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2. A 47-year-old CKD 5 has kidney transplantation from his brother, 111 mismatch, no DSAs. Excellent kidney function and Tacrolimus-based immunosuppression. One year later, he presented to you with a headache, confessional states/mental status changes, and seizure. T1 MRI picture is shown below.
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Explain the image finding
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What is the difference between T1 and T2-weighted images?
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What is your differential diagnosis?
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How would manage this case?
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2. A 47-year-old CKD 5 has kidney transplantation from his brother, 111 mismatch, no DSAs. Excellent kidney function and Tacrolimus-based immunosuppression. One year later, he presented to you with a headache, confessional states/mental status changes,…
2. A 47-year-old CKD 5 has kidney transplantation from his brother, 111 mismatch, no DSAs. Excellent kidney function and Tacrolimus-based immunosuppression. One year later, he presented to you with a headache, confessional states/mental status changes,…
2. A 47-year-old CKD 5 has kidney transplantation from his brother, 111 mismatch, no DSAs. Excellent kidney function and Tacrolimus-based immunosuppression. One year later, he presented to you with a headache, confessional states/mental status changes,…
2. A 47-year-old CKD 5 has kidney transplantation from his brother, 111 mismatch, no DSAs. Excellent kidney function and Tacrolimus-based immunosuppression. One year later, he presented to you with a headache, confessional states/mental status changes,…
2. A 47-year-old CKD 5 has kidney transplantation from his brother, 111 mismatch, no DSAs. Excellent kidney function and Tacrolimus-based immunosuppression. One year later, he presented to you with a headache, confessional states/mental status changes,…
> MRI of brain shows 2 ring enhancing lesion with perilesional oedema in left cerebral hemisphere.
> T1-weighted image enhances fat tissue signals like CT scan & T2- weighted image enhances water signals.
>D/D: brain metastasis, brain abscess, tuberculoma, toxoplasmosis, PTLD, fungal infection ( aspergilloses, histoplasmosis).
> further evaluation ( Toxoplasma IgM, PCR for EBV, CSF study, CBC, CXR, FNAC if possible). Management by I/V steroids, anticonvulsant, specific theray according to cause.
Explain the image finding
MRI of brain showing two circumscribed lesions with peri-lesional oedema in the sub-cortical region of left cerebral hemisphere
What is the difference between T1 and T2-weighted images?
T1 weighted MRI shows CSF, Infection, inflammation & demyelination as dark (like CT scan); whereas T2 weighted images enhances water signals and is opposite of T1.
What is your differential diagnosis?
Toxoplasmosis
PTLD
Tubercular abscess
Cryptococcosis
How would manage this case?
Investigations
Managment
Specific treatment according to cause
Reference:
Meena P, Bhargava V, Rana D, Bhalla A, Gupta A. An Approach to Neurological Disorders in a Kidney Transplant Recipient. Kidney360. 2020 Jun 16;1(8):837-844. doi: 10.34067/KID.0002052020.
2 incomplete rings suggestive of PTLD
DD:
viral fungal and bacterial infection
other malignancy
Explain the image finding
This is T1 MRI (CSF appear dark) image that shows two ring enhancing lesions in the LT hemisphere (multifocal, thick and irregular wall mostly PTLD)that are surrounded by oedema and compressing the LT ventricle
What is the difference between T1 and T2-weighted images?
T1-weighted MRI enhances the signal of the fatty tissue signal and suppresses the water signal, so CSF appear dark like the above picture.
T2-weighted MRI enhances both the fatty tissue and the water signals. So, CSF appear bright
What is your differential diagnosis?
· Infectious causes:
· Bacterial: Brain abscess, Mycobacterium TB, Listeria, Nocardia
· Viral: CMV, JC Virus, VZV
· Fungal: Cryptococcus, Aspergillus
· Toxoplasmosis
· Non Infectious cases:
· Primary Brain tumors (glioblastoma)
· Brain metastases
· PTLD
How would manage this case?
Diagnostic Work-up:
· FBC, Inflammatory markers, U&E, TAC trough level LDH
· Sputum for AFBs smear, culture, genXpert.
· Viral serology: EBV PCR, CMV PCR, JC PCR, HIV
· Blood cultures, Serum Beta D-glucan and galactomannan
· Serum cryptococcal antigen and toxoplasma antibodies.
· CXR to detect any primary lung malignancy or any lesion suspicious of pulmonary TB
· CT chest, abdomen and pelvis to look for any primary tumour that may cause a distant brain metastasis.
· PET-CT
· Finally, -CT -guided biopsy to establish a diagnosis (depending on the patient general condition)
Management:
· ITU admission for cardio-respiratory support and neuro-vital observation
· MDT including neurosurgery, neurologist, ID team, hemato-oncology team and the transplant team.
· Control seizures with Benzodiazepines and anti-epileptic drugs.
· Start high dose steroids for brain oedema
· Careful reduction of Immunosuppression and follow graft function.
· Further management depends on the cause
· For PTLD:
The modalities of treatment include reduction in immunosuppression, cranial radiotherapy, intravenous and intrathecal rituximab when CD20 is expressed on B-lymphocytes and PTLD cells, and chemotherapy.
References:
: Explain the image finding
CE-MRI of brain – shows 2ring-enhancing lesions surrounding oedema; incomplete ring (interruption of the wall by soft tissue), suggestive more of PTLD.
Q2: What is the difference between T1 and T2-weighted images?
T1-weighted MRI enhances signals of fatty tissue, and suppresses signals of water; whereas T2-weighted image enhances water signals.
So, on MRI, fluids look (black in T1 and white in T2).
Oedema and inflammatory tissue on T2 will appear bright, due to high water content.
Q3: Differential diagnosis
· PTLD
· Tuberculoma
· Brain abscess
· Fungal infections (aspergillus, histoplasmosis, cryptococcus)
· Toxoplasmosis
· Brain Tumor (Primary, GBM) and Metastatic – less likely, as the patient must be evaluated before transplant to rule out active malignancy.
Q4: How would manage this case?
Comprehensive history and examination:
· history of TB symptoms; contact with TB patient;
· Lymphadenopathy, organomegaly
· neurologic examination
· fundoscopy
Lab Tests:
· CBC, LFT, RFT, U/A, U/C,
· CSF analysis (Fundoscopy to rule out papilledema) – protein, cytology, ADA, Culture and TB-Gold
· TB tests – IGRA, TSTS, Quantiferon-TB Gold on blood and CSF
· EBV-DNA qPCR, CMV-DNA qPCR
· Toxoplasma Antibody / DNA detection in CSF or blood.
CT / MRI – guided BIOPSY of the lesion — gold standard for diagnosis.
Treatment:
· Treatment for PTLD
Ø IS Reduction:
Ø Reduction or Stop MMF; CNI minimization targeting lowest Trough level (5ng/ml); Switch to mTOR inhibitors.
Ø Rituximab alone or in combination with chemotherapy (R-CHOP) and Radiotherapy for localized CNS PTLD.
Ø EBV-DNA viral load to monitor treatment-response.
Ø Adoptive immunotherapy with EBV-specific cytotoxic-T lymphocyte (EBV-CTLs) or donor lymphocyte infusion (DLI) against EBV infected cells may be tried in refractory CNS-PTLD.
· Treatment for tuberculoma (CSF analysis / culture / PCR confirmation) – ATT – 4drugs regimen x 3months + 2 drugs x 12-18 months
Ø Rifampicin (preferable) may affect drug level of CNI through Cyp-450 enzyme induction à needs increase dose of Tacrolimus 2-3times, with frequent monitoring of C0 level.
Ø Replacement of rifampin by rifabutin may be considered to avoid drug interaction with CNI.
Ø MMF dose reduction
Ø Response monitoring – clinically as well as
· Brain abscess needs surgical excision + antibiotics / antifungal / ATT
· Primary Tumors or Brain mets need evacuation / excision of Tumor + adjuvant Radiotherapy.
o Gamma knife / focused image-guided radio-surgery, are effective with less morbidity – getting popular now days.
· Anti-convulsion therapy needs to be given for long term.
Q1: MRI shows two ring-enhanced lesions in the brain of TX recipient with surrounding edema.
Q2: T1-weighted image enhances fat tissue signals, but T2-weighted image enhances water signals.
Q3: Differential diagnosis are:
PTLD
Brain metastasis
Tuberculoma
Toxoplasmosis
Brain abcess
Fungal infections (cryptosporidium, aspergillus, histoplasmosis)
Q4: Comprehensive history and physical examination such as history of B symptoms, contact with patient with TB, fundoscopy and neurologic examination, evidence of lymphadenopathy or organomegaly.
Laboratory tests such as CBC. Diff, biochemistry, LFT, RFT, U/A, U/C, CSF analysis and PCR for TB, toxoplasmosis, CMV or EBV. Before CSF analysis confirm that there is no papilledema. Biopsy of the lesion remains the gold standard for diagnosis.
Treatment includes: Reduction of IS. Stop MMF and reduce CNIs with level monitoring. Switch to mTOR inhibitors and use monoclonal CD20 antibody (Rituximab) alone or in combination with chemotherapy in form of R-CHOP.
Radiotherapy for localized CNS PTLD. Adoptive immunotherapy with EBV-specific T cytotoxic lymphocyte (EBV-CTLs) or donor lymphocyte infusion (DLI) against EBV infected cells. It could be associated with the development of GVHD.
Treatment for tuberculoma if CSF analysis, culture or PCR confirms it, should be performe with four anti- TB drugs with replacement of rifabutin instead of rifampin (due to drug interaction with CNIs) for 9-12 months or even for longer periods.
· Explain the image finding:
2 ring enhancing lesions with surrounding eodema, interruption of the wall of the ring.
· What is the difference between T1 and T2-weighted images?
· T1 enhances fat and suppresses water signals, while T2 enhances water signals
· What is your differential diagnosis?
Infectious causes: TB, Toxoplasma, other fungal infection
Non infectious, malignancy: Primary CNS tumour
Metastatic Lesion
PTLD
· How would manage this case?
ICU admission
Routine investigations
Anti brain oedema medications and seizure control.
Specific investigation to confirm diagnoses: culture, ESR, CRP, CSA after controlling oedema, neurosurgical consultation.
Management according to result.
What is your differential diagnosis?Malignancy
Metastatic
PTLD
TB
Abcess
Explain the image finding
2 contrast-enhanced oval shaped lesion in the left hemisphere surrounded by brain edema compressing the ledft ventricle with midline shift.
What is your differential diagnosis?
PCNS lymphoma
glioblastoma (GBM),
metastatic disease,
abscess, or other infection: Infections in transplant patients can include Aspergillus, Nocardia asteroides, Toxoplasma gondii, Listeria monocytogenes, Mucorales, Tuberculosis, and less commonly Cryptococcus.
How would manage this case?
-ICU admission, neurology consultation, start control of seizures with anti-epileptic drugs , dexamethasone to decrease brain edema.
– kidney function tests , electrolytes, CBC , CRP.
– detection of viruses mainly CMV ,and EBV .
-chest x-ray and CT for for detection of primary malignancy , metastasis , TB lesion.
– PET-CT.
– Antiviral ttt according to results.
-Treatment according to cause, in case of PTLD reduction of IS (reduction of tacrolimus by 50 %) is the first step shifting to mTORi can be also a good option as it has protective antitumor effect, Intrathecal chemotherapy with rituximab , CHOP and radiotherapy.
there is insufficient evidence suggesting EBV+ and EBV− PTLD should be treated differently, except of course in case of EBV-directed therapy.4
Surgery and radiotherapy (T1)
The application of surgery or radiotherapy in treatment of PTLD is limited to some rare specific situations, including treatment of local disease (with RIS), symptomatic control, palliative care or as part of a combined (immuno-) chemoradiotherapeutic approach.
Adoptive immunotherapy using EBV-specific cytotoxic lymphocytes (CTLs) aiming to induce a strong EBV-specific cellular immune response without risk of graft-versus-host disease.
Reference
· White, M.L., Moore, D.W., Zhang, Y. et al. Primary central nervous system post-transplant lymphoproliferative disorders: the spectrum of imaging appearances and differential. Insights Imaging 10, 46 (2019).
· Dierickx, Daan; Vergote, Vibeke. Management of post-transplant lymphoproliferative disorders. HemaSphere 3():p 74-77, June 2019.
-The image shows MRI of the brain showing 2 enhanced lesions in the left hemisphere.
-The difference between T1 and T2 images depends on mapping of proton energy;
*T1 images; images highlight fat tissue within the body; SC fat and bone marrow.
*T2 images; highlight fat and water within the body.
Differential diagnosis;
-PTLD
-Abscess
-Toxoplasmosis
-Fungal (Aspergillus, Cryptococcus).
-Mycobacterium tuberculosis.
Work up:
-CT-guided biopsy.
-CBC, ESR, CRP, LDH, Cultures; Bacterial and fungal.
-Viral serology
-Sputum for AFBs smear, gene-expert
-Serum galactomannan
-FK drug level.
Management:
–ICU admission, ABC support, Antiepileptics
-Treatment of the cause+reduction of IS
· Explain the image finding
Presence of two oval-shaped lesions with presence of halo and vasogenic edema, without midline shift and without signs of intracranial hypertension
· 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 diagnoses would be between:
1 – Malignancy
– Primary CNS lymphoma?
– Metastasis?
2 – Infectious diseases:
– Neurotoxoplasmosis
– Nocardiosis
– Tuberculosis
– Criptococosis
· How would manage this case?
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 (reduce 25% of them).
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.
Explain the image findings: MRI axial view shows 2 round lesions surrounded by perilesional edema in the right side of frontal region.
T1 and T2 weighted images in MRI are used for different diagnosis… Fat sensitive T1 images provide good anatomical detail of the area being studied; T1 weighted images suppress the water….T2 weighted images enhances the intensity of water…So CSF is bright on T2 and dark on T1….
Differential diagnosis include tuberculomas, toxoplasmosis, cryptococcus, cerebral abscess, neurocysticercosis, metastatic lesions… One should not exclude PTLD presenting as brain lesions….
The history of the patient should be collected…History of fever, weight loss, cough, diarrhoea, night sweats…examination to rule out lymphadenopathy and hepatosplenomegaly is needed… The basic investigations like CBc, RFT, LFT, TB quantiferon gold, Blood PCR for TB, blood PCR for toxoplasmosis, cyrptococci, HIV serology,
One should be careful about doing LP CSF analysis as these lesions have significant perilesional edema and would lead to coning..IV dexa should be given and then CSF can be at the earliest… CSF fluid can be sent for cultures, TB PCR, Gene Xpert MTB, PCR for cryptococcus and Toxoplasmosis….Gold standard is excision biopsy of the lesion….
Treatment would be a multidisciplinary approach….I would add anticonvulsants to reduce the irritability….Patient needs treatment for the infection after diagnosis if any…
PTLD will need IV rituximab with chemotherapy….. targeted brain radiotherapy is needed for the treatment
There are 2 rings enhanced lesions in the left side of the brain.
In T1 there is fat signal enhancement while water signals depressed, while in T2 the reverse occurs.
Include infectious and non infectious causes,
The infectious causes include Toxoplasmosis, cryptococcosis,histeiocytosi, Tuberculosis, Neurosistecercosis.
The non infectious causes include malignancy, brain abscess, PTLD , metastatic lesions.
Detailed history of the duration , medical history, family history, any history of contact with a person with chronic cough, history of travel.
Full physical examination.
Full investigation including: CBC, ESR, CRP, Coagulation profile, RFT, LFT, LDH,Sputum study for TB, PCR for CMV , EBV, Cryptococcal infection and if possible lesional biopsy is the gold standard for diagnosis.
Imaging for chest, abdomen and pelvis.
Treatment includes MDT , TB management considering drug interaction and GFR , PTLD Mx by RTx, RI, chemotherapy and sirolimus.
Consider steroid to decrease ICP
Anticoagulants
Anticonvulsant therapy if needed.
Specific treatment according to the results of investigations.
Explain the image findingThere are two ring-enhancing lesions on the left side of the brain.
What is the difference between T1 and T2-weighted images?In T1 weighted images the signal of the fatty tissues is enhanced, and the signal of water is suppressed. In T2 weighted images the water signal is enhanced.
On the film, T1- and T2-weighted images can be easily differentiated by looking at the CSF. CSF is dark on T1-weighted imaging and bright on T2- weighted imaging.
What is your differential diagnosis?Infectious diseases: Toxoplasmosis. Histoplasmosis. Cryptococcosis.Brain abscess, Neurocysticercosis. Tuberculoma
Noninfectious cause: Brain tumor. Metastases. Resolving hematoma. Granuloma
How would manage this case?
A history of duration of symptoms; contact with potential risks; past medical history; social history
A clinical examination especially of the Nervous system to find other signs that may indicate the cause
Lab investigations: full blood count; ESR; CRP; procalcitonin; Tb Quantiferon tests; LFTs, EUCrs, Urine anakysis and microscopy; Abdominal and thoracic imaging; blood culture; stool examinations andn microscopy
Medications: PArenteral antibiotics. Parenteral anti seizure medications. Prophylactic anticoagulants; Other medications based on the test results
REFERENCES
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;
T1 vs T2 images on MRI;
DDX for ring enhancing lesions;
Management;
Ref;
Explain the image finding
There are two circle lesions in the left side with edema around the lesions, middle line shift and compression of lt ventricle
What is the difference between T1 and T2-weighted images?
Fatty tissue is enhanced in T1, while water signal is enhanced in T2
What is your differential diagnosis?
*Infectious causes:
-Toxoplasmosis
-Cryptococcosis
-TB
-Abscess
*Non infectious
-Malignancy
-PTLD
-Mets
How would manage this case?
Full history
Full physical examination
Full investigation as routine labs, sputum TB, CMV PCR ,
Imaging ct chest, abdomen and pelvis
Consider anticonvulsant, anticoagulants
Treatment according the cause
With 111 mismatch and no DSAs, a 47-year-old man with CKD 5 had a kidney donation from his brother. Excellent renal function and immunosuppression based on tacrolimus. He came to see you a year later with a headache, confessional states or shifts in his mental status, as well as a seizure. The T1 MRI image is displayed below.
Describe the image?
In the right front parietal area of the MRI, there were two spherical lesions surrounded by hyperintense edema.
What distinguishes T1 weighted images from T2 weighted images?
the fat-sensitive T1 pictures, which frequently give the area being analyzed good anatomical information.
the T2-weighted pictures, which are water-sensitive.
What other possible diagnoses do you have?
CNS tuberculoma.
Toxoplasmosis.
Abscess in the brain caused by Cryptococcus.
PTLD brain damage.
Neurocysticercosis
Metastatic tumor
How would you handle this situation?
Full medical history, including weight loss, a persistent cough, chronic diarrhea, a nighttime temperature or night sweat, and TB history.
Complete clinical evaluation
-Basic tests like the complete blood count, KFT, LFT, blood and urine culture, LDH, and coagulation profile.
Blood cultures, sputum analysis, PCR for TB, quantiferone testing, and CSF analysis.
-PCR for the cryptococcal antigen in addition to EBV, CMV, HIV, and Toxoplasma
The lesional excisional pathology is the gold standard.
-CT scans of the chest, abdomen, and pelvis to rule out additional lesions and seek for tissue biopsies.
Treatment: management of MDT.
-Supportive measures (dexamethasone to reduce edema, anticonvulsant if necessary).
Immunosuppression is lessened.
-Treating the infection’s underlying causes, such as TB, toxoplasmosis, and cryptococci.
PTLD therapy:
-Reducing or stopping the usage of rituximab and immunosuppressive drugs.
-Depending on the stage of the cancer, systemic and intrathecal chemotherapy, radiation therapy, and surgery may be utilized in conjunction.
Explain the image findingCerebral two ring enhancing lesions with surrounding edema and compression of left lateral ventricle
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
DDx
A helpful mnemonic is MAGIC DR
How would manage this case?
Follow you ABC
control of seizures
full metabolic profile and cultures (including CSF aspiration if not contraindicated) and virology screening
Admission to ITU for support
MDT discussion
lowering Tacrolimus level
m-TOR INHIBITORS
immunomodulatory therapy [interferon (IFN)-alpha, interleukin (IL)-6 antibodies, intravenous immunoglobulin (IVIg), EBV-specific T-cell therapy)
2. A 47-year-old CKD 5 has kidney transplantation from his brother, 111 mismatch, no DSAs. Excellent kidney function and Tacrolimus-based immunosuppression. One year later, he presented to you with a headache, confessional states/mental status changes, and seizure. T1 MRI picture is shown below.
Issues/ concerns
– 47yo man, CKD5, kidney transplant
– donor brother, 111 mismatch, no DSAs
– excellent kidney function, tacrolimus-based immunosuppression
– 1-year posttransplant presents with headache, confusion, seizures
Explain the image finding
– the left hemisphere has two ring-enhancing lesions, perilesional edema, obliteration of the lateral ventricles
What is the difference between T1 and T2-weighted images? (1)
– T1-weighted MRI images enhance the signal of the fatty tissue and suppress the signal of the water
– T2-weighted MRI images enhance the signal of the water
What is your differential diagnosis? (2-4)
– Infectious causes: –
· Tuberculoma
· Toxoplasmosis
· Abscess
· Cryptococcus
· Nocardia asteroids
· Aspergillus
· Listeria monocytogenes
– Non-infectious causes: –
· PCNS lymphoma (primary CNS lymphoma)
· PCNS-PTLD
· Metastatic disease
How would manage this case? (4)
– multidisciplinary approach: neurologist, infectious disease specialist, oncologist
– detailed history and thorough physical examination
– baseline investigations: CBC, ESR, CRP, UECs, LFTs, urinalysis, tacrolimus trough levels, LDH, EBV PCR, EBV IgM/ IgG/ IgA Ab, CMV PCR, HIV PCR, toxoplasmosis IgM Ab and PCR, serum CrAg, coccidioides IgG/ IgM Ab, aspergillus PCR, BDG
– CSF analysis: CrAg, AAFB, PCR, gene xpert, india ink, bacterial, viral and fungal cultures, cytology, flow cytometry
– stereotactic biopsy, histology
– imaging: chest radiograph, abdominopelvic CT scan to check for masses
– Management depends on the specific cause
– there is no standardized management for PCNS-PTLD or PTLD
– immunosuppression reduction is the cornerstone of therapy then reassess the patient after several weeks
– discontinue/ reduce the dose of mycophenolate
– additional therapies include: rituximab, chemotherapy, radiation therapy or a combination of these therapies
– adoptive immunotherapy is reserved for persistent disease despite initial therapy
– management largely depends on the type of PTLD: –
· Early lesions – reduce immunosuppression alone
· Polymorphic PTLD – rituximab in addition to reduction in immunosuppression ± chemotherapy
· Monomorphic PTD -rituximab, either alone or in combination with chemotherapy in addition to immunosuppression reduction, surgery is reserved for patients with complications like obstruction, perforation
· Classical Hodgkin lymphoma-like PTLD -chemotherapy with or without radiation
· Rituximab is only used in patients who express CD20
– Bacterial meningitis – antibiotics based on culture and sensitivity
– Tuberculoma – antitubercular therapy
– Cryptococcal meningitis – IV amphotericin B and fluconazole
– Aspergillus – voriconazole, amphotericin B
– CMV – ganciclovir, valganciclovir
– Toxoplasmosis – pyrimethamine and folinic acid
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. Rudresh K, Karthik SJ, Sebastin J. Clinical and aetiological profile of ring-enhancing lesions on CT brain. Journal of Indian Academy of Clinical Medicine. 2008;9(2):100-2.
3. 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.
4. Meena P, Bhargava V, Rana D, Bhalla A, Gupta A. An Approach to Neurological Disorders in a Kidney Transplant Recipient. Kidney360. 2020 Aug 27;1(8):837-44. PubMed PMID: 35372958. Pubmed Central PMCID: PMC8815733. Epub 2020/06/16. eng.
A 47-year-old CKD 5 has kidney transplantation from his brother, 111 mismatch, no DSAs. Excellent kidney function and Tacrolimus-based immunosuppression. One year later, he presented to you with a headache, confessional states/mental status changes, and seizure. T1 MRI picture is shown below.
Explain the image finding;
T1 vs T2 images on MRI;
DDX for ring enhancing lesions;
Management;
Ref;
image shows two cystic lesion in frontal lobes which can be
TB lesion
neurocysticercosis
abscess
tumor
PTLD
biop[sy is best way to diagnose the ;lesion
T1- weighted images fat is bright and appear white
T2- fluid is bright and appear as white like urine
involve neurosurgical team along with neurologist
reduce intracerebral pressure to alleviate symptoms
reduction of IS is important step
and disease specific treatment like AKT and antifungal
· Explain the image finding– Two rounded lesions encircled with hyper intense edema in the parietal region of the right frontal lobe , no midline shift.· What is the difference between T1 and T2-weighted images?– T1-weighted images have a short TR (300–1000 ms) and a short TE (10–30 ms) and provide great anatomical detail.- T2-weighted images, on the other hand, have long TR (1800–2500 ms) and long TE (40–90 ms) and are sensitive to detecting fluid and edema. – T1-weighted images display soft-tissue anatomy and fat optimally. (eg, to confirm a fat-containing mass).- T2-weighted images best illustrate fluid and abnormalities. (eg, tumors, inflammation, trauma).· What is your differential diagnosis?– PTLDs- Tuberculoma- toxoplasmosis- cerebral abscess- neurocysticercosis- metastasis- glioblastoma· How would manage this case?– Detailed hx focusing on hx of weight loss, night sweets & fever or any specific symptoms- Detailed examination focusing on LNs enlarged, organomegaly – Investigations: – 1- basic work up (CBC, lytes, LDH, cultures)- 2- radiology for any lesions? ct chest, Abd, & pelvis without contrast initially.- 3-CSF analysis- 4-PCR for toxoplasma, TB, EBV – 5-quantiferon test for TB- 6-gold standard for diagnosis is to biopsy the lesion- Ttt according to the cause, if PTLDs, the main management is to reduce immunosuppression by holding or decreasing MMF , reduce tac level to around 5 , consider shifting to mTORi.- Rituximab, chemotherapy, Radiotherapy & surgical excision is considerable options , decision to be made as an MDT management between oncology , neurosurgery & transplant physician.
· There are 2 ring-enhancing lesions with surrounding edema, compressing the left ventricle
· T1 weighted MRI enhances the signal of the fatty tissue but T2 weighted images enhance the signal of water.
· CSF is dark on T1-weighted imaging and bright on T2-weighted imaging.
Differential diagnosis:
Toxoplasmosis
Tuberculomas
Criptococosis
Aspergilloma
Neurocysticercosis
CNS abscesses
Primary CNS lymphoma
Primary CNS PTLD
Metastasis
Management
· This patient should be admitted to ICU for supportive treatment until he is stable
· CBC, full chemistry, ABG, CRP, ESR, Blood culture,
· Quanteferone test.
· PCR for (EBV, CMV, HIV, Toxoplasma) and Cryptococci antigen
· CAP CT
· Possible lesion biopsy
· High-dose corticosteroids for edema and anticonvulsant drugs.
· Reduction of immunosuppressive drugs
· According to the result of investigations and biopsy result specific treatment can be given
· If TB was diagnosed, anti-TB drugs should be given, with strict observation of drug interaction
· PTLD can be treated with Rituximab and the reduction of immunosuppressive drugs
· For toxoplasmosis: sulfadiazine and pyrimethamine or clindamycin plus pyrimethamine
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976142/#:~:text=PMID%3A%2016219834-,Brain%20MR%20Imaging%20Abnormalities%20in%20Kidney%20Transplant%20Recipients,-Nada%20Besenski%2C
https://link.springer.com/article/10.1007/s00467-013-2499-3#:~:text=07%20June%202013-,Successful%20treatment%20of%20central%20nervous%20system%20PTLD%20with%20rituximab%20and%20cranial%20radiotherapy,-Valerie%20Said%2DConti
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9505385/#:~:text=Mycobacterium%20Tuberculosis%20Infection%20after%20Kidney%20Transplantation%3A%20A%20Comprehensive%20Review
Explain the image finding
MRI shows two ring enhanced lesions with surrounding vasogenic oedema
What is the difference between T1 and T2 weighted imaging?
T1 enhances the signal of the fatty tissue and suppresses the signal of the water
T2 enhances the signal of the water
Differential diagnosis
Malignancy: PTD, metastasis
Infectious: cerebral abscesses, toxoplasmosis, tuberculomas, Cryptococcus neoformans, A. fumigates.
Management
History: weight loss, fever, night sweat, cough, diarrhoea, history of previous TB, possible exposure, residence or travel to endemic area
Examination; To look for focal neurological deficient, systemic examination including Lymph node examination
Seizure control with anti-epileptic
Dexamethasone given surrounding oedema
MDT discussion, with transplant nephrologist, radiologist. Neurosurgical and haematologist
Imaging; CT TAP/ PET
CT guided biopsy
CSF analysis and cytology
Serum cryptococcal antigen, Toxoplasma IgG serology, Viral serology, Blood culture
Treatment depends largely on the cause however reduction of immunosuppression is an important measure
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
Treatment is based clear diagnosis but immunosuppression modifications usually needed until reach final diagnosis
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.
Explain the image finding
There are two ring enhancing lessons with perilessional edema and compression of the lateral ventricles with no associated shift of the midline.
What is the difference between T1 and T2-weighted images?
T1 weighted images enhances the signal of fat and suppresses the signal of water, while T 2 weighted enhances the signal of water. Thus in T1 css is black while in T2 is bright.
What is your differential diagnosis?
PTLD2-
Infections : toxoplasmosis , tuberculoma
Brain tumor :primary or metastasis
How would manage this case?
Detailed history and thorough physical examination.
Initial blood work: CBC, UECS, LFT,ESR,CRP, procalcitonin, LDH, tacrolimus trough levels
PCR for EBV, toxoplasmosis, HIV
Serum crag for cryptococcus
Toxoplasma antibodies
Lumbar puncture for CSF analysis will be contraindicated in this patient
Imaging- CXR, PET scan, CT abdomen to look for other lesions.
Patient requires management in collaboration with intensivist, transplant physician and neurologist.
Management in ICU/HDU setup.
Anticonvulsants due to the convulsions.
Dexamethasone due to the edema
Reduction of the immunosuppression- withdrawal of the antimetabolite and reduction of CNI trough level by 50%.
Specific management will depend on the specific cause.
Explain the image finding-2 well-circumscribed ring-enhancing lesions with perilesional oedema.
What is the difference between T1 and T2-weighted images?T1 enhances fat, while T2 enhances water.
What is your differential diagnosis?1.Tuberculoma
2.Cryptococcus
3.PTLD
4.Toxoplasmosis
5.Brain abcess
How would you manage this case?1.History on TB contact, contact with cats, EBV status and induction immunosuppression
2.Nerological examination for any focal deficit
3.Control the seizure
4.Brain biopsy
5.TB Quanteferone gold
6.Toxoplasma serology
7.To enquire if patient is taking MMF-If so to hold the medications
8.Virology screen ie HIV
9.Treatment is according to the cause
References
1.White, M.L., Moore, D.W., Zhang, Y. et al. Primary central nervous system post-transplant lymphoproliferative disorders: the spectrum of imaging appearances and differential. Insights Imaging 10, 46 (2019). https://doi.org/10.1186/s13244-019-0726-6
· Explain the image findingMRI brain show 2 well circumscribed masses with prepheral ring enhancement ,surrounded by brain edema , no midline shift.
· What is your differential diagnosis?1- PTLD2- Infections : toxoplasmosis , tuberculoma3- Brain tumor :primary or metastasis
· How would manage this case? Detailed history and examination is mandatory including pretransplantation EBV, CMV , toxoplasma status, risk factors for TB as contact with TB patient , family history of malignancy -Examination for lymadenopathy ,organomegaly -Further investigations to reach a specific diagnosis are needed-For TB : Quantiferon TB Gold test-PCR for toxoplasma , EBV and CMV-HIV Ab and PCR -Radiology screening for other masses including CT head , neck , chest and pelvi abdomen – Excisional biopsy and histological evalution – Monitor graft function – check electrolytes , CBC , blood suger, thyroid function Treatment:1- Stabilization of the patient : maintain patent air way and supplemental O2 if needed , good hydration , check and correct any electrolytes disturbance , anti epileptic drugs to control seizure 2- Adjust IS dose to decrease or even stop MMF and reduce Tac level by 50%Specific treatment according to the cause :In PTLD 1- Decrease Tac by 50% and monitor trough level , shift from MMF to sirolimus , rituximab for B cells NHL 2- Chemotherapy : – Prednisolone and cyclophosphamide– CHOP– ACVPB– Adoptive immunotherapy if conventional treatment fail
Explain the image findingThere are two ring enhancing lessons with perilessional edema and compression of the lateral ventricles with no associated shift of the midline.
What is the difference between T1 and T2-weighted images?T1 weighted images enhances the signal of fat and suppresses the signal of water, while T 2 weighted enhances the signal of water. Thus in T1 css is black while in T2 is bright.
What is your differential diagnosis?PTLD
Tuberculoma
Toxoplasmosis
Cryptococcoma
Brain metastasis
How would manage this case?Detailed history and thorough physical examination.
Initial blood work: CBC, UECS, LFT,ESR,CRP, procalcitonin, LDH, tacrolimus trough levels
PCR for EBV, toxoplasmosis, HIV
Serum crag for cryptococcus
Toxoplasma antibodies
Lumbar puncture for CSF analysis will be contraindicated in this patient
Imaging- CXR, PET scan, CT abdomen to look for other lesions.
Patient requires management in collaboration with intensivist, transplant physician and neurologist.
Management in ICU/HDU setup.
Anticonvulsants due to the convulsions.
Dexamethasone due to the edema
Reduction of the immunosuppression- withdrawal of the antimetabolite and reduction of CNI trough level by 50%.
Specific management will depend on the specific cause.
References
Posttransplant lymphoproliferative disorders: current concepts and future therapeutics by Fedaey Abbas et al.
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.
Uptodate
Explain the image finding.
MRI showed two rounded lesions surrounded by hyper intense oedema in the right front parietal region with some evidence of invasion.
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?
How would manage this case?
Detailed history about source of infection (weight loss, cough, chronic diarrhoea, night fever , night sweat , past history of TB, etc. ).
Full clinical examination, fundus examination for papilloma oedema, Lymph nodes examination
Laboratory investigations:
Treatment:
References:
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.
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.
MRI Brain (axial) view shown two well circumscribed ring enhancing lesion in the right parietal region with surrounding edema and no midline shift.
What is the difference between T1 and T2-weighted images?
T1-weighted MRI enhances fat signal and take less time to echo ,while T2 weighted MRI image enhances water signal.
What is your differential diagnosis?
Likely differentials in the above case ar:
Tuberculomas, Lymphoma (PTLD), Toxoplasmosis, Cerebral abscess. Cryptococcus’s
How would manage this case?
After taking detailed history and thorough examination-Investigations which will help in confirming the diagnosis include:
CBC,LFT ,RFTs, urine and Blood culture, serum LDH, Quantiferon TB Gold test followed by PCR for EBV,CMV, Toxoplasma, Hepatitis B , C and HIV serologies ,CSF analysis for T.B, Cryptococcus with special stains(Indian ink ),Toxoplasma for PCR for (EBV, CMV, HIV, Toxoplasma) and serum for Cryptococcal antigen. Excisional biopsy remains the gold standard. Imaging studies include Ultrasound abdomen ,X-ray Chest followed by CT Abdomen and pelvis and CT chest if needed.
-Treatment: will depend on the cause. Patient should be admitted , Blood sugar should be checked first –Immediately anti-metabolite should be stopped ,Tac level to be maintained around5-7ng/ml and adjunctive dexamethasone should be given. Supportive measures like I/V Fluids, I/V antibiotics and anti-epileptics started and then treatment according to the cause-ATT for TB, anti-fungal for Cryptococcus, Sulfadiazine, Pyrimethamine with leucovorin, lymphoma needs chemotherapy , radiotherapy and surgery depending on the stage.
REFERENCES
Meena, Priti; Bhargava, Vinant; Rana, et al.An Approach to Neurological Disorders in a Kidney Transplant Recipient. Kidney360 1(8):p 837-844, August 2020..
Explain the image finding:
T1 MRI image shows two ring enhancing lesions surrounded by Vasogenic edema in the left cerebrum temporo-parietal and sign of tissue invasion and mass effect , one year after a kidney transplantation.
What is the difference between T1 and T2-weighted images?
The T1 MRI enhances fat and suppress water signals, while T2 MRI enhances water signals.
T1 requires less time to echo than T2 (23ms vs 100ms), less repetition time (2100ms vs 3000ms), and less acquired matrix (288×197 vs 512×336), thus less time.
T1 has an inversion time of 1000ms but T2 not.
T2-weighted images offer the best representation of disease, because affected areas appear bright on T2-weighted images because fluid (such as CSF fluid) causes affected tissues to have a higher water content than usual.
What is your differential diagnosis?
EBV / PTLD
Toxoplasmosis encephalitis
Primary CNS lymphoma
Tuberculoma, Disseminated TB
Brain metastasis
Fungal infections such as cryptococcosis or histoplasmosis
Brain abscess , Neuro-Cysticercosis
How would manage this case?
Detailed history: contact with sick person, TB, , contact with Pet animals (cats) and pre transplant viral screen documented (EBV D+/R-) that may increase the risk of EBV related post-transplant PTLD, and history of prophylactic antibiotics, and induction immunosuppressive medications.
Full examination: CNS evaluation, vital signs, chest abdomen and pelvic exam, and ophthalmic examination for retinitis, uveitis.
Laboratory: CBC, Lytes, BUN, Creatinine, ALT, AST, alkaline phosphatase, LDH, CRP & ESR.
PCR for both toxoplasmas, cysticercosis, EBV, and Mycobacterium (highly specific 96-100% but variable sensitivity from 58-98%)
Antibodies assay for Neuro-cysticercosis, and toxoplasmosis.
CSF analysis: protein, glucose, gram stain and culture((cytology, chemical, & bacteriological)
Positron emission tomography can distinguish toxoplasma from lymphoma.
Brain Biopsy: either open or stereotactic and tissue histopathologic examination.
Treatment plan:
ABCs
ICU admission for stabilization
Oxygen support
May require incubation and mechanical ventilation.
Anti-convulsant; monitor for drug-drug interactions.
Start empirical antibiotics while awaiting the possible final diagnosis.
Reduction of immunosuppressive medications: in mild cases reduce MMF 50-75% of the current dose and in severe cases MMF should be stopped, and CNI kept to lower therapeutic range with trough level (4-8 ng/dl).
Treatment according to Aetiology:
Management CNS PTLD:
It may be reasonable to reduce immune suppression especially anti-metabolite and see the overall clinical picture in 2 to 4 weeks is the cornerstone of therapy.
Chemoimmunotherapy: R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone), radiation therapy, or a combination of these.
Intrathecal rituximab had been successful in treating primary CNS lymphoma.
Other treatments, such as adoptive immunotherapy with EBV specific cytotoxic T cells, are generally reserved for persistent disease despite initial therapy.
Management CNS Toxoplasmosis:
With this multiple brain enhancing lesion after the workup should start treatment for toxoplasmosis as follow:
Sulfadiazine (1000 mg four times daily among patients <60 kg or 1500 mg four times daily among patients ≥60 kg). If there are concerns about non-adherence, 2000 mg of sulfadiazine can be administered twice daily; one study documented equivalent pharmacokinetic parameters of this dosing schedule compared with 1000 mg given four times a day.
Plus
Pyrimethamine (200 mg loading dose followed by 50 mg daily among patients <60 kg or 75 mg daily among patients ≥60 kg).
Plus
Leucovorin (10 to 25 mg daily). This agent should be administered to prevent pyrimethamine-induced hematologic toxicity.
Or
Parenteral trimethoprime-sulphamethexazole in severely ill patients who cannot have oral medications.
Or
parenteral clindamycin (600 mg q 6 hours) + pyrimethamine+ leucovorin.
Or
Atovaquone 1500 mg twice daily + pyrimethamine+ leucovorin
Or
Atovaquone +sulfadiazine
Or
Atovaquone alone
(These regimens need PCP prophylaxis)
Duration of treatment is: six weeks.
Adjunctive therapy:
Steroids: dexamethasone 4 mg q6 hours with mass effect and surrounding edema.
Anti-convulsant.
Management CNS Tuberculoma:
Anti-TB for 12 months; starting with the 4 first line agents (INH, Rifampicin, Ethambutol, & Pyrazinamide for the first 2 months, then continuation phase with INH & Rifampicin, if appropriate.
Response to therapy:
Repeat imaging in a week in 2 weeks, post treatment if the patient did not show any clinical improvement.
References:
UpToDate
Samant H; Vaitla P; Kothadia J. Post Transplant Lymphoproliferative Disorders.Feb 12, 2023.
Cohen A, Sugo E, Chacko B. Isolated cerebral toxoplasmosis 17 years post renal transplant. Transpl Infect Dis. 2022 Aug;24(4):e13880. doi: 10.1111/tid.13880. Epub 2022 Jun 16. PMID: 35690470.
Gaillard F, Knipe H, Baba Y, et al. Cerebral ring enhancing lesions. Reference article, Radiopaedia.org (Accessed on 26 Mar 2023)
Explain the image finding.This MRI showed two ring enhancement lesion, which is surrounded by oedema.
This could be due to the following factors:
Tubercloma
PTLD
Toxoplasmosis
brain Mets
What is the difference between T1 and T2-weighted images?MRI differentiation of fluids (black in T1 and white in T2) due to high water content eg edema inflammation, while on T2 tissue with low water content
How would manage this case?
This patient needs to be admitted to HDU with anti-seizure
need to reduce IS
Explain the image finding
MRI image shows two ring enhancing lesions surrounded by edema and sign of tissue invasion and mass effect
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.
MRI differentiation of fluids (black in T1 and white in T2) due to high water content eg edema inflammation while on T2 tissue with low water content will appear bright.
What is your differential diagnosis?
How would manage this case?
Admission in HDU/ICU
Control seizures with IV lorazepam or midazolam,
IV steroids (dexamethasone) to reduce the brain edema.
Reduction of immunosupression ie MMF and CNI
Through history and clinical examination.
Investigation to rule out other cause.
-CBC, RFT, LFT, Blood and urine culture, LDH
-CSF analysis(not in this case with midline shift) and sputum, blood cultures, PCR for TB,QuantiFERON test.
-PCR for (EBV, CMV, HIV, Toxoplasma) and Cryptococci antigen.
-Lesional excisional pathology if any thing is available in clinical examination or in imaging.
-CT abdomen-pelvis and chest to exclude other lesions and looking for tissue biopsy.
Targeted treatment according to etiology.
Reduction of Immunosuppression: 50% reduction of calcineurin inhibitors (cyclosporine or tacrolimus) and discontinuation of antimetabolic.
Chemoimmunotherapy: R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone)
Radiation Therapy
Adoptive Immunotherapy– adoptive immunotherapy is associated with a high risk of developing acute and chronic graft-versus-host disease (GVHD).
References
Samant H; Vaitla P; Kothadia J. Post Transplant Lymphoproliferative Disorders.Feb 12, 2023.
Gaillard F, Bell D, Hacking C, et al. Primary central nervous system posttransplant lymphoproliferative disorder, Radiopaedia.org 2022.
That is a very good description of the index MRI
Exellent plan
Thank you Prof
In T1 images, 1 tissue type is bright which is FAT, while in T2 images, 2 tissue types are bright (fat & water). This image seems like T1. 2 lesions are present surrounded by edema (?).
Being multifocal can be metastases or multifocal CNS lymphoma (PTLP).
I will consult a radiologist and search for other foci of malignancy, any lymph node etc. After diagnosis confirmation, a treatment plan can be done
supposing this is a post-transplant lymphoproliferative disease as it seems like a ring, not a solid mass (contrary to primary CNS lymphoma) (source 1-table 1)
Withdrawal or decreasing the immunosuppression balanced against risk of rejection should be considered, and both chemotherapy and radiotherapy should be considered. Methotrexate, Rituximab, cytarabine has been used.
—-
1- https://insightsimaging.springeropen.com/articles/10.1186/s13244-019-0726-6
Thankyou
Explain the image finding
MRI image shows two ring enhancing lesions with adjacent edema.
What is the difference between T1 and T2-weighted images?
MRI differentiation of fluids (black in T1 and white in T2) due to high water content eg edema inflammation while on T2 tissue with low water content will appear bright. What is your differential diagnosis?
· PTLD· Tuberculoma · Abscess · Nocardiosis · CNS lumphoma
How would manage this case?
· Supportive care in HDU/ICU
· Control seizures with iv lora or midazolam
· Iv steroids in case
· Reduced IS ie MMF and CNI
· Simultaneous target work up for etiology like for TB, PTLD including brain biopsy if needed.
· Targeted treatment according to etiology.
References
UpToDate
Short but too the point.
give one most conclusive investigation for each DD!
to
Thanks prof.
Work up would include;
IGRA,TST,CXR and ESR
EBV PCR, LDH and Neuro imaging,
MRI showed unilateral tow ring enhancing lesions with surrounding brain edema in post kidney transplant patients present with headache ,altered mental status and seizure .
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.
Specific treatment of PTLD :
Reduction of Immunosuppression: 50% reduction of calcineurin inhibitors (cyclosporine or tacrolimus) and discontinuation of antimetabolic.
Rituximab : Rituximab is a monoclonal anti-CD20 antibody which can be used as a single agent after reducing the immunosuppression medications or in combination with chemotherapy .
Chemoimmunotherapy : R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) is commonly used in chemotherapy regimen for most patients with PTLD.
Radiation Therapy: Radiation therapy is used for patients with localized disease and those with central nervous system (CNS) involvement either alone or in combination.
Adoptive Immunotherapy : In patients with EBV-associated PTLD, adoptive Immunotherapy uses EBV-specific cytotoxic T lymphocytes (EBV-CTLs) or donor lymphocyte infusion (DLI) to induce a robust EBV-specific cellular immune response. is used . However, adoptive immunotherapy is associated with a high risk of developing acute and chronic graft-versus-host disease (GVHD).
CNS tuberculoma specific treatment :
Diagnosis :
CSF usually reveals a lymphocytic pleocytosis with low glucose and elevated protein; but can be normal . Acid-fast stains that have low yield may be increased with sampling larger volumes of CSF. Polymerase chain reaction has a reported sensitivity of 4–100 % and specificity approaching 100 %. Diagnosis of tuberculosis is established by biopsy and culture of sites of infection. When pulmonary MTB is not present, brain biopsy may be necessary to establish the diagnosis.
Treatment :
Reference :
1 . Post Transplant Lymphoproliferative DisordersHrishikesh Samant; Pradeep Vaitla; Jiten P. Kothadia.
Last Update: February 12, 2023.
2. Opportunistic Infections of the Central Nervous System in the Transplant Patient Current Neurology and Neuroscience Reports 13, Article number: 376 (2013)
volu 13, Article number: 376 (2013)
Good clinical management.
Can you notice radiological signs in the index MRI of increased ICT.
Thank you Prof Dawlat yes this MRI showed tow ring enhancing lesions with surrounding brain edema .
Explain the image finding
Head MRI demonstrating left frontoparietal mass
CNS lymphoma lesions are often supratentorial and multicentric, enhance uniformly and have surrounding edema. However, the two lesions can present very similarly and can be hard to distinguish radiographically.
What is the difference between T1 and T2-weighted images?
T1-weighted images optimally show normal
soft-tissue anatomy and fat (eg, to confirm a fat-containing mass). T2-weighted images optimally show fluid and abnormalities (eg, tumors, inflammation, trauma). In practice, T1- and T2-weighted images provide complementary information, so both are important for characterizing abnormalities
What is your differential diagnosis?various opportunistic infections, such as disseminated mycobacterial or fungal infections.
Cerebral toxoplasmosis
Primary CNS lymphoma
CNS tuberculoma
CNS cryptococcosis
CNS cysticercosis
Cerebral abscess
Cerebral metastasis
Glioblastoma multiforme
How would manage this case?
Management of PTLD has varied significantly according to the type of lymphoproliferative disease present, as well as from institution to institution. Immunosuppression reduction is the cornerstone of therapy. Additional therapies include immunotherapy with the CD20 monoclonal antibody rituximab, chemotherapy, radiation therapy, or a combination of these. Other treatments, such as adoptive immunotherapy with EBV specific cytotoxic T cells, are generally reserved for persistent disease despite initial therapy.
Well done short but well planned.
THANK YOU Prof. Dawlat Belal
Two ring enhancing leisons with surrounding brain 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.
Differential Diagnosis
PTLD
Abscess
Tuberculoma
Metastasis
Primary CNS lymphoma
Management
Definitive management would depend upon final diagnosis
He would require multidisciplinary approach
Need to know EBV status of patient?
Pre transplant result of TB Gold.or history of contact
HIV status?
History and physical exam suggestive of any primary disease.? With possible brain mets
A brain biopsy may be needed
Is this a well circumscribed lesion or there are signs of tissue invasion.
⭐ The MRI imaging shows 2 ring enhanced lesions with surrounding brain edema.
⭐ Differentiation of MRI by appearance of CSF (black in T1 and white in T2).
⭐ Differential diagnosis:
_ PTLD.
_primary CNS lymphoma.
_Abscess.
_tuberculoma.
_poat irradiation
⭐ ⭐ treatment;
_ICU admission, correct fluid status and give oxygen supplementation.
_contril seizures by IV tiratam or dormicum infusion.
_Do CBC, CRP, TB work up, electrolytes and EBV PCR.
_postpone CSF analysis till patient stabilization.
_Reduction of IS (stop MMF, decrease dose of CNI or shift to MTORi , increase steroids).
_start empirical antibiotics till result of CSF analysis and culture.
_Tisaue biopsy to confirm PTLD ..if so we may add CHOP, rituximab to the reduction of IS therapy. also, adoptive immunotherapy can be used in refractory cases of EBV postive cases
Thankyou
How would you rule out the other possibilities?
The MRI findings shows
T1 MRI
T2 MRI
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
This is an extensive anti TB
How about PTLD
Explain the image finding T1 weighted MRI :
two ring liked lesion with surrounding edema on left hemisphere
What is the difference between T1 and T2-weighted images?
T1….rapid decay ,showing fat and more anatomical detail
T1…delay decay, water bright ,more information about the pathology
What is your differential diagnosis?
How would manage this case?an MDT Discussion involving nephrologist, microbiologist and neurosurgeon
in this case scenario raise the possibility of PTLD
What about T2.!
What congenital causes do you have in mind! could that have been detected during preparation before TX.
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.
Thank you. I agree with most of your response but has a comment. You mentioned: ‘effacement of ipsilateral lateral ventricle and perilesional edema’ In the context of these findings do you proceed for Lumbar puncture? With the presence of seizure, confusion state and pre-lesioned oedema, do you wait for neurosurgical consultation and investigation results without any supportive treatment before specific treatment?
Thanks so much; our Prof.
In such a case with increased ICT with midline shift , it is better to postpone L.P. for CSF tapping at time being.
and start steroid(Dexamethasone)for relive brain edema and aborted seizures with anti epileptic medications and close monitoring their levels, with close Neuro vital observation, and for safety for pt to be admitted under ITU.
I appreciate your reply to Prof Kossi’s comments.
What is your differential diagnosis?
The differential for peripheral or ring enhancing cerebral lesions includes:
· Cerebral abscess.
· MB tuberculomas.
· PTLD & Lymphoma.
· Toxoplasma infection.
· Glioblastoma.
· Neurocysticercosis.
· Aspergilloma.
· Metastatic lesion.
How would you manage this case?
MB tuberculomas is likely provided the enhancement of meninges.
PTLD coming next in the differential. Overall, treatment is accordingly.
A. For MB tuberculomas:
1. General investigations: CBC, RFT, LFT, CRP, RBG, Urinalysis and LDH.
2. Screening for TB:
· sputum microscopy and culture for AAFB.
· Rapid molecular test(the Xpert MTB/RIF assay) is highly specific and has an estimated sensitivity in smear positive and smear negative respiratory samples of 98% and 67%, respectively(2).
3. Treatment of the causative agent; in case of active TB infection(3):
a) The optimal period of treatment could vary from 6 to 24 months. Recommended to be at least 9–12 months.
b) According to AST-IDCOP, the first-line treatment should be a four-drug regimen containing rifamycin used both in severe and non-severe cases.
c) The standard regimen is similar to that used for the general population and consists of a 2-month intensive phase of isoniazid, rifampicin, pyrazinamide and ethambutol, followed by a 4-month continuation phase of isoniazid and rifampicin.
d) Adjustment of immunosuppression as Rifampicin reduces the level of CNIs and mTORi:
· the dose of CNIs and mTORi should be increased between three- and five-fold and the glucocorticoid dose should be doubled during treatment and adjusted thereafter to obtain the therapeutic target.
B. For PTLD management :
Adjustment of immunosuppression: the treatment of PTLD: the goal is to cure and the mainstay is IS reduction(2):
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. Radiology masterclass; https://www.radiologymasterclass.co.uk/
2. Santoro-Lopes G, Subramanian AK, Molina I, Aguado JM, Rabagliatti R, Len O. Tuberculosis Recommendations for Solid Organ Transplant Recipients and Donors. Transplantation. 2018 Feb;102(2S Suppl 2):S60-S65. doi: 10.1097/TP.0000000000002014. PMID: 29381579.
3. 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.
4. 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.
Explain the image finding
T1-MRI image of the brain is showing:
· Ring enhancing lesions(2 lesions) with surrounded edema causing mild midline-shift.
· Meningeal enhancement.
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.(1)
What is your differential diagnosis?
The differential for peripheral or ring enhancing cerebral lesions includes:
· Cerebral abscess.
· MB tuberculomas.
· PTLD & Lymphoma.
· Toxoplasma infection.
· Glioblastoma.
· Neurocysticercosis.
· Aspergilloma.
· Metastatic lesion.
How would you manage this case?
MB tuberculomas is likely provided the enhancement of meninges.
PTLD coming next in the differential. Overall, treatment is accordingly.
A. For MB tuberculomas:
1. General investigations: CBC, RFT, LFT, CRP, RBG, Urinalysis and LDH.
2. Screening for TB:
· sputum microscopy and culture for AAFB.
· Rapid molecular test(the Xpert MTB/RIF assay) is highly specific and has an estimated sensitivity in smear positive and smear negative respiratory samples of 98% and 67%, respectively(2).
3. Treatment of the causative agent; in case of active TB infection(3):
a) The optimal period of treatment could vary from 6 to 24 months. Recommended to be at least 9–12 months.
b) According to AST-IDCOP, the first-line treatment should be a four-drug regimen containing rifamycin used both in severe and non-severe cases.
c) The standard regimen is similar to that used for the general population and consists of a 2-month intensive phase of isoniazid, rifampicin, pyrazinamide and ethambutol, followed by a 4-month continuation phase of isoniazid and rifampicin.
d) Adjustment of immunosuppression as Rifampicin reduces the level of CNIs and mTORi:
· the dose of CNIs and mTORi should be increased between three- and five-fold and the glucocorticoid dose should be doubled during treatment and adjusted thereafter to obtain the therapeutic target.
B. For PTLD management :
Adjustment of immunosuppression: the treatment of PTLD: the goal is to cure and the mainstay is IS reduction(2):
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. Radiology masterclass; https://www.radiologymasterclass.co.uk/
2. Santoro-Lopes G, Subramanian AK, Molina I, Aguado JM, Rabagliatti R, Len O. Tuberculosis Recommendations for Solid Organ Transplant Recipients and Donors. Transplantation. 2018 Feb;102(2S Suppl 2):S60-S65. doi: 10.1097/TP.0000000000002014. PMID: 29381579.
3. 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.
4. 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.
Thankyou but always in your answer deal with the index case ie.
control of seizures.
ICU admission.
measures to reduce the increased ICT.
Image discription:
Difference between T1 & T2:
Differential diagnosis:
Management:
References:
Are there signs of high intracranial pressure ,what are your precautions before requesting a CSF profile?
MRIT1 shows interrupted ring enhancing lesions with mass effect due to vasogenic edema
DDX
infectious vs non infectious etiologies including PTLD , primary or secondary brain tumors bacterial pyogenic abscess, tuberculoma with mycobacterial abscess , more in developing countries , tuberculoma appearance like multiple abscesses usually appearance in T1MRA as complete ring enhancing lesions not like this images with irregular and incomplete peripheral hypo-intense rings which is likely due to deposition of hemorrhagic products at the edges of the lesion which in favor CNs tumor like PTLD or gliomas.
What is the difference between T1 and T2-weighted images?
1.DWI provides quantitative information about the microscopic motion of water molecules in a tissue by calculating apparent diffusion coefficient (ADC)(3). T1 offers no clear advantage in differentiating tuberculomas from metastasis and gliomas(2).
Need to ask about the ethnics back ground of the recipient if he is from endemic area of TB or recent travel to endemic area, latent TB or previous exposure or treatment for active TB ,also EBV sero status of both donor and recipient
For the definite diagnosis need MDT with ID ,onco- hematologist and transplant team with further laboratory panel including FBC , peripheral smear , LDH ,CSF analysis and send for serology culture viral PCR screen, EBV PCR , listeria PCR , cryptococcal antigen and CSF cultures , microbiology with gram stain , AFB and TB
CXR ,CT chest , abdomen , pelvis screen from pulmonary or extra pulmonary lesions primary tumor
the definite diagnosis by tissue biopsy and accordingly will decide further management plan.
References
1. Garg RK, Sinha MK. Multiple ring-enhancing lesions of the brain. J Postgrad Med. 2010 Oct-Dec;56(4):307-16.
2. Parry AH, Wani AH, Shaheen FA, Wani AA, Feroz I, Ilyas M. Evaluation of intracranial tuberculomas using diffusion-weighted imaging (DWI), magnetic resonance spectroscopy (MRS) and susceptibility weighted imaging (SWI). Br J Radiol. 2018 Nov;91(1091):20180342. doi: 10.1259/bjr.20180342. Epub 2018 Jul 23. PMID: 29987985; PMCID: PMC6475934.
3.Bammer R. Basic principles of diffusion-weighted imaging. Eur J Radiol 2003; 45: 169–84. doi: 10.1016/S0720-048X(02)00303-0
Well done you noticed the invasive character of the lesion.
Measures to reduce the high preasure before lumber puncture for the CSF.
thank you prof Dawalat, dexamethasone, and mannitol to reduce the mass effect, control the seizures with antiepileptic medication
Explain the image finding
2 contrast-enhanced lesions with ring enhancement surrounded by vasogenic oedema obscuring the left ventricle
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?
PCNS-PTLD is the most probable diagnosis in this case scenario
Other DD
CNS lymphoma
Brain metastasis
Cerebral abcess
Cerebral tuberculoma
CNS toxoplasmosis
Fungal infection as aspergillosis
How would manage this case?
The seizures have to be controlled .
The case need to be admitted to ICU to monitor his conscious and vitals closely
Full basic labs including CBC, KFT,LFT, electrolytes, INR ,urine analysis , gamma interferon, virological screening specially for EBV ,cultures ,inflammatory markers , Tacrolimus level.
CSF by lumbar puncture for analysis better avoided with the signs of increased ICT
Treatment include
– Immunosuppression reduction by lowering Tac level
-m-TOR inhibitors can be used as it have dual functions; antitumor and immunosuppression, also it had shown a positive effect on grafts salvage and managing PTLD
-Rituximab and CHOP-based chemotherapy
-Antiviral therapy
– immunomodulatory therapy [interferon (IFN)-alpha, interleukin (IL)-6 antibodies, intravenous immunoglobulin (IVIg), EBV-specific T-cell therapy)
Reference
-Kawahara D, Nagata Y. T1-weighted and T2-weighted MRI image synthesis with convolutional generative adversarial networks. Rep Pract Oncol Radiother. 2021;26(1):35-42. Published 2021 Feb 25.
– Zimmermann H, Trappe RU. Therapeutic options in post-transplant lymphoproliferative disorders. Ther Adv Hematol. 2011;2(6):393-407.
MDT have to be involved including a hematologist for further management including PET CT and radiotherapy as needed
Thankyou PTLD is a lymphoma.
There are signs of increased IC tension seen by surrounding oedema ,midline shift so lumbar puncture could be dangerous at this stage.
Very good you are controlling the seizures and ICU admission.
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.
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 presented with 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, HIV
-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.
-IGRA and TST
-Beta D-glucan, Serum galactomannan
-Tacrolimus drug level.
-PET-CT
-CSF if possible for if no raise in ICP; cell count, glucose, protein, cultures, smear, PCR TB
-Pan-CT to look for any primary tumor with distant CNS-metastasis.
-CT -guided biopsy to establish a diagnosis.
Management:
– Admission to ICU.
– ABC cardio-respiratory support
– Abort the seizure with anti-epileptic drugs, close monitoring to their level.
– Close neuro-vital observation.
– Control the pain.
– MDT; hematooncologist, 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.
– Reduce immunosuppression while careful monitore graft function for any rejection.
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 antimetabolite, 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.
-If it is toxoplasmosis: sulfadiazine and pyrimethamine or clindamycin plus pyrimethamine
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
This is exellent as usual.
Thank you prof.
Image findingIn post renal TX patient on immunosuppression.
Several ring-enhancing lesions with regular walls and considerable edema are shown on the brain’s MRI scan.
T1 and T2-weighted images?
The signal of fatty tissue is enhanced while the signal of water is suppressed in T1-weighted MRI.
The signal of the water is strengthened by T2-weighted MRI.
T2-weighted images offer the most accurate representation of disease because they highlight diseased areas because most tissues engaged in a pathologic process have higher water content than normal.
Differential diagnosis?
Aspergillus,
Nocardia asteroides,
Toxoplasma gondii, ,
Mucorales and Tuberculosis,
PTLD
How to manage;
FBC + differential, CRP, LDH,
CSF analysis
Sputum for AFB, Culture, and Gene-Xpert
Blood culture
Tacrolimus trough level
Histology of the brain mass (if possible)
Chest CT,Abdominopelvic CT to rule primary
Further Treatment
Admit in ICU
Control fits, hemodynamic assessment.
Fluid replacement if dehydrated,
Stop metabolites
High dose hydrocortisone for brain edema.
Further treatment according to cause
References;
Intracranial cysts: an imagery diagnostic challenge
Alexandra Oprişan, Bogdan O Popescu
Post transplant lymphoproliferative disorders: risk, classification, and therapeutic recommendations
Deepa Jagadeesh, Bruce A Woda, Jacqueline Draper, Andrew M Evens
An immune assay for all the mentioned causes is needed!
With the obvious signs of increased ICT a lumbar puncture is dangerous.
OK prof.
1- There is 2 enhanced well demarcated spherical lesions surrounded with edema
2- 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.
3- Differential diagnosis:
· Could be primary brain tumours such as glioma
· Brain Abscess,
· Cystic Metastases,
· Parasitic Infections,
· Tuberculosis.
· Hydatid Cysts
4- Management depends on identification of the cause
Laboratory tests should be done to rule out infectious pathology, such as:
· CSF fluid for viral and bacterial analysis
· Toxoplasmosis and Cryptococcal Ag testing
· Acid fast bacillus stain and PCR
· Further testing to rule out brain tumours and secondary metastasis.
References:
· Oprişan A, Popescu BO. Intracranial cysts: an imagery diagnostic challenge. ScientificWorldJournal. 2013 May 2;2013:172154. doi: 10.1155/2013/172154. PMID: 23737706; PMCID: PMC3659469.
· 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.
Remember a lumber punture for CSF analysis could end up with conisation in such a case.
A 47-year-old CKD 5 has kidney transplantation from his brother, 111 mismatch, no DSAs. Excellent kidney function and Tacrolimus-based immunosuppression. One year later, he presented to you with a headache, confessional states/mental status changes, and seizure. T1 MRI picture is shown below.
===================================================================
Explain the image finding
What is the difference between T1 and T2-weighted images?
The fat-sensitive T1 pictures, which frequently give the area being analyzed good anatomical information.
The T2-weighted pictures, which are water-sensitive.
====================================================================
What is your differential diagnosis?
====================================================================
How would manage this case?
====================================================================
Reference
An ICU management is needed as you mentioned with measures to reduce a high intracranial tension(steroids).
IF confirmed PTLD what is your IS plan.
Many thanks Prof.Dawlat
IF confirmed PTLD what is your IS plan
Explain the image finding:
There is enhancing brain lesions on MRI with surrounding brain tissue edema in post renal TX patient on immunosuppression.
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.
Clinically, T2-weighted images provide the best depiction of disease, because most tissues involved in a pathologic process have a higher water content than normal, and fluid causes affected areas to appear bright on T2-weighted images.
What is your differential diagnosis?
-First DD to rule out infectious processes including Aspergillus, Nocardia asteroides, Toxoplasma gondii, Listeria monocytogenes, Mucorales, Tuberculosis, and less commonly Cryptococcus.
-Primary CNS posttransplant lymphoproliferative disorder which range from early lymphoid proliferations to malignant lymphomas.
-stroke and posterior reversible encephalopathy syndrome.
How would manage this case?Investigations to find the cause of the brain lesions:
-Laboratory tests to rule out infective causes:
HIV PCR
Toxoplasmosis IgM Ab and PCR
Cryptococcal Ag
Coccidioides IgG/IgM Ab
CMV PCR
EBV PCR,EBV capsid IgM Ab,EBV capsid IgA Ab,EBV early antigen IgG Ab.
CSF Flow cytometry
Cryptococcal Ag
Acid fast bacillus stain and PCR
India ink
Bacterial, fungal, mycobacterial cultures.
-Imaging:
Gadolinium-enhanced brain MRI which revealed revealed multiple enhancing brain lesions.
-Chest X rays and CT scan with contrast of the abdomen and pelvis to rule out masses.
-May be stereotactic brain biopsy will be needed to confirm the diagnosis.
Management :
In view of brain edema and neurologic manifestations of mass effect to commence dexamethasone in the interim.
If proved PTLD :
Hold MMF and reduce CNI dose and follow up the effect.
References:
Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR) OPTN / SRTR 2010 Annual Data Report. Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation; 2011.
Nabors L, Palmer C, Julian B, Przekwas A, Kew C. Isolated central nervous system posttransplant lymphoproliferative disorder treated with high-dose intravenous methotrexate. Am J Transplant. 2009;9(5):1243–1248
Good you started Dexamethasone for the obvious brain oedema.
Does an interrupted circomferance give a clue about the nature of the lesion?wether invasive or not.
What is your differential diagnosis?Tuberculoma
PTLD
Toxoplasmosis
Cryptococcus
PTLD
Metastasis
How would manage this case?History
History of cough, fever, weight loss, pruritis, night fever, abdominal pain or history of pulmonary or abdominal TB, Any malignancy, fits
Examination
General physical examination, lymph node examination , chest and abdominal examination
check ICP.
Investigations
Blood CP, ESR, Real and liver functions, LDH, PSA
CT chest abdomen and pelvis
Quantiferon TB test
Lumbar puncture
PCR for CMV, HIV, EBV
Lesion Biopsy
Treatment
MDT Approach- Involve neuology, neurosurgery, ID Consultants
Anti convulsants
Steroids
Modification of immune suppression
Final treatment will depend on the diagnosis
For PTLD
The modalities of treatment include reduction in immunosuppression, cranial radiotherapy (CRT), intravenous and intrathecal rituximab when CD20 is expressed on B-lymphocytes and PTLD cells, and chemotherapy.
Meena P, Bhargava V, Rana D, Bhalla A, Gupta A. An Approach to Neurological Disorders in a Kidney Transplant Recipient. Kidney360. 2020 Jun 16;1(8):837-844. doi: 10.34067/KID.0002052020.
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.
Thankyou ,what are the symptoms and radiology signs of increased intracranial tension in this case.?
would you be enthusiastic for lumbar puncture?
Symptoms include Headache.. Blurred vision., Confusion, High blood pressure, Shallow breathing, Vomiting, Changes in your behavior, Weakness or problems with moving or talking.
Ct findings cab be odema, enlarged ventricles, herniation, or mass effect
Lumbar puncture should be avoided in high intra cranial tension
Explain the image finding
T1 MRI brain shows multiple ring enhancing lesions with smooth and regular walls and significant edema. No midline shift
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. PTLD
2. Toxoplasma gondii
3. Tuberculoma
4. Brain abcess
5. Primary Brain tumours (glioblastoma)
6. Brain metastases
7. Cryptococcus neoformans (crytococcocosis )
8. JC virus
9. Others: CMV, VZV, candida species, aspergillus fumigates, syphilis, neurocystericercosis
How would you manage this case?
o MDT
o Immediate involvement of the neurosurgeon
o Corticosteroids
o Detailed history and comprehensive examination
o CBC, CRP, urine analysis, HIV, urine and blood culture
o Screen for TB, cryptoccocal antigen, toxoplasma and neurocystericercosis serology
o EBV/CMV viral load
o Tissue biopsy may be recommended
o Symptomatic treatment and 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)
CNS-PTLD
o Occur in 10-20% of PTLD
o The histology is typically monomorphic, highgrade B-cell lymphoma and all are EBV-positivecur
o Tissue biopsy is recommended given that opportunistic infections may present with similar radiological findings
o The overall prognosis is poor
o Options of treatment: reduction of immunosuppression, intrathecal chemotherapy, whole-brain radiotherapy and systemic chemotherapy (a regimen of high-dose methotrexate with rituximab)
A British Society for Haematology Guideline recommendatios
o Patients with CNS-PTLD should be offered treatment with RIS (it may not always be possible to wait for response to initial RIS before embarking on secondary therapy) followed by combination chemotherapy with rituximab in suitable patients depending on adequate organ function and comorbidity (1C).
o Local radiotherapy +/- corticosteroids with RIS where fitness and comorbidity are limiting factors may be offered in CNS-PTLD (2C).
o Where available EBV-specific CTL can be considered for EBV-positive CNS-PTLD (1C).
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
The ring lesions are not smooth and actually interupted does this give you a clue for DD?
Otherwise your review is very sufficient with downsizing DD between two options.
Thank you prof.
A thick, irregular, interrupted, ring enhancement lesion suggests a necrotic brain tumor
Explain the image finding
This is a T1 weighted MRI image of multiple irregularly shaped ring-enhanced lesions located at the right frontal and parietal lobe and with perilesional edema around the lesions.
What is the difference between T1 and T2-weighted images?
The T1- weighted MRI will suppress the signal of the water while enhancing the signal of the fatty tissue
The T2- weighted MRI will enhance the signal of the CSF, fluids, and grey matter
What is your differential diagnosis?
How would manage this case?
Further history of occurrence of acute rejection, use of the depleting agent for rejection if it occurs, and EBV status of the donor and recipient prior to kidney transplants. It has been observed that PTLD is present early after kidney transplant if the primary EBV is from the donor and late if is the reactivation of the primary infection from the recipient. CNS PTLD is reported in 30% of cases
Further Investigations
Treatment
References
Any idea about adoptive theray trials!
otherwise good plan for diagnosis, apart from the suggestive MRI how can you rule out TB?
Explain the image finding:
The T1 MRI is showing 2 ring enhancing lesions with perilesional edema and a subtle midline shift with compression of the left lateral ventricle. The posterior lesion is partially ring enhancing
Difference between T1 and T2 weighted imaging:
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 matter darker than the white matter
Differential diagnosis:
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
Moscato M et al. The Neurohospitalist 3(1) 15-19
Ram R et al. Nephrology (Carlton). 2013 Jun;18(6):479-480.
Thankyou ,you cautiously mentioned the danger of conisation with CSF tapping in such a case with midline shift and increased ICT.
Explain the image finding
What is the difference between T1 and T2-weighted images?
What is your differential diagnosis?
Primary CNS PTLD
How would you manage this case?
To reach to a definitive diagnosis
Management is according to the diagnosis
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.
Thankyou this is an excellent answer,but reviewing the index MRI and according to your description of T1 for fat tissue and T2 for water can you suggest why it darker around the lesion (oedema).
The circumference is interrupted ( invasive spread)!
Explain the image findingMRI shows two round lesions with central low intensity, surrounding enhancement (ring) and edema. The left ventricular is compressed.
What is the difference between T1 and T2-weighted images?
T1-weighted images
○are produced by using short TE and TR times.
○It inhances the signal of the fatty tissue
○It suppresses the signal of the water
T2-weighted images
■ are produced by using longer TE and TR times.
■It enhances the signal of the water
■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
about this case
MRI
T1: iso- to hypointense to cortex
T1 C+ (Gd): vivid contrast enhancement
T2variablemajority are iso to hypointensehyperintense is more common when necrosis is presentsurrounding vasogenic edema
What is your differential diagnosis?
●PTLD
●Tuberculoma
●Abscess (bacterial- fungus)
●Brain toxaplasmosis
●Criptococosis
●Neurosarcoid
●Metastasis
How would manage this case?
□We should ask about the EBV test in donor and recipient before transplantation
□Also the TB evaluation in donor and recipient before transplantation
A- Primary CNS PTLD is uncommon and the diagnosis and treatment are difficult
□The diagnosis should be suspected in transplant recipients with mental status changes or new neurologic findings.
□Diagnostic tests include (MRI) of the head
□analysis of (CSF) by cytology, flow cytometry, and for EBV genes by (PCR)
□ PCR (EBV) clear positive
□Sometimes, the diagnosis should be confirmed either by the presence of malignant lymphocytes in the CSF or by direct biopsy of the lesion
□Neurologist consultation for controlling seizures
□CBC – LDH – UA- CA
□CXR – CT (chest- abdomin)
□ the best management iniate with the reduction of immunosuppression agents with close monitoring (clinically and laboratory ) for rejection.
□Rituximab (anti CD20) is the treatment of choice for PTLD
□chemotherapy in addition to Rituximab, cyclophosphamide- doxorubicin- vincristine- prednisolone
□radiation therapy
□ Adoptive immunotherapy — Adoptive immunotherapy uses EBV-specific cytotoxic T lymphocytes (EBV-CTLs) or donor lymphocyte infusion (DLI) in an attempt to kill dividing B cells in EBV-associated PTLD.
This therapy needs more evidence.
B- The wide spectrum antibiotics and anti fungal treatment may consider if the diagnosis is not clear
C- evaluation of tuberculosis is essential notably when the recipient or donor has been treated previously. In addition to the recipient in endemic regions or patient with HIV
♡CXR – CT chest
♤IGRA- BAL sputum samples
♡CSF examination and culture- blood culture.
♤Depending an the BTS RECOMMENDATIONS
Rifampicin can interact with IS regimens, Increasing the chance ofgraft rejection, and doses of MMF, TAC and ciclosporin may need adjustment. Corticosteroid doses should be doubled in patients receiving rifampicin. (B)
♤the treatment consists of 4 drugs for two months then 2 drugs for two months
REFERENCES
1- Central nervous system tuberculosis (UpToDate)
2- Prevention and treatment of Post-transplant lymphoproliferative disorders (UpToDate)
3- Intracranial tuberculous granuloma.Last revised by Travis Fahrenhorst-Jones on 21 Aug 2022
4- phoproliferative disorder. Last revised by Frank Gaillard on 15 Mar 2023
Is adoptive immunotherapy clinically established?
Explain the image finding.
=====================
What is the difference between T1 and T2-weighted images?
=====================
What is your differential diagnosis?
=====================
How would manage this case?
References
I appreciate that CNS PTLD is one of your DDs even though lower down at no 9.
Explain the image findingThe MRI revealed ring-enhanced lesions together with diffuse edema in the surrounding area.
What is the difference between T1 and T2-weighted images?
The timing of radiofrequency pulse sequences used to make T1 images results in images that highlight fat tissue within the body. The timing of radiofrequency pulse sequences used to make T2 images results in images that highlight fat and water within the body.
What is your differential diagnosis?PTLD, tuberculoma, glioblastoma, Nocardia, toxoplasmosis, Mets, and neurocysticercosis
How would manage this case?A management plan should be agreed upon by a core multidisciplinary team (MDT) which should include transplant physicians, haemato-oncologists, hematopathologists, radiation oncologists, and radiologists.
The management strategy will depend on the reason in a significant way.
A sample is taken from this lesion, such as a biopsy or CT-guided.
Positron Emission Tomography–Computed Tomography (PET-CT)
CSF: for cytology and chemistry analysis.
EBV, Nocardia, and Toxoplasma PCR
blood and CSF culture
QUANTIFERON test
ESR, CRP, LFT, Procalcitonin
anticonvulsants, and careful monitoring for any medication interactions
broad-spectrum antibiotic and antifungal.
If proven as a PTLD:
It is possible that lower immune suppression, particularly through anti-metabolites, reduction in immunosuppression by stopping azathioprine and MMF, and reduction of CNIs by 30–50% whilst maintaining or reducing corticosteroids, is recommended in all patients whenever possible, under the guidance of the transplant physician with surveillance of graft function.
Treatment for PTLD includes decreasing or discontinuing the use of immunosuppressant drugs and the administration of rituximab.
Rituximab monotherapy is recommended for patients with CD20-positive PTLD who fail to respond adequately to RIS as initial therapy (1B).
REFERENCES:
SHAH, Nimish, et al. Front‐line management of the post‐transplantation lymphoproliferative disorder in adult solid organ recipient patients—A British Society for Haematology Guideline. British Journal of Haematology, 2021, 193.4: 727-740.
I appreciate that you consider PTLD very early during investigations. I would recommend principles of CCRISP or ACCC in saving such a patient before planning definitive treatment
Explain the image finding:
Ring enhancing lesions in T1 brain MRI (two) with surrounding edema in the left cerebrum temporo-parietal but no midline shift, one year after a kidney transplantation.
What is the difference between T1 and T2-weighted images? The T1 MRI enhances fat and suppress water signals, while T2 MRI enhances water signals.
T1 requires less time to echo than T2 (23ms vs 100ms), less repetition time (2100ms vs 3000ms), and less acquired matrix (288×197 vs 512×336), thus less time.
T1 has an inversion time of 1000ms while T2 not.
What is your differential diagnosis? Differential diagnosis is:
Toxoplasma encephalitis (toxoplasmosis)
Primary brain lymphoma
Brain abscesses
Nocardiosis
Disseminated TB
Cysticercosis
Cryptococcus neoformans
EBV, and JC virus (polyomavirus)
Metastatic tumor
progressive multifocal leukoencephalopathy (rare)
NB: prevalence of infection 4-29%, primary PTLD 0.3-1% How would manage this case? Detailed history – contact with sick person, contact with cats and feline feces, and pretransplant viral screen documented (EBV D+/R-) that may increase the risk of EBV related post transplant PTLD, and history of prophylactic antibiotics, and induction immunosupreesive medications.
Full examination – CNS evaluation, vital signs, chest abdomen and pelvic exam, and ophthalmic examination by ophthalmologist (chorioretinitis/posterior uveitis)
Laboratory: CBC, BUN, Creatinine, ALT,AST, alkaline phosphatase, LDH, CRP.
Antibodies assay for cysticercosis, and toxoplasmosis.
PCR for both toxoplasma, cystirecosis, EBV, and Mycobacterium (highly specific 96-100% but variable sensitivity from 58-98%)
CSF analysis: protein, glucose, gram stain and culture.
Positron emission tomography can distinguish toxoplasma from lymphoma.
Brain biopsy either open or stereotactic and tissue histopathologic examination.
Treatment plan:
With this multiple brain enhancing lesion after the workup should start treatment for toxoplasmosis as follow:
Sulfadiazine (1000 mg four times daily among patients <60 kg or 1500 mg four times daily among patients ≥60 kg). If there are concerns about non-adherence, 2000 mg of sulfadiazine can be administered twice daily; one study documented equivalent pharmacokinetic parameters of this dosing schedule compared with 1000 mg given four times a day.
+
Pyrimethamine (200 mg loading dose followed by 50 mg daily among patients <60 kg or 75 mg daily among patients ≥60 kg).
+
Leucovorin (10 to 25 mg daily). This agent should be administered to prevent pyrimethamine-induced hematologic toxicity.
NB: this regimen does not require PCP prophylaxis, pyrimethamine should not be administered in pregnancy.
Or parenteral trimethoprime-sulphamethexazole in severely ill patients who cannot have oral medications.
Or parenteral clindamycin (600 mg q 6 hours) + pyrimethamine+ leucovorin.
Or Atovaquone 1500 mg twice daily + pyrimethamine+ leucovorin
Or Atovaquone +sulfadiazine
Or Atovaquone alone
NB: these regimens require PCP prophylaxis.
Duration of treatment is: six weeks.
Adjunctive therapy:
(1) Steroids: dexamethasone 4 mg q6 hours with mass effect and surrounding edema.
(2) Anti-convulsants.
Response to therapy:
Repeat imaging in a week – 2 weeks, post treatment if the patient did not show any clinical improvement.
Secondary prophylaxis for six months with the same drugs given on treatment but lower doses and less frequency.
Reduction of immunosuppressive medications: in mild cases reduce MMF 50-75% of the current dose and in severe cases MMF should be stopped, and CNI kept to lower therapeutic range with trough level (4-8 ng/dl).
Intrathecal rituximab had been successful in treating primary CNS lymphoma.
References:
(1) Cohen A, Sugo E, Chacko B. Isolated cerebral toxoplasmosis 17 years post renal transplant. Transpl Infect Dis. 2022 Aug;24(4):e13880. doi: 10.1111/tid.13880. Epub 2022 Jun 16. PMID: 35690470.
(2) Myeong H, Park M, Kim JE, Park SW, Lee SH. Delayed Cerebral Toxoplasmosis in a Kidney Transplant Patient: a Case Report. Korean J Parasitol. 2022 Feb;60(1):35-38. doi: 10.3347/kjp.2022.60.1.35. Epub 2022 Feb 23. PMID: 35247952; PMCID: PMC8898645.
(3) Bagchi S, Sachdev SS, Nalwa A, Das CJ, Sinha S, Suri V, Mahajan S, Bhowmik D, Agarwal S. Multiple intracranial space-occupying lesions in a renal transplant recipient from an area endemic for tuberculosis (TB): TB vs. toxoplasmosis. Transpl Infect Dis. 2014 Oct;16(5):838-42. doi: 10.1111/tid.12262. Epub 2014 Jul 7. PMID: 25040057.
(4) Yaginuma T, Yamamoto H, Mitome J, Tanno Y, Yamamoto I, Kobayashi A, Mafune A, Hayakawa H, Yokoyama K, Mori R, Ohashi H, Kaito N, Joki T, Miki J, Yamada H, Furuta N, Matsushima S, Fukuda T, Hosoya T. Successful treatment of monomorphic primary central nervous system post-transplantation lymphoproliferative disorder 5 years after kidney transplantation. Transpl Infect Dis. 2012 Oct;14(5):E102-6. doi: 10.1111/j.1399-3062.2012.00781.x. Epub 2012 Aug 30. PMID: 22931101.
-Explain the image finding
What is the difference between T1 and T2-weighted images?
What is your differential diagnosis?
How would manage this case?
Source;
I appreciate your carefully balanced clinical approach, that begins with resuscitation of this patient.
thnxs, prof
A 47-year-old CKD 5 has kidney transplantation from his brother, 111 mismatch, no DSAs. Excellent kidney function and Tacrolimus-based immunosuppression. One year later, he presented to you with a headache, confessional states/mental status changes, and seizure. T1 MRI picture is shown below.
Explain the image finding.
MRI axial view shown two rounded lesion surrounded by hyper intense edema in the right front parietal region.
What is the difference between T1 and T2-weighted images?
The fat-sensitive T1 images which often provide good anatomical detail of the area being studied.
The water-sensitive images – such as the T2-weighted.
What is your differential diagnosis?
Tuberculoma of CNS.
Toxoplasmosis.
Cryptococcus’s
Cerebral abscess.
PTLD brain lesion.
Neurocysticercosis
Metastatic lesions
How would 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, fundus 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-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.
2- 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.
That is a high quality well referenced reply.
Multiple enhanced ring lesions with cerebral edema.
T1 vs T2 MRI image:
depend on timing of radiofrequency pulse T2 reflect water and fat image in the body. T1 reflects only fat tissues within the body.
differential diagnosis of ring cerebral lesions,
1] cerebral abscesses
2]Tuberculosis
3] Neurocysticercosis .
4] Secondary metastasis tumors.
5] Primary cerebral tumors , such as glioblastoma
6] Cerebral infarction.
Management :
Biopsy of the lesion
Too short a reply. Would you not consider PTLD?