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A 64-year-old lady presented with a one-week history of subtle behavioural change and increased emo- tionality. She then suffered multiple focal seizures followed by a prolonged period of intense agitation and abnormal behaviour. She had no prior neurological or psychiatric history.An EEG demonstrated features of severe encephalopathy with bilateral occipital sharp-wave tran- sients. Levetiracetam was commenced and resulted in dramatic clinical and electrographic improve- ment. Detailed investigation to establish the underlying aetiology was negative. This included MRI head, CSF analysis, body CT and an extensive panel of autoantibody testing. She was discharged home after a period of observation.Two months later she re-attended with an almost identical presentation of acute behavioural change and focal seizures. When obtaining a collateral history from her husband, he reported that both admissions had been preceded by a course of eradication therapy for Helicobacter pylori, including clarithromycin.Clarithromycin-induced neurotoxicity is rarely reported and can manifest with psychiatric presentations, delirium, seizures and status epilepticus. The active metabolite, 14-hydroxyclarithromycin, is directly neurotoxic. Clarithromycin-induced allosteric modulation of GABA-A receptors with increased cellular excitability may be another reason for seizures.

The complement system is a powerful member of the innate immune system. It is highly adept at protecting against pathogens, but exists in a delicate balance between its protective functions and overactivity, which can result in autoimmune disease. A cascade of complement proteins that requires sequential activation, and numerous complement regulators, exists to regulate a proportionate response to pathogens. In spite of these mechanisms there is significant evidence for involvement of the complement system in driving the pathogenesis of variety of diseases including neuromyelitis optica spectrum disorders (NMOSD) and myasthenia gravis (MG). As an amplification cascade, there are an abundance of molecular targets that could be utilized for therapeutic intervention. Clinical trials assessing complement pathway inhibition in both these conditions have recently been completed and include the first randomized placebo-controlled trial in NMOSD showing positive results. This review aims to review and update the reader on the complement system and the evolution of complement-based therapeutics in these two disorders.

Antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) have been described in patients with neuromyelitis optica spectrum disorders (NMOSD) without aquaporin-4 antibodies (AQP4-IgG). We aimed to identify the proportion of AQP4-IgG-negative NMOSD patients who are seropositive for MOG-IgG. In a cross sectional study, we reviewed all patients seen in the National NMO clinic over the last 4 years (after the availability of MOG-IgG testing), including clinical information, MRI, and antibody tests. 261 unique patients were identified. 132 cases satisfied the 2015 NMOSD diagnostic criteria. Of these, 96 (73%) were AQP4-IgG positive and 36 (27%) were AQP4-IgG negative. These 36 patients were tested for MOG-IgG and 15/36 (42%) tested positive. 20% (25/125) of the patients who did not satisfy NMOSD criteria had MOG-IgG. Approximately half of seronegative NMOSD is MOG-Ig seropositive and one in five of non-NMOSD/non-MS demyelination is MOG-IgG positive. Since MOG-associated demyelinating disease is likely different from AQP4-IgG disease in terms of underlying disease mechanisms, relapse risk and possibly treatment, testing for MOG-IgG in patients with AQP4-IgG-negative NMOSD and other non-MS demyelination may have significant implications to management and clinical trials.

ObjectiveTo identify factors predictive of relapse risk and disability in myelin oligodendrocyte glycoprotein associated disease (MOGAD).SettingPatients were seen by the neuromyelitis optica spectrum disorders (NMOSD) service in Liverpool, UK, a national referral centre for adult patients with MOGAD, NMOSD and related conditions.ParticipantsPatients with MOGAD=76 from England, Northern Ireland and Scotland were included in this cohort study.ResultsRelapsing disease was observed in 55% (42/76) of cases. Steroid treatment >1 month (OR 0.2, 95% CI 0.05 to 0.80; p=0.022), transverse myelitis (TM) at first attack (OR 0.03, 95% CI 0.004 to 0.23; p=0.001) and male sex (OR 0.16, 95% CI 0.04 to 0.68; p=0.014) were associated with monophasic disease (area under the curve=0.85). Male sex (HR 0.46, 95% CI 0.24 to 0.89; p=0.011) and TM at disease onset (HR 0.42, 95% CI 0.22 to 0.82; p=0.011) were also associated with an increased latency to first relapse. 45% (32/71) of patients became MOG-antibody negative and in relapsing patients negative seroconversion was associated with a lower relapse risk (relative risk 0.11 95% CI 0.05 to 0.26; p<0.001). No specific factors were predictive of visual or overall disability.ConclusionsMale patients with spinal cord involvement at disease onset have a lower risk of relapsing disease and longer latency to first relapse. Steroid treatment for at least 1 month at first attack was also associated with a monophasic disease course. MOG-antibody negative seroconversion was associated with a lower risk of relapse and may help inform treatment decisions and duration.

Corticosteroids are established as the first-line treatment of progressive HTLV-1-associated myelopathy (HAM), but evidence to guide management of refractory cases is lacking. We present a case of subacute onset HAM, in which a marked improvement was seen following administration of second line pulsed IV cyclophosphamide. We are aware of only one previous case report of cyclophosphamide being used to treat HAM.A 57-year-old man of Jamaican descent presented with a 4-month history of progressive spastic para- paresis. At presentation, he was paraplegic with Medical Research Council (MRC) scores of 0-1 in all lower limb muscle groups. MR imaging revealed longitudinally extensive intramedullary T2-hyperintensity. Following positive serology, the diagnosis of HAM was confirmed by demonstration of a high CSF/blood ratio for HTLV-1 viral load in mononuclear cells. Intravenous methylprednisolone 1000mg daily was given for three days, followed by prednisolone 60mg daily for four weeks. MRC scores did not improve, so on week five pulsed intravenous cyclophosphamide was commenced (six 1.2g pulses given over 13 weeks), and prednisolone was tapered to 15mg daily. By week 18 MRC scores had improved to 4-5 and he could walk 20m with a Zimmer frame.

The evolution of neuromyelitis optica spectrum disorder (NMOSD) from a rare, incurable and misunderstood disease with almost universally poor outcomes to its present state in just over a decade is unprecedented in neurology and possibly in medicine. Our knowledge of NMOSD biology has led to the recognition of wider phenotypes, new disease mechanisms, and thus clinical trials of new and effective treatments. This article aims to update readers on the recent developments in NMOSD with particular emphasis on clinical advances, the 2015 diagnostic criteria, biomarkers, imaging, and therapeutic interventions.

Rituximab is a widely used B-cell-depleting monoclonal antibody. It is unlicensed for use in neurological disorders and there are no treatment guidelines. However, as a rapidly acting, targeted therapy with growing evidence of efficacy and tolerability in several neuroinflammatory disorders, it is an attractive alternative to conventional immunomodulatory medications. This practical review aims to explain the basic principles of B-cell depletion with therapeutic monoclonal antibodies. We present the evidence for using rituximab in neurological diseases, and describe the practical aspects of prescribing, including dosing, monitoring, safety, treatment failure and its use in special circumstances such as coexisting viral hepatitis, pregnancy and lactation. We provide an administration guide, checklist and patient information leaflet, which can be adapted for local use. Finally, we review the safety data of rituximab and ocrelizumab (a newer and recently licensed B-cell-depleting therapy for multiple sclerosis) and suggest monitoring and risk reduction strategies.

The original version of this article unfortunately contained a mistake. Fifth sentence of the fourth paragraph in the section “Non-nAChR autoantibody targets in MG” should read as

We describe a man with an intracranial dural arteriovenous fistula that presented as a subacute longitudinally extensive cervical myelopathy. The uncommon location of the fistula and the absence of specific radiological signs resulted in initial misdiagnosis as longitudinally extensive transverse myelitis. Neurologists should have a high index of suspicion for dural arteriovenous fistula in older men, especially those with subacute or chronic symptoms, acellular cerebrospinal fluid and, particularly, if there is neurological deterioration soon after corticosteroid treatment. Patients need early angiography to identify this treatable cause of myelopathy.