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ObjectiveTo describe an adult patient with Rasmussen’s disease with focal dystonia as the most disabling symptom and the good response to unilateral globus pallidus internus (GPi) deep brain stimulation (DBS).MethodsRetrospective review of clinical records and diagnostic tests.ResultsThe patient had displayedmild focal seizures with sensory and motor symptoms on the left arm and hemiface since the age of 22. Ten years later she experienced abrupt onset of focal left dystonia involving mainly the leg. Brain MRI showed progressive right hemisphere atrophy, and 18fluorodeoxyglucose-positron emission tomography (18FDG-PET) showed right hypometabolism mainly over the frontal and insular regions. Brain biopsy confirmed chronic encephalitis. The dystonia became very severe and made walking extremely difficult. Different treatments including dopaminergic, anticholinergic, immunomodulatory drugs and botulinum toxin were ineffective. Finally the patient was treated with unilateral GPi DBS. Shortly after the onset of the stimulation, the dystonia started to improve. Parameters have been adjusted, and 18 months after surgery the patient is able to walk and run unaided, although a mild left leg dystonia persists.ConclusionRasmussen’s disease may be difficult to diagnose in adult patients. Associated movement disorders may be more disabling than seizures. Focal dystonia may be treated successfully with DBS.

Tuberculosis (TB) remains the most common infection in developing countries and India contributes the maximum number of cases to the global burden. Primary healthcare physicians across the country face major challenges in diagnosis and treatment of childhood TB. In this context, clinical cases of paradoxical responses to antitubercular therapy seem to be under-reported. We report a case of tubercular meningitis in an adolescent girl who belonged to a remote village. She developed a paradoxical immune response to TB while on anti-TB treatment (ATT). She presented with raised intracranial tension and neurological deficits during the continuation phase of ATT after stopping corticosteroids. The ring-enhancing lesions of tuberculomas in the brain and spine characterised the diagnosis of paradoxical response to TB. Brain biopsy suggested necrotising granulomatous disease and was negative for S100 and CD1a marker, ruling out active TB. Retreatment with a prolonged course of steroids and ATT resulted in the clinical and radiological recovery, though some motor and visual deficits persisted. Clinical risk factors and socioeconomic factors also contributed to the present state of the child.

Neuro-Sweet disease (NSD) is defined as Sweet disease with central nervous system (CNS) involvement. Also known as acute febrile neutrophilic dermatosis, NSD is characterised by painful erythematous plaques and multisystem neutrophilic infiltration.1 Familial Mediterranean fever (FMF), characterised by recurrent fever and serositis, is caused by mutations of the Mediterranean fever ( MEFV ) gene. FMF is rarely reported in patients with Sweet’s syndrome.2 In this report, we discuss three cases of possible NSD. Our findings indicate that some mutations in the MEFV gene may act as additional susceptibility factors in autoimmune inflammatory neurological diseases, including NSD. We conducted MEFV mutation analyses on genomic DNA samples from three patients diagnosed with possible NSD between 1 April 2014 and 31 October 2016. Patients were diagnosed with NSD in accordance with previously described criteria.1 In all patients, infection, malignancy and other autoimmune diseases were clinically excluded. All patients provided written informed consent to participate in this study. MEFV gene analyses were performed via PCR (see online supplementary file 1). ### Supplementary file 1 [SP1.pdf] ### Patient 1 A 62-year-old man presented with headache and difficulty understanding spoken language in June 2014, following which he experienced a generalised seizure and was transferred to our hospital. Dark-red, mottled erythema was observed on the surface of his skin. High levels of protein and interleukin (IL)-6 were observed in the cerebrospinal fluid (CSF). MRI revealed a tumefactive lesion in the left temporo-occipital region on T1, gadolinium-enhanced, fluid-attenuated inversion recovery (FLAIR) sequences (figure 1A,B). Brain biopsy of the lesion demonstrated perivascular inflammation (figure 1C), while skin biopsy revealed mild …

Progressive multifocal leukoencephalopathy (PML) is a severe adverse event in patients with multiple sclerosis (MS) treated with natalizumab. Brain MRI can detect small PML lesions at an early disease stage.1 Therefore, MRI screening is recommended for patients at high risk of developing PML.2 Diagnosis of PML is confirmed by brain biopsy or detection of JC virus (JCV) DNA from cerebrospinal fluid (CSF).3 However, in spite of using ultrasensitive quantitative PCR (qPCR) protocols, patients with PML can be JCV DNA negative in CSF, hampering the diagnosis. Recently, we demonstrated that the detection of intrathecally produced anti-JCV IgG antibodies is highly specific for diagnosis of PML, making the so-called CSF JCV antibody index (AIJCV) a candidate tool for earlier diagnosing of PML in a proportion of natalizumab-associated PML patients.4 The aim of this study was to assess the value of the AIJCV in a case series of natalizumab-treated patients with MS undergoing enhanced MRI pharmacovigilance for PML. Natalizumab-treated MS patients screened for PML using MRI (T2, fluid attenuation inversion recovery (FLAIR), diffusion weighted imaging) at the VU University Medical Center Amsterdam, and referrals, were included in the study. Patients with MRI suspicion of PML and a serum/CSF pair for assessment of the AIJCV at time of first MRI suspicion of PML were eligible. JCV DNA by qPCR and the AIJCV in CSF were determined at the Institute of Virology, University of Dusseldorf, Germany, and methods and cut-points (1.5 for the AIJCV) were applied as recently described.4 The study was approved by the local institutional review board, and written informed consent was obtained from all participants. Basic characteristics of the patients included are provided in the online supplementary table. Median age was 46 years, and five of eight patients (63%) were female. Six …

An 8-year-old boy presented with fatigue, weakness and altered mental status necessitating intubation. Contrast-enhanced magnetic resonance imaging (MRI) of the brain revealed multifocal perivascular enhancement at the supratentorial juxtacortical white matter (figure 1A) and diffuse cerebellar leptomeningeal enhancement (figure 1B), suggestive of central nervous system (CNS) vasculitis versus infection versus acute disseminated encephalomyelitis (ADEM). Workup for infectious and autoimmune encephalitis was unremarkable. Methylprednisolone (20 mg/kg/day) was initiated for presumed ADEM. Brain biopsy, obtained due to continued deterioration in mental status, revealed extensive meningoencephalitis (figure 2A) and …

Amyloid-β (Aβ) is a peptide deposited in the brain parenchyma in Alzheimer’s disease and in the wall of small cortical and leptomeningeal vessels in cerebral amyloid angiopathy (CAA). Sporadic CAA is prevalent in an ageing population and is a major cause of intracerebral haemorrhage and dementia. There is evidence of Aβ transmission through medical procedures, such as injection of cadaver-derived growth hormone (GH) or cadaveric dura mater graft in humans, in the context of iatrogenic Creutzfeldt-Jakob disease (iCJD).1 Interestingly, there is increasing evidence to suggest that Aβ transmission may also occur in the absence of iCJD through neurosurgical procedures.2 3 This paper describes a case of early onset, pathologically proven CAA presenting with multiple symptomatic intracerebral haemorrhages occurring three decades after cardiac surgery involving a cadaveric dura mater patch. A young male with multiple intracerebral haemorrhages underwent an extensive multimodal evaluation including clinical examination, cerebral MRI, amyloid positron emission tomography using 18F-florbetapir, apolipoprotein E (APOE) genotype, genetic testing for mutations or duplication causing hereditary CAA (amyloid precursor protein (APP), gelsolin, transthyretin and cystatin 3) and neuropathological examination of a brain biopsy. Sporadic CAA was confirmed pathologically. Childhood exposure to cadaveric dura mater was suspected based on the surgical history for congenital heart disease, then confirmed. The patient’s informed consent was obtained. A man aged 34 years presented with multiple symptomatic lobar intracerebral haemorrhages. He had a medical history of transposition of the great arteries, requiring neonatal cardiac surgery with the Rashkind procedure. At 2 years of age, the patient underwent repeat surgery with a Senning …

Early brain biopsy may be indicated in HIV patients with focal brain lesion. This study aimed to evaluate and compare the safety and diagnostic value of brain biopsy in HIV patients in the pre-highly active antiretroviral therapy (HAART) versus post-HAART era via meta-analysis. Appropriate studies were identified per search criteria. The local database was retrospectively reviewed to select a similar patient cohort. Patient demographics, brain biopsy technique, histopathology and patient outcomes were extracted from each study. Study-specific outcomes were combined per random-effects model. Outcomes were compared between the pre-HAART and post-HAART era. Correlations between outcomes and baseline characteristics were assessed via meta-regression analysis. The proportions of histopathological diagnosis were tabulated and compared between the pre- and post-HAART era. Survival analysis was performed for patients in the post-HAART era. A total of 26 studies (including the local database) with 1209 patients were included in this meta-analysis. The most common indications for brain biopsy were diagnosis unlikely to be toxoplasmosis (n=8, 42.1%), focal brain lesion (n=5, 26.3%) or both (n=3, 15.8%). The weighted proportions for diagnostic success were 92% (95% CI 90.0% to 93.8%), change in management 57.7% (45.9% to 69.1%) and clinical improvement 36.6% (26.3% to 47.5%). Morbidity and mortality were 5.7% (3.6% to 8.3%) and 0.9% (0.3% to 1.9%), respectively. Diagnostic success rate was significantly higher in the post-HAART than the pre-HAART era (97.5% vs 91.9%, p=0.047). The odds ratio (OR) for diagnostic success in patients with contrast-enhanced lesions was 2.54 ((1.25 to 5.15), p

BackgroundConditions such as primary CNS lymphoma (PCNSL) or demyelinating/inflammatory diseases may present with similar clinical and neuroradiological features to gliomas. These ‘glioma mimics’ are commonly diagnosed with brain biopsy, but this is not always possible. We aim to optimize the contribution of less invasive investigations to the diagnostic pathway.MethodRetrospective review of the diagnostic process of glioma mimics between September to November 2018 in a tertiary Neuro–oncology unit.ResultsThe Neuro-oncology MDT gave 558 opinions excluding post –operative reviews. Twelve cases were identified as glioma mimics. 6/12 were new cases. Further investigations in five new cases took 2.5 – 11 weeks to complete. Two patients deteriorated during diagnostic workup and had expedited brain biopsies which confirmed PCNSL. One proceeded with chemotherapy and one was referred to palliative care.ConclusionDiagnostic tests prior to brain biopsy were not performed in all glioma mimic cases. This was because test results excluding brain biopsy were not available to start treatment before the patient deteriorated clinically. We anticipate that the frequency of glioma mimics will increase due to the greater use of immunomodulatory therapies. A dedicated protocol to achieve rapid diagnosis of glioma mimics is imperative to facilitate early, appropriate treatment.

IntroductionImmune-mediated encephalitis can occur in the absence of measurable pathogenic antibodies in CSF or serum.Methods and resultsWe present the case of a 29-year-old Sudanese woman presented with four days history of meningism. She is three months post-partum with her fifth child and does not have significant past medical history. She is a current smoker with history of methamphetamine and heroin use until 5 years ago. There were no focal neurological deficits on examination. CT brain was normal and her CSF had 420×106/L leucocytes (Polymorphs 18, Mononuclears 402). Three days later, she deteriorated clinically with GCS 11 and developed left sided hemiplegia requiring intubation and ventilation in intensive care.The CSF culture along with autoimmune encephalitis panel, anti-neuronal antibodies, HSV, VZV, Enterovirus, cryptococcal antigen, TB quantiferon, HIV, Malaria were negative. Her immunology tests were unremarkable including rheumatoid factor, complements, anti-nuclear antibodies, dsDNA, PR3, MPO, RNP, Smith, Ro, La, Scleroderma 70 and Jo-1 antibodies. The MRI Brain showed persistent changes in right hemispheric cortical and subcortical gyriform FLAIR hyperintensities which were also present in DWI images. The EEG showed right temporo-occipital region 7–8 Hz rhythmic discharges with generalised diffuse slowing. She had right parietal lobe brain biopsy which shows perivascular and intramural inflammation by mononuclear cells almost comprised of CD3 T-cells consistent with encephalitis associated with secondary lymphocytic vasculitis. She was treated with intravenous pulsed methylprednisolone and IVIg followed by plasma exchange. Then given high dose oral corticosteroids with slow tapering and intravenous Cyclophosphamide four weekly. Significant neurological improvement noted over next 8 weeks with patient being alert and participating in ongoing multidisciplinary rehabilitation for hemiplegia.ConclusionA case of cerebral biopsy confirmed, CSF and serum antibody-negative encephalitis is presented.

IntroductionParadoxical reactions (PRs) during treatment of neurotuberculosis are common but late-onset PRs after completion of anti-tuberculous treatment are reported very rarely. The management of late-onset PRs is challenging as excluding other diagnoses is difficult without invasive testing.MethodsTwo cases of late-onset PRs after treatment for neurotuberculosis are reported. The timing of onset, clinical and radiological features of these PRs are described and the diagnostic work up and outcomes after empiric immunosuppression reviewed.ResultsA 24-year-old woman presented with right-sided focal motor seizures 18 months after receiving anti-tuberculous treatment for neurotuberculosis. MRI showed enlargement of a previous left frontal tuberculoma with extensive oedema. A biopsy was not performed as the lesion involved eloquent brain and the patient declined a lumbar puncture. She was treated empirically with corticosteroids for six months and had clinical and radiological improvement.A 56-year-old woman presented with left leg weakness and numbness 20 years after treatment for multiple cerebral tuberculomas. MRI showed a new confluent area of T2 hyperintensity in the right frontal and parietal lobes. Cerebrospinal fluid was negative for acid-fast bacilli. She was treated with corticosteroids for 2 months with progressive improvement.ConclusionsLate onset PRs to neurotuberculosis can occur months to years after completing anti-tuberculous therapy. Recognising this entity is important so unnecessary treatments and brain biopsy may be avoided. Empiric immunosuppression with corticosteroids appears to be safe if early follow up and repeat imaging is arranged.

IntroductionGlial fibrillary acidic protein (GFAP) astrocytopathy is a lesser recognised immune-mediated meningo-encephalomyelitis, which is steroid responsive in the majority of cases. Neuroimaging is unique with a distinctive symmetric white matter perivascular linear and punctate enhancement pattern. We present a case with classical phenotype but delayed clinical response, and highlight the importance of early recognition and treatment.CaseA 59-year-old Caucasian female presented with a two month history of headache, gait disturbance, insomnia, agitation, disorientation and reduced oral intake. Examination revealed a high frequency upper limb tremor, hypertonicity and pathologically brisk reflexes with impaired cognitive function. MRI brain and spinal cord demonstrated high T2 signal and striking perivascular and punctate enhancement in supratentorial white matter, cervical and upper thoracic cord. CSF examination revealed lymphocytic pleocytosis and elevated protein. Brain biopsy demonstrated reduced GFAP expression, perivascular T-lymphocytic infiltrate, and recent white matter microinfarction. CSF and serum GFAP antibodies were positive.Motor deterioration accompanied progression to a stuporous state. High dose corticosteroids were commenced, followed by intravenous immunoglobulin and mycophenolate. While there was marked improvement of perivascular contrast enhancement on imaging, the patient continued to demonstrate prominent tremor, gait disturbance and behavioural issues 9 months following symptom onset.ConclusionsThe persistence of disability in this case is likely the result of axonal loss from the initial insult, reflected by the biopsy evidence of microinfarction. Awareness of the unique pattern on MRI and the clinical phenotype will aid in early recognition and prompt treatment of this condition, thus preventing the potential long term morbidity.

Gliomatosis cerebri is a rare malignant tumour originating from cerebral glial cells. Most experts currently view gliomatosis cerebri as a pattern of extensive glioma infiltration encompassing at least three cerebral lobes.1 It occurs at any age, with peak incidence between 40 years and 50 years and it is slightly more common in men.2 On MRI, gliomatosis cerebri shows no, or minimal, contrast enhancement; however, it has a diffuse hyperintense infiltrative process on T2-weighted fluid-attenuated inversion recovery (FLAIR) sequence. It is usually possible to diagnose gliomatosis cerebri using an open biopsy or a stereotactic biopsy. Despite treatment, its median survival varies from 6 months to 39 months.3 We report an unusual presentation of gliomatosis cerebri, which underscores the difficulty in pinpointing the correct diagnosis after corticosteroids have modified the disease course. A 78-year-old woman had an episode of acute onset slurred speech and confusion. Her initial CT scan of head showed diffuse left hemispherical white matter hypodensity with sulcal effacement and minimal midline shift to the right. Cerebrospinal fluid (CSF) examination suggested viral encephalitis for which she was empirically given intravenous dexamethasone and acyclovir, with oral levetiracetam 500 mg twice daily. After initially improving, she rapidly worsened with corticosteroid tapering. A repeat CT scan of head showed no change. She took dexamethasone 4 mg twice daily before undergoing a brain biopsy, which showed mild hypercellularity suspicious but not definitive for glioma. Two weeks later, we saw her for a second opinion. The MRI of …

Objective To investigate the association of apolipoprotein E ( APOE ) genotype, especially the APOE4 allele, to (1) idiopathic normal pressure hydrocephalus (iNPH) and (2) amyloid-β (Aβ) plaques in cortical brain biopsies of presumed NPH patients with and without a final clinical diagnosis of Alzheimer9s disease (AD). Methods 202 patients with presumed NPH were evaluated by intraventricular pressure monitoring and frontal cortical biopsy immunostained against Aβ (134 semiquantified by Aβ plaques/mm 2 ). The 202 patients and 687 cognitively healthy individuals were genotyped for APOE . The final clinical diagnoses in a median follow-up of 3.9 years were: 113 iNPH (94 shunt responsive, 16 shunt non-responsive, three not shunted); 36 AD (12 mixed iNPH + AD); 53 others. Results The APOE genotypes distributed similarly in the 94 shunt responsive and 16 non-responsive iNPH patients and healthy controls. In multivariate analysis, the APOE4 allele correlated independently with Aβ plaques in the cortical biopsies (OR 8.7, 95% CI 3.6 to 20, p APOE4 allele in presumed NPH predicted later AD as follows: sensitivity 61%; specificity 77%; positive predictive value 37%; negative predictive value 90%. Conclusion In presumed NPH patients, APOE4 associates independently with the presence of Aβ plaques in the frontal cortical biopsy. APOE4 is not a risk factor for iNPH and does not predict the response to shunt. Our data further support the view that the iNPH syndrome is a distinct dementing disease. Trial registration number Kuopio NPH Registry (http://www.uef.fi/nph)

ObjectivesStereotactic brain biopsy is among the most common neurosurgical procedures. Planning a safe surgical trajectory requires careful attention to a number of features including:traversing the skull perpendicularly;avoiding critical neurovascular structures; andminimising trajectory length.The aim of this study was to develop a platform, SurgiNav, for automated trajectory planning in stereotactic brain biopsy.MethodsA prospectively maintained database was searched between February and August 2017 to identify all adult patients that underwent stereotactic brain biopsy in whom post-operative imaging was available. In each case, the standard pre-operative T1-weighted gadolinium-enhanced MRI was used to generate models of the cortex and vasculature. A surgical trajectory was then generated using automated computer-assisted planning (CAP) and metrics compared to the trajectory of the implemented manual plan (MP) using the paired T-test.Results15 consecutive patients were identified; who had a diagnostic biopsy and there were no immediate complications. Feasible trajectories were generated using CAP in 12 patients, and in these the mean trajectory length using CAP was comparable to MP (31.7 mm vs. 37.1 mm; p=0.3), and mean angle was similarly perpendicular from orthogonal (9.3° vs. 15.3° p=0.1), but the risk-metric was significantly lower (0.16 vs. 0.48; p=0.03).ConclusionsComputer-assisted planning for stereotactic brain biopsy appears feasible in most cases and may be safer in selected cases.

ObjectivesStereotactic brain biopsy is an established neurosurgical procedure utilised in times of diagnostic or therapeutic uncertainty. Achieving a definitive tissue diagnosis allows tailored surgical, medical or oncological management. We present a 1 year case review of brain biopsies and compare suspected pre-operative diagnosis with final tissue outcome.DesignRetrospective analysis of all brain biopsies performed in 2017 in an adult-only neurosurgical unit.SubjectsAll patients undergoing brain biopsy.MethodsTheatre records were retrospectively analysed to identify patients undergoing brain biopsy in 2017. Further information was obtained using electronic patient records and radiology reports.Results41 patients underwent brain biopsy in 2017. Only 1 proved inconclusive and required repeat procedure. 26 patients had a suspected diagnosis documented pre-operatively based on radiological/clinical evidence. The most commonly suspected pathologies were low grade and high grade gliomas (9 and 15 patients). Of 25 patients with both a pre-operative differential and subsequent conclusive tissue diagnosis, 10 (40%) were ultimately given diagnoses which did not match the suspected pathology. Significantly, 1 biopsy diagnosed cerebral lymphoma.ConclusionsBrain biopsy is a relatively safe and simple neurosurgical procedure which can reliably provide a definitive tissue diagnosis. We have demonstrated how it remains a crucial component in formally establishing diagnosis prior to determining optimum management plans.

Susac's syndrome (SS) is the triad of encephalopathy, branch retinal artery occlusions and sensorineural hearing loss. While rare, it has become increasingly recognised since characteristic ‘snowball’ corpus callosum lesions were appreciated on MRI.1 We present clinical and histopathological findings on three patients with SS. Our findings demonstrate a T-cell-mediated inflammatory contribution to lesion pathogenesis. Treatment with the tumour necrosis factor (TNF) inhibitor, infliximab was beneficial in two patients, including in one previously reported,2 and in another who failed rituximab. This report provides a histological rationale for the observed benefit of infliximab, and suggests that infliximab should be considered as an adjunct therapy in patients with refractory SS. Three patients with SS most recently diagnosed among the authors’ practices who had undergone brain biopsy as part of their diagnostic clinical workup were identified. The clinical features, radiology, treatment and outcomes for the three patients are presented as online supplementary data (tables S1–S5 and figures S1 and S2). Extensive serum autoantibody screening was negative. Headache was present in all patients, highlighting the fact that it is a common manifestation of encephalopathy in SS. All three cases reported relatively non-specific auditory and visual symptoms, emphasising that fluorescein angiography±audiology testing should be considered in the diagnostic workup of patients with unexplained encephalopathy. Two patients underwent cerebellar biopsies and one a frontal lobe biopsy. One biopsy was from a treatment-naive patient (case 1). All contained variable numbers of wedge-shaped microinfarcts surrounded by microglia. In cerebellar biopsies (cases 1 and 3), …

A 58-year-old man with a history of recurrent aphthous ulcers since childhood was admitted to the hospital with acute neurological decline characterised by loss of motor dexterity, dysarthria, dysphagia and unsteady gait. MRI brain was significant for symmetrical hyperintense T2 fluid attenuated inversion recovery (FLAIR) in the corticospinal tracts, including parts of the pons and the mesodiencephalic junction. Though initial concern was for neuro-Behçet’s disease, brain biopsy ultimately revealed a diagnosis of astrocytoma. This report demonstrates a mimic of neuro-Behçet’s disease and the importance of confirming the correct diagnosis prior to initiating therapy.

We present a case of a 23-year-old man with history of fever followed by painless complete vision loss, with subsequent new-onset refractory status epilepticus (NORSE). He initially developed bilateral retinitis. A few days later, he started having focal seizures, and subsequently developed super-refractory status epilepticus, requiring anaesthetic agents. MRI brain revealed multifocal cortical and subcortical hyperintensities in occipital and temporoparietal regions without contrast enhancement. MRI repeated a month later showed new lesions with non-visualisation of some previous lesions. Finally, a brain biopsy was done which revealed presence of lymphocytic infiltrate with SV40 inclusions in oligodendrocyte. We propose the affliction of an atypical virus affecting the retina and brain grey and white matter, presenting with NORSE in our patient. Future similar cases and isolation of the virus may help in establishing the conclusive diagnosis.

A 57-year-old woman presented with several weeks of headache associated with neck stiffness, drowsiness and nausea. She developed diplopia with right-sided 6th nerve palsy and subsequently developed a complex ophthalmoplegia and right-sided ptosis.Repeated lumbar punctures showed high opening pressures of up to 60 cm H2O and high protein levels up to 2.48 g/L. She developed episodes of marked loss of responsiveness but EEGs showed only generalised slowing. Brain imaging was essentially normal. An MRI Spine showed an enhancing intramedullary hyperintensity T8-T10 with overlying meningeal enhancement. A CT-PET scan revealed uptake along the cord consistent with diffuse infiltration or a meningitis – biopsy was inconclusive but macroscopically the dura was thickened with calcification observed on the spinal cord surface. A brain biopsy did not aid diagnosis and unfortunately the patient deteriorated with increasing severity of headaches and drowsiness. She died after a number of cardiorespiratory arrests.At post-mortem, thickened meninges showed a glioneuronal cell infiltrate and a diagnosis of diffuse leptomeningeal glioneuronal tumour (DL-GNT). WHO recently described DL-GNT in the 2016 update of CNS tumour classification. Previous case reports of this rare disease have concerned adults and children. DL-GNT should be considered in cases of radiological leptomeningeal enhancement and high CSF protein levels.

BackgroundPACNS is a rare and heterogeneous disorder with many uncertainties regarding management and outcomes. Published adult UK series total just 20 patients.MethodHospital record search of an adult tertiary neurosciences centre identified 14 cases of PACNS from 1033 potential cases over 20 years.ResultsAll 14 cases were ‘definite’ by Calabrese Criteria (1988), confirmed by brain biopsy in 8/14 and by angiography in 6/14.The median age of onset was 52 years and most presented with focal deficits (86%), headache (36%) and cognitive change (29%). MRI showed multifocal deep white matter change in 86% and infarcts in 50%. Gadolinium enhancement was seen in 43%. Two patients had solitary ring-enhancing lesions and one patient had signs of cord ischaemia. CSF was abnormal in 90%.All patients received corticosteroids, 11/14 cyclophosphamide, 3/14 Mycophenolate Mofetil, 3/14 Methotrexate and 2/14 Azathioprine. At 13.3 months median follow-up, all but the two patients with solitary lesions remained on immunosuppression. Clinical relapses occurred in 30% and radiological relapse in one case despite immunosuppression.Only 62% had a favorable outcome (mRS 0–2). One patient died as a direct consequence of PACNS and one patient died due to co-morbidities.ConclusionPACNS remains a treatable neuroinflammatory disease with poor outcomes.

Mefloquine, an antimalarial medication with efficacy against JC virus, was used to treat progressive multifocal leukoencephalopathy. A 54-year-old woman with sarcoidosis presented with a progressive cerebellar syndrome. MRI showed lesions affecting the right cerebellum that progressed over time to the brainstem. JC virus was found in the cerebrospinal fluid (CSF), and brain biopsy confirmed the diagnosis of progressive multifocal leukoencephalopathy. Mefloquine 1000 mg/week was initiated 6 months after symptom onset. Clinical progression stopped immediately, and JC virus became undetectable in the CSF. No clinical or imaging evidence of disease progression has occurred over 20 months of follow-up. This is the first report of successful treatment of progressive multifocal leukoencephalopathy with mefloquine.

IntroductionWe present an unusual case of adult-onset leukoencephalopathy with neuroaxonal spheroids and pigmented glia (ALSP) mimicking systemic lupus erythematosus (SLE) cerebral vasculitis. ALSP is an autosomal dominant progressive leukodystrophy, associated with mutations in the CSF1R gene, which induce dysregulation of microglia. The case was compiled from records of clinical data, imaging, brain biopsy and genetic studies.CaseA 56 year old previously high functioning man of Southern Chinese origin was hospitalised with recurrent seizures. He had a prior 4 year history of progressive neuropsychiatric features, and 1 year of cognitive decline and occasional falls. Within the year prior, he had positive SLE serology and a renal biopsy consistent with lupus nephritis treated with steroids, mycophenolate, hydroxyl-chloroquine, and later rituximab due to concerns of evolving cerebral vasculitis on cerebral MRI and SPECT scan with MoCA of 20/30. Examination after seizure therapy revealed hyperreflexia, fine tremor, myoclonus, pseudobulbar affect, ideomotor apraxia and slow, independent gait. RUDAS was 6/30 with perseveration. CSF examination and SLE serology were quiescent. Consecutive brain MRIs showed multiple regions of worsening high T2/FLAIR signal in the corpus callosum and supra-tentorial white matter with persistent restricted diffusion. IV steroids and cyclophosphamide were added. Following treatment unresponsiveness, a frontal lobe brain biopsy demonstrated white matter gliosis with prominent axonal spheroids consistent with a primary leukoencephalopathy, with no inflammation, vasculitis nor infection. Immunotherapy was weaned. Genetic testing confirmed a positive CSF1R mutation (c.2329C>T; p. Arg777Trp in Exon 18). A positive family history of dementia in the patient’s elderly mother overseas was identified. The patient remained mobile but mute, and fatally aspirated 8 months after final presentation.ConclusionThis report illustrates an unusual presentation of ALSP, initially misdiagnosed as SLE vasculitis. Clinicians should consider an adult onset leukodystrophy and proceed to biopsy and CSF1R gene testing early in suspected ‘refractory cerebral vasculitis’.

IntroductionWe report a case of an isolated acute neuropsychiatric presentation due to rheumatoid meningitis (RM), successfully treated with steroids and rituximab.CaseA 41 year old man with a chronic headache and acute neuropsychiatric disturbance including impulsivity, grandiose delusions and agitation on a background of no known psychiatric history. Incidentally, he reported migratory palindromic, large and small joint polyarthritis over the preceding 18 months accompanied by headache, symptomatically treated with indomethacin. He had no prior diagnosis of rheumatoid arthritis (RA) or other connective tissue disorder. Serum and cerebrospinal fluid (CSF) cyclic citrullinated peptide antibodies were strongly positive, with a normal serum rheumatoid factor. An interferon-gamma release assay was positive, suggestive of prior tuberculosis (TB) exposure. CSF examination was unremarkable with an MRI brain demonstrating asymmetric features of leptomeningeal thickening and enhancement over both cerebral cortices, suggesting an inflammatory or infiltrative leptomeningitis. Lymphoma, IgG4–related disease, granulomatous diseases such as TB, granulomatosis with polyangiitis, neurosarcoidosis, neurosyphilis and meningeal metastasis were considered as differential diagnoses. A leptomeningeal and brain biopsy showed necrotising inflammation with ill-defined granulomas and a dense lymphoplasmacytic infiltrate. No organisms were identified. Mycobacterial polymerase chain reaction and cultures over three months were negative. RM was the favoured histological diagnosis. Empirical treatment for prior TB exposure was commenced in conjunction with steroids. Subsequent addition of iv rituximab resulted in sustained improvement of neuropsychiatric and joint symptoms.ConclusionThis report illustrates for the first time isolated acute neuropsychiatric disturbances attributable to RM without a prior history of RA that was responsive to rituximab. Clinicians should consider infiltrative and inflammatory leptomeningeal causes, particularly with asymmetric meningeal thickening and enchantment on MRI and should commit to a tissue biopsy when no other systemic connective tissue, infective or neoplastic causes are identified.

Objectives: To elucidate the importance of clinically diagnosed cerebral comorbidity in idiopathic normal-pressure hydrocephalus (INPH) and its effect on improvement after shunt surgery as well as concordance with parenchymal pathological changes described in frontal cerebral biopsy specimens. Methods: In 28 consecutive patients diagnosed with INPH and shunted according to clinical, radiological and cerebrospinal fluid dynamic criteria, concomitant disorders were carefully registered, with special emphasis on cerebrovascular disease (CVD) and possible Alzheimer’s disease. During shunt surgery, a frontal cerebral biopsy specimen was obtained and subsequently analysed for pathological changes. Results: One or several concurrent disorders were present in 89% of the patients, most often CVD (n = 17) and possible Alzheimer’s disease (n = 12), of which eight patients presented both, diagnosed according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association. The shunt success rate was 33%. A clear tendency towards increasing prevalence of CVD or Alzheimer’s disease was found in the subgroups with no improvement or clinical deterioration compared with the patients improving after shunt surgery. The presence of CVD tended towards an unfavourable shunt outcome. The pathological parenchymal changes reflected the clinical diagnoses of comorbidity, and were described in about half of the biopsy specimens, with Alzheimer’s disease (n = 7) and vascular changes (n = 7) being the most common findings. However, no significant correlation was found with the clinical diagnoses of Alzheimer’s disease and CVD. The presence of cerebral comorbidity, whether diagnosed clinically or by brain biopsy, did not preclude clinical improvement after shunt operation. Conclusions: A high prevalence of CVD and Alzheimer’s disease was found in patients shunted for INPH, which was reflected, although less commonly, by similar neuropathological biopsy findings. No significant correlation was found between the presence of comorbidity and shunt outcome. The findings support the perception of INPH as a multiaetiological clinical entity, possibly overlapping pathophysiologically with CVD and Alzheimer’s disease.

Craniometaphyseal dysplasia (CMD) is a rare condition characterised by progressive, diffuse hyperostosis of cranial and long bones, with compression of cranial nerves, linked to mutations in ANKH or GJA1 genes. Here we describe an adult case with clinical features of CMD, who developed cerebral expansive lesion of undetermined nature. Brain biopsy revealed active demyelinating lesions, consistent with multiple sclerosis. The genetic screening of target genes for CMD (ANKH and GJA1) resulted negative in this patient. The peculiar clinical association and the negativity of genetic analyses allow to hypothesise that other genetic causes, not already known, are responsible for the combination of these pathological conditions. Future studies aim to identify the genetic causes of CMD, which will be important to further understand the pathogenetic mechanism of this rare and invalidating disease.

Objective Histological evidence is considered the only proof of primary central nervous system vasculitis (PCNSV). However, brain biopsy is often omitted or delayed because of the invasiveness and possible complications of the procedure. Circulating endothelial cells (CEC) were shown to be elevated in patients with active antineutrophil cytoplasmic antibody-associated vasculitis. We hypothesise that CEC are also elevated in patients with active PCNSV and may contribute to the diagnosis. Methods CEC were assessed in 18 patients, 3 of whom had biopsy-proven PCNSV and 15 clinical, cerebrospinal fluid and imaging data, highly suggestive of PCNSV. In 3 of these 15 patients CEC assessment was performed after initiation of successful immunosuppressive therapy. CEC numbers of all patients were compared to those of 16 healthy volunteers and 123 subjects with cerebrovascular risk factors and/or ischaemic stroke, who had been studied in our group before. CEC were assessed by immunomagnetic isolation from peripheral blood. Results In patients with proven and suspected active PCNSV, CEC were extremely elevated (>400 cells/ml in most of the patients) and significantly higher than in healthy and disease controls (p≤0.01 for each group). CEC significantly decreased with immunosuppressive treatment. Conclusions For the first time it is shown that CEC are significantly elevated in patients with active PCNSV in contrast to other pathologies associated with brain infarction and correlate with disease activity. Sensitivity and specificity of the method for diagnosing PCNSV and the use of the method for treatment monitoring should be addressed in future prospective studies with a larger patient group.

Case A 21-year-old male immigrant from Afghanistan presented with seizures 2 years previously. MRI brain was suggestive of a possible low-grade glioma affecting the right temporal lobe. After 2 years, he re-presented with symptoms of headache, intermittent pyrexia, raised intracranial pressure (opening pressure of >42 cm/H2O) requiring ventriculoperitoneal shunt to preserve his vision. MRI head revealed slight progression in appearance within the right medial temporal lobe and extension into the right cerebral peduncle with enhancement of the basal meninges as well as 7th and 8th nerve complexes. CSF consistently showed two-digit lymphocytes, with raised protein and moderately reduced glucose ratio. Large CSF samples for cytology and flow-cytometry, Acid-Fast-Bacilli, and IgG subtypes remained negative. He had lymphopaenia. CT body/PET scans revealed no lymphadenopathy. Originally, tuberculosis was considered and quadruple anti-tuberculosis therapy was given along with oral Prednisolone. His first negative tuberculosis culture after 6 weeks coincided with increasing widespread leptomeningeal spread into the intradural spinal cord. Brain biopsy from the basal leptomeninges and temporal lobe confirmed anaplastic astrocytoma. Conclusion Anaplastic astrocytoma can present as aggressive and diffuse leptomeningeal brain and spinal disease mimicking CNS tuberculosis. Persistently negative Acid-Fast-Bacilli from the CSF samples should prompt consideration of less typical primary brain tumours.

A 70-year-old man with history of heart transplant performed in 1986, presented with altered mental status. CT scan of brain showed ring-enhancing lesions, raising suspicion for metastatic malignancy. Work-up revealed bilateral adrenal masses, biopsy showed granulomatous changes consistent with histoplasmosis. The possibility of histoplasmosis was less likely as the patient had no prior history of symptomatic disease and had lived in the endemic area 30 years prior to presentation. Brain biopsy confirmed central nervous system involvement. Amphotericin B was initiated for disseminated disease but his hospital course was complicated by renal failure and new liver hypodensities on follow-up imaging. Acute progressive disseminated histoplasmosis can manifest after decades of initial exposure and should always be in differential diagnosis even in non-endemic areas for prompt diagnosis and better clinical outcome.

Objectives We report an unusual presentation of reversible methotrexate (MTX) induced leukoencephalopathy due to a malfunctioning Ommaya reservoir. A subacute presentation of hemiplegia and encephalopathy alerted to the possibility of device malfunction. Expedited reservoir removal and corticosteroids resulted in neurological recovery. We hope to highlight the importance of considering MTX toxicity and Ommaya reservoir device malfunction in patients who receive intrathecal treatment. Methods A case report describes the evolution of leukoencephalopathy after an instillation of MTX through an Ommaya reservoir. Prior reports suggest direct chemotherapy toxicity from back flow of CSF along the catheter, due to obstruction or malfunctioning devices. Case A 67-year-old woman with breast cancer carcinomatous meningitis developed subacute onset left sided hemiplegia and impaired sensorium, three days after her last instillation of 12 mg MTX through an Ommaya reservoir. The device was inserted through the right frontal cortex and had four prior MTX instillations (45 mg MTX total) without any reported complications. There was no trauma to the device or changes in the chemotherapy administration protocols. MRI showed a 24 mm×16 mm×27 mm fluid collection in the right sub cortical matter with extensive white matter increased T2 signal change with sulcal and ventricular effacement. Prompt recognition warranted intravenous steroid administration and subsequent reservoir and catheter removal. CSF demonstrated aseptic meningitis. A brain biopsy demonstrated inflammatory changes with reactive gliosis and some haemorrhage. No evidence of malignancy. Testing of the removed Ommaya reservoir ex-vivo demonstrated a small leak from the underside of the reservoir, suggesting needle penetration through the base of the reservoir. The patient made a good clinical recovery and returned home. Conclusions This report illustrates an unusual presentation of reversible MTX leuknoencephalopathy due to Ommaya reservoir malfunction. Early clinical review and imaging post instillation of chemotherapy through the Ommaya reservoir maybe beneficial to detect early complications.

Objectives Neurosarcoidosis is a rare disorder with diverse clinical manifestations and a wide range of radiological features on MRI that make diagnosis challenging. Here we present a case of neurosarcoidosis with perivascular punctate enhancement on brain and spine MRI. Differential diagnosis of this characteristic radiological pattern are discussed. Case A 43 year old man presented with progressive cognitive decline and severe fatigue. Brain MRI demonstrated confluent white matter changes with punctate, perivascular gadolinium enhancement. Spine MRI showed increased signal intensity with punctate enhancement. A brain biopsy revealed a non-caseating granulomatous process related to blood vessels and the Virchow-Robin space, without necrosis, vascular destruction or any signs of vasculitis. Systemic sarcoidosis was excluded. Cyclophosphamide with steroids was effective. Conclusions Perivascular punctate enhancement on MRI has been described in a number of neurological conditions including chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS), isolated angiitis of the CNS, lymphoma, multiple sclerosis and natalizumab-associated progressive multifocal leukoencephalopathy. Although rare, it can also be observed in patients with neurosarcoidosis. Recognition of punctuate enhancement on brain or spine MRI should expedite further investigations and include work up for this condition. This case emphasises the inclusion of neurosarcoidosis in the differential diagnosis of perivascular punctate enhancement on brain and spine MRI. Enhancement is caused by perivascular granulomata and although rare, cerebrovascular sarcoidosis is a recognised entity.

Objectives A sarcoid-like pathological reaction has been well described to occur in response to germ cell tumours of the testes, most commonly seminoma. This reaction has been seen both within the testes and sites of metastatic disease including the lungs and lymph nodes. There are very few preceding reports of seminoma metastasising to the central nervous system (CNS) and no cases have been reported of a neurosarcoid-like reaction to such metastases, nor distant sarcoidal reaction beyond sites of tumour cell metastasis. Case A 29 year old male presented with seizures and an amnestic syndrome. CSF was inflammatory with raised mononuclear cells. MRI revealed left mesial temporal lobe and cerebellar peduncle hyperintensities. Investigations for viral and autoimmune limbic encephalitis were performed. Autoantibodies for limbic encephalitis were negative as was initial malignancy screen. The patient deteriorated despite treatment trials with steroids and intravenous immunoglobulin. Brain biopsy was performed and revealed non-necrotising epithelioid granulomas consistent with a histopathological diagnosis of neurosarcoidosis. A secondary screen for malignancy lead to a diagnosis of metastatic seminoma with involvement of the abdominal lymph nodes. There was no evidence of metastatic seminoma to the CNS on biopsy or non-invasive investigation. Conclusions This case represents the first description of neurosarcoidosis developing as an antigen driven paraneoplastic phenomenon in the context of metastatic seminoma with an absence of CNS metastatic disease.

Linear scleroderma "en coup de sabre" (LScs) is associated with neurological complications, the pathogenesis of which is uncertain. A 27 year old woman is reported on who developed epilepsy and focal neurological signs in association with LScs. Brain MRI demonstrated predominantly ipsilateral relapsing and remitting grey and white matter lesions. Analysis of CSF and pathology obtained at brain biopsy provides evidence of an inflammatory process which may be amenable to immunosuppressive treatment.

Toxoplasmic encephalitis associated with immune reconstitution inflammatory syndrome (TE-IRIS) is rarely described.To identify TE-IRIS cases, the authors performed a retrospective study of all HIV-infected patients diagnosed as having TE in our unit between January 2000 and June 2009, and a review of published cases.Three patients out of 65 toxoplasmic encephalitis (TE) cases, together with six from the literature, fulfilled the unmasking TE-IRIS definition. None fulfilled the paradoxical TE-IRIS definition. TE occurred within a median time of 48.5 days (IQ(25-75) 21-56) after starting antiretroviral therapy. Cases did not have distinctive clinical or neuroimaging features from TE occurring without immune reconstitution. However: (1) cases occurred at a median CD4 lymphocytes count of 222/μl (IQ(25-75) 160-280); (2) TE occurred in five patients who were supposed to take an effective chemoprophylaxis; (3) two patients had a brain biopsy showing an intense angiocentric inflammatory infiltrating with predominantly CD8 lymphocytes; (4) in one patient, the abnormal length of evolution under treatment might be due to the heightened immune response.Although rare, unmasking TE-IRIS exists and might occur despite effective prophylaxis and an unusually high CD4 lymphocyte count. Immune reconstitution inflammatory syndrome does not modify TE diagnosis and treatment but might extend its clinical course.

The clinical presentation and evolution, neuropathological findings, and genotyping of three members of a Spanish family affected with fatal familial insomnia are reported. The mother and two of her offspring developed a rapidly evolving disease with insomnia and behavioural disorders as the initial symptoms and died between 5 and 10 months after the onset of the illness. Frontal brain biopsy in the mother disclosed only non-significant spongiosis, and full neuropathological examination of her offspring showed thalamic and olivary degeneration with isolated focal cortical spongiosis. Genetic examination could only be performed in the contemporary patients and both harboured the prion protein (PrP) 178Asn mutation and homozygous 129 Met/Met genotype.

Creutzfeldt–Jakob disease (CJD) is a rapidly progressive, fatal and transmissible neurodegenerative disorder. The clinical features of typical CJD are progressive dementia, generalised myoclonus and, in the later stages, akinetic mutism. Characteristic findings in laboratory examinations include periodic sharp wave complexes (PSWCs) on electroencephalogram and elevated 14-3-3 protein in CSF. However, these tests cannot be applied to assessment of the progression of the lesion. Brain biopsy confirms the diagnosis of CJD but it does not reveal how the lesion develops in the brain. MR examinations are routinely performed in Japan for patients with suspected CJD. Diffusion weighted imaging (DWI) is now accepted as the most useful imaging modality for diagnosing patients with CJD, even in the early stages or without PSWCs.1 DWI demonstrates hyperintensity for lesions in the striatum and the cerebral cortex, with high sensitivity.2 However, the underlying pathomechanism of the abnormal signals remains unclear. Diffusion tensor imaging (DTI) is a new MR technique that can indirectly assess the integrity of tissue. The diffusivity and anisotropy of water molecular displacement are quantified by apparent diffusion coefficient (ADC) and fractional anisotropy (FA), respectively. To our knowledge, however, the utility of DTI in CJD has not been reported. Here …

OBJECTIVES: To compare the results of magnetic resonance imaging (MRI) and thallium-201 (201Tl) SPET scanning with laboratory analyses including CSF DNA detection, brain biopsy, and necropsy in the discrimination of cerebral lymphoma and toxoplasmosis in patients with AIDS. METHODS: A retrospective study of 32 patients infected with HIV who had focal CNS lesions on MRI as a result of either lymphoma or toxoplasmosis. RESULTS: 18 patients had lymphoma, 12 had toxoplasmosis, and two had both. Toxoplasma IgG antibodies were detected in only seven patients--four with toxoplasmosis, two with lymphoma, and one with both diagnoses. Epstein-Barr virus DNA was detected in CSF of all six patients with lymphoma and none of two with toxoplasmosis. MRI showed multiple lesions in 23 patients, appearances did not discriminate between lymphoma and toxoplasmosis; nine patients had single lesions, of these eight had lymphoma (p = 0.044, two tailed Fisher's exact test) 201Tl SPET showed accumulation in 17 with lymphoma and six with toxoplasmosis (p = 0.034, two tailed Fisher's exact test). Of nine patients with single lesions on MRI and 201Tl SPET with focal accumulation eight had lymphoma. 201Tl SPET uptake ratios of > or = 2.9 were only seen with lymphoma. CONCLUSION: Knowledge of patients' toxoplasma serostatus does not aid discrimination between lymphoma and toxoplasmosis. Single lesions on MRI with focal accumulation of 201Tl strongly suggest lymphoma. Multiple lesions on MRI with 201Tl SPET uptake ratios > or = 2.9 also suggest lymphoma; uptake ratios less than 2.1 do not aid discrimination. Detection of Epstein-Barr virus DNA in CSF is highly sensitive and specific for cerebral lymphoma.

A case is reported of idiopathic CD4+T lymphocytopenia with progressive multifocal leukoencephalopathy and cervical lymph node tuberculosis. A 57 year old Japanese man presented with cervical lymphadenopathy and progressive neurological deficits, and six months later he developed akinetic mutism. He had a persistent severely depressed number of circulating CD4+T lymphocytes in the absence of human immunodeficiency virus infection. T1 weighted MRI showed a diffuse decreased signal intensity limited to the white matter without mass effect. A brain biopsy specimen had a morphology similar to that of progressive multifocal leukoencephalopathy. Polyomavirus antigen was detected in the brain lesion, and viral DNA was identified in nucleated blood cells and urine. Unusually this serious medical condition has lasted for more than three years without remission. To our knowledge this is the first patient with CD4+T lymphocytopenia with progressive multifocal leukoencephalopathy, suggesting that similar opportunistic infections should be considered even in previously normal people.

The antemortem diagnosis of Balo's concentric sclerosis was made in a 52 year old woman with subacute right hemiparesis on the basis of brain MRI and stereotactic brain biopsy, which showed multiple ring-like lesions of lamellated demyelination alternating with spared white matter. Proton magnetic resonance spectroscopy (1H-MRS) was carried out one and nine months after the onset of illness. The first 1H-MRS showed a decreased N-acetyl aspartate peak, an increased choline peak, presence of large lipid peaks, and high resonance at 1.4 ppm. The second 1H-MRS disclosed changes such as a decrease of lipid signal, a decrease of resonance at 1.4 ppm, and an increase in the myoinositol peak. These findings are similar to those reported for multiple sclerosis. It seems that this is the first report of 1H-MRS findings in Balo's concentric sclerosis.

Objective Brain biopsy is an established procedure for the histological diagnosis of malignancy but its diagnostic role in cryptogenic neurological disease is less clear. This service evaluation reviews the procedure in a single centre (University Hospital Birmingham, UHB) by assessing indications, outcomes and complications in patients with neurological disease of uncertain aetiology. Methods We retrospectively identified patients referred for brain biopsy by neurology from 2005 to 2015. 19 patients were identified although 5 were excluded due to destroyed or missing notes. Results Histological report was definitive (n=8) or suggestive (n=2) in 10 of the 14 patients (71%) and non-diagnostic in 4 others (29%). The most common diagnosis was lymphoma in 3 patients (21.4%). Brain biopsy altered management in 64% (9/14) of patients. Importantly, there were no deaths or haemorrhage reported, and only 2 patients with documented headache reported after the procedure. Direct communication with neuropathology was documented in 1 case. Conclusions Few biopsies were undertaken for cryptogenic neurological disease in this time period, amounting to approximately 2 cases per year in our centre. However, management was changed in up to two-thirds of cases with no significant complications. Thus, brain biopsy is both safe and helpful in managing difficult neurological cases.

Introduction Progressive Multifocal Leukoencephalopathy (PML) is a rapidly progressive demyelinating disorder of the central nervous system, caused by reactivation of JC virus under conditions of cellular immunosuppression. Stereotactic brain biopsy provides a gold standard for diagnosis. Though PCR for the JC virus in the CSF is the method of first choice, the sensitivity is reported as only 74% to 82%, with specificity from 96% to 100%. Case presentation We report a 59-year old man with a previous history of biopsy-proven pulmonary fibrosis and 5 years of treatment with Azathioprine 75 mg per day and Prednisolone 5 mg daily, who presented with unusual symptoms of loss of colour vision over 6 months. His imaging was suggestive of PML, but JC virus PCR in the CSF was negative. However, brain biopsy confirmed the diagnosis of PML through histological evidence of demyelination and visualisation of viral inclusions. Despite terminating the immunosuppression, and treating with Cidofovir and Mirtazapine, the disease rapidly advanced and was fatal within a few months. Conclusion Patients with low dose immunosuppression are at risk of PML, and this diagnosis cannot be ruled out by a negative PCR for the JC virus in the CSF.

A 56-year-old man presented with evolving symptoms of left-sided weakness and fatigue over six months. Examination revealed spastic hemiparesis. MR brain imaging revealed confluent, oedematous white matter lesions in the right hemisphere without restricted diffusion or enhancement. Initial CSF analysis was unremarkable, including negative JC virus. Blood screen revealed a mild lymphopaenia. CT scanning of the viscera showed pulmonary changes which revealed, via transbronchial biopsy, non-caseating granulomata suggesting pulmonary sarcoidosis. High dose prednisolone was commenced following which the weakness improved. Methotrexate was initiated 3 weeks later, with the assumption the brain pathology was neurosarcoid. However, there then ensued a rapid deterioration with resurgence of left-sided weakness, difficulties within visuospatial, memory and executive cognitive domains and associated radiological progression. Urgent brain biopsy was arranged which showed numerous JC Virus particles within the parenchyma, consistent with progressive multifocal leukencephalopathy (PML). Repeat CSF analysis returned a now positive JC Virus PCR. Occult pulmonary sarcoidosis can be associated with immunoparesis and PML irrespective of immunosuppressive pharmacotherapy and necessitates a high index of suspicion.

Introduction Primary Central Nervous System Vasculitis (PCNSV) can be diagnosed using cerebral angiography and/or biopsy as gold-standard tests. Diagnostic criteria weight each equally but are unvalidated and limited sensitivity and specificity for both tests is recognised. A systematic literature review was undertaken to investigate the performance of diagnostic tests in cases of PCNSV. Methods We searched the OVID Medline database for original cases of PCNSV. We recorded information on diagnostic tests used and assessed agreement between angiography and biopsy as well as ancillary tests. Results 701 original cases of PCNSV were found. Only 248 cases (34%) had both angiography and brain biopsy performed in the same patient. Both tests showed classical vasculitis features in just 32 individual cases (5%). 74 cases with abnormal angiography had normal brain biopsy, while 99 patients with abnormal biopsies had normal cerebral angiography. Brain MRI and CSF were usually abnormal. Conclusion Cerebral angiography and biopsy were performed together in only a minority of published cases of PCNSV. When both were performed, conflicting results from each gold-standard test were much more likely than agreement. The diagnostic criteria for PCNSV require revision in order to classify it correctly and to exclude mimics.

Introduction Primary CNS angiitis is a challenging diagnosis to make. Without treatment it is relentlessly progressive and fatal. Case A 44 year old gentleman from Sierra Leone presented to A&E with a 4.5 hour history of left facial weakness and slurred speech. CT was normal and a diagnosis of minor stroke made. The patient was discharged on Clopidogrel and Simvastatin, with outpatient MRI. 2 weeks later the patient re-presented with a 3 day history of worsening left sided hemi-chorea. MRI revealed diffuse right hemisphere vasculopathy. Routine bloods, thrombophilia, infection and autoimmune screens were normal, as were carotid doppler9s, ECHO, CXR and CSF. 24 hr ECG revealed bursts of AF. The patient was diagnosed with paroxysmal AF and discharged with a follow up MRI, which revealed worsening vasculopathy. A brain biopsy was arranged, showing non-specific chronic inflammation with focal non-necrotising granulomatous vasculitis, confirming ‘Primary CNS Angiitis’. The patient was treated with Prednisolone and Cyclophosphamide, making a full recovery. Discussion Making this diagnosis is challenging, as brain imaging often shows non specific changes and blood results are usually normal. CSF may reveal raised proteins and WBCs. A high index of suspicion is required to arrange a brain biopsy as this confirms the diagnosis.

Case A 17 year old man presented with acute headache and bilateral abducens nerve palsies. CT scan revealed obstructive hydrocephalus caused by a third ventricular lesion. He was managed with a ventriculoperitoneal shunt and biopsies of the lesion were taken. Histologically, the lesion contained non-caseating epitheliod cell granulomas, suggestive of sarcoidosis. He was treated with high dose prednisolone and remained clinically well but follow up brain MRI revealed a significant increase in volume of the third ventricular lesion. Following unsuccessful investigations to find any evidence of systemic sarcoid, the patient underwent a second brain biopsy which confirmed the diagnosis of germinoma. Both the biopsies were done through a craniotomy and transcallosal dissection in order to have a good view of the abnormalities from within the ventricles and recover decent tissue samples that at least macroscopically were representative and large enough to try to prevent sampling error. The patient was then successfully treated with targeted radiotherapy, resulting in complete regression of the tumour. Discussion Non-caseating granulomas are the characteristic histological finding in sarcoidosis but are not specific for the disease. The differential diagnosis for non-caseating granulomas is wide and includes Germinoma. Neurologists should be aware of the association between non-caseating granulomas and germinoma, and should always be considered when granulomas are seen in the pineal gland, posterior third ventricle, suprasellar region and midline lesions because patients with germinoma do well with radiotherapy. Early recognition and appropriate management is associated with survival rates over 90%.

Introduction Cerebral amyloid angiopathy-related inflammation (CAA-I) is a rare neurological condition with significant morbidity and mortality. Here we present a case of CAA-I that demonstrates its varied clinical course. Case A 76-year-old woman presented with subacute headache. Further assessment revealed mild cognitive impairment and left quadrantanopia. Right hemisphere hyperdensity was observed on MRI FLAIR sequence suggesting inflammatory amyloid. Steroid treatment was commenced for probable CAA-I but was eventually discontinued due to severe side effects. Clinical improvement was noted and corroborated by re-imaging which demonstrated complete resolution of the inflammatory changes. Cognitive decline occurred again 8 months later. MRI showed right hemisphere hyperdensity with microbleeds on gradient echo, in keeping with a CAA-I relapse. She underwent brain biopsy which confirmed underlying CAA although no inflammatory cells were seen. Remarkably she subsequently improved clinically and radiologically without having undergone any medical treatment suggesting a spontaneous remission of her CAA-I. Discussion Despite criteria for non-invasive diagnosis of CAA-I, using clinical features and radiology (Chung criteria), brain biopsy is still sometimes required to make the diagnosis. Successful treatment can be achieved, particularly with corticosteroids. Our case not only highlights how patients can relapse off of treatment but also that spontaneous remission is possible.

Multiple subpial transection (MST) is a novel technique in surgery for epilepsy, employed in patients where some or all of the epileptogenic zone cannot be resected because it lies in a vital cortical area. Twenty one patients subjected to MST were reviewed. Eighteen patients had medically intractable epilepsy and three patients had Landau-Kleffner syndrome. Their ages ranged from 6 to 47 (mean 15-9) and duration of epilepsy ranged from 0.33 to 42 (mean 8.6) years. Preoperative MRI showed focal abnormalities in eight cases. Detailed electrophysiological examination was carried out on all patients. Brain resection was performed in addition to MST in 12 patients. A further six patients underwent brain biopsy. Three patients with Landau-Kleffner syndrome were subjected neither to resection nor to biopsy. Histopathological examination showed Rasmussen's syndrome in six patients, cortical dysplasia in six, cerebral tumour in one, and non-specific changes in five. Multiple subpial transection was carried out mainly in precentral and postcentral regions. Eighteen patients have been followed up for one to five years, and three for 10 months. The three patients with Landau-Kleffner syndrome were mute before operation and have shown substantial recovery of speech. Of the other 18, 11 showed a worthwhile decrease in seizure frequency. None of the patients developed chronic neurological deficits attributable to MST. It is concluded that MST leads to worthwhile seizure control without major neurological deficit in patients who would otherwise be inoperable.

The case is reported of a patient with central nervous system systemic lupus erythematosus (SLE) with features of progressive multifocal leucoencephalopathy (PML) seen clinically and by magnetic resonance imaging. A brain biopsy sample showed microinfarcts. The use of magnetic resonance imaging and IgG synthesis rates in evaluating central nervous system lupus, the co-occurrence of SLE and PML, and the differentiation of these entities by magnetic resonance imaging and by histology are considered.

A patient with isolated cerebral Whipple's disease presented with signs of raised intracranial pressure and multiple ring enhancing intracerebral mass lesions evident on CT and MRI imaging. Characteristic intracellular bacilliform inclusions were identified in a brain biopsy. Clinical improvement followed treatment with parenteral antibiotics for two weeks and long term sulphamethoxazole-trimethoprim. As CNS relapse of Whipple's disease may occur after several years, long term treatment should include antibiotics that are able to cross the blood-brain barrier.

A 49 year old white man was admitted after an episode of uncontrolled “twitching” of his left arm and hand that lasted 5–10 minutes. He reported difficulty in finding his words for a few days. Past medical history included three unexplained deep vein thromboses, therefore he was receiving long term warfarin. Clinical examination and limited laboratory tests were unremarkable and he was discharged the same day with no follow up. In the following days he gradually developed weakness of the right side of his body, headaches, nausea and increasing speech difficulties. He was readmitted four weeks later, after a sustained episode of “twitching” of the right arm, which on this occasion was correctly recognised to be a focal seizure. Systemic features such as malaise, fever or weight loss were absent and recent foreign travel was denied; 4/5 weakness of the right limbs, an expressive dysphasia and apathy were noted but no other psychiatric symptoms were present. Chest radiography was normal. Brain computed tomography showed an area of mixed attenuation in the left posterior frontal region extending into both the temporal and parietal region. There was mass effect with compression of the left anterior horn and slight bowing of the anterior midline structures to the right. These appearances suggested a left frontoparietal malignant tumour, probably a diffuse glioma. He was given carbamazepine 200 mg twice daily and dexamethasone 4 mg four times a day. Smear examination of a stereotactic brain biopsy from the left frontal lobe, rather than confirming a glioma, revealed a granulomatous inflammatory process and as tuberculosis could not be excluded, triple therapy was started (isoniazid, rifampicin, pyrazinamide) and samples sent for microbiology. Postoperative brain magnetic resonance imaging showed a diffuse swelling with ill defined enhancing abnormality in the left frontoparietal region. The appearances were unusual suggesting a granulomatous …

A 7.5 year old boy, known to have a seizure disorder, presented with an infarct in the left middle cerebral artery territory, 10 weeks after severe chickenpox. Immunofluorescent antibody titre to the varicella zoster virus in the cerebrospinal fluid was 1:32. Cerebral angiography showed evidence of focal vasculitis. He presented again seven months later with an acute exacerbation of seizures. Magnetic resonance imaging of the brain showed an old posterior extension of the infarct, but a repeated angiography demonstrated an improvement in the vasculitic process. Cerebrospinal fluid antibody titre was again 1:32. Although this may have been an unfortunate coincidence, a possible association between chickenpox and vasculitis, similar to that reported with herpes zoster, and with potentially significant clinical implications, should be considered. As a definite proof can be obtained only by a brain biopsy, however, which is generally not indicated in such cases, only additional clinical reports can lead to delineation of this association as a definite entity.