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Journal of Medical Imaging and... Aug 2022We aim to assess the imaging manifestations of brain involvement in paediatric immunocompromised patients with haematological malignancies on chemotherapy presenting...
INTRODUCTION
We aim to assess the imaging manifestations of brain involvement in paediatric immunocompromised patients with haematological malignancies on chemotherapy presenting with encephalitis and positive HSV CSF PCR. We also aim to determine whether our findings are similar or different to those described in literature for paediatric patients in general.
METHODS
A retrospective study was performed in paediatric ALL/lymphoma patients on chemotherapy, and cases with positive CSF HSV-PCR with at least one head MRI scan were included. On imaging, location(typical/atypical), post-contrast enhancement and haemorrhage/diffusivity/gliosis were evaluated.
RESULT
A total of 28 scans were included in study from 16 patients fulfilling inclusion criteria, 12 (75%) HSV-1 and 4 (25%) HSV-2. Of the 16 initial scans (CT n = 10, MRI n = 6), 11 were normal (CT = 7, MRI = 4). Fourteen patients had follow-up MRI, of which two had normal scans. On the abnormal initial scan (5/16), only 20% had typical medial temporal/inferomedial frontal/cingulate involvement. Most had frontal (80%), parietal (60%) and non-medial temporal (40%) lesions. Abnormal diffusivity/haemorrhage was absent in all, and postcontrast enhancement was seen in 20%. On follow-up, more patients (33%) had typical medial temporal/inferomedial frontal/cingulate involvement. Widespread atypical site involvement of frontoparietal (75%), thalamus (58%), non-medial temporal (50%), occipital/basal ganglia (33%) and cerebellum (8%) was noted. Most lesions were cortical (91%)/subcortical (75%) with few periventricular lesions (58%). Few showed abnormal diffusivity (16%), post-contrast parenchymal enhancement/haemorrhage (8%), post-contrast meningeal enhancement (25%) and gliosis (16%).
CONCLUSION
Immunocompromised paediatric patients with haematological malignancies have widespread atypical brain involvement in herpes simplex encephalitis with lack of diffusion restriction and post-contrast enhancement, likely due to haematogenous spread of HSV across the blood-brain barrier, lack of cellular immunity and limited inflammatory cytokine response.
Topics: Child; Encephalitis, Herpes Simplex; Gliosis; Hematologic Neoplasms; Humans; Immunocompromised Host; Magnetic Resonance Imaging; Neoplasms; Retrospective Studies; Simplexvirus
PubMed: 34519419
DOI: 10.1111/1754-9485.13326 -
Vaccines Jan 2021Corticosteroids, when given in high dosages, have long been recognized as a risk factor for severe infection with wild-type varicella-zoster virus in both children and... (Review)
Review
Corticosteroids, when given in high dosages, have long been recognized as a risk factor for severe infection with wild-type varicella-zoster virus in both children and adults. The goal of this review is to assess the degree to which both low-dosage and high-dosage corticosteroids contribute to serious adverse events (SAEs) following live varicella vaccination and live zoster vaccination. To this end, we examined multiple published reports of SAEs following varicella vaccination (Varivax) and zoster vaccination (Zostavax). We observed that five of eight viral SAEs following varicella vaccination, including two deaths, occurred in children receiving corticosteroids, while one of three fatal viral SAEs following live zoster vaccination occurred in an adult being treated with low-dosage prednisone. The latter death after live zoster vaccination occurred in a 70 year-old man with rheumatoid arthritis, being treated with prednisone 10 mg daily. Thus, corticosteroids contributed to more severe infectious complications in subjects immunized with each of the two live virus vaccines. Further, when we surveyed the rheumatology literature as well as individual case reports, we documented examples where daily dosages of 7.5-20 mg prednisone were associated with increased rates of severe wild-type varicella-zoster virus infections in children and adults.
PubMed: 33418856
DOI: 10.3390/vaccines9010023 -
BioRxiv : the Preprint Server For... Dec 2023Leptomeningeal disease (LMD) occurs when tumors seed into the leptomeningeal space and cerebrospinal fluid (CSF), leading to severe neurological deterioration and poor...
Leptomeningeal disease (LMD) occurs when tumors seed into the leptomeningeal space and cerebrospinal fluid (CSF), leading to severe neurological deterioration and poor survival outcomes. We utilized comprehensive multi-omics analyses of CSF from patients with lymphoma LMD to demonstrate an immunosuppressive cellular microenvironment and identified dysregulations in proteins and lipids indicating neurodegenerative processes. Strikingly, we found a significant accumulation of toxic branched-chain keto acids (BCKA) in the CSF of patients with LMD. The BCKA accumulation was found to be a pan-cancer occurrence, evident in lymphoma, breast cancer, and melanoma LMD patients. Functionally, BCKA disrupted the viability and function of endogenous T lymphocytes, chimeric antigen receptor (CAR) T cells, neurons, and meningeal cells. Treatment of LMD mice with BCKA-reducing sodium phenylbutyrate significantly improved neurological function, survival outcomes, and efficacy of anti-CD19 CAR T cell therapy. This is the first report of BCKA accumulation in LMD and provides preclinical evidence that targeting these toxic metabolites improves outcomes.
PubMed: 38187773
DOI: 10.1101/2023.12.18.572239 -
Cureus Apr 2023Sarcoidosis is a systemic disease of unknown etiology with multi-system affection. It typically involves the skin, eyes, hilar lymph nodes, and pulmonary parenchyma....
Sarcoidosis is a systemic disease of unknown etiology with multi-system affection. It typically involves the skin, eyes, hilar lymph nodes, and pulmonary parenchyma. However, as any organ system could be involved, one has to be aware of its atypical manifestations. We present three uncommon manifestations of the disease. Our first case presented with fever, arthralgias, and right hilar lymphadenopathy with a history of tuberculosis in the past. He was treated for tuberculosis but had a relapse of symptoms three months after completion of treatment. The second patient presented with a headache for two months. On evaluation, cerebrospinal fluid examination showed evidence of aseptic meningitis, while an MRI of the brain demonstrated enhancement of the basal meninges. The third patient was admitted with a mass on the left side of the neck for one year. On evaluation, he was found to have left cervical lymphadenopathy, with its biopsy showing non-caseating epitheloid granuloma. Immunofluorescence did not show evidence of leukemia or lymphoma. All the patients had negative tuberculin skin tests and elevated serum angiotensin-converting enzyme levels supporting the diagnosis of sarcoidosis. They were treated with steroids with complete resolution of symptoms and no recurrence at follow-up. Sarcoidosis is an underdiagnosed entity in India. Thus, awareness of the atypical clinical features could lead to early recognition of the disease and its treatment.
PubMed: 37159764
DOI: 10.7759/cureus.37208 -
Child's Nervous System : ChNS :... Dec 2023Intracranial myeloid sarcoma is a rare extramedullary presentation of acute myeloid leukemia (AML). It can involve the meninges and ependyma presenting as extra-axial... (Review)
Review
INTRODUCTION
Intracranial myeloid sarcoma is a rare extramedullary presentation of acute myeloid leukemia (AML). It can involve the meninges and ependyma presenting as extra-axial mass lesion. Rarely, it can also invade the brain parenchyma. It is commonly seen in children. It is usually misdiagnosed due to its close resemblance to other intracranial tumors (meningioma, metastasis, Ewing's sarcomas, and lymphoma). These are underdiagnosed if they precede the diagnosis of leukemia.
CASE REPORT
A 7-year-old boy with isolated intracranial myeloid sarcoma who presented with raised intracranial pressure (ICP) which was successfully managed by surgical excision.
CONCLUSION
Isolated intracranial myeloid sarcoma is a rare presentation of AML. Leukemia can be diagnosed early during the postoperative period and can be started on therapy timely. These patients requires regular follow-ups (clinical, laboratory and radiological) to detect relapses early.
Topics: Male; Child; Humans; Sarcoma, Myeloid; Leukemia, Myeloid, Acute; Sarcoma, Ewing; Meningeal Neoplasms; Brain Neoplasms
PubMed: 37300577
DOI: 10.1007/s00381-023-06016-w -
Indian Journal of Cancer 2021Acute neurological complications occur in 3.6-11% of children treated for acute lymphoblastic leukemia (ALL). This analysis aimed to evaluate the profile of acute...
BACKGROUND
Acute neurological complications occur in 3.6-11% of children treated for acute lymphoblastic leukemia (ALL). This analysis aimed to evaluate the profile of acute neuro-toxicity and its etiology in children with ALL.
METHODS
A retrospective case analysis of central nervous system events in children treated for ALL at our center was performed. Details of events were retrieved from the case records (January 2006-December 2015) and analyzed.
RESULTS
Ninety (9.5%) neurological events occurred in 923 patients treated for ALL. Phase of therapy were: induction (38), consolidation (5), interim maintenance (5), intensification (15) and maintenance (27). Seizures and neurological deficits were the presenting features in 64 and 40 children, respectively. Events included : neuro-infections in 18, posterior reversible encephalopathy syndrome (PRES) in 7, epilepsy in 6, intracranial bleed in 5, systemic infection with neurological complication in 4, hydrocephalus and aseptic meningitis in 3 each, methotrexate encephalopathy and metabolic seizures in 2 children each. Seizures and status epilepticus of unknown etiology and neurological deficits of unknown etiology was observed in 26 and 13 children, respectively. Seizures occurred mainly in induction (12) and intensification phase (9). Status epilepticus transpired in maintenance phase in 9/14 patients. Induction phase was complicated by PRES in 7, intracranial bleed in 5 and cerebral sinus venous thrombosis in 1 patient. Neuroimaging was done in 86% of events. There were 18 (20.6%) deaths: neuro-infections (8), status epilepticus (6), systemic infection (2), bleed (1), and unexplained encephalopathy (demyelination)(1). At last follow-up, 53 patients were well and 7 children persist to have a neurological disability.
CONCLUSION
Ten percent of children on treatment for ALL suffered an acute neuro-toxicity. Morbidity and high-incidence of neuroinfections are major concerns.
Topics: Female; Humans; Male; Nervous System Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Risk Factors; Time Factors
PubMed: 34380827
DOI: 10.4103/ijc.IJC_422_19 -
Journal of Hematology Apr 2024Intracerebral hemorrhage is a potentially fatal complication in patients with acute leukemia and contributing factors include thrombocytopenia and coagulopathy. Patients...
Intracerebral hemorrhage is a potentially fatal complication in patients with acute leukemia and contributing factors include thrombocytopenia and coagulopathy. Patients with acute leukemia may develop subdural hematoma (SDH) spontaneously or secondary to trauma. In patients with acute leukemia and SDH, the surgical evacuation of the hematoma causes significant morbidity and mortality. New approaches and strategies to reduce the need for surgical evacuation are needed to improve outcomes in patients with acute leukemia and intracerebral hemorrhage. We report two cases of acute SDH in patients with acute leukemia successfully treated with middle meningeal artery embolization, a minimally invasive interventional radiology technique, obviating the need for a surgical intervention. The first patient with acute promyelocytic leukemia (APL) presented with coagulopathy and developed an acute SDH after a fall. The second patient with acute myeloid leukemia presented with gum bleeding and also sustained an acute SDH after a fall. Both patients underwent middle meningeal artery embolization for treating their SDHs while actively receiving induction chemotherapy for acute leukemia. Both patients had resolution of their acute SDH and are in remission from their acute leukemia. Middle meningeal artery embolization is a very effective, and within the context of this setting, a novel, minimally invasive technique for management of SDH in acute leukemia patients, which can prevent the need for surgical interventions with its associated comorbidities and high risk of fatal outcomes in patients with acute leukemia and acute SDH.
PubMed: 38644984
DOI: 10.14740/jh1215 -
Orvosi Hetilap Oct 2021Összefoglaló. Az emlőtumor miatt kezelt, majd gondozott beteget - több tünetmentes év után - fejfájás, szédülés, ataxia, megváltozott, furcsa viselkedés,...
Összefoglaló. Az emlőtumor miatt kezelt, majd gondozott beteget - több tünetmentes év után - fejfájás, szédülés, ataxia, megváltozott, furcsa viselkedés, emlékezetzavar és dezorientáció miatt neurológiai, majd belgyógyászati osztályokon vizsgálták. Az alapos kivizsgálás ellenére a tüneteit magyarázó organikus eltérést nem igazoltak, ugyanakkor már a kezdetektől felmerült a szomatizációs tünetképzés lehetősége, ezért pszichiátriai osztályos felvételére került sor. Az elvégzett vizsgálatok, illetve a klinikai kép regresszív állapotot valószínűsítettek. Terápiás próbálkozásaink ellenére a páciens állapota romlott, végül a megismételt neurológiai vizsgálatok meningitis carcinomatosát igazoltak. Az esettel szemléltetni kívánjuk, hogy a beteg premorbid működési nívója, személyiségstruktúrája hogyan képes befolyásolni az ellátószemélyzetet, milyen külső és belső konfliktusokat válthat ki. A diagnózishoz vezető folyamat bemutatásával fel kívánjuk hívni a figyelmet az interdiszciplináris együttműködés fontosságára. Orv Hetil. 2021; 162(43): 1744-1748. Summary. Our patient with known breast cancer in her past medical history was hospitalized - after several asymptomatic years - for headache, dizziness, ataxia, changed behaviour and disorientation. Thorough internal and neurologic investigations did not find any disease underlying her symptoms, therefore the possibility of somatization disorder was raised. Despite lege artis therapeutic interventions carried out on the psychiatry ward, the patient's condition deteriorated and repeated neurological examinations eventually revealed carcinomatous meningitis. With this case, we would like to illustrate how the patient's premorbid function level and personality features might influence the attitude and opinion of the health care personnel, and what kind of external and internal conflicts might be triggered. By presenting the complexity of the diagnostic work-up, we would like to emphasize the importance of interdisciplinary cooperation in the interest of our patients. Orv Hetil. 2021; 162(43): 1744-1748.
Topics: Female; Humans; Leukemia; Meningeal Carcinomatosis; Vertigo
PubMed: 34689135
DOI: 10.1556/650.2021.32175 -
EJHaem Feb 2024Hairy cell leukemia (HCL) is a rare lymphoproliferative disorder classically presenting with cytopenia and recurrent infections but atypical manifestations such as bone...
Hairy cell leukemia (HCL) is a rare lymphoproliferative disorder classically presenting with cytopenia and recurrent infections but atypical manifestations such as bone lesions, skin lesions and effusion have been described. We report here an unusual meningeal localization in a 33 years old man who presented with headache, hand paresthesia and visual symptoms. Brain magnetic resonance imaging revealed an occipital meningeal lesion. Diagnostic explorations led to the diagnosis of classical HCL with meningeal localization. After treatment by cladribine and rituximab the patient rapidly improved and is still in complete remission 12 months after end of treatment. The literature review identified 9 other cases of HCL with central nervous system localization (CNS) presenting with brain parenchyma and/or meninges localization. Four out of 9 patients presented with hyperleukocytosis. Most patients experienced good responses with various treatments. Cladribine alone or with rituximab led to complete responses similar to our patient. In our patient, molecular biology revealed KLF2 mutations, which implication in the atypical localization could be suspected but would need dedicated studies. In conclusion, CNS localizations of HCL are rare but can be observed and treatment with cladribine alone or with rituximab appears as an effective strategy.
PubMed: 38406549
DOI: 10.1002/jha2.841 -
Chemotherapy 2021A patient with a therapy-related acute myeloid leukaemia (AML), NPM1mut, and FLT3-ITD+ was treated with induction and consolidation with CPX-351, obtaining a complete...
A patient with a therapy-related acute myeloid leukaemia (AML), NPM1mut, and FLT3-ITD+ was treated with induction and consolidation with CPX-351, obtaining a complete response (CR) but minimal residual disease persisted positive. Later, she complained progressive burning leg pain, weakening of the right hand and leg muscles, associated with absence of osteotendinous leg reflexes. Examination of cerebrospinal fluid (CSF) showed a meningeal relapse of AML. Moreover, a magnetic resonance imaging (MRI) showed 2 right meningeal implants of myeloid sarcoma and bone marrow revealed haematologic relapse of disease. She was treated with medicated lumbar punctures (LPs) followed by an FLA-Ida scheme, and she achieved a 2nd CR. Unfortunately, the patient developed hyperleucocytosis and reappearance of meningeal myeloid sarcoma at MRI. For this reason, a monotherapy with gilteritinib (an FLT3 inhibitor) was started: after 3 months of therapy, central nervous system (CNS)-disease shrunken and then faded, while AML in the bone marrow achieved only a partial response. This is the 1st report of a positive biological effect of gilteritinib on CNS (meningeal) myeloid sarcoma. There are no studies of gilteritinib concentration into CSF and penetration of gilteritinib into the blood-brain barrier should be further studied, given the paucity of drugs active on CNS relapse of AML. In patients receiving CPX-351 only, diagnostic LP should be considered after induction.
Topics: Aniline Compounds; Bone Marrow; Brain; Humans; Leukemia, Myeloid, Acute; Magnetic Resonance Imaging; Mutation; Neoplasm Recurrence, Local; Protein Kinase Inhibitors; Pyrazines; Treatment Outcome; fms-Like Tyrosine Kinase 3
PubMed: 34515081
DOI: 10.1159/000518356