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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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Well-circumscribed intra-axial CNS tumors encompass a wide variety of gliomas and glioneuronal tumors, usually corresponding to WHO grades I and II. Nonetheless, sometimes high-grade 'diffuse' gliomas such as gliosarcoma and giant cell glioblastoma can be relatively circumscribed but are often found to have foci of diffuse infiltration on careful examination, harboring distinct molecular alterations. These tumors are excluded from the discussion in this chapter with the current review emphasizing on lower-grade entities to include a brief description of their histology and associated molecular findings. Like elsewhere in brain biopsy evaluation, imaging is crucial and acts as a surrogate to gross examination. Given the circumscribed nature of these tumors, surgery alone is the mainstay treatment in most entities.

BACKGROUND/PURPOSE To report a case of serology-negative severe disseminated Bartonella neuroretinitis in an immunocompromised patient in which diagnosis was made by detection of B. henselae DNA by universal polymerase chain reaction of brain tissue. METHODS Case report. RESULTS A 57-year-old man with immunoglobulin A vasculitis on immunosuppressive therapy presented with lethargy, weight loss, and bilateral decreased vision. Fundus examination revealed bilateral mild vitritis, marked optic disc edema, vascular sheathing, and numerous white inner retinal and preretinal lesions. Brain magnetic resonance imaging revealed multiple foci of restricted diffusion and a ring-enhancing focus in the left parietal lobe. Serologies, cerebrospinal fluid, and vitreous biopsies were all negative for Bartonella. A brain biopsy was performed and B. henselae DNA was detected by universal polymerase chain reaction of the specimen. The patient demonstrated resolution of fundus findings with antibiotic treatment. Repeat serological testing demonstrated seroconversion. CONCLUSION In immunocompromised patients, infection by Bartonella henselae can present as severe disseminated disease. Establishing the diagnosis can be challenging as serologic testing is often unrevealing in the setting of a blunted immune response. Polymerase chain reaction has been used in select cases to establish the diagnosis.

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.

A patient with advanced HIV/AIDS presented with a brain abscess. While brain biopsy culture and pathology were unrevealing, universal broad-range PCR (uPCR) demonstrated Mycobacterium avium complex (MAC). We review the clinicopathologic characteristics of MAC brain abscesses and highlight the effectiveness of uPCR as a diagnostic tool in partially-treated infections.

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.

Toxin-induced leukoencephalopathy is a rare neurological condition that has been previously associated with intracranial radiation, chemotherapy, drugs of abuse, and environmental exposures. Herein, we present a patient with brain-biopsy proven toxin-induced leukoencephalopathy, likely secondary to multiple environmental offenders including insecticides and non-Food and Drug Administration approved anabolic steroids, opioids, and benzodiazepines. A 60-year-old man presented to our service as a direct transfer from an outside facility for evaluation of a rapidly progressive neuropsychiatric decline. Extensive workup with blood work, cerebrospinal fluid analysis, paraneoplastic panel, serial magnetic resonance imaging brain with and without contrast, and electroencephalograms were unrevealing. Magnetic resonance imaging brain showed diffuse confluent white matter disease, which was non-specific. The patient was treated with high-dose methylprednisolone and trials of intravenous immunoglobulin without any significant improvement. Finally, a brain biopsy was performed, and pathology confirmed a spongiform leukoencephalopathy, favoring a toxin-related etiology. The diagnosis of toxin-induced leukoencephalopathy should be considered in patients with steep neuropsychiatric decline and associated diffuse white matter disease. Diagnosis relies heavily on history of exposure, clinical presentation, imaging findings, and ultimately, histopathology from brain biopsy. The recognition of the clinical presentation is important to pursue the appropriate diagnostic workup and treatment.

Toxoplasmic encephalitis (TE) and post-transplant lymphoproliferative disorder of the central nervous system (CNS-PTLD) are major complications after allogeneic hematopoietic stem cell transplant (allo-SCT); both are fatal without timely diagnosis and disease-specific treatment. Differential diagnosis of TE and CNS-PTLD can be challenging because brain biopsy, a gold standard for diagnosis, is sometimes not possible, owing to poor patient condition after allo-SCT. Here, we describe a case of isolated CNS-PTLD arising during the therapeutic course of TE. A 51-year-old man was admitted with mental abnormalities and fever on Day 106 after allo-SCT to treat myelodysplastic syndrome. Magnetic resonance imaging (MRI) revealed multiple nodular and ring-enhanced lesions in the brain, and the result of polymerase chain reaction (PCR) for Toxoplasma gondii in cerebrospinal fluid was positive; therefore, he was diagnosed with TE. Anti-Toxoplasma therapy led to clinical improvement, and the result of subsequent PCR was negative. However, he developed left-sided hemiplegia on Day 306. Head MRI revealed a new lesion and a growing lesion, presenting as ring-enhanced nodules. Brain biopsy was performed, and a pathologic diagnosis of Epstein-Barr virus-associated CNS-PTLD was made. There was no evidence of TE. He was treated successfully by reducing immunosuppressants, followed by rituximab administration and a donor lymphocyte infusion, resulting in complete remission. While T.gondii-specific PCR has great value for diagnosis of TE, CNS-PTLD can be diagnosed only by brain biopsy; hence, brain biopsy may be warranted in cases of suspected PTLD.

We herein report the case of a 67-year-old man who presented with the acute onset of limb weakness. Brain magnetic resonance imaging revealed multiple abnormal-signal-intensity lesions. Steroids were administered, and the patient initially responded. Nerve conduction testing findings were consistent with demyelinating polyneuropathy. A sural nerve biopsy specimen revealed fascicles with extensive onion-bulb formation. Although skin and sural nerve biopsies showed no atypical cellular infiltration, the histopathological diagnosis of intravascular large B-cell lymphoma was obtained by a brain biopsy. The neuropathy in this patient may be attributed to a demyelinating process independent of ischemic damage by lymphoma.

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.

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.

Susac syndrome is a rare, immune-mediated disease characterized by encephalopathy, branch retinal artery occlusion, and hearing loss. Herein, we describe the electron microscopic findings of three brain biopsies and two brain autopsies performed on five patients whose working clinical diagnosis was Susac syndrome. In all five cases, the key findings were basement membrane thickening and collagen deposition in the perivascular space involving small vessels and leading to thickening of vessel walls, narrowing, and vascular occlusion. These findings indicate that Susac syndrome is a microvascular disease. Mononuclear cells were present in the perivascular space, underlining the inflammatory nature of the pathology. Though nonspecific, the changes can be distinguished from genetic and acquired small vessel diseases. The encephalopathy of Susac syndrome overlaps clinically with degenerative and infectious conditions, and brain biopsy may be used for its diagnosis. Its vascular etiology may not be obvious on light microscopy, and electron microscopy is important for its confirmation.

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.

A 75-year-old Japanese woman with a 20-year history of rheumatoid arthritis presented with symptomatic bilateral pleural effusion and lung and brain tumors. She had received methotrexate for five years and tacrolimus for one year. A brain biopsy specimen showed the pathological features of lymphoproliferative disease, but a bone marrow biopsy showed proliferation of plasma cells. She was finally diagnosed with coexistent lymphomatoid granulomatosis (LYG) of the brain and lung and multiple myeloma (MM) of the bone marrow and received chemotherapy for both. This report shows that immunodeficient patients are at risk of developing the unusual coexistence of LYG and MM.

Amyloid-β-related angiitis (ABRA), a subtype of cerebral amyloid angiopathy (CAA), is vasculitis occurring in relation to amyloid-β (Aβ) deposition in the walls of intracranial blood vessels. ABRA is presumed to be caused by some immune response to the deposited Aβ. An 81-year-old man on oral anticoagulant therapy complained of headache, nausea, and difficulty with standing after a head injury. Head computed tomography revealed subcortical bleeding in the right temporoparietal lobe, and 3 days after admission, magnetic resonance imaging (MRI) showed subarachnoid hemorrhage (SAH) around the hematoma. Cerebral microbleeds, a characteristic of CAA, were not detected on MRI. On worsening of his symptoms, intracranial brain biopsy and hematoma removal were performed. Intraoperative rapid diagnosis with a frozen section suspected vasculitis, which enabled the prompt initiation of steroid therapy. He was pathologically diagnosed with ABRA (granulomatous angiitis) using a formalin-fixed paraffin-embedded section. Vasculitis was prominent around blood vessels in the pia matter covering the cerebrum. In this case, the inflammatory cells seemed to appear via the subarachnoid space following cerebral hemorrhage and SAH. ABRA seemed to be developed by intracranial hemorrhage in this case.

Creutzfeldt-Jakob Disease (CJD) is a rare invariably fatal neurodegenerative disease believed to be caused by an abnormal isoform of cellular infectious glycoprotein called prion protein. Though it is arare disease; yet it is the most common among prion diseases. Clinical presentation consists of rapidly progressive loss of memory, cognitive & visual disturbance, lack of coordination, myoclonus, cerebellar, pyramidal and extra pyramidal signs, akineticmutism & with progression of disease deterioration in higher mental functions become more pronounced. Periodic sharp triphasic wave complexes on EEG, high signal abnormalities in caudate nucleus and putamen on diffusion weighted (DW) or FLAIR MRI of Brain and positive 14-3-3 protein in CSF substantiate the diagnosis of CJD but definitive diagnosis is established by brain biopsy or autopsy materials. We report a case of 58-year old female patient who was admitted with complaints of rapidly progressive dementia, cognitive disturbance, blurring of vision and myoclonic jerks. Initial MRI brain and CSF findings were normal. Differential diagnoses that can present with rapidly progressive dementia and thereby mimic sporadic Creutzfeldt-Jakob disease were considered after review of literature. In EEG triphasic wave complexes were seen, repeat DWMRI after two weeks showed bilateral hyper-intensities in basal ganglia involving caudate nucleus and putamen, suggesting a diagnosis of probable CJD on the basis of center for disease control and prevention (CDC) criteria. The case is reported because of its rarity and also to emphasise that patients with rapidly progressive dementia, associated visual and cognitive disturbances and myoclonus should be investigated with DW MRI, EEG&CSF for diagnosis of CJD.

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 .

The patient was a 74-year-old woman with rheumatoid arthritis who developed ataxia. MRI revealed T2-hyperintense lesions predominantly in the left middle cerebellar peduncle. Punctate or linear Gd enhancement was also observed on T1-weighted images. A brain biopsy was conducted and the pathology revealed a mild demyelinated lesion. Polymerase chain reaction (PCR) of biopsied brain tissues revealed the presence of JC virus (JCV) DNA, but JCV-infected oligodendroglia-like cells were not apparent on immunohistochemistry. Sensitive in-situ hybridization, however, detected three JCV-positive cells and the infiltration of CD4+ and CD8+ T cells and plasma cells was also observed. Immunosuppressants were tapered off and mirtazapine and mefloquine administered, resulting in a favorable outcome.

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.

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.

Se presenta el caso de un niño de 5 años sin antecedentes de enfermedad, que se internó en terapia intensiva por convulsiones tónico-clónicas focalizadas en la cara y en el hemicuerpo derecho, con documentación de temperatura axilar de 37,4°C. Se descartó la presencia de gérmenes comunes y la etiología viral a través de estudios de muestras de líquido cefalorraquídeo (LCR). Se sospechó la presencia de Mycoplasma pneumoniae por comprobarse inmunofluorescencia positiva en suero para anticuerpos de clase IgM. El diagnóstico se confirmó mediante la detección del ADN de dicho patógeno sobre la biopsia cerebral efectuada por el método de la reacción en cadena de la polimerasa (PCR) y una histología compatible con encefalomielitis aguda diseminada. El paciente recibió tratamiento con claritromicina y su evolución fue favorable. Al menos dentro de nuestros conocimientos, este es el primer caso en el que se detectó ADN de M. pneumoniae en una biopsia cerebral por el método de PCR. We present here the case of a previously healthy 5 year-old boy hospitalized in an intensive care unit due to tonic-clonic seizures focused on the face and right side of the body, and axillary temperature of 37.4 °C. Common bacterial and viral etiology was ruled out through studies of cerebrospinal fluid (CSF) samples. Mycoplasma pneumoniae was suspected by a positive immunofluorescence serum test for IgM class antibodies. Finally, with a brain biopsy, M. pneumoniae was confirmed by polymerase chain reaction (PCR) and acute disseminated encephalomyelitis by pathological anatomy. The patient was treated with clarithromycin and had an uneventful evolution. At least to our knowledge, this is the first case in which M. pneumoniae DNA was detected by PCR in a brain biopsy.

Primary central nervous system lymphoma (PCNSL) and chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) can share clinical features and may be indistinguishable, even after brain biopsy. We encountered a case of Epstein-Barr virus-positive (EBV+) PCNSL recurrence in a patient with clinical features of CLIPPERS, and repeat brain biopsy was required to reach the correct diagnosis. Four years after the initial diagnosis and treatment of PCNSL, "peppering" punctate enhanced lesions with transient steroid responsiveness were detected during brain magnetic resonance imaging (MRI). A second brain biopsy supported a diagnosis of CLIPPERS, while a third biopsy confirmed the diagnosis of recurrent PCNSL.