2-weighted imaging.
T1-weighted images CSF appears dark , white matter light, cortex appears gray, fat is bright
T2-weighted images CSF appears bright, white matter dark gray, cortex light gray, and fat is light
3- DD a- tubercloma
b- neurocysticercosis (NCC)
c- PTLD
d-lymphoma
e- brain metastasis
f- cerebral abscess
g- glioblastoma
h-demyelinating disease
i-subacute infarct/contusion or heamorrhge
j-toxoplasmosis
k-radiation necrosis
4- management
1- CBC to show WBC
2- CSF analysis
3- PCR for TB
4-CXR and CT chest and abdomen
5- detailed history from recipient and donor socioeconomic level, endemic area residency or travel to endemic area
6- start broad spectrum antibiotic like vancomycin, metronidazole, and cefepime
7-start antiTB medications
8-adjust immunosuppressive medications ; increase dose of CNI when use rifampicine, or add ketoconazole to keep good trough level with decreased dose of tacrolimus
9-follow up liver and graft function
10-neurosurgical brain exploration if needed
Guruprasada SHETTY, Kadke Shreedhara AVABRATHA, Boodyar Sanjeev RAI. Ring-Enhancing Lesions in the Brain: A Diagnostic Dilemma. Iran J Child Neurol. 2014 Summer; 8(3): 61–64.
Frank Gaillard. Cerebral ring enhancing lesions. Radiopedia. 2022
Daniel Tran, Qasim Rahman, Michael Weed, Bernard Chow. Differential diagnosis of a ring-enhancing brain lesion in the setting of metastatic cancer and a mycotic aneurysm. Radiology Case Reports.Volume 16, Issue 12, December 2021, Pages 3850-3854.
Explain the image finding
–MRI brain T1 with contrast showing 2 lesions with central necrosis, surrounded by vasogenic oedema.
What is the difference between T1 and T2-weighted images?
T1: the lesion is iso- to hypointense to cortex
T2 The lesion’s intensity is variable but usually it’s hyperintense is more common when necrosis is present surrounding vasogenic oedema
What is your differential diagnosis?
Mostly a case of PTLD
Differential diagnosis includes
CNS lymphoma
Cerebral abcess
Tuberculoma of CNS
Toxoplasmosis of CNS
Brain metastasis
How would you manage this case?
This case need to be evaluated by MDT involving haematologist ,oncologist and neurosurgeon along with transplantation team
Investigations
PET CT and a directed accessible biopsy (bone marrow or lymph node) to attain e a histopathologic diagnosis
EBV viral load evaluation
Along with full basic labs and kidney function and further evaluation of the graft
Treatment
Reduction of immunosuppression is the main treatment approach that can prolongs survival for those cases including reducing CNI dose (targeting 50% reduction of trough levels), discontinuing antimetabolites, and continuing steroids if possible
aggressive immunochemotherapy combined with rituximab if CD20 expression is noted ,antiviral is doubtful, radiation therapy, surgery, or a combination can be applied
Newer agents
· Brentuximab Vedotin is an antibody-drug conjugate combining a CD30 monoclonal antibody with the microtubule.
· Small molecules targeting B cell receptor signaling and other intracellular pathways
· Checkpoint Inhibition and Chimeric Antigen Receptor T Cells
· EBV-Specific Cytotoxic T Cells
Reference
-Gaillard F, Bell D, Hacking C, et al. Primary central nervous system posttransplant lymphoproliferative disorder, Radiopaedia.org 2022
-Sprangers B et al. Post transplant Lymphoproliferative Disorder Following Kidney Transplantation: A Review Am J Kidney Dis.
78(2):272-281. Published online March 25, 2021
5. Substantiate your answer. A 56-year-old kidney transplant patient presented to you in the clinic 6 months after ABOI transplantation with severe headache and blurring of vision. He has excellent kidney function and currently on Tacrolimus-based triple immunosuppression. T1 MRI picture is shown below.====================================================================
Explain the image finding
=================================================================
What is the difference between T1 and T2-weighted images?
=================================================================
What is your differential diagnosis?
Other
====================================================================
How would you manage this case?
====================================================================
Reference
·Explain the image finding
=========================
·What is the difference between T1 and T2-weighted images?
=========================
·What is your differential diagnosis?
=========================
·How would you manage this case?
Further investigations include:
Treatment
Reference
Radiological findings;
Numerous ring-enhancing lesions with perilesional edema and effacement of the ipsilateral lateral ventricle
Differences B/W T1 and T2
T1 makes the CSF seem very black, the gray matter dark, and the white matter light by enhancing the signal of fatty tissue and suppressing the signal of water.
Water’s signal is amplified by T2, making CSF appear extremely white, grey matter appear light, and white matter appear black.
Differential; diagnosis
Tuberculoma
PTLD
Nocardia infection
Brain abcess
Toxoplasmasma CNS
Management includes;
Results of the prior TST/ or IGRA, donor history about TB, contacts with TB, a history of fever, neck stiffness, night sweats, or weight loss,
Regular blood work; FBC,UECs, and LFTs Inflammatory indicators, such as CRP, CSF fluid analysis for chemistry and for ADA.(adenosine deaminase)
patients should be advised of the challenging diagnosis, risk of rejection, need for frequent monitoring, increased prescription dosages, and potential side effects of the anti-TB drugs.
Upon confirmation of the TB diagnosis treatment should include
For two months, isoniazid, rifampin , pyrazinamide , and either streptomycin or ethambutol (EMB) were administered daily; this was followed by seven to ten months of isoniazid and rifampin.
The use of systemic corticosteroids as an additional therapy for TBM has been justified by the idea that reducing morbidity and mortality can be achieved by reducing the inflammatory response.
References;
]Daniel Tran et al. Differential diagnosis of a ring-enhancing brain lesion in the setting of metastatic cancer and a mycotic aneurysm. Radiol Case Rep. 2021 Dec; 16(12): 3850–3854
Hand book of kidney transplanataion 6 th edition,
sharma, V., Prabhash, K., Noronha, V., Tandon, N., & Joshi, A. (2013). A systematic approach to the diagnosis of cystic brain lesions. South Asian Journal of Cancer, 2(2), 98.
I appreciate your DD
Explain the image finding
T1 MRI brain shows complete multiple ring enhancing lesions with thick and irregular walls with one of them causing mid line shift. No obvious related edema
Radiological features:
What is the difference between T1 and T2-weighted images?
Definitions:
Repetition Time (TR) is the amount of time between successive pulse sequences applied to the same slice
Time to Echo (TE) is the time between the delivery of the RF pulse and the receipt of the echo signal
MRI sequences:
T1-weighted images are produced by using short TE and TR times. The contrast and brightness of the image are predominately determined by T1 properties of tissue
T2-weighted images are produced by using longer TE and TR times. In these images, the contrast and brightness are predominately determined by the T2 properties of tissue.
In general, T1- and T2-weighted images can be easily differentiated by looking the CSF. CSF is dark on T1-weighted imaging and bright on T2-weighted imaging. T1 is good for anatomy and T2 is good for pathology
What is your differential diagnosis?
1. Brain tumours (glioblastoma)
2. Lymphoma, PTLD
3. Brain metastases
4. tuberculosis (Tuberculous abscess and tuberculoma)
5. Brain abcess
6. Toxoplasma gondii
7. Cryptococcus neoformans
8. JC virus
9. Others: CMV, VZV, candida species, aspergillus fumigatus
How would you manage this case?
o MDT
o Immediate involvement of the neurosurgeon
o Corticosteroids
o Treat the underlying cause
Screening of active TB and other extra-pulmonary TB
History of previous TB infection, contact with active TB patient, and prophylaxis and vaccination
Symptoms: Chronic cough, weight loss, night sweats, and anorexia
Clinical examination: Examine for active pulmonary tuberculosis, and exclude other extra pulmonary TB
Investigations: CBC, CRP, RFT, LFT, microscopy for AFB and culture, lymph nodes aspiration, and urinary tract
Tests for LTBI (TST and IGRA assays)
Imaging: Chest x ray, renal ultrasound, spinal MRI accordingly
Treatment of CNS TB (at least 9–12 months)
First-line treatment should be a four-drug regimen containing rifamycin used both in severe and non-severe cases (2-month intensive phase of isoniazid, rifampicin, pyrazinamide and ethambutol, followed by isoniazid and rifampicin)
Rifampicin-immunosuppression interaction:
o Rifampicin and transplant-associated immunosuppression interaction
o Rifampicin is a potent inducer of cytochrome P450 3A4 and P-glycoprotein
o Rifampicin decrease the levels of CNIs, mTOR inhibitors, and affects glucocorticoids
o CNIs and mTOR inhibitors levels should be closely monitored during rifampicin-based regimen
o The dose of CNIs and mTOR inhibitor should be increased between 3-5 folds and the glucocorticoid dose should be doubled during treatment
Adverse effects of TB therapy:
The most common adverse event is hepatotoxicity (liver enzymes should be closely monitored with bi-weekly evaluation during the intensive phase of treatment and monthly thereafter)
1. Hepatotoxicity (isoniazid, rifampicin, pyrazinamide, ethambutol)
2. Neurotoxicity (isoniazid, ethambutol)
3. Cytopenia (isoniazid, rifampicin, pyrazinamide, ethambutol)
4. Visual disturbances (rifabutin, ethambutol)
5. Skin lesions (rifampicin)
6. Hyperuricemia (pyrazinamide)
7. Interstitial nephritis (rifampicin, pyrazinamide)
Severe TB or when a vital organ is involved:
Reduce immunosuppression (risk of immune reconstitution inflammatory syndrome, which is associated with the reduction of immunosuppression and the use of rifampicin)
For PTLD: reduce immunosuppression
References
1. Christina A. Nelson, Joseph R. Zunt, Tuberculosis of the Central Nervous System in Immunocompromised Patients: HIV Infection and Solid Organ Transplant Recipients, Clinical Infectious Diseases, Volume 53, Issue 9, 1 November 2011, Pages 915–926.
2. Yadegarynia D, Merza MA, Sali S, Seghatoleslami ZS. Multiple intracranial tuberculomas in a post-kidney transplant patient. Saudi J Kidney Dis Transpl 2016;27:135-8
3. Magnetic Resonance Imaging (MRI) of the Brain and Spine: Basics
4. Krishnamoorthy S, Kumaresan N, Zumla A. Latent tuberculosis infection and renal transplantation – Diagnosis and management. Int J Infect Dis. 2019 Mar;80S:S73-S76. doi: 10.1016/j.ijid.2019.01.049. Epub 2019 Feb 6. PMID: 30738187.
5. Sorohan, B.M.; Ismail, G.; Tacu, D.; Obris ,ca˘, B.; Ciolan, G.; Gîngu, C.; Sinescu, I.; Baston, C. Mycobacterium Tuberculosis Infection after Kidney Transplantation: A Comprehensive Review. Pathogens 2022, 11, 1041. https://doi.org/10.3390/ pathogens11091041
That is a well-structured and well referenced reply.
The image finding
Ring enhanced lesion
Multi-focal
Differences between T1 and T2 MRI;
T1;
T2;
T1 is best for old lesions with absorbed content and dark holes where the lesion was.
T2 is best for mature, dance, scarred lesions where they appear brighter than the surrounding brain tissue.
Diferential diagnosis
Management of Brain tuberculoma in a transplanted recipient
Drug level monitoring;
The trough level for TAC should be closely monitored at least biweekly in the first 2 months, and adjust the dose accordingly.
Drug interaction
References
World Health Organization. Global Tuberculosis Control: Epidemiology, Strategy, Financing. WHO Report 2009. WHO/HTM/TB/2009.411. Geneva, Switzerland: WHO; 2009. 2. Vachharajani T, Abreo K, Phadke A, Oza U, Kirpalani A. Diagnosis and treatment of tuberculosis in hemodialysis and renal transplant patients. Am J Nephrol 2000;20:273-7. 3. Simon HB, Weinstein AJ, Pasternak MS, Swartz MN, Kunz LJ. Genitourinary tuberculosis. Clinical features in a general hospital population.
Tonelli, M.; Wiebe, N.; Knoll, G.; Bello, A.; Browne, S.; Jadhav, D.; Klarenbach, S.; Gill, J. Systematic Review: Kidney Transplantation Compared with Dialysis in Clinically Relevant Outcomes. Am. J. Transplant. Off. J. Am. Soc. Transplant. Am. Soc. Transpl. Surg. 2011, 11, 2093–2109. [CrossRef] [PubMed] 2. Gill, J.S.; Abichandani, R.; Kausz, A.T.; Pereira, B.J.G. Mortality after Kidney Transplant Failure: The Impact of Non-Immunologic Factors. Kidney Int. 2002, 62, 1875–1883. [CrossRef] [PubMed] 3. Kim, J.; Watkins, A.; Aull, M.; Serur, D.; Hartono, C.; Kapur, S. Causes of Graft Loss After Kidney Transplantation Following Rabbit-Antithymocyte Gobulin Induction and Steroid-Sparing Maintenance. Abstract# 2922. Transplantation 2014, 98, 146. 4. Chan, S.; Pascoe, E.M.; Clayton, P.A.; McDonald, S.P.; Lim, W.H.; Sypek, M.P.; Palmer, S.C.; Isbel, N.M.; Francis, R.S.; Campbell, S.B.; et al. Infection-Related Mortality in Recipients of a Kidney Transplant in Australia and New Zealand. Clin. J. Am. Soc. Nephrol. 2019, 14, 1484–1492. [CrossRef] [PubMed] 5. Karuthu, S.; Blumberg, E.A. Common Infections in Kidney Transplant Recipients. Clin. J. Am. Soc. Nephrol. 2012, 7, 2058–2070.
That is a well-structured and well-referenced reply.
The image finding
It is a T1 weighted MRI of the brain showing multiple thick wall irregular ring enhanced lesions with one of them crossing the corpus callosum
Difference between T1 and T2 -weighted images
The T1- weighted MRI will suppresses the signal of the water while enhances the signal of the fatty tissue
The T2- weighted MRI will enhances the signal of the CSF, fluids and grey matter
Differential Diagnosis
How will you manage this case
The management will depend largely on the final diagnosis from the above differential, however, base on the following history and symptoms:
CNS PTLD is a strong differential
Further Investigations
A multidisciplinary care will be deployed including, neurologist, neurosurgeon, ophthalmologist, transplant physician, infectious disease, and oncologist
Treatment if CNS PTLD
If the diagnosis is TB
References
That is a well-structured and well-referenced reply.
Thank you Prof Ajay
d. Treatment is directed at the cause.
Tuberculous meningitis – RHZE for 2 months, then RH for 10 months. Monitor CNI levels for dose adjustment with rifampin. Rifabutin is an alternative with less interaction.
Thankyou well done.
Multiple ring enhancing lesions .
The difference between T1 and T2 weighted images hang on the utilization of short TE and TR times, conversly T2 weighted image produced by using longer Time TE and TR.T1 enhances the picture of fatty tissues and T2 elicit picture of water and suppresses fatty tissues signals
TE: is the minimal time allowed for pulse sequence from delivery to receipt of RF..
TR: its the time between successive pulse sequences.
Differential diagnosis:
1] Abscess
2] secondary metastasis
3] resolving hematoma.
4] Infarct,
5] primary cerebral tumors glioplastoma.
Management:
Involving neurosurgery team is first step.
craniotomy with biopsy is the primary plan of care.
Reference:
1]Daniel Tran et al. Differential diagnosis of a ring-enhancing brain lesion in the setting of metastatic cancer and a mycotic aneurysm. Radiol Case Rep. 2021 Dec; 16(12): 3850–3854
Well done
Thanks, All
This is a ring-enhanced lesion. Could it be a PTLD of the brain?
PTLD is presenting as multiple masses with necrotic center and enhanced peripheral ring in MRI study as its highly cellular surrounded by vasogenic edema similar to primary lymphoproliferative disease of central nervous system in non immune compromized. Its differential diagnosis is pyogenic abscess.
Reference:
1] Daniel J Bell. Primary central nervous system posttransplant lymphoproliferative disorder. Radiopedia;on 12 Dec 2022.
yes, I note
Yes
Welcome prof, yes
Source; BSH guidlines
‘Brevity for the sake of clarity’, I admire you for that approach.
Thnxs prof
Primary CNS PTLD is not common and usually the diagnosis is difficult, and require high index of suspicion (1)
Any post-transplant recipient presenting with new onset of neurological deficit or disturbance of the level of consciousness should be suspected to have PTLD
The diagnosis is usually settled by
MRI with gadolinium (suggestive not diagnostic) , typically it shows irregular, iso- or hypointense lesions on T1-weighted images lesions with homogeneous contrast enhancement after gadolinium administration, in immunocompromised patients (including those with HIV and transplant), lymphoma could presents with multiple ring enhanced lesions.
CSF analysis, cytology and flow cytometry, presence of malignant lymphocytes in CSF is diagnostic
Assessment of EBV both in blood and CSF (suggestive)
Sometimes if the above is not conclusive definitive diagnosis is settled by taking a biopsy from the lesion (diagnostic)
Use of steroid may make the diagnosis even more difficult as it will alter both the radiologic and histopathologic diagnostic evaluation
References
1- Cavaliere R, Petroni G, Lopes MB, et al. Primary central nervous system post-transplantation lymphoproliferative disorder: an International Primary Central Nervous System Lymphoma Collaborative Group Report. Cancer 2010; 116:863.
I appreciate your clinical approach
Yes ,it could be PTLD as PTLD can occur early during first year post transplantation and in T1 MRI image it gives iso to hypointense lesions with surrounding vasogenic odema similar to opportunistic infections
Yes, I agree
Primary CNS PTLD is not common and usually the diagnosis is difficult, and require high index of suspicion (1)
Any post-transplant recipient presenting with new onset of neurological deficit or disturbance of the level of consciousness should be suspected to have PTLD
The diagnosis is usually settled by
Use of steroid may make the diagnosis even more difficult as it will alter both the radiologic and histopathologic diagnostic evaluation
References
1- Cavaliere R, Petroni G, Lopes MB, et al. Primary central nervous system post-transplantation lymphoproliferative disorder: an International Primary Central Nervous System Lymphoma Collaborative Group Report. Cancer 2010; 116:863.
Yes, that is a pragmatic approach well supported by evidence
Both TB tuberculoma and CNS-PTLD give the same features on MRI brain imaging
A well-enhanced ring and multifocal lesion and both lesions can be a risk for the patient who receives immunosuppressant medication.
Short and sweet
Yes mostly a case of PTLD
The risk of developing PTLD is increased in renal transplant recipients of Incompatible transplant with highest risk in the first year posttransplant but remaining increased beyond 10 years
Many thanks Prof.Halawa
Yes
could be, but should know because of different management as immunosuppressive here is this sitting should be reduced or stopped
CNS-PTLD tend to be multifocal rather than unifocal, and it is lobar predominant as basal ganglia or thalamic lesions, it is heterogenous with ill-defined margin of enhancement
Matthew L. White, Drew W. Moore,Yan Zhang,Keiper D. Mark,Timothy C. Greiner,Philip J. Bierman. Primary central nervous system post-transplant lymphoproliferative disorders: the spectrum of imaging appearances and differential. Insights Imaging. 2019 Dec; 10: 46.
This is a ring-enhancing lesion.
The differential diagnosis of such lesion post-transplant on MRI would be
Infectious causes:
Noninfectious causes:
MRI findings in favour of PTLD:
There are no highly sensitive or specific serum and CSF tests to help make the diagnosis of PCNS-PTLD
But, to rule out other etiologies, we need to perform serum and CSF testing.
CT chest and abdomen to rule out other masses.
SOS, stereotactic brain biopsy.
Managment:
First step: reduce immunosuppression, stop MMF, decrease dose of tacrolimus
If still of no benefit, additional treatments like anti-B-cell therapies, methotrexate, chemotherapy regimens, and whole brain radiation can be tried.
Moscato M, Boon-Unge K, Restrepo L. Enhancing brain lesions in a renal transplant patient. Neurohospitalist. 2013 Jan;3(1):15-9. doi: 10.1177/1941874412459333. PMID: 23983883; PMCID: PMC3726124.
Yes, my first differential diagnosis is cerebral PTLD.
it appear as
Lesion number-Multifocal more common than unifocal
Lesion location-Lobar predominantly, numerous basal ganglia and thalamic lesions, less commonly abuts CSF surface
Enhancement pattern-Ring
Enhancement-Heterogeneous
Margin of enhancement-Irregular/Ill-defined
ADC-Elevated compared to lymphoma, will still have focal areas of restricted diffusion.
Spectroscopy- Increased choline, lipid and lactate
Decreased NAA
Intratumorally susceptibility signal -Peripheral pattern of punctate hypo intensities, tendency to bleed
Reference
White ML, Moore DW, Zhang Y, Mark KD, Greiner TC, Bierman PJ. Primary central nervous system post-transplant lymphoproliferative disorders: the spectrum of imaging appearances and differential. Insights Imaging. 2019 Apr 11;10(1):46. doi: 10.1186/s13244-019-0726-6. PMID: 30972513; PMCID: PMC6458224.
Thank you Prof. Ahmad..
Yes, sure solitary >4 cm lesion on T2 MRI/ high uptake on SPECT is highly suggestive, EBV PCR on CSF may indicate it.
Refernce:
Yes PTLD is highly suspected.
· Typically monomorphic, high grade B-cell lymphoma and all are EBV-positive.
· Usually multifocal and detectable by MRI but tissue biopsy is recommended given that opportunistic infections may present with similar radiological findings.
· The overall prognosis is generally considered poor.
Reference:
Shah N, Eyre TA, Tucker D, Kassam S, Parmar J, Featherstone C, Andrews P, Asgari E, Chaganti S, Menne TF, Fox CP, Pettit S, Suddle A, Bowles KM; Haemato-Oncology Task Force of the British Society for Haematology and the British Transplantation Society. Front-line management of post-transplantation lymphoproliferative disorder in adult solid organ recipient patients – A British Society for Haematology Guideline. Br J Haematol. 2021 May;193(4):727-740. doi: 10.1111/bjh.17421. Epub 2021 Apr 20. PMID: 33877688.
Thanks;our Prof.
Yes: it is one from my differential diagnosis;
and to exclude others;
Neoplastic causes;
-CNS primary lymphoma
-Glioblastoma
-Metastasis
-Demyelinating disease
-Radiation necrosis
-Resolving Hematoma
Infectious causes;
-CNS tuberculosis (Tuberculoma)
-Cerebral abscess
-CNS toxoplasmosis
-Neurocysticercosis
-Fungal infections;(Cryptococcosis or Histoplasmosis).
Yes PTLD could have homogenous enhancement or heterogenous enhancement and also ring enhancement lesions surrounding by vasogenic edema similar to the provided MRI images
main DDX in this indexed case including infection vs CNs malignancy
YES, sure.
It is on the top of the list.
There is a tendency for CNS-PTLD lesions to be ring enhancing, have ill-defined enhancing margins, multifocal, supratentorial, and lobar in location.
Reference:
Ginat DT, Purakal A, Pytel P. Susceptibility-weighted imaging and diffusion-weighted imaging findings in central nervous system monomorphic B cell post-transplant lymphoproliferative disorder before and after treatment and comparison with primary B cell central nervous system lymphoma. J Neurooncol. 2015;125(2):297-305. doi:10.1007/s11060-015-1903-1
Dear All
The MRI or CT examinations should be performed with and without intravenous contrast. Contrast greatly helps to define the lesions in CNS-PTLD. MRI is superior to CT in sensitivity and for detailed analysis of CNS-PTLD lesions. An MRI protocol to best delineate and characterize the brain lesions should include T2-weighted/T2 fluid-attenuated inversion recovery (FLAIR), T1-weighted pre-contrast, a gradient-echo or susceptibility-weighted imaging sequence, diffusion-weighted/diffusion tensor imaging (DWI), and the post-contrast T1-weighted images. Perfusion-weighted imaging (PWI) should also be useful to help differentiate CNS-PTLD from other potential diagnostic considerations.
There is a tendency for CNS-PTLD lesions to be ring-enhancing, have ill-defined enhancing margins, and be multifocal, supratentorial, and lobar in location. The ring enhancement is secondary to central necrosis, which is a frequent microscopic finding. A partial ring of enhancement appearance has been described. Diffuse enhancement, in general, is less common but Cavaliere et al. in a large series of 34 patients reported a higher percentage with homogeneous enhancement (41%) or heterogeneous enhancement (56%) and only 29% had ring enhancement. Snanoudj et al. described 87% of cases to have at least one ring-enhancing lesion and all cases have lesions with enhancement.
Yes Professor.
One of the differential diagnosis of a ring-enhancing lesion in a transplant recipient is a primary CNS PTLD (1).
Reference:
Yes it could be , usually these show homogenous ring enhancement as compared to primary CNS tumors which have heterogeneous enhancements.
Yes.
PTLD may present as multiple contrast enhancing lesion.
Yes, this is an important differential
This is a ring-enhanced lesion. Could it be a PTLD of the brain? (1, 2)
– yes, it can be primary CNS post-transplant lymphoproliferative disorder (PCNS-PTLD)
– PCNS-PTLD is a rare complication of SOT
– it is usually multifocal and enhances in either a homogenous pattern or a ring-enhancing pattern
– diagnosis typically requires a brain biopsy since CSF and neuro-ophthalmologic assessments are usually non-diagnostic
– most are B-cell EBV-induced lymphomas
– therapeutic options: immune reconstitution, corticosteroids, antiviral agents although their role remain unclear
– the response rates to chemotherapy, radiotherapy and rituximab are favourable
References
1. Buell JF, Gross TG, Hanaway MJ, Trofe J, Roy-Chaudhury P, First MR, et al. Posttransplant lymphoproliferative disorder: significance of central nervous system involvement. Transplantation proceedings. 2005 Mar;37(2):954-5. PubMed PMID: 15848587. Epub 2005/04/26. eng.
2. Cavaliere R, Petroni G, Lopes MB, Schiff D. Primary central nervous system post-transplantation lymphoproliferative disorder: an International Primary Central Nervous System Lymphoma Collaborative Group Report. Cancer. 2010 Feb 15;116(4):863-70. PubMed PMID: 20052713. Pubmed Central PMCID: PMC4113953. Epub 2010/01/07. eng.
1st yr post renal transplant in a pt on immunosuppression meds with a ring enhancing lesions, the differential diagnosis is wide with TB and PTLD being high on the list. PTLD appears mostly as a ring enhancing lesion with rugged margins, mostly focal but multifocal lesions have also been defined. Histology to R/O other infections and differentials prior to initiating treatment.
Many of the PTLD cases had central nervous system (CNS) involvement.
The risk is especially true for EBV-seronegative individuals who received belatacept
The risk is high within the first year of transplant.
Yes PTLD could have homogenous enhancement or heterogenous enhancement and also ring enhancement lesions surrounding by vasogenic edema similar to the provided MRI images
main DDX in this indexed case including infection vs CNs malignancy
Yes, it could be one of the different radiologic presentations of PTLD.
Reference:
Imafuku, A., Tanaka, K., Marui, Y., Ubara, Y., Takaichi, K., Tomikawa, S., Ota, Y., Fujii, T., & Ishii, Y. (2018). Primary central nervous system post-transplant lymphoproliferative disorder diagnosed by peripheral facial nerve palsy. Internal Medicine, 57(13). https://doi.org/10.2169/internalmedicine.9613-17
Q1.
Q2.
Q3.
Any patient with headache on tarclimus, you don’ want to forget PRES syndrome but looking at this image;
The differential diagnosis is simplified by MAGIC DR mnemonic:
Q4.
Management is MDT including , neurosurgeon, infectious disease, conselor & radiologist and it is largely depend on the cause. One would consider further evaluation
Source; Hand book of kidney transplanataion 6 th edition, M.tuberculosis after kidney transplanataion by Bogdan et al., Radiopaedian.org, T1-weighted and T2-weighted synthesis with convolutional generative adversarial networks by Daisuke Kawahara & Yasushi Ngata
Thanks, Ben
I agree with the difference between T1 and T2. Since T2 enhances water, it good for pathology (oedema), while T1 is good for the anatomy (brain structures).
Please review your DD as it not correct.
Yes, we ca add these ;
And, in addition to your list the following need to be considered:
There are different contrast images in magnetic resonance MRI types. T1-weighted MRI enhances the signal of the fatty tissue and suppresses the signal of the water. T2-weighted MRI enhances the signal of the water.
What is your differential diagnosis?
Confirm the diagnosis first
this supports the diagnosis of TB.
CSF sample should be sent for acid-fast smear
CSF adenosine deaminase.
send for NAA assays utilizing polymerase chain reaction (PCR)
PET-CT scan
Treatment:
If confirmed the diagnosis of TB is, The recommended treatment regimen for presumed drug-susceptible TBM consists of two months of daily INH, rifampin (RIF), pyrazinamide (PZA), and either streptomycin (SM), or ethambutol (EMB), followed by 7–10 months of INH and RIF.
systemic corticosteroids have been used as an adjunctive treatment for TBM on the basis of the notion that dampening the inflammatory response can lessen morbidity and mortality.
Reference:
Sharma, V., Prabhash, K., Noronha, V., Tandon, N., & Joshi, A. (2013). A systematic approach to the diagnosis of cystic brain lesions. South Asian Journal of Cancer, 2(2), 98.
Typing whole sentence in bold or typing in capitals amounts to shouting.
I like your detailed summary.
Explain the image finding
What is the difference between T1 and T2-weighted images?
What is your differential diagnosis?
How would you manage this case?
To reach to a definitive diagnosis
Management is according to the diagnosis
I like your detailed summary.
Explain the image finding
Cerebral PTLD, MRI in T1 with gadolinium.
What is the difference between T1 and T2-weighted images?
T1 for longitudinal and T2 for transverse relaxation
. T1 is the time constant of the exponential describing the rate of realignment with the longitudinal axis of the main magnetic field.
T2 is the time constant of the exponential describing the decay of the transverse magnetization.
These time constants, T1 and T2, in turn depend on the local chemical microenvironment, which varies between tissues.
Therefore, three independent properties of tissue (proton density, T1, and T2) can be determined by magnetic resonance imaging (MRI).
What is your differential diagnosis?
The differential diagnosis of tuberculoma includes:
● Neurocysticercosis (NCC) and tuberculoma share similar epidemiologic, clinical, and radiographic features.
(identification of a scolex within a cystic lesion is a pathognomonic radiographic finding for NCC)
●Cryptococcoma and tuberculoma share similar clinical and radiographic features. Cryptococcus gattii is more likely than Cryptococcus neoformans to cause cryptococcoma (of the lungs and/or brain)
In the absence of contraindication to lumbar puncture, CSF should be examined; routine studies should be performed, in addition to cryptococcal antigen, India ink staining, and fungal culture. Alternatively, brain biopsy may be warranted.
●CNS toxoplasmosis –
Toxoplasmosis is the most common CNS infection in HIV-infected patients with CD4 count <100 cells/microL who are not receiving appropriate prophylaxis. Patients typically present with headache, fever, and altered mental status; focal neurologic deficits or seizures are also common. A definitive diagnosis requires a compatible clinical syndrome, identification of ≥1 mass lesions on brain imaging, and detection of the organism in a biopsy specimen; for most patients a presumptive diagnosis is made to avoid a brain biopsy.
●Brain abscess – Clinical manifestations of brain abscess may be subacute and nonspecific. Lumbar puncture is contraindicated in patients with papilledema or focal symptoms or signs; if it is feasible to obtain CSF, findings may demonstrate elevated protein concentration, low glucose concentration, and pleocytosis. A microbiologic diagnosis may be established culture of material obtained via stereotactic-guided aspiration or surgery.
●CNS lymphoma – CNS lymphoma is an important cause of CNS lesion in HIV-infected patients. Clinical presentation is typically acute to subacute, with symptoms such as confusion, lethargy, memory loss, hemiparesis, aphasia, and/or seizures progressing over days to weeks. The diagnosis is established via brain biopsy.
●Brain tumor (primary or metastatic brain) – Clinical manifestations of brain tumor include headache, seizures, focal deficits, cognitive dysfunction, and increased intracranial pressure. The diagnosis is suspected based on radiographic finding
How would you manage this case?
Management of PTLD has varied significantly according to the PTLD subtype and the type of transplant, as well as from institution to institution [15-17]. The main options for initial treatment are reduction of immunosuppression, immunotherapy with the CD20 monoclonal antibody rituximab, chemotherapy, radiation therapy, or a combination of these.
DIAGNOSIS
The diagnosis of active TB often requires an invasive procedure, such as bronchoscopy with bronchoalveolar lavage or lung biopsy.
Nucleic acid amplification methods
It should be noted that neither tuberculin skin testing nor interferon-gamma release assays distinguish between active and latent TB.
Treatment of tuberculoma consists of
antituberculous therapy;
isoniazid plus rifapentine for 12 weeks,
adjunctive glucocorticoids. for patients with cerebral edema (particularly when edema is out of proportion to mass effect in the setting of associated altered mental status or focal neurologic deficits), increased intracranial pressure, and/or presence of concomitant meningitis.
Surgical consultation is warranted for patients with obstructive hydrocephalus or brainstem compression.
Thanks, Hamada
This is a ring-enhanced lesion. Could it be a PTLD?
Yes. Clinical sceniro support PTLD
Patient ABOi
Desensitization
Heavy immunotherapy
First 6 months
Noted
Explain the image finding
This is Magnetic resonance imaging appearance of tuberculoma T1 with contrast.
There are at least two lesions of granuloma, hypointense on T1, the lesion shows rim enhancementThese lesions press on the left lateral ventricle and cause midline shift.
What is the difference between T1 and T2-weighted images?
based on different stage of maturation, there are differences of granuloma appearance on MRI .
T1 and T2 ca help to evaluate;
(A) A noncaseating granuloma, isointense on T1-weighted and hyperintense on T2-weighted images.
(B) A caseating solid granuloma, isointense on T1-weighted and strikingly hypointense on T2-weighted images with rim enhancement on postcontrast image.
(C ) A caseating granuloma with central liquefaction, hypointense on T1-weighted and hyperintense on T2-weighted images with peripheral hypointense rim of collagenous capsule.
This table shows the difference between T1 – T2 – flair
T1-Weighted
CSF Dark
Wight matter Light
Cortex Gray
Fat Bright
Inflammation Dark
T2-Weighted
CSF Bright
Wight matter Dark Gray
Cortex Light Gray
Fat Light
Inflammation Bright
Flair
The same as t2 but CSF CSF appeares dark
What is your differential diagnosis?
fungal granulomas,
pyogenic brain abscess,
primary brain tumours (glioma and lymphoma),
and metastases.
neurocysticercosis
The parenchymal lesions of TB in the CNS are:
tuberculous granuloma (tuberculoma),
cerebritis,
abscess,
military TB,
or tuberculous encephalopathy.
How would you manage this case
Depending on the BTS RECOMMENDATIONS
Rifampicin in particular can interact with immunosuppressive regimens, increasing the chance of graft rejection, and doses of mycophenolate mofetil, tacrolimus and ciclosporin may need adjustment. Corticosteroid doses should be doubled in patients receiving rifampicin. (B)
Dose modifications may be necessary depending on the level of transplant function drugs levels should be monitored.
In general, standard therapy for 6 months of 2RHZE/M followed by 4RH should be used.
Antituberculosis drug interactions with immunosuppressive drugs are important and can lead to graft rejection.
Rifampicin is the drug most likely to interfere with immunosuppressive treatment by induction of a number of liver enzymes including cytochrome P450.
The daily corticosteroid dose should be increased to twice the baseline dosage in patients taking rifampicin.
Rifampicin also lowers blood levels of ciclosporin, which should be monitored and the dose adjusted.
There are case reports describing renal transplant recipients who demonstrated an increase in tacrolimus metabolism as a result of rifampicin administration .
Rifampicin also interacts with mycophenolate mofetil and resulting functional inhibition of enterohepatic recirculation of mycophenolate.
Once rifampicin has been stopped, liver enzyme induction usually takes 2 weeks to return to normal.
Azathioprine sometimes causes hepatotoxicity, which has to be differentiated from the hepatotoxicity due to antituberculosis drugs.
REFERENCES
Guidelines for the prevention and management of Mycobacterium tuberculosis infection and disease in adult patients with chronic kidney disease.
British Thoracic SocietyCentral Nervous System Tuberculosis: An Imaging Perspective Vikas Chaudhary, MDa, Shahina Bano, MDb,*, Umesh Chandra Garga,MD
https://case.edu/med/neurology/NR/MRI%20Basics.htm#:~:text=The%20most%20common%20MRI%20sequences,longer%20TE%20and%20TR%20times.
Sorry for repeating the answer but I still have technique error on this platform, notably when I use the format bar below.
OK
Explain the image finding
This is Magnetic resonance imaging appearance of tuberculoma T1 with contrastThere are at least two lesions of granuloma, hypointense on T1, the lesion shows rim enhancementThese lesions press on the left lateral ventricle and cause midline shift
What is the difference between T1 and T2-weighted images?
based on different stage of maturation, there are differences of granuloma appearance on MRI .
T1 and T2 ca help to evaluate;
(A) A noncaseating granuloma, isointense on T1-weighted and hyperintense on T2-weighted images.(B) A caseating solid granuloma, isointense on T1-weighted and strikingly hypointense on T2-weighted images with rim enhancement on postcontrast image. (C ) A caseating granuloma with central liquefaction, hypointense on T1-weighted and hyperintense on T2-weighted images with peripheral hypointense rim of collagenous capsule.
This table shows the difference between T1 – T2 – flair
T1-Weighted
CSF Dark
Wight matter Light
Cortex Gray
Fat Bright
Inflammation Dark
T2-Weighted
CSF Bright
Wight matter Dark Gray
Cortex Light Gray
Fat Light
Inflammation Bright
Flair
The same as t2 but CSF CSF appeares dark
What is your differential diagnosis?
fungal granulomas, pyogenic brain abscess, primary brain tumours (glioma and lymphoma), and metastases.neurocysticercosisThe parenchymal lesions of TB in the CNS are
tuberculous granuloma (tuberculoma), cerebritis, abscess, military TB, or tuberculous encephalopathy.
How would you manage this case
Depending on the BTS RECOMMENDATIONS
Rifampicin in particular can interact with immunosuppressive regimens, increasing the chance of graft rejection, and doses of mycophenolate mofetil, tacrolimus and ciclosporin may need adjustment. Corticosteroid doses should be doubled in patients receiving rifampicin. (B)
Dose modifications may be necessary depending on the level of transplant function drugs levels should be monitored. In general, standard therapy for 6 months of 2RHZE/M followed by 4RH should be used.Antituberculosis drug interactions with immunosuppressive drugs are important and can lead to graft rejection. Rifampicin is the drug most likely to interfere with immunosuppressive treatment by induction of a number of liver enzymes including cytochrome P450. The daily corticosteroid dose should be increased to twice the baseline dosage in patients taking rifampicin. Rifampicin also lowers blood levels of ciclosporin, which should be monitored and the dose adjusted. There are case reports describing renal transplant recipients who demonstrated an increase in tacrolimus metabolism as a result of rifampicin administration .
Rifampicin also interacts with mycophenolate mofetil and resulting functional inhibition of enterohepatic recirculation of mycophenolate.
Once rifampicin has been stopped, liver enzyme induction usually takes 2 weeks to return to normal. Azathioprine sometimes causes hepatotoxicity, which has to be differentiated from the hepatotoxicity due to antituberculosis drugs.
REFERENCES
Guidelines for the prevention and management of Mycobacterium tuberculosis infection and disease in adult patients with chronic kidney diseaseBritish Thoracic SocietyCentral Nervous System Tuberculosis: An Imaging Perspective Vikas Chaudhary, MDa, Shahina Bano, MDb,*, Umesh Chandra Garga,MDbhttps://case.edu/med/neurology/NR/MRI%20Basics.htm#:~:text=The%20most%20common%20MRI%20sequences,longer%20TE%20and%20TR%20times.
Please review your DD
Explain the image findingThis is Magnetic resonance imaging appearance of tuberculoma T1 with contrastThere are at least two lesions of granuloma, hypointense on T1, the lesion shows rim enhancementThese lesions press on the left lateral ventricle and cause midline shiftWhat is the difference between T1 and T2-weighted images?based on different stage of maturation, there are differences of granuloma appearance on MRI .
T1 and T2 ca help to evaluate;
(A) A noncaseating granuloma , isointense on T1-weighted and hyperintense on T2-weighted images,
(B) A caseating solid granuloma, isointense on T1-weighted and strikingly hypointense on T2-weighted images with rim enhancement on postcontrast image.
(C ) A caseating granuloma with central liquefaction, hypointense on T1-weighted and hyperintense on T2-weighted images with peripheral hypointense rim of collagenous capsule.
This table shows the difference between T1 – T2 – flair
Tissue T1-Weighted T2-Weighted Flair
CSF Dark Bright Dark
Wight matter Light Dark Gray Dark Gray
Cortex Gray Light Gray Light Gray
Fat Bright Light Light
Inflammation Dark Bright b Bright
What is your differential diagnosis? fungal granulomas, pyogenic brain abscess, primary brain tumours (glioma and lymphoma), and metastases.neurocysticercosisThe parenchymal lesions of TB in the CNS are
tuberculous granuloma (tuberculoma), cerebritis, abscess, military TB, or tuberculous encephalopathy.How would you manage this caseDepending on the BTS RECOMMENDATIONS
Rifampicin in particular can interact with immunosuppressive regimens, increasing the chance of graft rejection, and doses of mycophenolate mofetil, tacrolimus and ciclosporin may need adjustment. Corticosteroid doses should be doubled in patients receiving rifampicin. (B)
Dose modifications may be necessary depending on the level of transplant function and additional drugs, and levels should be monitored. In general, standard therapy for 6 months of 2RHZE/M followed by 4RH should be used.Antituberculosis drug interactions with immunosuppressive drugs are important and can lead to graft rejection. Rifampicin is the drug most likely to interfere with immunosuppressive treatment by induction of a number of liver enzymes including cytochrome P450. The daily corticosteroid dose should be increased to twice the baseline dosage in patients taking rifampicin. Rifampicin also lowers blood levels of ciclosporin, which should be monitored and the dose adjusted. There are case reports describing renal transplant recipients who demonstrated an increase in tacrolimus metabolism as a result of rifampicin administration . Patients should be monitored. Rifampicin also interacts with mycophenolate mofetil by induction of hepatic, renal and gastrointestinal uridine diphosphate-glucuronosyl transferases and organic anion transporters with resulting functional inhibition of enterohepatic recirculation of mycophenolate.Once rifampicin has been stopped, liver enzyme induction usually takes 2 weeks to return to normal. Azathioprine sometimes causes hepatotoxicity, which has to be differentiated from the hepatotoxicity due to antituberculosis drugs.REFERENCES
Guidelines for the prevention and management of Mycobacterium tuberculosis infection and disease in adult patients with chronic kidney disease British Thoracic SocietyCentral Nervous System Tuberculosis: An Imaging Perspective Vikas Chaudhary, MDa, Shahina Bano, MDb,*, Umesh Chandra Garga, MDbhttps://case.edu/med/neurology/NR/MRI%20Basics.htm#:~:text=The%20most%20common%20MRI%20sequences,longer%20TE%20and%20TR%20times.
Please review your DD
Explain the image finding
Oval lesions with mass effect and generating midline deviation with signs of intracranial hypertension and significant perilesional edema leading to compression mainly of the left cerebral hemisphere.
There are signs of breakdown of the blood-brain barrier.
Assess on subsequent images whether there is brain herniation, which would contraindicate cerebrospinal fluid puncture.
What is the difference between T1 and T2-weighted images?
T1 high signal for fat
Elevated signals for paramagnetic substances such as MRI contrast agents. The contrast agent commonly used in T1-weighted imaging is gadolinium. It is a non-toxic agent that appears very bright on T1-weighted images. For this reason, the use of gadolinium-enhanced T1-weighted imaging is very useful to observe vascular structures and breakdown of the blood-brain barrier.
Reduced signal for content consisting mainly of water, such as edema, tumors or hemorrhages.
T2 has high signal for higher water content, which allows this sequence to visualize edema, tumors, strokes, infections and inflammation
Reduced sign for fat
Reduced signal for paramagnetic substances (MRI contrast agents).
What is your differential diagnosis?
Neurotuberculosis
Neurotoxoplasmosis
Primary Central Nervous System Lymphoma
Brain metastases
How would you manage this case?
1. Corticosteroids to reduce cerebral edema and the inflammatory process
2. Empirical start of the scheme for Tuberculosis (extend the scheme time to 9 months to one year)
3. If possible, collect cerebrospinal fluid in an attempt to collect it for molecular diagnosis of tuberculosis (in our case GeneXpert in Brazil)
4. Do not consider the ADA, as the breakdown of the blood-brain barrier naturally increases its values
5. Hospitalization for constant neurological evaluation
6. Measure serum levels of immunosuppressants and remove Tacrolimus from the scheme due to its high interaction with Rifampicin. Neurotuberculosis, as it is quite serious, we must give priority to the classic scheme of greater effectiveness.
7. Mycophenolate and Azathioprim do not interact with the tuberculostatic scheme. mTor inhibitors can be used but with very close monitoring.
8. Measure antiagglutinin antibody titers to assess the risk of graft rejection after starting the antituberculostatic regimen
Please review your DD
I forgot Invasive Fungal Diseases, Meningitis, Vascular diseases (Stroke)
Explain the image finding
MRI brain shows a ring enhancing lesion .
What is the difference between T1 and T2-weighted images?
Image attached
What is your differential diagnosis?
The differential diagnosis for a ring-enhancing cerebral lesion-
tuberculoma
metastasis
Abscess
Glioblastoma
Infarct
Contusion
demyelinating disease
radiation necrosis
resolving hematoma
PTLD
How would you manage this case?
Treatment will be as per cause
PTLD IN MRI BRAIN
Primary CNS PTLD is often multifocal. On CT and MRI, the lesions may manifest with hemorrhage, necrosis, and surrounding vasogenic edema. The enhancement pattern is typically peripheral. These features are nonspecific and closely resemble those of brain metastases
Radiologic Differentiation of Primary CNS Posttransplant Lymphoproliferative Disorder From Brain Metastasis
Matthew L. White et al
T1 vs T2