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A 3-year-old boy presented with acute onset of prolonged right sided focal seizures with secondary generalisation. The investigation findings were suggestive of a neoplastic process more than an inflammatory process. Decision to perform brain biopsy from the lesion to establish the precise nature of lesion was undertaken.

OBJECTIVE The objective of this study was to determine the frequency with which brain biopsy for presumed CNS relapse of systemic hematological malignancies yields new, actionable diagnostic information. Hematological malignancies represent a disparate group of genetic and histopathological disorders. Proclivity for brain involvement is dependent on the unique entity and may occur synchronously or metasynchronously with the systemic lesion. Diffuse large B-cell lymphomas (DLBCLs) have a high propensity for brain involvement. Patients in remission from systemic DLBCL may present with a lesion suspicious for brain relapse. These patients often undergo brain biopsy. The authors’ a priori hypothesis was that brain biopsy in patients with a history of systemic DLBCL and a new brain MRI lesion would have lower diagnostic utility compared with patients with non-DLBCL systemic malignancies. METHODS The authors performed a retrospective review of patients who underwent brain biopsy between 2000 and 2019. Inclusion criteria were patients ≥ 18 years of age with a prior systemic hematological malignancy in remission presenting with a new brain MRI lesion concerning for CNS relapse. Patients with a history of any CNS neoplasms, demyelinating disorders, or active systemic disease were excluded. The main outcome was the proportion of patients with a distinct histopathological brain diagnosis compared with the systemic malignancy. The authors secondarily assessed overall survival, procedure-related morbidity, and 30-day mortality. RESULTS Sixty patients met inclusion criteria (40 males and 20 females); the median age at brain biopsy was 67 years (range 23–88 years). The median follow-up was 8.5 months (range 0.1–231 months). Thirty-nine (65.0%) patients had DLBCL and 21 (35%) had non-DLBCL malignancies. Thirty-five of 36 (97.2%) patients with prior systemic DLBCL and a diagnostic biopsy had histopathological confirmation of the original systemic disease versus 0 of 21 patients with non-DLBCL systemic malignancies (p < 0.001). Morbidity and 30-day mortality were 8.3% and 10.0%, respectively; 2 of 6 30-day mortalities were directly attributable to the biopsy. The median overall survival following brain biopsy was 10.8 months. CONCLUSIONS Patients with a history of systemic DLBCL and presumed CNS relapse gained minimal clinical benefit from brain biopsy but were at high risk of morbidity and mortality. In patients with a history of non-DLBCL systemic malignancies, brain biopsy remained critical given the high likelihood for discovery of distinct diagnostic entities. It was determined that patients with a prior systemic DLBCL and presumed brain relapse should likely receive empirical therapy obviating treatment delay and the risks of brain biopsy.

Purpose To report a case of bilateral ocular ischemia caused by intravascular lymphoma with presence of bilateral Triangular Sign of Amalric. Observations A 67-year-old female was admitted to our hospital for progressive paraplegia and a 6-month history of acute painless vision loss OD. Initial exam showed vision of CF OD and 20/20 OS with normal anterior exam. Fundus exam revealed a likely previous CRAO OD with pale nerve and attenuated vessels. Both fundi had triangular regions of pigmentary change known as the Triangular Sign of Amalric, indicative of choroidal ischemia. However, the left eye was asymptomatic. Neuro-imaging revealed multifocal enhancing lesions throughout the central nervous system of unclear etiology. An extensive neurologic and systemic workup was unrevealing, including a brain biopsy, and empiric treatment for an unspecified inflammatory condition with IV corticosteroids was initiated. During her hospitalization, she developed acute painless vision loss OS, and exam showed NLP vision OU with signs of acute retinal and choroidal ischemia OS. A subsequent brain biopsy revealed intravascular lymphoma. Conclusions and Importance: Triangular pigmentary changes indicate choroidal ischemia, and can be seen in many conditions. This patient presented with the Triangular Sign of Amalric in both eyes, including her asymptomatic left eye. Intravascular lymphoma should be considered in cases of concomitant inflammatory brain lesions and chorio-retinal ischemia.

Introduction: The Covid-19 pandemic has resulted in a spark in interest in the subject given the high exposure rate to viral antigens in the form of infections and vaccines. It is expected that acute disseminated encephalomyelitis (ADEM) cases see a rise in incidence during this period. Given the plethora of Covid-19-related central nervous system (CNS) involvement, it is important to be aware of the varied presentations of ADEM. Case reports: In this paper, we report 3 cases of ADEM following Covid-19 infection. Patients presented with polyfocal neurological symptoms 6 to 18 days after respiratory symptoms onset. The diagnosis of Covid-19 was made based on nasal swab reverse transcriptase-polymerase chain reaction (RT-PCR) and chest computerized tomography (CT). Discussion: These cases illustrate both classic and atypical presentations requiring exclusion of a spectrum of CNS conditions to be able to retain the diagnosis of ADEM. Consequently, we stress the importance of context, clinical examination and MRI findings in the differentials. In addition, we discuss workup, and particularly, the indication of brain biopsy. Also, the paper discusses options in therapy and the prognosis. The prognosis of covid-associated ADEM is dependent on the extent of pathology intrinsic to ADEM and the intrication of the prognosis of Covid-19 infection. Conclusion: The key message in these 3 cases is that clinicians should have a low threshold of suspicion of ADEM in the Covid-19 context, adopt appropriate workup strategies, and initiate adequate treatment for better outcomes.

Objective new-onset refractory status epilepticus (NORSE) is defined as de novo refractory seizures occurring in previously healthy adults, without a clear underlying etiology. Due to refractory seizures and insufficient understanding of pathophysiology, management of these patients remains challenging and often leads to poor clinical outcomes. Various infectious and autoimmune mechanisms have been proposed but have not been validated and a large number of patients are thus labeled ‘cryptogenic’. Moreover, histopathological findings have rarely been described in NORSE and are usually autopsy evaluations. In this paper, we describe the clinical correlates and histopathological findings in patients presenting with NORSE. Methods A case series of five patients with NORSE who underwent neurosurgical intervention and had histopathological examination during their acute clinical course. Results In all patients,status epileptics was refractory to treatment with antiseizure drugs (ASDs) and anesthetic agents. Autoimmune work-up revealed elevated titer of anti-GAD antibody in one patient but was unremarkable in others. Empiric use of immunomodulation therapy in three patients did not lead to cessation of status epilepticus (SE). Due to failure of prolonged medical management, three patients underwent palliative surgery for resection of epileptogenic tissue whereas the other two had diagnostic brain biopsy. Histopathology obtained during biopsy revealed evidence of vasculitis in one and necrotizing vasculopathy in another. The patient with anti-GAD antibodies had evidence of lymphocytic infiltration in limbic structures. The remaining two had nonspecific histopathological findings. Significance Although our findings are limited by a small number of patients, it adds to the growing premise of NORSE being related to an underlying autoimmune process. Additional studies, especially with histopathological data are needed to better understand this devastating disorder.

Here, we report two cases showing tumor-like white matter lesions; one case was diagnosed as having inflammatory disease, and the other was diagnosed as having astrocytoma. Their outcomes were completely distinct despite similar pathology. Prior to biopsy, perfusion computed tomography (CT) and magnetic resonance imaging (MRI) were conducted. The two mass-forming lesions were distinct in edema level and vascularity patterns on CT and MRI. However, pathological examination of brain biopsy specimens revealed commonalities, including (1) proliferation of glial cells, (2) perivascular lymphocytic infiltration, and (3) appearance of numerous macrophages. Although atypical astrocytes proliferated in both cases, nuclear atypia was more distinct in case 2 than in case 1. The immunohistochemical results were the same for both cases: isocitrate dehydrogenase 1 (IDH1) R132H mutation was negative, and alpha thalassaemia mental retardation X-linked (ATRX) was retained. Faint immunoreactivity for p53 was observed in a few glial cells, and Ki-67 immunoreactive cells were markedly reduced in numbers (< 1%). Inflammatory reactions were evident in both cases: T cells dominantly infiltrated over B cells in the perivascular area in case 1, whereas both T and B cells infiltrated in case 2. Molecular analysis revealed wild-type IDH1 and IDH2 in both cases. However, a telomerase reverse transcriptase (TERT) sequence mutation was detected in case 2 but not in case 1. Eventually, case 1 was diagnosed as having inflammatory lesions, whereas case 2 was diagnosed as having diffuse astrocytoma associated with inflammatory reactions. The prognosis was favorable for case 1, whereas case 2 died 10 months following biopsy. These data indicated the diagnostic value of molecular analysis, for example, a TERT mutation, in association with the radiological findings. Although in case 2, histopathological evidence did not suggest high-grade glioma, the case met the new diagnostic criteria: "diffuse astrocytic glioma, IDH wild-type, with molecular features of glioblastoma, World Health Organization (WHO) grade IV," according to cIMPACT-NOW, update 3. Thus, interdisciplinary approaches are essential for accurate diagnosis of newly categorized white matter diseases.

Background We aimed to investigate the detection rate of body CT or PET/CT for sites of extracranial disease in patients with a new pathological diagnosis of CNS DLBCL and to identify factors associated with sites of extracranial disease. Methods An international multicenter cohort study of consecutive immunocompetent patients with a new diagnosis of CNS DLBCL confirmed by brain biopsy who underwent CT and/or PET/CT to evaluate for sites of extracranial disease between 1998 and 2019. The primary outcome was the detection rate of extracranial lymphoma by CT or PET/CT. Subgroup analyses according to age and EBV status were also performed. Logistic regression analyses were performed to determine factors related to sites of extracranial disease. Detection rates of CT and PET/CT were compared. Results One thousand and forty-three patients were included. The overall detection rate of CT or PET/CT was 2.6% (27/1043). The treatment approach was adjusted in 74% of these patients. Multivariable analysis demonstrated that age >61 years (OR, 3.10; P = .016) and EBV positivity (OR, 3.78; P = .045) were associated with greater odds of extracranial lymphoma. There was no statistically significant difference in detection rate between CT and PET/CT (P = .802). In patients ≤61 years old, the false-referral rates were significantly higher than the detection rates (P < .001). Conclusion Our results showed increased odds of extracranial lymphoma in patients with older age or EBV-positive lymphoma. Treatment was adjusted in a majority of patients diagnosed with extracranial lymphoma, thereby supporting the current guidelines for the use of contrast-enhanced body CT or PET/CT in patients with newly diagnosed CNS DLBCL.

Intraocular lymphomas are among the rare malignancies that present with a wide variety of clinical manifestations. Differential diagnosis can be very troublesome due to its mimicking nature, insidious disease onset, and partial treatment response to steroids. The most important step in diagnosis is a high index of suspicion. Signs of the disease are now easier to detect using multimodal imaging techniques. In this case series, we reviewed the clinical characteristics of two women aged 70 and 71 years and a 72-year-old man with intraocular lymphoma and described their multimodal imaging findings in detail. Bilateral eye involvement was present in all three cases at our first ophthalmological examination. While the disease first presented with ocular involvement in two of the three cases, ocular involvement was detected seven years after initial heart involvement in one patient. All three patients had diffuse large B-cell lymphomas (one diagnosed with retinal biopsy, one with conjunctival biopsy, and the remaining with stereotactic brain biopsy). Intraocular lymphoma should be diagnosed and treated using a multidisciplinary approach, and we share our experience in this case series.

This article reports a rare case of Brain Mucormycosis in a 12 year-old girl who presented with relapse Acute Lymphoblastic Leukemia (ALL). On the 12th day of chemotherapy, although there was no CNS symptoms, the second Lumbar Puncture (LP) revealedmthe CNS relapse which developed to Into brain abscess presenting with right side hemiparesis. The brain magnetic resonance imaging (MRI) and the brain biopsy revealed small, multifocal necrosis and acute inflammation with septal fungal hyphae branching, which was proven to be caued by Mucormycosis according to Polymerase Chain Reaction (PCR). The patient responded to treatment with intravenous liposomal Amohotericin B and Caspofungin after two months, suggesting that Brain Mucormycosis in ALL cases can be managed with sequential therapy by antifungals.

Toxoplasmosis is an infection caused by Toxoplasma gondii, an intracellular protozoan that is often associated with immunocompromised patients and is rare in immunocompetent. A 60-year-old man was admitted with a history of 2 days of headache and right-sided weakness. There was no history of fever, surgeries, or any other comorbid illness. Cerebrospinal fluid showed just mild pleocytosis with 15 cells/mm3, predominantly lymphomononuclear. MRI showed Peripheral enhancing lesion with central diffusion restriction and perivascular enhancing lesion with restricted diffusion with vasogenic edema and leptomeningeal enhancement in the white matter. Viral serologies, tumor markers, protein electrophoresis were normal. The patient was submitted to brain biopsy, revealing necrotic brain parenchyma with predominantly acute inflammation, with diffuse encephalitis pattern, and cysts with bradyzoites (cystozoites) of Toxoplasma gondii in the brain parenchyma. The central nervous system infection by Toxoplasma gondii can present as meningoencephalitis during primary infection in an immunocompetent, although it is rare. Central nervous system lymphoma is the main differential diagnosis of neurotoxoplasmosis by imaging, especially in our case.

Cerebral amyloid angiopathy related inflammation (CAA-ri) is a rare encephalopathy resulting from perivascular inflammation after β-βamyloid (A) deposition in cerebral vessels leading to progressive dementia, focal neurological signs, seizures and intracerebral hemorrhages. This condition is characterized on magnetic resonance imaging (MRI) by patchy or confluent T2/fluid attenuation inversion recovery (FLAIR) hyperintensities in the cortex and subcortical white matter located mainly in the same areas of pre-existing multiple microhemorrhages. In this report of 2 cases of "probable" CAA-ri women aged 71 and 68, we propose a review on the pathophysiological, clinical, radiological, therapeutic and prognostic aspects of this little-known and poor outcome condition. Even though an apparently favorable initial evolution after steroid and/or immunosuppressive treatment, CAA-ri course is unpredictable and often associated with low survival rates. We suggest the importance of timely and proper clinico-radiological evaluation in suspected CAA-ri cases, in order to start an appropriate treatment even without the brain biopsy.

Background Acute disseminated encephalomyelitis (ADEM) followed by optic neuritis (ADEM-ON) is characterized by the following features: early onset, monophasic or multiphasic ADEM followed by one or more episodes of ON, and the presence of serum anti-myelin oligodendrocyte glycoprotein (MOG) antibodies. Case report We report a case of ADEM-ON without anti-MOG antibodies in a 78-year-old woman. The patient developed acute-onset neurological findings and was diagnosed with ADEM. She was treated with intravenous methylprednisolone (IVMP), and oral corticosteroids. Her clinical symptoms and MRI findings subsequently improved. Left optic neuritis emerged 6 months later, and we made a diagnosis of ADEM-ON. A brain biopsy performed during the acute phase of ADEM showed perivascular infiltration of macrophages with demyelination. Conclusion The majority of the reported ADEM-ON cases are pediatric cases with serum anti-MOG antibodies, but our patient was the elderly, without anti-MOG antibodies. Moreover, the pathological features of our case were similar to those observed in patients with typical ADEM and in patients with anti-MOG antibody-positive ADEM. Although ADEM-ON is related to the presence of anti-MOG antibodies, factors other than anti-MOG antibodies could contribute to the development of ADEM-ON.

Aims Histiocytoses are a heterogeneous group of localized or disseminated diseases. Clinical presentation and patients' outcome vary greatly, ranging from mild to life-threatening disorders. Rare cases of systemic or localized histiocytosis harboring ALK rearrangement have been reported. Methods Two cases of CNS histiocytosis were thoroughly investigated by implementing multiple molecular tests, i.e. FISH, RT-qPCR, NGS analysis. Results In a 10-month old girl (patient #1), MRI showed two left hemispheric lesions and a right fronto-mesial lesion histologically consisting of a moderately cellular infiltrative proliferation, composed by CD68(PGM1)+/CD163+ spindle cells. ALK 5'/3'-imbalance and a KIF5B(exon 24)-ALK(exon 20) fusion were documented by RT-qPCR and NGS analysis, respectively. A subsequent CT scan showed multiple hepatic and pulmonary lesions. The patient was started on chemotherapy (vinblastine) associated to an ALK-inhibitor (Alectinib) with remarkable response. In a 11-year-old girl (patient #2), MRI showed a right frontal 1.5 cm lesion. Neuropathological examination revealed a histiocytic proliferation composed by medium sized CD68(PGM1)+/HLA-DR+ cells, showing moderate ALK1 positivity. ALK rearrangement and a KIF5B(exon 24)-ALK(exon 20) fusion were demonstrated also in this case. Subsequent CT, 18F-FDG-PET and MRI scans showed the presence of a single right femoral lesion, proved to be a fibrous cortical defect. Conclusions In ALK-histiocytoses, CNS involvement may occur as part of a systemic disease or, rarely, as its only primary disease localization, which could remain otherwise asymptomatic. The diagnosis often relies on neuropathological examination of brain biopsy, which may pose a diagnostic challenge due to the variable histopathological features. An integrated histological and molecular approach in such cases is recommended.

Background Cerebral venous thrombosis (CVT) occurs rarely in the general population and is frequently associated with confused clinical findings and delayed diagnosis. Isolated cerebellar cortical vein thrombosis is a very rare phenomenon. Case presentation This report describes a case with CVT, which is manifested as space-occupying lesions of the cerebellar hemisphere and mimics a cerebellar tumor at the beginning. The diagnosis of CVT was finalized given the laboratory and brain biopsy findings. The etiology may be related to polycythemia vera with Janus Kinase 2 V617F mutation. Conclusion Isolated cerebellar vein thrombosis should be considered when swelling and enhancing cerebellar lesions are detected. Polycythemia vera, especially with a positive JAK2 V617F mutation, may be a rare risk factor for CVT.

Objective Design 3D printed skull contoured brain biopsy guides (3D-SCGs) from computed tomography (CT) or T1-weighted magnetic resonance imaging (T1W MRI). Study Design Feasibility study. Sample Population Five beagle dog cadavers and two client-owned dogs with brain tumors. Methods Helical CT and T1W MRI were performed on cadavers. Planned target point was the head of the caudate nucleus. Three-dimensional-SCGs were created from CT and MRI using commercially available open-source software. Using 3D-SCGs, biopsy needles were placed into the caudate nucleus in cadavers, and CT was performed to assess needle placement accuracy, followed by histopathology. Three-dimensional-SCGs were then created and used to perform in vivo brain tumor biopsies. Results No statistical difference was found between the planned target point and needle placement. Median needle placement error for all planned target points was 2.7 mm (range: 0.86-4.5 mm). No difference in accuracy was detected between MRI and CT-designed 3D-SCGs. Median needle placement error for the CT was 2.8 mm (range: 0.86-4.5 mm), and 2.2 mm (range: 1.7-2.7 mm) for MRI. Biopsy needles were successfully placed into the target in the two dogs with brain tumors and biopsy was successfully acquired in one dog. Conclusion Three-dimensional-SCGs designed from CT or T1W MRI allowed needle placement within 4.5 mm of the intended target in all procedures, resulting in successful biopsy in one of two live dogs. Clinical Significance This feasibility study justifies further evaluation of 3D-SCGs as alternatives in facilities that do not have access to stereotactic brain biopsy. Center for Strategic Scientific Initiatives, National Cancer Institute [P01CA207206, R01CA213423]; American College of Veterinary Internal Medicine Advanced Clinical Training Fellowship Published version Center for Strategic Scientific Initiatives, National Cancer Institute, Grant/Award Numbers: P01CA207206, R01CA213423; American College of Veterinary Internal Medicine Advanced Clinical Training Fellowship

Introduction Aβ-related angiitis (ABRA) is a very rare disease entity with combined features of cerebral amyloid angiopathy and primary angiitis of the CNS. However, the pathogenesis has not been conclusively described yet. Interestingly though, a possible paraneoplastic origin has been reported in the past. ABRA leads to severe encephalopathy with a broad spectrum of unspecific neurological symptoms and usually occurs in older patients. Because of the response to immunological treatment, it is important to confirm the diagnosis as fast as possible. Unfortunately, the pathway to a definite diagnosis is often complicated and prolonged. Case report Here, we describe a 48-year-old-female patient presenting headache, behavioral changes as well as subacute fatigue and epileptic seizures in the recent past. The initial neuroradiological examination demonstrated extended lesions in the left hemisphere compatible with an inflammatory or neoplastic disease. After extensive investigations, initially without a definite result, we finally validated the diagnosis of ABRA by brain biopsy. Shortly afterwards a routine check-up revealed an invasive mammary carcinoma. Owing to a mandatory mastectomy and chemotherapy, an immunosuppressive therapy was not implemented. Conclusions The reported case demonstrates our diagnostic approach and the clinical difficulties in validating a rare cause of encephalopathy in a young patient with nonspecific clinical and neuroradiological findings. Because of the possibility of an effective treatment, it is important to consider ABRA in the differential diagnosis especially when blood tests, analysis of cerebrospinal fluid, and angiography show normal results. Since a paraneoplastic genesis is presumed, a search for an underlying tumor disease should be considered.

Primary central nervous system lymphoma (PCNSL) is a rare subtype of extranodal non-Hodgkin lymphoma, and the most frequent histological type is diffuse large B‐cell lymphoma (DLBCL). Bruton’s tyrosine kinase inhibitor (BTKi) has shown clinical activity in DLBCL. We herein report a 53-year-old man who presented with binocular diplopia, gait instability, dizziness and bucking. He was diagnosed with PCNSL by cranial magnetic resonance imaging (MRI) scan and brain biopsy. Next-generation sequencing (NGS) examination identified multiple genetic abnormalities. The patient was started on a high-dose methotrexate (HD-MTX)-based protocol for two courses. However, the patient developed disease progression. The patient’s phenotypic and genetic characteristics strongly suggested BN2-DLBCL, and zanubrutinib was added to the subsequent chemotherapy regimen. The treatment was well tolerated, and complete remission (CR) was achieved after three courses of chemotherapy with the new regimen. The patient then received autologous hematopoietic stem cell transplantation after four courses of chemotherapy with the new regimen. MRI revealed stable CR. Here, we report a successful case of refractory PCNSL treated with zanubrutinib. Small molecules, such as zanubrutinib, may be selectively integrated into first-line regimens of PCNSL to enhance curative effect and reduce recurrence.

Pseudotumoral forms of demyelination are related to central nervous system demyelinating disorders, usually considered to be an atypical presentation of multiple sclerosis including its different varieties such as Balo’s, Schilder’s, and Marburg diseases. These lesions could also be seen in myelin oligodendrocyte glycoprotein antibody-associated demyelination, acute disseminated encephalomyelitis (ADEM), and neuromyelitis optica spectrum disorder. The pseudotumoral aspect may be mistakenly considered as an abscess or a cancerous tumor, in which case, patients could endure unnecessary possibly harmful brain biopsy and have a delay in their disease diagnostics and management. Once latter differential diagnosis is discarded, pseudotumoral demyelination prompts uncertainties concerning the nature of the underlying demyelinating condition as prognosis and management differ from multiple sclerosis to other syndromes, especially whether a chronic treatment is needed or not. In this case report, we present a 35-year-old male patient hospitalized in the department of neurology for a rapidly progressive onset of encephalopathy and polyfocal neurological deficits, with pseudotumoral lesions shown on brain MRI. On further investigations, ADEM was the more likely diagnosis that could fit the patient’s clinical and radiological presentation. Thence, he was put on high dose of intravenous corticosteroids, with a followed good recovery within the first week of the treatment.

The study objective was to evaluate a single institution experience with adult stereotactic intracranial biopsies and review any projected cost savings as a result of bypassing intensive care unit (ICU) admission and limited routine head computed tomography (CT). The authors retrospectively reviewed all stereotactic intracranial biopsies performed at a single institution between February 2012 and March 2019. Primary data collection included ICU length of stay (LOS), hospital LOS, ICU interventions, need for reoperation, and CT use. Secondarily, location of lesion, postoperative hematoma, neurological deficit, pathology, and preoperative coagulopathy data were collected. There were 97 biopsy cases (63% male). Average age, ICU LOS, and total hospital stay were 58.9 years (range; 21–92 years), 2.3 days (range; 0–40 days), and 8.8 days (range 1–115 days), respectively. Seventy-five (75 of 97) patients received a postoperative head CT. No patients required medical or surgical intervention for complications related to biopsy. Eight patients required transfer from the ward to the ICU (none directly related to biopsy). Nine patients transferred directly to the ward postoperatively (none required transfer to ICU). Of the patients who did not receive CT or went directly to the ward, none had extended LOS or required transfer to ICU for neurosurgical concerns. Eliminating routine head CT and ICU admission translates to approximately $584,971 in direct cost savings in 89 cases without a postoperative ICU requirement. These practice changes would save patients’ significant hospitalization costs, decrease healthcare expenditures, and allow for more appropriate hospital resource use.

Background: Longitudinal changes in cerebrospinal fluid (CSF) biomarkers are seldom studied. Furthermore, data on biomarker gradient between lumbar (L-) and ventricular (V-) compartments seems to be discordant. Objective: To examine alteration of CSF biomarkers reflecting Alzheimer's disease (AD)-related amyloid-beta (A beta) aggregation, tau pathology, neurodegeneration, and early synaptic degeneration by CSF shunt surgery in idiopathic normal pressure hydrocephalus (iNPH) in relation to AD-related changes in brain biopsy. In addition, biomarker levels in L- and V-CSF were compared. Methods: L-CSF was collected prior to shunt placement and, together with V-CSF, 3-73 months after surgery. Thereafter, additional CSF sampling took place at 3, 6, and 18 months after the baseline sample from 26 iNPH patients with confirmed A beta plaques in frontal cortical brain biopsy and 13 iNPH patients without A beta pathology. CSF Amyloid-beta(42) (A beta(42)), total tau (T-tau), phosphorylated tau (P-tau(181)), neurofilament light (NFL), and neurogranin (NRGN) were analyzed with customized ELISAs. Results: All biomarkers but A beta(42) increased notably by 140-810% in L-CSF after CSF diversion and then stabilized. A beta(42) instead showed divergent longitudinal decrease between A beta-positive and -negative patients in L-CSF, and thereafter increase in A beta-negative iNPH patients in both L- and V-CSF. All five biomarkers correlated highly between V-CSF and L-CSF (A beta(42) R = 0.87, T-tau R = 0.83, P-tau R = 0.92, NFL R = 0.94, NRGN R = 0.9; all p < 0.0001) but were systematically lower in V-CSF (A beta(42) 14 %, T-tau 22%, P-tau 20%, NFL 32%, NRGN 19%). With APOE genotype-grouping, only A beta(42) showed higher concentration in non-carriers of allele epsilon 4. Conclusion: Longitudinal follow up shows that after an initial post-surgery increase, T-tau, P-tau, and NRGN are stable in iNPH patients regardless of brain biopsy A beta pathology, while NFL normalized toward its pre-shunt levels. A beta(42) as biomarker seems to be the least affected by the surgical procedure or shunt and may be the best predictor of AD risk in iNPH patients. All biomarker concentrations were lower in V-than L-CSF yet showing strong correlations.

Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection of the central nervous system caused by reactivation of JC virus (JCV). Typical PML shows confluent, bilateral but asymmetric, subcortical lesions in the supratentorial white matter on magnetic resonance imaging (MRI). We report here a 50-year-old woman with systemic lupus erythematosus complicated with lymphoma who developed PML with atypical brain MRI findings limited to the infratentorial area at presentation. She presented with numbness on the right side of the face, including her tongue, clumsiness of the right hand, and gait disturbance, after completion of remission induction therapy for lymphoma, including rituximab. Brain MRI demonstrated a solitary lesion limited to the cerebellum and brainstem, but a definitive diagnosis could not be made from cerebrospinal fluid study or tentative histologic evaluation of brain biopsy specimens. Despite methylprednisolone pulse therapy, her neurological deficits progressively worsened. One month later, in-depth analysis of her cerebrospinal fluid and brain biopsy specimens confirmed the presence of JCV. Eventually, the localised unilateral crescent-shaped cerebellar lesions on MRI expanded to the contralateral cerebellum, middle cerebellar hemisphere, pons, and midbrain and finally developed multifocal invasion into the white matter of the cerebral hemispheres. Our case suggests that PML could first present with a solitary infratentorial lesion in immunocompromised patients.

Acquired demyelinating syndromes (ADS) are frequently associated with myelin oligodendrocytes glycoprotein (MOG) antibodies in children. Clinical phenotypes are heterogeneous and may delay the diagnosis, especially when they relapse and are atypical, mimicking diseases such as multiple sclerosis or neuromyelitis optica spectrum disorders . Here, we describe two children: one with a progressive cognitive and behavioral deterioration with seizures after only one relapse and the other with similar clinical impairments associated with multiple relapses. Brain magnetic resonance imaging revealed a subsequent progressive leukodystrophy-like lesion with diffuse bilateral white matter injuries in both patients. Cerebrospinal fluid analysis showed pleiocytosis, increased level of proteins with no oligoclonal bands. Metabolic and inflammatory blood markers were all negative. Brain biopsy was performed in the second child and nonspecific inflammatory lesions with no argument for histiocytosis or tumor were observed. Clinical and radiological stabilization were obtained after active immunotherapy. Retrospective analysis of anti-MOG antibodies in these two children was positive at the earlier stage of the disease and turned negative after treatment and during follow-up. Leukodystrophy-like ADS with anti-MOG-antibodies may display distinct progressive phenotype and have a severe neurological prognosis. Early diagnosis and appropriate treatment may improve outcome in these children.

Central nervous system (CNS) tuberculosis is a rare manifestation of all tuberculosis presentations. The incidence of brain tuberculoma is increasing in developed countries due to HIV infection and immigration from tuberculosis-endemic countries. Symptoms and radiologic findings of CNS tuberculosis can be non-specific and lead to misdiagnosis or mistreatment. Intracranial tuberculoma can present with a seizure, intracranial hypertension, or focal neurologic symptoms. In our case, the diagnosis was challenging between neurosarcoidosis and intracranial tuberculoma due to inconclusive results of stereotactic brain biopsy and clinical presentation. The pathology result of the open brain biopsy revealed non-caseating granuloma. Finally, we were able to diagnose intracranial tuberculoma following acid-fast bacilli culture results of open brain biopsy. This report highlights the importance of including intracranial tuberculoma in the differential diagnosis of cerebral space-occupying lesions, even in patients with negative laboratory findings of tuberculosis.

Cerebral phaeohyphomycosis refers to central nervous system infection caused by dematiaceous molds, which have many genuses. Cladophialophora bantiana is a member of the phylum ascomycota, which is found in soil samples from all over the world. This organism typically infects immunocompromised patients and associated with 70% mortality rate even after weeks of antifungal agent administration and surgical debridement. Two such cases of fungal brain abscess caused by cladophialophora bantiana were presented here. Both patients presented with complaints of headache, vomiting, drowsiness and impaired cognition. A brain biopsy together with microbiological culture and VITEK 2 helped in reaching to a final diagnosis. Key Words: Cladophialophora bantiana, Dematiaceous, Intracerebral, Phaeohyphomycosis.

We report a 57-year-old man with recurrent meningoencephalitis resulting in bouts of altered consciousness, encephalopathy, tremors, focal seizures, and paraparesis. The neurological manifestations were accompanied by fever and leukocytosis in the absence of other systemic manifestations. MRI abnormalities of the brain, brainstem, spinal cord and meninges and CSF pleocytosis and elevated protein were observed. Exhaustive studies failed to reveal an etiology. Brain biopsy revealed nodules of neutrophils and macrophages, but no vasculitis. The lesions were not vasocentric as would be expected with neuro-Behcet's disease and neuro-Sweet's disease. The disorder was responsive to high-dose corticosteroid therapy and, ultimately, to anakinra, an IL-1α and IL-1β receptor antagonist.

A 9-year-old girl presented with morning headaches associated with vomiting, gait ataxia, and facial and ocular motor nerve palsies. Her initial imaging was concerning for demyelinating disease. After extensive infectious and rheumatologic workup returned negative, she was treated twice with intravenous immunoglobulin and intravenous steroids with near-complete resolution each time. She returned, however, with worsening neurologic deficits and imaging revealing focal ischemic infarction in the brainstem as well as new-onset hydrocephalus. A multispecialty workup was initiated without conclusive diagnosis. A novel, noninvasive test for plasma cell-free DNA established a diagnosis of Cladophialophora bantiana that was confirmed and validated by a brain biopsy taken during a clinical decompensation. Treatment was initiated with systemic voriconazole and intraventricular amphotericin B.

Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a rare but increasingly recognized subtype of CAA. CAA-RI consists of two subtypes: inflammatory cerebral amyloid angiopathy and amyloid β (Aβ)-related angiitis. Acute or subacute onset of cognitive decline or behavioral changes is the most common symptom of CAA-RI. Rapid progressive dementia, headache, seizures, or focal neurological deficits, with patchy or confluent hyperintensity on T2 or fluid-attenuated inversion recovery sequences and evidence of strictly lobar microbleeds or cortical superficial siderosis on susceptibility-weighted imaging imply CAA-RI. The gold standard for diagnosis is autopsy or brain biopsy. However, biopsy is invasive; consequently, most clinically diagnosed cases have been based on clinical and radiological data. Other diagnostic indexes include the apolipoprotein E ε4 allele, Aβ and anti-Aβ antibodies in cerebral spinal fluid and amyloid positron emission tomography. Many diseases with similar clinical manifestations should be carefully ruled out. Immunosuppressive therapy is effective both during initial presentation and in relapses. The use of glucocorticoids and immunosuppressants improves prognosis. This article reviews the pathology and pathogenesis, clinical and imaging manifestations, diagnostic criteria, treatment, and prognosis of CAA-RI, and highlights unsolved problems in the existing research.

The detection of atypical and sometimes aggressive or tumefactive demyelinating lesions of the central nervous system often poses difficulties in the differential diagnosis. The clinical presentation is generally aspecific, related to the location and similar to a number of different lesions, including neoplasms and other intracranial lesions with mass effect. CSF analysis may also be inconclusive, especially for lesions presenting as a single mass at onset. As a consequence, a brain biopsy is frequently performed for characterization. Advanced MRI imaging plays an important role in directing the diagnosis, reducing the rate of unnecessary biopsies and allowing a prompt start of therapy that is often crucial, especially in the case of infratentorial lesions. In this review, the main pattern of presentation of atypical inflammatory demyelinating diseases is discussed, with particular attention on the differential diagnosis and how to adequately define the correct etiology.

Epidemiological trends have demonstrated re-emergence of neurosyphilis in the twenty-first century. As prevalence rises in clinical practice, neurosyphilis must be considered in the differential diagnosis even if initial diagnostic workup is unrevealing, especially in patients with human immunodeficiency virus (HIV). Co-infection of neurosyphilis and HIV can result in atypical presentations. In this report, we discuss a challenging diagnosis of neurosyphilis in a man with HIV who presented with atypical imaging findings and initially negative cerebrospinal fluid (CSF) nontreponemal testing. Our patient underwent repeated CSF evaluation and a comprehensive diagnostic workup, including brain biopsy, to arrive at the appropriate diagnosis. He received antibiotic treatment with excellent outcome. We review typical imaging features of neurosyphilis and highlight other neurological diseases that may mimic these radiographic findings. We discuss CSF testing and interpretation in this high-risk patient population.

Background Inflammatory demyelinating changes in the absence of malignant cells can sometimes be found on initial biopsies preceding the diagnosis of primary central nervous system lymphoma (PCNSL), resulting in the term “sentinel” lesion. Sentinel lesions have been reported sporadically in literature, resulting in many cases of misdiagnosis and delayed treatment. We aim to address the problem of misdiagnosis in PCNSL presenting as inflammatory demyelinating changes or sentinel lesions on initial biopsies, and to discuss our view of the mechanism underlying this phenomenon. Case Description Herein we report 3 cases of PCNSL that were diagnosed via brain biopsy. We retrospectively reviewed 2 cases of initially misdiagnosed PCNSL presenting with sentinel lesions at our institution. Careful revision of preoperative magnetic resonance imaging (MRI) revealed heterogeneously enhancing tumors with strong peripheral enhancement and hypoenhancing cores. Analysis of our 2 cases revealed that initial biopsy samples in both patients were taken from the hypoenhancing regions on MRI. In the third case, we targeted the peripherally enhancing region for sampling and arrived at the proper diagnosis of PCNSL on initial biopsy. Conclusions Based on our cases and those reported in literature, we speculate that the inflammatory demyelinating changes observed on initial biopsies are immune-mediated responses that coexist with PCNSL in different tumor regions, and that they are the direct result of inadvertent sampling from hypoenhancing regions of the tumor, rather than sentinel lesions, as their name implies. We strongly recommend that biopsy target the most enhanced region on MRI when there is high clinical and radiologic suspicion for PCNSL.

Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection caused by JC virus (JCV) activation. We report an 85-years old man who had been diagnosed to have rheumatoid arthritis (RA) 1.5 years prior to diagnosis of PML, and had been treated with salazosulfapyridine (SASP). He developed weakness of the left upper limb, which progressed gradually for two months. A neurological examination on admission revealed severe palsy of the left upper limb without sensory disturbance, cognitive decline or gait disturbance. Brain MRI revealed white matter lesions in the right frontal lobe around the precentral gyrus. Cerebrospinal fluid (CSF) examination and peripheral lymphocyte counts were normal. HIV was ruled out serologically. There were no findings suggestive of malignancy. We suspected PML and stopped SASP. JCV-DNA was detected in CSF. There were enlarged nuclei positive with VP-1 immunostaining in the brain biopsy materials. Thus, the diagnosis of PML was definitive. Paralysis of the left upper limb began to improve one week after discontinuing SASP. Treatment with mefloquine and mirtazapine was initiated, but he developed severe interstitial pneumonia, which might be caused by mefloquine. Therefore, he underwent rehabilitation without medication. JCV-DNA became undetectable and white matter lesions decreased 6 months later. Paralysis improved and he had no problem with activities of daily living a year later. The risk factor for PML has changed over the last decade, and drugs such as biologics became significant risk factors for patients with autoimmune diseases. There are reports suggesting that systemic lupus erythematosus (SLE) and RA themselves might be independent risk factors for PML. Although there is no previous report of SASP inducing PML, SASP might be the culprit in our case. However, there is another possibility that SAPS and RA worked synergistically for the onset of PML.

We report a 66-year-old man with primary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD). He had received a living-donor kidney transplantation at the age of 64 years. Although he had a good postoperative course by continuing to take oral immunosuppressive agents, he was admitted to our hospital for subacute cognitive impairment and urinary retention two years after the transplantation. Brain MRI revealed high-intensity lesions on FLAIR and T2-weighted images in the left parietal operculum, deep white matter around the anterior horn of the lateral ventricle, and the genu and splenium of the corpus callosum. A part of these lesions showed ring enhancement. The cerebrospinal fluid examination revealed lymphocytic pleocytosis, elevation of protein level, and mild hypoglycorrhachia. Blood tests showed no abnormalities except for positive serum VCA-IgG antibody of Epstein-Barr virus. A brain biopsy was performed and diagnosis of PCNS-PTLD was made. There was no evidence of systemic PTLD. We reduced the dose of immunosuppressive agents and started the initial treatment with methylprednisolone pulse therapy. The patient showed a partial response to the treatment and transferred to another hospital for subsequent chemotherapy. PTLD is an important post-transplant complication that can affect the patient's prognosis. The incidence of PTLD is increasing with the growing numbers of transplantations and older age of donors and recipients. Although CNS involvement is known to be rare, PCNS-PTLD is an important differential diagnosis when symptoms of CNS origin develop in post-transplant patients.

There have been few reports on central nervous system (CNS) involvement in chronic lymphocytic leukemia (CLL). This is an extremely rare disease with poor prognosis, owing to resistance to various treatments. We describe a 33-year-old man with intractable CLL with CNS involvement. He was diagnosed with CLL, with diplopia as the first manifestation. Magnetic resonance imaging revealed a contrast-enhancing tumor in the right temporal lobe, which was diagnosed as CNS involvement in CLL on brain biopsy. High-dose methotrexate therapy was ineffective for this lesion, which was also resistant to subsequent whole-brain irradiation, treatment with fludarabine–cyclophosphamide–rituximab chemoimmunotherapy, and ibrutinib administration. Because no standard protocol exists for CLL with CNS involvement, it is important to accumulate case data to verify the choice of new drugs for administration at an early stage. Therefore, we also conducted a literature review of 50 case reports of CNS lesions in the last 10 years to consider the pathophysiology, diagnosis, and treatment of CNS involvement in CLL. The possibility of new therapeutic agents, eg, ibrutinib and venetoclax, or a combination of these agents and methotrexate, can be envisioned as a treatment strategy for CLL with CNS involvement.

CSF1R-related leukoencephalopathy, mainly caused by the mutation of the colony stimulating factor 1 receptor (CSF1R) gene on chromosome 5, is an underestimated neurological disease typically presenting as early-onset cognitive decline and personality changes. Currently, there is no specific treatment for CSF1R-related leukoencephalopathy. Most clinicians failed to recognize this disease during an early disease stage, leading to a high rate of misdiagnosis. Although rare, an increasing amount of CSF1R-related leukoencephalopathy cases have been reported recently. In this study, we first report a 35-year-old woman with CSF1R-related leukoencephalopathy carrying a novel missense mutation c.2463G >C (p.W821C) of CSF1R. An extensive literature research was performed in order to better understand the broader genetic and clinical characteristics of CSF1R-related leukoencephalopathy. A total of 147 patients with CSF1R-related leukoencephalopathy confirmed either by the genetic test or brain biopsy were identified. Among them, 49 patients were sporadic, and the rest of individuals had a family history originating from 46 different families. Our study indicated that the average age of CSF1R-related leukoencephalopathy onset was 41.4 years. Typical clinical symptoms of CSF1R-related leukoencephalopathy include cognitive decline, movement disorders, behavior changes and mental disorders. Genetic studies have reported 93 missense mutations, 13 splicing mutations, 6 deletion/insertion mutations, 1 code shift mutation and 1 nonsense mutation of the CSF1R gene in patients with CSF1R-related leukoencephalopathy. Early genetic detection and brain biopsy would be helpful for a confirmed diagnosis, and more translational studies are needed to combat this devastating disease.

Autoimmune manifestations are known to occur in patients with chronic lymphocytic leukemia (CLL) and of these hemolytic anemia and immune thrombocytopenia are the most well recognized. Autoimmunity may also be triggered by some of the therapeutic agents used like purine analoges and these events may sometimes be severe and even fatal. Non-hematological autoimmune stigmata occur far less frequently and are rarely encountered. Here we report a 59 year-old-woman, with CLL, who complained of recurrent headache starting 1 month after completing 6 cycles of fludarabine, cyclophosphamide, and rituximab combination therapy. Computed tomography scan of the brain showed a contrast enhancing lesion of 1 cm in diameter, with surrounding edema in the right frontal lobe. Brain MRI revealed ring enhancing lesions in the right frontal lobe and some additional small lesions in the left parietal lobe. Brain biopsy showed an inflammatory demyelinating lesion, not associated with JC virus. The patient subsequently improved after steroid therapy. Currently, after 2 years of follow-up, she remains in complete hematologic remission, has no neurological deficits, and is carefully followed by a team of neurologists and hematologists. Treating physicians should be aware of this rare autoimmune inflammatory demyelinating lesion which can occur in patients with CLL during the course of treatment and that may be linked to treatment with purine analogues like fludarabine.

Anti-myelin oligodendrocyte glycoprotein antibodies (anti-MOG), directed against a component of the myelin sheath, are sometimes detected in the blood or cerebrospinal fluid (CSF) of patients with acute demyelinating conditions. Cortical encephalitic presentations in anti-MOG-antibody-positive patients are recognized but rare, and few pediatric cases have been described. We describe clinical, biochemical, and MRI findings in two children presenting with generalized seizures due to cortical encephalitis, and review potential underlying immunological processes. In both patients, anti-MOG antibodies were detected. Both underwent MRI scans which demonstrated bilateral cortical swelling and T2/fluid-attenuated inversion recovery (FLAIR) hyperintensity with corresponding regions of reduced diffusion. Early detection of anti-MOG antibodies in patients with a similar presentation and imaging features would enable rapid institution of appropriate treatment, and potentially reduce the need for invasive diagnostic procedures such as brain biopsy.

Background The early diagnosis of basal ganglia and thalamus germinomas is often difficult due to the absence of elevated tumor markers, and atypical clinical symptoms and neuroimaging features. Case summary Four male children aged 8 to 15 years were diagnosed with germinomas in the basal ganglia and thalamus by stereotactic biopsy from 2017 to 2019. All patients developed hemiplegia except patient 4 who also had cognitive decline, speech disturbance, nocturnal enuresis, polydipsia, polyuria, precocious puberty and abnormalities of thermoregulation. All four cases were alpha-fetoprotein and beta-human chorionic gonadotrophin (β-HCG) negative except patient 3 who had slightly elevated β-HCG in cerebrospinal fluid (CSF). No malignant cells were detected in the patients' CSF. Brain magnetic resonance imaging findings were diverse in these patients with the exception of the unique and common characteristics of ipsilateral hemisphere atrophy, especially in the cerebral peduncle. All patients were diagnosed with germinomas of the basal ganglia and thalamus by stereotactic brain biopsy. Conclusion Stereotactic brain biopsy is necessary to confirm the diagnosis of ectopic germinomas. Serial neuroimaging studies can not only differentiate disease but also determine the biopsy site.

Aggressive immunosuppressive therapies have been proposed to treat primary angiitis of the central nervous system (PACNS). Here, we report the first successfully stabilized case of childhood, small-vessel PACNS with intravenous immunoglobulin (IVIG) therapy. A 12-year-old boy was admitted to our hospital complaining of recurrent headaches and upper-left homonymous quadrantanopia, since the age of 11 years. Brain computed tomography scans revealed fine calcification in the right temporal and occipital lobes. Brain magnetic resonance imaging scans revealed white matter lesions, with gadolinium enhancement, which waxed, waned, and migrated for 1 year, without immunomodulatory therapies. A cerebrospinal fluid study showed pleocytosis (12 cells per µl). No clinical or serological findings suggested systemic inflammation or vasculitis. Brain angiography was unremarkable. Brain biopsy revealed thickened and hyalinized small vessels, with intramural infiltration of inflammatory cells, which confirmed the diagnosis of small-vessel PACNS. Because the patient developed surgical site infection following biopsy, the administration of monthly IVIG (2 g/kg) was prescribed, instead of immunosuppressive agents. After IVIG therapy, the patient remained stable, except for a single episode of mild radiological exacerbation at 16 months, which occurred when the IVIG interval was expanded. Oral prednisone was added and gradually tapered. At 50 months, his intellectual abilities and motor functions were normal, although he showed residual upper-left homonymous quadrantanopia and post-exercise headache. A temporary headache, associated with the immunoglobulin infusion, was resolved by slowing the infusion rate. PACNS should be treated aggressively to improve prognosis. However, when immunosuppressants are contraindicated, IVIG may be an alternative therapeutic option.

Introduction Mycophenolate Mofetil (MMF), although a widely used immunosuppressant; an increasing concern of MMF induced Primary Central Nervous System Lymphoma (PCNSL) are being reported. Timely diagnosis and management of MMF induced PCNSL can play a vital role in improved outcomes. Case Presentation Eighty-one-year-old female with history of Eosinophilic Granulomatosis with Polyangiitis (EGPA) presented with word finding difficulty, right-hand weakness and right foot clumsiness. EGPA had been stable with MMF for 6 years. Physical examination revealed weakened right-hand grip, positive right-sided dysdiadokokinesia and right foot drop. MRI-brain identified three enhancing solid lesions – in right parietal, left insular and left mid brain extending into the left thalamus. Brain biopsy revealed a focally dense lymphoid infiltrate with CD20 positive B cells, with large atypical cells resembling Hodgkin Reed-Sternberg cells. With concern for immunosuppression related PCNSL, MMF was stopped. Patient was treated with 8 weeks of rituximab therapy for its least toxic profile and concomitant benefit in EGPA. On a 2 month follow up MRI-brain, near total resolution of the intracranial lesion was observed. Patient still had some residual right lower extremity incoordination, however, strength and speech normalized with resolution of dysdiadokokinesia. Patient was advised to discontinue MMF indefinitely and remains on low dose prednisone daily. Conclusion MMF is an inhibitor of Inosine Monophosphate Dehydrogenase which prevents T- and B-cell proliferation. PCNSL is a potential complication of chronic immunosuppression with this medication. Discontinuation of the drug along with immunosuppressive therapies have been the effective therapeutic options till date.

Cerebral rheumatoid vasculitis (CRV) is a rare, fatal, and diagnostically challenging disorder. We herein report an 81-year-old woman with a 4-year history of rheumatoid arthritis who presented with a fever, progressive disturbance of consciousness, high level of rheumatoid factor, and hypocomplementemia. The enhancement of the perforating branches in the left middle cerebral artery led us to suspect CRV. A brain biopsy could not be performed. After we intensified steroid therapy, the size of the cerebral lesions temporarily decreased. However, recurrence in the left frontal lobe occurred one month later, and the patient subsequently died. Early intensive treatments may be needed for CRV.

ObjectiveTo better understand the heterogeneous population of patients with new-onset refractory status epilepticus (NORSE), we studied the most severe cases in patients who presented with new-onset super-refractory status epilepticus (NOSRSE).MethodsWe report a retrospective case series of 26 adults admitted to the Columbia University Irving Medical Center neurologic intensive care unit (NICU) from February 2009 to February 2016 with NOSRSE. We evaluated demographics, diagnostic studies, and treatment course. Outcomes were modified Rankin Scale score (mRS) at hospital discharge and most recent follow-up visit (minimum of 2 months post discharge), NICU and hospital length of stay, and long-term antiepileptic drug use.ResultsOf the 252 patients with refractory status epilepticus, 27/252 had NORSE and 26/27 of those had NOSRSE. Age was bimodally distributed with peaks at 27 and 63 years. The majority (96%) had an infectious or psychiatric prodrome. Etiology was cryptogenic in 73%, autoimmune in 19%, and infectious in 8%. Seven patients (27%) underwent brain biopsy, autopsy, or both; 3 (12%) were diagnostic (herpes simplex encephalitis, candida encephalitis, and acute demyelinating encephalomyelitis). On discharge, 6 patients (23%) had good or fair outcome (mRS 0–3). Of the patients with long-term follow-up data (median 9 months, interquartile range 2–22 months), 12 patients (71%) had mRS 0–3.ConclusionAmong our cohort, nearly all patients with NORSE had NOSRSE. The majority were cryptogenic with few antibody-positive cases identified. Neuropathology was diagnostic in 12% of cases. Although only 23% of patients had good or fair outcome on discharge, 71% met these criteria at follow-up.

International audience; Background and purpose: The rationale for performing a second brain biopsy after initial negativity is not well evaluated in the literature. This study was designed to 1) assess the efficacy of a second brain biopsy when the first biopsy was nondiagnostic, 2) identify possible factors associated with an increased diagnostic rate in the second biopsy, and 3) analyze additional morbidity induced by the second biopsy.Methods: We performed a retrospective cohort study from 2009 to 2019, during which 1,919 patients underwent a brain biopsy, including 30 who were biopsied twice (1.6%). The specific histological diagnosis rate, diagnosis-associated factors, and complication rate were assessed for the 30 twice-biopsied patients.Results: The second biopsy allowed a specific histological diagnosis in 86.7% of the patients who had initially undergone a nondiagnostic brain biopsy [odds ratio (OR)=7.5, 95% confidence interval (CI)=3.0-18.7, p

Gliomatosis Cerebri (GC) is a rareand rapidly progressive pattern of growth of diffusely infiltrating gliomas with limited treatment options. Imaging findings are usually nonspecific and can mimic other neurologic disorders, including demyelination, encephalitis, and multicentric/multifocal glioma. In this report, we describe a case of a 53-year-old female who presented with left hemiparesis, global headache, and gait ataxia with imaging features initially thought to represent demyelinating disease. A combination of conventional and advanced imaging findings with brain biopsy was utilized to make the diagnosis of GC. In patients with widespread abnormalities on brain imaging, GC should strongly be considered when cortical expansion, involvement of the septum pellucidum and elevated myoinositol levels are observed and the clinical and laboratory findings are atypical for demyelination or infection. Considering GC in such cases can facilitate early biopsy with prompt diagnosis and avoid delay in appropriate treatment.

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the central nervous system caused by JC virus (JCV) and is difficult to diagnose. We report on a male HIV-positive patient with PML finally diagnosed by 3 times lumbar punctures and 2 times brain biopsies. Negative results of JCV-PCR in cerebrospinal fluid (CSF) do not rule out the diagnosis of PML when clinical manifestations and neuroimaging features suspected PML. It is necessary to obtain new CSF and make repeat tests and even perform brain biopsy.

Background and importance Rasmussen's Encephalitis (RE) is a chronic and progressive childhood disease caused by an inflammatory disorder that affects a cerebral hemisphere. On the other hand, Gliomatosis Cerebri (GC) is a rare primary neoplastic glial process with a diffuse and infiltrative growth. Clinical presentation We present two clinical cases with a history of continuous focal epilepsy refractory to antiepileptic drugs. They share similar clinical and radiologic features, but a different histopathological diagnosis. A brain biopsy was needed to distinguish GC from a RE. Conclusion The debut of a drug-resistant epilepsy with focal seizures and an ipsilateral progressive hemiparesis suggests the diagnosis of RE. However, there are other entities such as GC, which, despite its rarity, should be considered in the differential diagnosis. So, in some cases, histological diagnosis is needed.

BackgroundCommon variable immunodeficiency (CVID) is a group of heterogeneous primary immunodeficiencies characterised by a dysregulated and impaired immune response. In addition to an increased susceptibility to infection, it is also associated with noninfectious autoimmune and lymphoproliferative complications. CVID is rarely associated with neurological complications. Pulmonary involvement is more common, and patients can develop an interstitial lung disease known as granulomatous-lymphocytic interstitial lung disease (GLILD).Case presentationA 50-year-old Caucasian female with a history of Evans syndrome (idiopathic thrombocytopaenic purpura and autoimmune haemolytic anaemia) and hypogammaglobulinaemia initially presented to the neurology clinic with marked cerebellar ataxia and headaches. Following extensive investigation (which included brain biopsy), she was diagnosed with neuro-sarcoidosis and her symptoms resolved following treatment with immunosuppressive therapy. Over the following 10 years, she was extensively investigated for recurrent pulmonary infections and abnormal radiological findings, which included pulmonary nodules, infiltrates and splenomegaly. Subsequently, she was referred to an immunology clinic, where immunoglobulin replacement treatment was started for what was ultimately considered to be CVID. Shortly afterwards, evaluation of her clinical, radiological and histological findings at a specialist interstitial lung disease clinic led to a diagnosis of GLILD.ConclusionCVID is a condition which should be suspected in patients with immunodeficiency and recurrent infections. Concomitant autoimmune disorders such as haemolytic anaemia and immune thrombocytopenia may further support the diagnosis. As illustrated in this case, there is a rare association between CVID and inflammatory involvement of the neurological system. Respiratory physicians should also suspect CVID with associated GLILD in patients with apparent pulmonary granulomatous disease and recurrent infections. In addition, this case also highlights the challenge of diagnosing CVID and its associated features, and how the definitive exclusion of other pathologies such as malignancy, mycobacterial infection and lymphoma is required as part of this diagnostic process.

Purpose The pathological diagnosis of primary central nervous system lymphoma (PCNSL) by stereotactic brain biopsy and craniotomy is not often applicable due to the high cost and associated complications. In recent years, some biomarkers in cerebrospinal fluid (CSF), including interleukin 10 (IL-10), microRNAs, CXC chemokine ligand 13 (CXCL13), have been reported to be associated with PCNSL. However, this conclusion was controversial. Therefore, this study was to test whether Th17 cell-related cytokines could be used to distinguish PCNSL from other brain tumors. Patients and methods Th17 cell-related cytokines in CSF were measured in 108 patients with intracranial tumors, which included 66 PCNSL patients and 42 patients with other types of brain tumors. A receiver-operating characteristic (ROC) curve was utilized to analyze the diagnostic value of the cytokines based on the area under the curve (AUC). Results The CSF IL-10 level and IL-10/IL-6 ratios were significantly higher in PCNSL than in the other brain tumors (58.2 pg/mL VS 1.5 pg/mL, p=0.001; 24.3 VS 0.6, p=0.001). When the cutoff level of IL-10 was set at 8.3 pg/mL, its sensitivity and specificity for diagnosing PCNSL were 59.0% and 98%, respectively. The CSF IL-10 levels over 5pg/mL (+LR 12.3) were of significant value for the diagnosis of PCNSL. These parameters are highly valuable in PCNSL diagnosis, but their sensitivity is less valuable. The sensitivity of IL-4 and IL-17A, the ratio of mature lymphocytes and the monocytes/macrophages ratio in CSF were relatively high. In combination, the sensitivity increased by 15% and the specificity remained above 85%. The best combination was IL-10 and IL-17A, whose sensitivity was 70% and specificity was 96%. Conclusion The CSF level of IL-10 is a useful diagnostic biomarker in patients with PCNSL. The CSF levels of IL-4, IL-17A, mature lymphocytes and monocytes/macrophages can be used to increase the diagnostic value of CSF IL-10 level and IL-10/IL-6 ratio.

Reverse Takotsubo cardiomyopathy (rTTC) is a variant of Takotsubo cardiomyopathy (TTC) or stress-induced cardiomyopathy. TTC is a transient cardiomyopathy resulting in a heart failure syndrome, triggered by emotional and/or physical stressors, that is usually self-limited. rTTC is characterized by basal wall hypokinesis and apical wall hyperkinesis, the opposite of TTC. rTTC is more commonly associated with neurologic conditions, most notably intracranial hemorrhage. We present the first case in the literature of rTTC specifically following brain biopsy.

A 62-year-old healthy male presents with leg weakness and fever. Imaging revealed leptomeningeal enhancement (LE). After cerebrospinal fluid (CSF) cultures were negative, he was discharged with a diagnosis of aseptic meningitis, but was readmitted due to worsening symptoms. Brain biopsy suggested rheumatoid leptomeningitis associated with elevated serum rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACPA). Following discharge, the New York State Department of Health (NYSDOH) reported a polymerase chain reaction (PCR) on CSF and brain DNA consistent with Naegleria fowleri (NF). After dramatic improvement on steroids, the patient declined antimicrobial treatment. Upon prednisone taper, symptoms recurred which responded to rituximab (RTX). This case highlights a possible association between rheumatoid leptomeningitis (RM) onset and infection, in a patient without a history of rheumatoid arthritis (RA). Our goal is to assess whether this association is present in 69 RM cases reported since 2000. We also describe diagnosis and treatment of 31 new cases (January 2017 to March 2020). We did not identify evidence of active/latent infection in patients with RM and previous RA; however, patients without RA history appeared to have a significantly higher rate. This finding could demonstrate the necessity of evaluating for infection in de novo RM cases without antecedent RA history. We also describe characteristic clinical patterns for each group. More studies are needed to corroborate these results and expand into a possible distinct natural history of RM in each group, which might have an impact upon the clinical outcome.

Background: Hereditary diffuse leukoencephalopathy with spheroids (HDLS), first described in 1984 is a rare disorder. Generally, it presents at adulthood with dementia, motor impairment, extrapyramidal abnormalities, and epilepsy. Definitive diagnosis is made by brain biopsy. Neuroimaging studies have revealed confluent white matter lesions predominantly in the frontal lobes, corpus callosum, and corticospinal tracts on conventional magnetic resonance imaging. Only a few reports showed diffusion restriction in the cerebral white matter; furthermore, rarer reports emphasized persistent foci of diffusion restriction as a diagnostic imaging marker. Objective: Herein, we have aimed to illustrate the first biopsy-proven Turkish HDLS pedigree consisting of 18 persons in 3 generations which contained 4 affected individuals. Materials and Methods: Four individuals in the pedigree of HDLS [two affected patients (patient III-1 and patient III-2) and two unaffected individuals (patient II-4 and patient III-5)] were investigated with conventional MRI and Diffusion-weighted imaging (DWI) using 1.5 Tesla (T) scanner. All four individuals were evaluated via neurological examinations and Mini-Mental State Examination. Brain biopsy study was performed on patient III-2. Finally, an extensive literature review involving pathology investigations and neuroimaging studies of HDLS patients was conducted. Results: DWIs of two investigated patients showed deep white matter lesions with persistent diffusion restriction. Computed tomography imaging showed punctate mineralization in the lesions. Biopsy specimens of patient III-2 demonstrated axonal spheroids which were typical for HDLS. Conclusions: Via the presentation of our pedigree and literature review, we suggest HDSL as a first-line differential diagnosis in patients with undiagnosed adult-onset familial leukoencephalopathy, in particular, those with MRI lesions of frontal white matter and centrum semiovale associated with foci of diffusion restriction and mineralization. Finally, we think that the persistence of the diffusion restriction in deep white matter lesions should be kept in mind as a crucial neuroimaging sign for HDLS.