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Isolated left ventricular non-compaction (ILVNC) is a rare congenital cardiomyopathy and is associated with arrhythmias, heart failure and thromboembolism including ischaemic stroke. Pregnancy is a relative contraindication to thrombolysis for acute ischaemic stroke, although case reports suggest the treatment can be given in selected cases. We report a case of recurrent cryptogenic strokes in a 36-year-old female who was thrombolysed with good outcome at 37 weeks’ gestation and was eventually found to have ILVNC as the cause. She had a predilection to recurrent posterior circulatory strokes due to foetal posterior communicating arteries. To our knowledge this is the first case report of safe thrombolysis for acute ischaemic stroke in pregnancy caused by ILVNC.

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare prion disease that causes rapidly progressive fatal neurodegeneration. The rarer Heidenhain variant of sCJD presents with visual symptoms and is rarely reported in the literature from sub-Saharan Africa. We report the case of a 57-year-old male with a three-week history of losing direction when driving home and visual hallucinations described as seeing rainbows. Magnetic resonance imaging (MRI) of the brain revealed unilateral parieto-occipital sulcal hyperintensities with restriction on diffusion-weighted imaging (DWI), and electroencephalography (EEG) showed right para-central slowing leading to an initial diagnosis of non-convulsive status epilepticus. He was treated with anti-epileptic medication but was re-admitted less than a month later with worsening spatial memory, aggression, ataxia, dysarthria, myoclonic jerks and a positive startle response, later developing generalised tonic-clonic seizures. Repeat MRI brain scan showed widespread posterior-predominant sulcal DWI restriction in a cortical ribboning pattern pathognomonic for sCJD. EEG showed diffuse slowing, and cerebrospinal fluid was analyzed for abnormal prion protein using real-time quaking-induced conversion but was inconclusive due to suboptimal sample collection. The patient fulfilled the diagnostic criteria for probable sCJD, Heidenhain variant; the family declined brain biopsy for definitive diagnosis. He was subsequently palliated at a local hospice where he died approximately three months after the onset of symptoms. Our case highlights the presence of a rare form of sCJD, and the diagnostic challenges faced in our resource-limited setting.

Chronic headache can be a presenting manifestation of Takayasu arteritis, although patients usually have other characteristic features. A thorough clinical assessment remains key in the evaluation of chronic headache., Careful history taking and physical examination are invaluable in diagnosis of secondary causes of chronic headache.

In a patient with Collet‐Sicard syndrome and multiple myeloma, both extramedullary plasmacytomas and internal jugular vein‐sigmoid sinus thrombosis should be considered as they can coexist.

Background\ud Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency.\ud \ud Methods\ud In this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544.\ud \ud Findings\ud Between Jan 16, 2015, and May 31, 2017, we randomly assigned 368 patients to receive CBT plus standardised medical care (n=186) or standardised medical care alone (n=182); of whom 313 had primary outcome data at 12 months (156 [84%] of 186 patients in the CBT plus standardised medical care group and 157 [86%] of 182 patients in the standardised medical care group). At 12 months, no significant difference in monthly dissociative seizure frequency was identified between the groups (median 4 seizures [IQR 0–20] in the CBT plus standardised medical care group vs 7 seizures [1–35] in the standardised medical care group; estimated incidence rate ratio [IRR] 0·78 [95% CI 0·56–1·09]; p=0·144). Dissociative seizures were rated as less bothersome in the CBT plus standardised medical care group than the standardised medical care group (estimated mean difference −0·53 [95% CI −0·97 to −0·08]; p=0·020). The CBT plus standardised medical care group had a longer period of dissociative seizure freedom in the previous 6 months (estimated IRR 1·64 [95% CI 1·22 to 2·20]; p=0·001), reported better health-related quality of life on the EuroQoL-5 Dimensions-5 Level Health Today visual analogue scale (estimated mean difference 6·16 [95% CI 1·48 to 10·84]; p=0·010), less impairment in psychosocial functioning on the Work and Social Adjustment Scale (estimated mean difference −4·12 [95% CI −6·35 to −1·89]; p

Phenytoin is one of the most commonly used anticonvulsants in the developing world, but lack of monitoring and concurrent medications can easily lead to toxicity. We report the case of a 35-year-old female on phenytoin for symptomatic epilepsy due to previously treated glioblastoma multiforme, who presented with status epilepticus 1 week after being treated for a urinary tract infection. She was loaded with phenytoin and levetiracetam as per emergency protocol but had a persistently low level of consciousness, and her preloading phenytoin level result came back in the toxic range. She was managed conservatively, but after 4 days with no change she was dialyzed and her level of consciousness improved within 24 h, allowing for safe discharge home shortly after. Our case illustrates the option of haemodialysis in phenytoin-toxic patients who do not improve with conservative measures or who may need urgent reduction due to potentially fatal complications of phenytoin toxicity.

Background Neuromyelitis optica spectrum disorder (NMOSD) is an auto-immune disease of the central nervous system (CNS) associated with the IgG-antibody against aquaporin-4 (AQP4-IgG). There is little published epidemiology of NMOSD from sub-Saharan Africa (SSA). Methods We retrospectively collated NMOSD cases admitted to our tertiary regional neurology centre. Results We identified 11 cases (10 female, average age 30 years). 64% (7/11) were seropositive for AQP4-IgG, measured using indirect immunofluorescence. The remaining cases could either not afford tests, or had pathognomonic radiological features. 57% (4/7) of seropositive cases had concurrent/recent CNS infection. All patients were treated with high-dose intravenous methylprednisolone (IVMP), and 36% (4/11) also had plasma exchange. Only 55% (6/11) of the patients were seen by a neurologist at presentation: they had less relapses (1.3 vs 2.4), less diagnostic delay (2.3 vs 7.4 months), and were less disabled at the end of our review period. 10 cases were immunosuppressed long-term: 60% on mycophenolate, 30% azathioprine, and one on rituximab. Conclusion Our study is the largest case series of NMOSD from the East Africa region. Patients faced challenges of access to appropriate and affordable testing, and timely availability of a neurologist at onset, which had impacts on their functional outcomes. The majority of the seropositive cases had recent/concurrent CNS infections, suggesting triggered auto-immunity., Highlights • This is the largest case series of NMOSD from the East Africa region. • Early involvement of neurologists translated to early diagnoses and better outcomes. • There remain challenges in accessing appropriate diagnostics for NMOSD. • Half the seropositive cases had recent infections, suggesting triggered auto-immunity.

When an unidentified patient who cannot communicate presents with symptoms and signs suggesting an acute stroke, the decision to thrombolyse is a particular challenge. In a time-pressured environment, clinicians need clear thought processes for diagnosis and treatment. Ethical considerations, diagnosis, identity and previous history, contraindications, time of symptom onset (EDICT) can help decision-making in this situation.

The diagnostic distinction between epilepsy and psychogenic nonepileptic seizures (PNES) can be challenging. Previous studies have demonstrated that experts in conversation analysis can identify linguistic and interactional features in transcripts and recordings of interviews with patients that reliably distinguish between epilepsy and PNES. In this study, ten senior neurology trainees took part in a one-day intervention workshop about linguistic and interactional differences in the conversation behavior of patients with epilepsy and those with PNES. Participants were familiarized with a 12-item questionnaire designed to capture their conversational observations immediately after talking to a patient with seizures. After the intervention, 55 initial outpatient visits of patients referred to seizure clinics were video and audio recorded. All medical diagnoses were confirmed two years after initial presentation on the basis of a chart review (including MRI and EEG findings) by a fully trained epilepsy expert. Postvisit questionnaires relating to patients confirmed to have epilepsy (n=20) or PNES (n=13) were analyzed. Doctors' mean responses to 6 of the 12 questions about linguistic and interactional observations differed significantly between the groups with epilepsy and PNES. Receiver operating curve analysis showed that a summation scale based on items demonstrating significant between-group differences correctly classified 81.8% of patients as having epilepsy or PNES. This study shows that a brief Conversation Analytic teaching intervention can enable neurologists to identify linguistic and interactional features supporting the differentiation of epilepsy and PNES as they take their patients' history in routine seizure clinic consultations, potentially improving diagnostic accuracy.

Astrocytes are key players in the progression of amyotrophic lateral sclerosis (ALS). Previously, gene expression profiling of astrocytes from the pre-symptomatic stage of the SOD1G93A model of ALS has revealed reduced lactate metabolism and altered trophic support. Here, we have performed microarray analysis of symptomatic and late-stage disease astrocytes isolated by laser capture microdissection (LCM) from the lumbar spinal cord of the SOD1G93A mouse to complete the picture of astrocyte behaviour throughout the disease course. Astrocytes at symptomatic and late-stage disease show a distinct up-regulation of transcripts defining a reactive phenotype, such as those involved in the lysosome and phagocytic pathways. Functional analysis of hexosaminidase B enzyme activity in the spinal cord and of astrocyte phagocytic ability has demonstrated a significant increase in lysosomal enzyme activity and phagocytic activity in SOD1G93A vs. littermate controls, validating the findings of the microarray study. In addition to the increased reactivity seen at both stages, astrocytes from late-stage disease showed decreased expression of many transcripts involved in cholesterol homeostasis and decreased cholesterol synthesis has been confirmed in vitro. Staining for the master regulator of cholesterol synthesis, SREBP2, has revealed an increased localisation to the cytoplasm of motor neurons in late-stage SOD1G93A spinal cord, indicating that motor neurons may attempt to synthesise their own cholesterol in response to decreased astrocytic cholesterol provision. Our data reveal that SOD1G93A astrocytes are characterised more by a loss of supportive function than a toxic phenotype during ALS disease progression and future studies should focus upon restorative therapies.

In schizophrenia, auditory verbal hallucinations (AVHs) are likely to be perceived as gender-specific. Given that functional neuro-imaging correlates of AVHs involve multiple brain regions principally including auditory cortex, it is likely that those brain regions responsible for attribution of gender to speech are invoked during AVHs. We used functional magnetic resonance imaging (fMRI) and a paradigm utilising 'gender-apparent' (unaltered) and 'gender-ambiguous' (pitch-scaled) male and female voice stimuli to test the hypothesis that male and female voices activate distinct brain areas during gender attribution. The perception of female voices, when compared with male voices, affected greater activation of the right anterior superior temporal gyrus, near the superior temporal sulcus. Similarly, male voice perception activated the mesio-parietal precuneus area. These different gender associations could not be explained by either simple pitch perception or behavioural response because the activations that we observed were conjointly activated by both 'gender-apparent' and 'gender-ambiguous' voices. The results of this study demonstrate that, in the male brain, the perception of male and female voices activates distinct brain regions.

Navigating the online galaxy for up-to-date evidence-based knowledge in clinical neurology can be a challenge. Practical Neurology is a noted and popular online clinical resource,1 which according to its website is "…practical in the sense of being useful for everyone who sees neurological patients and who want to keep up to date, and safe, in managing them." As UK-based neurology trainees, we have been fortunate to have automatic access to Practical Neurology during our training. We found that the articles adequately covered most elements in our syllabus and were ideal reference material for our department. This accords with the recent readership survey: for almost 80% of readers, the journal impacts positively on their clinical work, contains reliable information and reflects real-life clinical neurology practice.2 Therein lay an opportunity to address the challenge of how to navigate online resources for high-standard reference material: that is, by using Practical Neurology as a standard knowledge base. We set about arranging all the articles from the …

Multiple sclerosis (MS) may run a rapidly progressive monophasic course (the Marburg, or malignant form), that carries a poor prognosis [1]. Autologous hematopoietic stem cell transplant (AHSCT), initially utilised in chronic MS [2], is now occasionally administered in acute aggressive relapsing–remitting MS (RRMS) [3]. We describe a case of malignant-type MS treated with pulsed cyclophosphamide (CY) and non-myeloablative AHSCT. A 21-year-old woman, presented with sensorimotor disturbance to all four limbs in April 2011. Neuro-imaging demonstrated demyelination with enhancement (Fig. 1a), cerebrospinal fluid (CSF) demonstrated 47 lymphocytes and was positive for oligoclonal bands. Serum was negative for aquporin4 (Aq4) antibodies. Three days of 1 g IV methylprednisolone (IVMP) failed to slow progression. A second course of IVMP 5 weeks later was unsuccessful, as were seven sessions of plasma exchange undertaken over a 2-week period and the patient became tetraplegic. A 5-day course of alemtuzumab with pulsed IVMP was completed (week 9) but deterioration continued with decreased visual acuity (right eye: counting fingers, left eye: 6/36), vertigo and respiratory compromise requiring ventilatory support. MRI demonstrated new lesions (Fig. 1b). Repeat CSF revealed 10 lymphocytes and Aq4 was negative in serum and CSF. Alemtuzumab can take up to 3 months to take effect, however, in July 2011 (13 weeks after presentation) treatment was intensified due to continued decline and stem cells mobilised with CY 2 g/m plus G-CSF (10 lg/kg/day). Stem cell harvest was undertaken 2 weeks later. A second dose of CY (2 g/m) 4 weeks poststem cell harvest was followed by improvement—return of sensorimotor function to the left arm, cessation of vertigo and weaning from ventilatory support. Two months after first treatment with CY the patient underwent AHSCT using CY 200 mg/kg ? rabbit antithymocyte globulin (ATG, total dose 6 mg/kg). At this point she had an Expanded Disability Status Score (EDSS) of 8.5. Routine toxicity, including neutropenic sepsis, was managed and engraftment prompt. Four months from AHSCT, she could walk a few steps using parallel bars and had visual acuities of 6/24 (right) and 6/9 (left); EDSS 7.5. Repeat MRI demonstrated a stable lesion load (Fig. 1c). One year from the initiation of treatment with CY (8 months from AHSCT) she was able to walk 10 M with bilateral support, EDSS 6.5. Further imaging demonstrated no change. EBMT guidance [4] advises that patients with an EDSS score higher than 6.5 be excluded from AHSCT, except in instances of ‘malignant’ MS. Our patient had a rapid-onset demyelinating illness that we have termed malignant MS. We cannot exclude neuromyelitis optica (NMO), although Aq4 antibodies were consistently negative, including in CSF. In such cases, the distinction between MS, NMO and J. J. P. Alix (&) D. J. Blackburn B. Sharrack Sheffield Institute for Translational Neuroscience, University of Sheffield, 385A Glossop Road, Sheffield S10 2HQ, UK e-mail: j.alix@sheffield.ac.uk

Discerning a speaker's gender from their voice is a basic and crucial aspect of human communication. Voice pitch height, the perceptual correlate of fundamental frequency, is higher in females and provides a cue for gender discrimination. However, male and female voices are also differentiated by multiple other spectral and temporal characteristics, including mean formant frequency and spectral flux. The robust perceptual segregation of male and female voices is thought to result from processing the combination of discriminating features, which in neural terms may correspond to early sound object analysis occurring in non-primary auditory cortex. However, the specific mechanism for gender perception has been unclear. Here, using functional magnetic resonance imaging, we show that discrete sites in non-primary auditory cortex are differentially activated by male and female voices, with female voices consistently evoking greater activation in the upper bank of the superior temporal sulcus and posterior superior temporal plane. This finding was observed at the individual subject-level in all 24 subjects. The neural response was highly specific: no auditory regions were more activated by male than female voices. Further, the activation associated with female voices was 1) larger than can be accounted for by a sole effect of fundamental frequency, 2) not due to psychological attribution of female gender and 3) unaffected by listener gender. These results demonstrate that male and female voices are represented as distinct auditory objects in the human brain, with the mechanism for gender discrimination being a gender-dependent activation-level cue in non-primary auditory cortex.

BACKGROUND: UK National Guidelines (UKNG) advise HIV testing in clinically indicated neurological presentations. We audited the impact of our practical strategies to increase uptake of HIV testing at a regional acute neurology admissions unit. METHODS: We audited HIV testing in 4 periods over 2 years: before we designed a UKNG-based "HIV testing in Neurology" protocol ("pre-protocol"); after dissemination of the protocol alone ("post-protocol"); post-protocol dissemination combined with both a tailored departmental admissions clerking proforma to prompt for HIV testing & consenting, and regular focussed tutorials to doctors on HIV testing in neurological patients ("post-proforma"); and finally one year after the post-proforma period ("+1 year"). We also looked at the total number of HIV tests sent from the unit during the two-year period. We assessed significance using Fisher's exact test. RESULTS: 47.8% of all acute neurology non-stroke admissions were eligible for HIV testing during all the audit periods. Testing rates were as follows: pre-protocol 21.9%; post-protocol 36.6%; post-proforma 83.3%; and at +1 year 65.4% (p