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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.

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.

OBJECTIVES We reviewed our institutional experience during a 10-year period for improvement of safety and efficacy of stereotactic biopsy procedures. METHODS We performed a retrospective review of inpatient summaries, stereotactic worksheets and radiologic investigations of 208 consecutive patients, who underwent MRI-guided stereotactic biopsies between March 2010 and March 2020. RESULTS The overall diagnostic yield was 96.2%. CT-confirmed intracranial hemorrhage occurred in 17 patients (8.2%), and the overall mortality rate was 0.5%. Combined MRS and PWI helped target selection in 27 cases (13.0%), the diagnostic yield was 100%. The results of the regression analysis revealed that non-diagnostic biopsy specimen significantly correlated with the cystic trait (p

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.

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.

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.

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.

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.

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.

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.

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.

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.

The aim of this study was to compare the efficacy, safety, and duration of Remebot robot-assisted frameless brain biopsy with those of standard frame-based stereotactic biopsy.A retrospective analysis of 66 patients undergoing stereotactic brain biopsy in our department from January 2015 to January 2019 was performed. We divided the patients into two groups: the frame-based group (No significant difference in diagnostic yield was detected in the two groups, with frame-based biopsy having a diagnostic yield of 91.4% and Remebot robot-assisted frameless brain biopsy having a diagnostic yield of 93.5%. The duration of the total procedure was 116.5 min for the frame-based biopsy and 80.1 min for the Remebot robot-assisted frameless brain biopsy (Remebot robot-assisted frameless brain biopsy was as efficacious and safe as standard stereotactic frame-based biopsy. However, frameless biopsy can alleviate the suffering of the patient and reduce the total duration of the procedure. Remebot robot-assisted frameless brain biopsy is easy to use and better accepted by patients than frame-based biopsy.

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

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.

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.

Simulation training improves technical skills in a safe environment. Stereotactic techniques are widely used in neurosurgery for different kinds of procedures. The objective of the study was to describe a combined cadaveric and synthetic low-cost stereotactic simulation model and its validation by neurosurgeons.The brain was made using self-supporting gel with solid and cystic lesions. We used imaging scans to calculate x, y, and z target coordinates. A standard frame needle biopsy was performed. We calculated the number of mistakes and time needed to accomplish the task, and we evaluated the frame assembly and biopsy performance. Wilcoxon signed rank was used to analyzed the data; we considered a P value0.05 as statistically significant.The median initial number of mistakes was 32 (interquartile range [IQR]: 27.5-37) and after repeated training and feedback the final median number was 3.5 (IQR: 2-6) (P0.001). The median time needed to finish the exercises before training was 1020.5 seconds (IQR: 908-1125.5) and after using the model the final median time was 479 seconds (IQR: 423-503) (P0.0001).We presented a stereotactic simulation model with immediate haptic feedback. The model can be easily handmade in any neurosurgical laboratory. This model allows neurosurgeons in training to acquire and improve stereotactic techniques, reducing the number of surgical mistakes and time needed to finish the task.

In this case report, we described a 15-year-old boy who presented with intermittent episodes of ataxia and diplopia since 6.5 years of age. Extensive workup done over several years was negative. Brain biopsy showed a neuroinflammatory disorder, and hence, differential diagnosis of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, central nervous system (CNS) lymphoma, and small vessel CNS vasculitis were considered. A final diagnosis of familial hemophagocytic lymphohistiocytosis was made when the patient developed episodes of prolonged fever with pancytopenia much later in the course of illness and genetic workup revealed pathogenic mutations in the PRF1 gene.

A 26-year-old woman presented for a routine contact lens evaluation but was found to have a subtle right sixth nerve paresis and adducting nystagmus of the left eye. She reported horizontal diplopia on far right gaze as well as subjective right-sided weakness and poor balance for 1 year. Brain and spinal MRI revealed multiple cystic lesions with variable enhancement throughout the posterior fossa and cervical spinal cord. These MRI findings were highly suspicious for an infectious central nervous system process, such as neurocysticercosis; however, primary or metastatic tumors were also important considerations. Tumor location and imaging characteristics were most helpful in differentiating among these etiologies. A brain biopsy ultimately established the diagnosis of a rosette-forming glioneuronal tumor.

The purpose of this study was to assess the reliability of fluorescein sodium in predicting conclusive tissue diagnosis in stereotactic brain biopsies and to characterize features of contrast-enhancing and non-enhancing MRI lesions associated with fluorescence. A total of 19 patients were studied, 14 of which had contrast-enhancing and 5 of which had non-enhancing lesions on preoperative T1 post-gadolinium MRI scan. All patients received 3 mg/kg fluorescein sodium during anesthesia induction. Biopsy specimens were photographed under the operating microscope, using the Yellow560 module, prior to histopathological analysis. Two observers blinded to the MRI scans and histopathological results categorized the photographs retrospectively as “fluorescent” or “not fluorescent.” Inter-rater agreement was assessed using Cohen’s kappa coefficient. Sensitivity, specificity, and positive predictive value of fluorescence reliability were calculated for MRI contrast-enhancing lesions and confirmed location-concordance of tumor pathology based on rater’s fluorescence status assessment. Results were correlated finally with final results on permanent sections. Strength of inter-rater fluorescence status agreement was found to be “substantial” (kappa = 0.771). Sensitivity, specificity, and positive predictive value for “fluorescent” and “not fluorescent” specimen in comparison with MRI contrast-enhancing lesions were 97%, 40%, and 82%, respectively. Sensitivity, specificity, and positive predictive value for confirmed tumor pathology were 100%, 63%, and 91%, respectively. Permanent pathology revealed high-grade glioma n = 5, low-grade glioma n = 3, lymphoma n = 5, pineal tumor n = 2, hamartoma n = 1, and nonspecific hypercellularity n = 3. Fluorescein-assisted stereotactic brain biopsies demonstrated a high likelihood to manifest fluorescence in contrast-enhancing MRI lesions, while adequately predicting conclusive tumor pathology.

Background Thalamic aphasia is an unusual clinical presentation of brain neoplasm with few cases reported. Herein, we present a case of an adult woman with thalamic aphasia due to glioblastoma of the thalamus. Case presentation A 57-year-old female patient presented with difficulty walking, slow speech and cognition and altered mental status. At baseline, she was conversant and interactive. Physical examination showed right hemiparesis in addition to word finding difficulties, an impaired naming of objects and semantic paraphasia but preserved repetition and comprehension. The remaining neurological exam was otherwise unremarkable. Brain CT and brain MRI scans showed a left thalamic lesion that is centrally necrotic and peripherally enhancing suggestive of a high-grade neoplasm. Eventually, histopathological examination of brain biopsy confirmed the diagnosis of glioblastoma multiforme. Thalamic aphasia was proposed as an explanation for the neurological symptoms observed in this patient. Conclusions This patient demonstrates an unusual presentation of glioblastoma multiforme as thalamic aphasia. It may also point to the potential contribution of the understanding of how thalamic aphasia evolves to characterize the role of the thalamus in language functions.

The role of neuroinflammation in epileptogenesis is extensively investigated, but short-term effects of seizures on established CNS pathologies are less studied and less predictable. We describe the case of a woman with previous recurrent episodes of focal cerebral haemorrhage of unknown cause who developed a pseudo-tumoural oedema triggered by provoked focal status epilepticus. A brain biopsy revealed that the underlying condition was primary angiitis of the CNS. Ictal-induced blood-brain barrier dysfunction allows the entry of water and inflammatory molecules that, in the context of CNS inflammatory diseases, may trigger a self-reinforcing process. Caution should be observed when tapering antiepileptic drugs in patients with such conditions.

Background The preoperative preparation of the planning dataset for frame-based stereotactic brain biopsy is often associated with logistical effort and burden on the patient. Intraoperative imaging modalities need to be investigated to overcome these limitations. Objective The objective of the study was to develop and apply a new method for the intraoperative acquisition of the planning dataset with the multiaxial robotic C-arm system Artis zeego. Methods An indication-customized dose-reduced protocol for Artis zeego was developed and implemented into the workflow. A sample of 14 patients who had undergone intraoperative imaging with Artis zeego was analyzed. A sample of 10 patients with conventional preoperative imaging by cranial computed tomography (CT) was used as a control group. Outcomes were compared with regard to target deviation, diagnostic value of the biopsies, complications, and procedure time. Results In all patients, a suitable intraoperative planning dataset could be acquired with Artis zeego. Total procedure time was shorter for the Artis zeego group (p = 0.01), whereas time in the operating room area was longer in the Artis zeego group (p = 0.04). Biopsy results were diagnostic in 12 patients (86%) in the Artis zeego group and in 8 patients (80%) in the control group. There were no significant differences in target size, trajectory length, or target deviation. Conclusion Intraoperative imaging for frame-based stereotactic brain biopsy with Artis zeego is an easy and feasible method. Accuracy is comparable to conventional CT, whereas radiation exposure could be additionally reduced. It allows a significant reduction of the total procedure length and improves the comfort for the patient and staff.

AIM Mitochondrial encephalomyopathy, lactic acidosis, and recurrent stroke-like episodes (MELAS) syndrome is a rare but one of the most common maternally inherited multisystem disorder. Although patients with MELAS present a variable clinical profile, stroke-like lesions have been detected in 90% of cases, with stroke being the first presenting symptom in 25% of cases. However, cases of local brain edema requiring decompressive craniectomy has not been reported. CASE DESCRIPTION A 12-year-old male patient was admitted to our pediatric intensive care unit with altered mental status, seizures, and vision loss. The patient was stuporous and presented neck stiffness. Complete blood count, serum electrolytes, biochemistry (including lactate level), acute phase reactants, and repeated blood gas analysis were unremarkable. Brain magnetic resonance imaging (MRI) revealed an edematous stroke-like lesion in the right occipital lobe accompanied by brain swelling. Intravenous ceftriaxone, acyclovir, intravenous immunoglobulin (IVIG), and pulse steroid therapy were started for possible diagnosis of viral/bacterial/autoimmune encephalitis; levetiracetam, phenytoin, and an infusion of sodium thiopental were started for refractory status epilepticus; and a 3% NaCl infusion was started for local brain edema. The results of serum autoimmune encephalitis panel were negative. Further investigations for rheumatic, vascular, and metabolic disorders were unremarkable. Despite these supportive treatments, the patient was clinically decompensated due to brain swelling that progressed to the left midline shift, and he underwent decompressive craniectomy. Histologic examination of brain biopsy specimen revealed non-specific encephalitis findings. A pathogenic variant of the MT-TL1 gene (m.3243A T), responsible for MELAS, was detected. The patient's condition dramatically improved after specific treatment for MELAS. CONCLUSION If the diagnosis and treatment are delayed, MELAS syndrome can cause serious brain edema, which may ultimately require decompressive craniectomy.

A 53-year-old woman was admitted to the hospital because she developed headache and malaise 3 months prior to her arrival, followed by gait disturbance, abnormal behavior, and hallucinations. On admission, she was stupor and showed left hemispatial neglect, and brain MRI showed extensive FLAIR high-signal lesions with contrast enhancement in the bilateral periventricular white matter, and CSF examination showed pleocytosis and elevated protein. A stereotactic brain biopsy was performed from the right temporal lobe lesion, and pathological findings demonstrated a perivascular inflammatory cell infiltrate. After the administration of intravenous methylprednisolone followed by oral prednisolone, she recovered almost completely within three months and the abnormal MRI findings disappeared. Anti-glial fibrillary acidic protein (GFAP) antibody in the cerebrospinal fluid turned out to be positive, then the diagnosis of autoimmune GFAP astrocytopathy was made. Reports of this disease are still rare, and we report this case because of its slowly progressive course and pathological evaluation by brain biopsy.

Corticobasal degeneration (CBD) is a rare progressive neurodegenerative disorder characterized by asymmetric presentation of cerebral cortex signs, cortical sensory disturbance and extrapyramidal signs. Herein, we report a case of a 66-year-old Japanese woman who presented with apraxia of the right hand. She subsequently developed postural instability and cognitive impairments that rapidly worsened. One and a half years later, the patient was wheelchair-bound and severely demented. Brain magnetic resonance imaging revealed left dominant atrophy of the frontoparietal lobe. There was a hyperintense lesion in the deep white matter expanding toward the subcortical area on fluid-attenuated inversion recovery (FLAIR) images. In order to rule out the possibility of an intracranial tumor such as an astrocytoma or malignant lymphoma, we performed a brain biopsy of the left frontal middle gyrus. The patient became bedridden and showed akinetic mutism 1 year after biopsy. Pathological examination revealed a large amount of 4-repeat tau-immunoreactive neuropil threads scattered predominantly in the corticomedullary junction and tau-immunoreactive structures, consistent with CBD. Immunostaining for p53 showed no positive cells, and there were very few Ki-67-positive cells. On immunoblots of sarkosyl-insoluble brain extracts, a major doublet of 64 and 68 kDa full-length tau with two closely related fragments of approximately 37 kDa were detected. Based on these results, the patient was pathologically diagnosed as having CBD, excluding the possibility of tumor. Taken together with previous similar case reports, our findings indicate that a deep white matter hyperintense lesion on FLAIR images may be a useful clue to CBD, predicting rapid clinical progression with severe dementia based on severe white matter degeneration with a large amount of tau accumulation on pathological examination.

Stereotactic frame-based brain biopsy is one of the most used procedures to obtain brain tissue. This procedure is usually considered as mini-invasive, quick, efficient, and safe even if results of the different studies are widely heterogenous. The objective of this review of the literature is to describe and analyze the complications of stereotactic frame-based brain biopsy. About 132 articles were found after a research in the Medline database. We only considered English references published between 1994 and June 2019. Additional studies were found by using the references from articles identified in the original search. This systematic review was conducted according to PRISMA guidelines. After applying exclusion criteria, we eventually considered 25 relevant studies. The mortality rate varies from 0.7 to 4%. Overall morbidity ranges from 3 to 13%. Most of the complications are revealed by the following symptoms: neurological impairment (transient or permanent), seizure, and unconsciousness. Symptomatic hemorrhage range varies from 0.9 to 8.6%, whereas considering asymptomatic bleeding, the range may be up to 59.8%. Complications were clinically evident within minutes to a few hours after the biopsy. Corrective surgeries are very rare (

Background and aims - Description of two cases of rare intravascular large B-cell lymphoma and secondary T-cell lymphoma diagnosed postmortem, that manifested clinically as longitudinally extensive transverse myelitis (LETM). We discuss causes of diagnostic difficulties, deceptive radiological and histological investigations, and outline diagnostic procedures based on our and previously reported cases. Case reports - Our first case, a 48-year-old female was admitted to the neurological department due to paraparesis. MRI suggested LETM, but the treatments were ineffective. She died after four weeks because of pneumonia and untreatable polyserositis. Pathological examination revealed intravascular large B-cell lymphoma (IVL). Our second case, a 61-year-old man presented with headache and paraparesis. MRI showed small bitemporal lesions and lesions suggesting LETM. Diagnostic investigations were unsuccessful, including tests for possible lymphoma (CSF flow cytometry and muscle biopsy for suspected IVL). Chest CT showed focal inflammation in a small area of the lung, and adrenal adenoma. Brain biopsy sample from the affected temporal area suggested T-cell mediated lymphocytic (paraneoplastic or viral) meningoencephalitis and excluded diffuse large B-cell lymphoma. The symptoms worsened, and the patient died in the sixth week of disease. The pathological examination of the presumed adenoma in the adrenal gland, the pancreatic tail and the lung lesions revealed peripheral T-cell lymphoma, as did the brain and spinal cord lesions. Even at histological examination, the T-cell lymphoma had the misleading appearance of inflammatory condition as did the MRI. Conclusion - Lymphoma can manifest as LETM. In cases of etiologically unclear atypical LETM in patients older than 40 years, a random skin biopsy (with subcutaneous adipose tissue) from the thigh and from the abdomen is strongly recommended as soon as possible. This may detect IVL and provide the possibility of prompt chemotherapy. In case of suspicion of lymphoma, parallel examination of the CSF by flow cytometry is also recommended. If skin biopsy is negative but lymphoma suspicion remains high, biopsy from other sites (bone marrow, lymph nodes or adrenal gland lesion) or from a simultaneously existing cerebral lesion is suggested, to exclude or prove diffuse large B-cell lymphoma, IVL, or a rare T-cell lymphoma.

A 62-year-old woman was transported to our hospital for management of generalized clonic seizures. Cerebrospinal fluid examination showed an increased monocyte-dominant cell count, high protein concentration, and low glucose concentration that was 17% of the plasma glucose concentration. Contrast-enhanced cranial magnetic resonance imaging revealed diffuse leptomeningeal enhancement with multiple nodular lesions. She underwent examinations that ruled out the following conditions: tuberculous meningitis, systemic sarcoidosis, malignant lymphoma, carcinomatous meningitis, and central nervous system vasculitis. On hospital day 13, dural and brain biopsies revealed neurosarcoidosis, for which steroid therapy was administered. Thereafter, imaging examinations showed marked improvement. Because isolated neurosarcoidosis is difficult to diagnose, early pathologic diagnosis may be essential.

Idelalisib, a selective phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor, is a newly approved second-line drug for patients with chronic lymphocytic leukemia. Recent clinical trials have suggested a possible association between idelalisib treatment and development of progressive multifocal leukoencephalopathy (PML) due to John Cunningham virus (JCV) reactivation. Nevertheless, clinical course and radiological and pathological features of idelalisib-induced PML still need to be clarified. We provide here the first clinicopathological description of idelalisib-associated PML in a patient who developed epilepsia partialis continua (EPC) as the first manifestation of the disease. Since EPC could present without electroencephalogram alterations, it is crucial to recognize the clinical features of this epileptic condition. EPC is characterized by the presence of repetitive, irregular, clonic jerking, often associated with hemiparesis and involvement of distal rather than proximal muscle groups. Moreover, we highlight the importance of brain biopsy in selected cases when there is a high clinical suspicion of PML, despite negative JCV testing in the cerebrospinal fluid. The pathological finding of prominent inflammatory infiltrate observed here was consistent with a diagnosis of immune reconstitution inflammatory syndrome (IRIS). IRIS is often associated with PML as a paradoxical worsening of clinical symptoms due to an overreacting immune response, in the context of previous immunosuppression. The unprecedented pathologic observation of IRIS in idelalisib-associated PML provides further insights into the pathogenesis of this rare neurological side effect.

Granulomatous amoebic encephalitis caused by free-living amoebae is a rare condition that is difficult to diagnose and hard to treat, generally being fatal. Anti-amoebic treatment is often delayed because clinical signs and symptoms may hide the probable causing agent misleading the appropriate diagnostic test. There are four genera of free-living amoeba associated with human infection, Naegleria, Acanthamoeba sp., Balamuthia and Sappinia. Two boys were admitted with diagnosis of acute encephalitis. The history of having been in contact with swimming pools and rivers, supports the suspicion of an infection due to free-living amoebae. In both cases a brain biopsy was done, the histology confirmed granulomatous amoebic encephalitis with the presence of amoebic trophozoites.

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease due to a lytic infection of oligodendrocytes caused by polyoma virus (JC virus) infection. PML usually occurs in a setting of severe immunosuppression and is most commonly associated with human immunodeficiency virus (HIV) infection. Idiopathic CD4+ lymphocytopenia is a very rare cause of PML and only a few cases have been reported in the literature. We present a case of a 45-year-old man who presented with behavioral alteration followed by progressive weakness of right side of the body. Contrast-enhanced magnetic resonance imaging of the brain revealed confluent irregular areas of T2-weighted/fluid-attenuated inversion recovery hyperintensities in left frontoparietal and right temporoparietal regions. His hematological work up showed a decreased absolute CD4+ count of 217 per microliter, but was negative for HIV serology. Keeping a differential diagnoses of central nervous system lymphoma, brain biopsy was performed. Histopathology revealed demyelination with presence of intranuclear inclusions in the oligodendrocytes, which were positive for SV40 immunostain. Adjacent areas showed reactive gliosis with hypertrophic astrocytes, hence a diagnosis of PML was made. The patient died due to aspiration pneumonia. PML can occur very rarely in association with idiopathic CD4+ lymphocytopenia in the absence of other immunosuppressive illnesses. This report highlights the importance of high index of clinical suspicion and need for a careful histological examination for diagnosis of PML to facilitate adequate patient management.

International audience; Encephalitides include a large variety of diseases with high morbidity and mortality. Although the majority of identified pathogens are viruses, the cause of the disease remains unexplained in more than half of the cases despite extensive testing. Neuropathology provides the bases of our understanding of the inflammatory lesions in the central nervous system. Brain biopsy proves to be necessary in cases of unknown etiology, which deteriorate despite treatment. Unexpected pathogens can be uncovered by untargeted transcriptomic analysis, based on deep sequencing of small quantities of pathological brain tissue. Combined with immunohistochemistry and in situ hybridization, using tailored antibodies and probes, this next generation sequencing method opens perspectives in the diagnosis of encephalitides with a high efficiency particularly in, but not limited to, immunocompromised patients.

Purpose of reviewA vasculitic pattern of injury seen on brain biopsy can be attributed to a multitude of primary or secondary disorders, leading to diagnostic challenges for clinicians.Recent findingsThis report describes the clinical presentation and histopathologic findings in 2 patients who initially received a diagnosis of primary CNS vasculitis, but did not show long-term response to treatment. In both cases, a second biopsy was performed, and the final diagnosis was primary CNS lymphoma (PCNSL).SummaryAnalyzing diagnostically challenging cases can increase recognition of PCNSL and improve outcomes in this rare condition.

Background Primary central nervous system (CNS) small lymphocytic lymphoma (SLL), as a type of low-grade lymphoma, is extremely rare. The diagnosis of CNS SLL is challenging due to its variable clinical and radiological features, which may overlap with those of diffuse large B-cell lymphoma (DLBCL). Primary CNS SLL differs from DLBCL in that it has an indolent clinical course and a good prognosis. Thus, it is important to distinguish SLL from DLBCL. By reviewing the literature, only two cases of low-grade SLL, primarily located in the CNS and involving the brain parenchyma and dura, have been reported. To our knowledge, primary CNS SLL in the bilateral ventricles has never been reported. Interestingly, the two cases in our report are identical in terms of the clinical presentations, magnetic resonance imaging (MRI) features, pathological results and prognoses. Case presentation Both patients presented with headaches. MRI suggested solid lesions located in the bilateral ventricles that were isointense on T1-weighted images and hypointense on T2-weighted images. After the injection of contrast agent (gadolinium, Gd), the intraventricular lesions were homogeneously enhanced and hyperperfused. CSF cytology revealed malignant cells. Brain biopsy revealed diffuse proliferation of small lymphocytes with positive labelling of B-cell immunomarkers. The primary origin in the CNS was confirmed with no evidence of systemic lymphoma. Two patients were given high doses of methotrexate-based chemotherapy and were free from symptoms and progression for more than 1-year of follow-up. Conclusions The presence of homogeneously enhanced intraventricular MRI lesions should raise the suspicion of primary CNS SLL.

We report a case of a young female patient who developed progressive neurological dysfunction with a ring-enhancing tumor-like nodule on brain magnetic resonance imaging. Urgent surgery was performed to remove the mass in the left basal ganglia. Pathological findings showed that the necrotic brain areas were accompanied by congestion, edema, discrete hemorrhage, and intestinal and perivascular lymphohistiocytic infiltration. Immunohistochemical staining results showed that Toxoplasma gondii (T. gondii) immunoreactivity was detected in both cysts and tachyzoites in these areas. The glycerol-3-phosphate dehydrogenase gene (B1) of T. gondii was amplified by sequence-specific polymerase chain reaction (PCR) and the PCR products were bi-directional Sanger sequenced. A 195 bp consensus sequence of the gene B1 was found to be 98% identical to a reference T. gondii sequence (GenBank accession No. kx270373). The final diagnosis was toxoplasmic encephalitis in the left basal ganglia. This report suggests that PCR and bi-directional DNA sequencing of T. gondii gene might be the most convenient and rapid tools for accurate diagnosis of toxoplasmic encephalitis .

Acquired polyneuropathies (PN) are rare in childhood and adolescent. We report on a 15-year-old male patient who presented with progressive gait instability, ataxia, neuropathic pain, distal muscle weakness and progressive loss of ambulation. Nerve conduction studies (NCS) revealed a progressive demyelinating sensorimotor polyneuropathy predominantly of the lower limbs. Cerebrospinal fluid (CSF) analyses revealed a cytoalbuminologic dissociation. Extensive diagnostic workup for autoantibodies and inflammatory markers was inconclusive. Corticosteroids and intravenous immunoglobulins did not affect. Cranial MRI revealed leptomeningeal enhancement of the cerebellum and the brainstem. Brain biopsy of the cerebellar lesions revealed an unclassifiable sarcoma. The patient was treated according to the CWS guidance study resulting in a decrease in enhanced lesion size. After two years NCS still revealed a demyelinating sensorimotor PN. This case report describes for the first time the clinical course of a chronic PN, putative paraneoplastic, associated with isolated unclassifiable CNS-sarcoma in an adolescent patient. Paraneoplastic pathogenesis should be considered in an unusual sequence of subacute progressive neurological symptoms even in children and adolescents.

Summary Febrile infection–related epilepsy syndrome (FIRES) is a severe epileptic encephalopathy with presumed inflammatory origin and lacking effective treatments. Anakinra is the human recombinant interleukin 1 receptor antagonist clinically used in autoinflammatory or autoimmune conditions. We report a case of FIRES for which the spatial and temporal match between electroencephalography (EEG) and magnetic resonance imaging (MRI) focal alterations provides support for the detrimental synergic interplay between seizures and inflammation that may evolve to permanent focal lesions and progressive brain atrophy in weeks to months. Brain biopsy showed aspects of chronic neuroinflammation with scarce parenchymal lymphocytes. We report the novel evidence that anakinra reduces the relapse of highly recurrent refractory seizures at 1.5 years after FIRES onset. Our evidence, together with previously reported therapeutic effects of anakinra administered since the first days of disease onset, support the hypothesis that interleukin 1β and inflammation‐related factors play a crucial role in seizure recurrence in both the acute and chronic stages of the disease.

Background Stereotactic needle biopsy provides a minimally invasive option for the diagnosis of intracranial lesions but is limited by inconclusive diagnoses on frozen pathology. For rapid pathology, 5-aminovelunic acid and sodium fluorescein have previously demonstrated potential as diagnostic adjuvants. Stereotactic biopsy with near-infrared (NIR) fluorophores has not been reported. We identified 5 representative cases using NIR fluorescent dye indocyanine green (ICG) administered in a high dose, delayed manner. Methods Five patients underwent second window indocyanine green (SWIG)-guided stereotactic biopsy for diagnosis of suspected glioma or tumor recurrence. Up to 5 mg/kg ICG was administered approximately 24 hours prior to surgery. Biopsies were conducted in the standard fashion, targeting regions of suspected tumor using intraoperative frameless navigation. Samples were examined intraoperatively under standard visible light and for fluorescence using conventional NIR imaging platforms. Findings were correlated with frozen and final tumor pathology for all cases. Results A total of 10 biopsy specimens were obtained. Three did not fluoresce and did not demonstrate tumor on preliminary or final pathology, including a non-gadolinium-enhancing sample taken proximal to the final target. The remaining 7 fluoresced, of which 6 contained tumor and 1 contained necrosis. Fluorescence was also noted in a patient with radiation treatment effect. Overall fluorescence characteristics were highly concordant with preliminary and final diagnoses. Conclusions SWIG provides rapid intraoperative confirmation of pathologic brain tissue by permeating neoplastic or inflammatory brain tissue via a mechanism similar to that of gadolinium enhancement. SWIG-guided stereotactic biopsy can improve surgical efficiency by enhancing confidence in acquisition of target tissue.

The diagnosis of atypical inflammatory demyelinating lesions can be difficult. Brain biopsy is often required to exclude neoplasms. Moreover, the relationship between these lesions and multiple sclerosis and NMOSD is not clear. Our objectives were to describe radiological and pathological characteristics of patients with acute inflammatory demyelinating lesions. We retrospectively identified patients with brain biopsy performed for diagnostic uncertainty revealing a demyelinating lesion. A complete clinical, biological, radiological and pathological analysis was performed. Twenty patients (15 with a single lesion) were included. MRI disclosed a wide range of lesions including infiltrative lesions (40%), ring-like lesion (15%) Balo-like lesion (15%) and acute haemorrhagic leukoencephalitis (20%). In spite of a marked heterogeneity, some findings were common: a peripheral B1000 hyperintense rim (70%), a slight oedema with mild mass effect (75%) and an open-rim peripheral enhancement (75%). Histopathology revealed that all cases featured macrophages distributed throughout, extensive demyelination, axonal preservation and absence of haemorrhagic changes. In the majority of cases, macrophages were the predominant inflammatory infiltrate and astrocytes were reactive and dystrophic. Aquaporin-4 staining was systematically preserved. After a mean follow-up of 5 years (1–12), 16/20 patients had a diagnosis of monophasic acute atypical inflammatory demyelinating lesion. One patient was diagnosed with MS and 3 with AQP4 negative NMOSD. Although imaging findings in patients with atypical inflammatory demyelinating lesions are heterogeneous, some common features such as peripheral DWI hyperintense rim with open-rim enhancement and absence of oedema argue in favour of a demyelinating lesion and should preclude a brain biopsy. In this context, AQP4 staining is systematically preserved and argues against an AQP4-positive NMOSD. Moreover, long-term follow-up is characterized by low recurrence rate.

Brain biopsy has a well-established role in the diagnosis of CNS neoplasia. Nevertheless, despite being essential for the diagnosis of some benign neurological diseases, little consensus exists regarding its indications for disease diagnosis and patient orientation. Our aim was to assess brain biopsy diagnostic yield in patients with neurological deterioration of unknown etiology, to identify the clinical characteristics associated with an increased likelihood of achieving a diagnostic biopsy as well as the characteristics linked to a particular diagnosis. A retrospective analysis of 62 consecutive brain biopsies performed at a single tertiary care center between January 2004 and December 2015 for suspected non-neoplastic neurological disease was performed. The clinical presentation, imaging, and laboratory results were collected and compared between diagnostic groups. Sixty-eight percent of the biopsies led to a definitive diagnosis. The most common histological diagnosis was central nervous system lymphoma (eight cases), followed by astrocytoma, demyelinating disease, and progressive multifocal leukoencephalopathy (four cases each). No clinical characteristics were found to predict a diagnostic biopsy or to correlate with a specific diagnosis. Importantly, a distinct diagnosis from the initially suspected was achieved in 52% of cases and biopsy findings led to a change of therapeutic orientation in 78% of the cases. Our results suggest that brain biopsies have a significant impact on patient management and should be considered early in selected cases in which less invasive testing was unable to reach a definitive diagnosis.