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Intravenous immunoglobulin (IVIg) has short and long-term efficacy in both chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy with conduction block (MMNCB). There is potential for under and over-treatment if trial regimens are strictly adhered to in clinical practice where titrating dose to clinical response is recommended. We report the response to high-dose IVIg (>2 g/kg/6 weeks) in a subgroup of patients with definite CIDP or MMNCB who were unresponsive to 'usual' dosing. IVIg frequency and dosing was determined for each individual by subjective and objective outcome measures for impairment, grip strength, and activity and participation. Six patients (three with chronic inflammatory demyelinating polyneuropathy (CIDP), three with MMN) were included. Two patients (one CIDP and one MMNCB) returned to full-time work on fractionated IVIg doses of 5 g/kg/month and 9 g/kg/month. Patient three (CIDP) failed numerous other immunosuppressants but responded to short-term fractionated 4 g/kg/month of IVIg. Patient four has severe, refractory, childhood-onset CIDP, remains stable but dependent currently on 6.9 g/kg/month of IVIg. Patients five and six, both with MMNCB, required short term 4.5–5 g/kg/month to recover significant bilateral hand strength. No IVIg-related adverse events occurred in any individual. These six cases demonstrate the safety and effectiveness of a treatment approach that includes individualised but evidence-based clinical assessment and, when necessary, high-doses of IVIg to restore patients' strength and ability to participate in activities of daily activities. Careful patient selection is important. [ABSTRACT FROM AUTHOR]

Regular immunoglobulin treatment maintains strength and prevents disability in chronic inflammatory demyelinating polyneuropathy (CIDP). Discrimination between active disease, with optimum symptom control on treatment, and disease in remission not requiring treatment is essential for therapeutic decision‐making and clinical trial design. To compare treatment cessation versus gradual dose reduction in assessment of disease activity (immunoglobulin dependence) in a cohort of stable CIDP patients on maintenance immunoglobulin treatment. An approach to restabilization of immunoglobulin‐dependent individuals is also described. Retrospective review of IVIg cessation or gradual reduction in 33 patients with stable CIDP on maintenance IVIg. Demographic, clinical and treatment data were collected; clinical monitoring data were recorded prospectively as part of routine clinical practice. A total of 21/33 patients (62.6%) were immunoglobulin dependent, (gradual dose reduction:11, cessation:10). Mean change in Inflammatory Rasch‐built Overall Disability Scale (I‐RODS) (−15, standard deviation [SD] 16) and Medical Research Council Sum Score (MRC‐SS) (−4, SD: 4) was clinically and statistically meaningful (>75% exceeded minimum clinically important differences). Mean time to deterioration was 5.0 (SD: 4.6) months, shorter in cessation group (3.5 months) than gradual reduction group (8.8 months). All patients were restabilized to previous baseline (M: 2.3, SD: 4.3 months), half within 1 week of retreatment. A total of 12 patients (37.4%) remained stable without treatment for ≥2 years (remission). A total of 50% were identified rapidly by cessation and 50% by gradual dose reduction requiring mean 4.8 (SD: 2.8) years follow‐up and costing £113 623 per person Ig spend. No predictors of disease activity were identified. A treatment cessation trial with close clinical monitoring is an efficient, cost‐effective and safe approach to assessing disease activity in CIDP. [ABSTRACT FROM AUTHOR]

Background: Neuroschistosomiasis is a severe complication of schistosomiasis, triggered by the local immune reaction to egg deposition, with spinal cord involvement the most well recognised form. Early treatment with praziquantel and high dose steroids leads to a reduction of neurological sequelae. The rarity of this condition in returning travellers to high income countries can result in delayed diagnosis and treatment. We aimed to evaluate the diagnosis and management of neuroschistosomiasis in a UK national referral centre. Materials/Methods: A retrospective review of confirmed clinical cases of spinal schistosomiasis referred to the Hospital for Tropical Diseases, UK, between January 2016 and January 2020 was undertaken. Electronic referral records were interrogated and patient demographic, clinical, laboratory, and radiological data collected. Results: Four cases of neuroschistosomiasis were identified. The median age at diagnosis was 28 (range 21 to 50) with three male patients. All patients had epidemiological risk factors for schistosomiasis based on travel history and freshwater exposure; two in Uganda (River Nile), one in Malawi and one in Nigeria. All patients presented with features of transverse myelitis including back pain, leg weakness, paraesthesia and urinary dysfunction. The mean time from presentation to health services to definitive treatment was 42.5 days (range 16–74 days). Diagnosis was confirmed with CSF serology for schistosomiasis in all cases. Radiological features on MRI spine included enhancement focused predominantly in the lower thoracic spinal cord in three cases and the conus in one patient. All patients received a minimum of three days of oral praziquantel and high dose steroids. At three-month follow-up, one patient had complete resolution of symptoms and three had residual deficit; one patient was left with urinary and faecal incontinence, another had urinary retention, and the final patient has persistent leg pains and constipation. Conclusion: We observed a marked delay in diagnosis of neuroschistosomiasis in a non-endemic country. We advocate undertaking a thorough travel history, early use of imaging and CSF schistosomal serology to ensure early diagnosis of neuroschistosomiasis in patients presenting with consistent symptoms. If schistosomal diagnostics are not immediately available, presumptive treatment under the guidance of a tropical medicine specialist should be considered to minimize the risk of residual disability. We advocate for consensus guidelines to be produced and reporting to be performed in a uniform way for patients with spinal schistosomiasis. Author summary: Schistosomiasis is a parasitic neglected tropical disease causing morbidity and mortality in several tropical regions. The most commonly described complications of schistosomiasis include urinary tract and gastrointestinal pathology. However, ectopic migration of parasitic worms and their eggs into the central nervous system can lead to profound and life altering disability. This phenomenon, referred to as 'Neuroschistosomiasis' is a rarely reported in non-endemic countries. However, occurrence is increasingly recognised in non-endemic regions due to the increase in global travel. We report the clinical and radiological characteristics of four patients who developed neuroschistosomiasis following tropical freshwater exposure. The report informs diagnosis of schistosomiasis, diagnostic features including subtle radiological findings typical of schistosomiasis, and management of neuroschistosomiasis. The report further highlights the delays in diagnosis of these patients, and the importance of travel history and seeking specialist parasitological advice when patients present with spinal cord syndromes following relevant exposures. [ABSTRACT FROM AUTHOR]

This series characterises nine patients with neurohistopathologically proven peripheral nerve neurolymphomatosis. A search of the hospital neuropathology database from 2002 to 2019 identified biopsy proven cases. Clinical data, investigation modalities, treatments, and outcomes were collated. Median age at neuropathy onset was 47 y, the neuropathy commonly as the initial lymphoma disease manifestation. Most (8/9) presented with painful asymmetrical sensory disturbance, with additional cranial nerve involvement in three. Neurophysiology typically demonstrated multiple axonal mononeuropathies. Cerebrospinal fluid protein was often raised (6/8). Magnetic resonance imaging suggested peripheral nerve infiltration in 6/9 and positron emission tomography CT in 4/9. Bone marrow biopsy was abnormal in 6/8. Treatment involved systemic or intrathecal chemotherapy and radiotherapy. Median survival was 23 mo. Neurolymphomatosis is a rare but important cause of neuropathy, particularly in those lacking systemic evidence of lymphoma as correct aggressive treatment can prolong survival. Nerve biopsy is essential to classify lymphoma type and rule out alternatives. [ABSTRACT FROM AUTHOR]

An elderly Caucasian man presented with a 10-month history of proximal myopathy and dysphagia. His serum creatine kinase (CK) was elevated at 877 U/L (normal 40-320) and electromyography confirmed a myopathic process. Blood and urine tests suggested myeloma; bone marrow examination showed 30% plasma cells and stained positive for amyloid. The muscle biopsy was initially reported as normal but in the light of the bone marrow report, the biopsy specimen was stained for amyloid, which was positive. We diagnosed systemic amyloidosis causing a myopathy and have started treatment for myeloma. [ABSTRACT FROM AUTHOR]

Neurological presentations are seen in about 1.5%-2.0% of returning travellers seeking medical attention, and may pose a particular challenge to diagnose and treat. These may be severe and life threatening, such as meningoencephalitic illnesses or inflammatory radiculoneuropathy (Guillain-Barré-like) syndromes requiring intensive care support. It is essential not to miss the potentially treatable and common diseases such as malaria, which can be lethal if undiagnosed. Herpes simplex virus remains the most common cause of encephalitis in returning travellers to the UK. Furthermore, common bacterial conditions such as pneumococcal meningitis may be associated with different resistance patterns globally, and this must be taken into account in treatment decisio.ns. This review provides a clinical approach, illustrated with a range of cases, and suggestions where to get further management advice. [ABSTRACT FROM AUTHOR]

Background Neurocysticercosis is the commonest infectious cause of epilepsy in endemic countries, and accounts for a greater number of cases worldwide than any other single pathology. Infection is associated with long-term exposure in low-income countries, although acquisition after travel has been recognized. The standard of care in the UK is inpatient treatment with anti-helminthic drugs and steroids. Methods The authors reviewed all cases of neurocysticercosis managed at the Hospital for Tropical Diseases in London, England, between 2001 and 2015. Active disease was defined as evidence of either viable cysts or involuting cysts with associated parenchymal inflammation. Results Of 26 active cases, 65.4% were migrants from nine different countries; 34.6% were UK-born travellers who had visited 19 countries across South and Central America, sub-Saharan Africa, South and South-east Asia; India was the commonest country of exposure in both groups. Only 73.1% presented with seizures; two diagnoses were made through brain imaging of patients with peripheral cysticerci; 53.8% had a single cyst. Migrants were more likely to be seropositive than travellers (p=0.033). Only two patients had seizures during admission, one of whom had multiple seizures prior to diagnosis. Conclusions Neurocysticercosis presents in a non-endemic setting in both migrants and travellers. Travellers are less likely to be sero-positive. Not all cases of neurocysticercosis present with seizures. Outpatient management could be considered for selected patients. [ABSTRACT FROM AUTHOR]

Autosomal recessive spastic ataxia of Charlevoix-Saguenay is a rare neurodegenerative disorder caused by mutations in the SACS gene. Thickened retinal nerve fibres visible on fundoscopy have previously been described in these patients; however, thickening of the retinal nerve fibre layer as demonstrated by optical coherence tomography appears to be a more sensitive and specific feature. To test this observation, we assessed 292 individuals (191 patients with ataxia and 101 control subjects) by peripapillary time-domain optical coherence tomography. The patients included 146 with a genetic diagnosis of ataxia (17 autosomal spastic ataxia of Charlevoix-Saguenay, 59 Friedreich's ataxia, 53 spinocerebellar ataxias, 17 other genetically confirmed ataxias) and 45 with cerebellar ataxia of unknown cause. The controls included 13 asymptomatic heterozygotes for SACS mutations and 88 unaffected controls. The cases with autosomal recessive spastic ataxia of Charlevoix-Saguenay included 11 previously unpublished SACS mutations, of which seven were nonsense and four missense mutations. Most patients were visually asymptomatic and had no previous history of ophthalmic complaints and normal or near normal visual test results. None had visual symptoms directly attributable to the retinal changes. Twelve of the 17 cases (70.6%) had thickened retinal nerve fibres visible on fundoscopy. All patients with autosomal recessive spastic ataxia of Charlevoix-Saguenay had thickening of the peripapillary retinal nerve fibre layer on optical coherence tomography, whereas all the remaining cases and controls except one showed normal or reduced average peripapillary retinal nerve fibre layer thickness on optical coherence tomography. We propose a cut-off value of 119 µm in average peripapillary retinal nerve fibre layer thickness, which provides a sensitivity of 100% and specificity of 99.4% amongst patients affected with ataxia. This is the largest cohort of patients with this condition to undergo systematic evaluation by optical coherence tomography. This is a useful tool in identifying cases of autosomal recessive spastic ataxia of Charlevoix-Saguenay from other causes of ataxia. Visualization of thickened retinal fibres by direct fundoscopy is less sensitive. We therefore advocate the use of this technique in the assessment of possible cases of this condition. [ABSTRACT FROM AUTHOR]

Objectives: To analyse and describe the clinical and genetic spectrum of Charcot-Marie-Tooth disease (CMT) caused by mutations in the neurofilament light polypeptide gene (NEFL).Methods: Combined analysis of newly identified patients with NEFL-related CMT and all previously reported cases from the literature.Results: Five new unrelated patients with CMT carrying the NEFL mutations P8R and N98S and the novel variant L311P were identified. Combined data from these cases and 62 kindreds from the literature revealed four common mutations (P8R, P22S, N98S and E396K) and three mutational hotspots accounting for 37 (55%) and 50 (75%) kindreds, respectively. Eight patients had de novo mutations. Loss of large-myelinated fibres was a uniform feature in a total of 21 sural nerve biopsies and 'onion bulb' formations and/or thin myelin sheaths were observed in 14 (67%) of them. The neurophysiological phenotype was broad but most patients with E90K and N98S had upper limb motor conduction velocities <38 m/s. Age of onset was ≤3 years in 25 cases. Pyramidal tract signs were described in 13 patients and 7 patients were initially diagnosed with or tested for inherited ataxia. Patients with E90K and N98S frequently presented before age 3 years and developed hearing loss or other neurological features including ataxia and/or cerebellar atrophy on brain MRI.Conclusions: NEFL-related CMT is clinically and genetically heterogeneous. Based on this study, however, we propose mutational hotspots and relevant clinical-genetic associations that may be helpful in the evaluation of NEFL sequence variants and the differential diagnosis with other forms of CMT. [ABSTRACT FROM AUTHOR]

A 60-year-old Nigerian man, who had lived in Europe for 30 years but had returned home frequently, presented with right frontalis muscle weakness and right ulnar nerve palsy, without skin lesions. Neurophysiology showed a generalised neuropathy with demyelinating features. Blood tests were positive for HIV, with a normal CD4 count. There was nerve thickening both clinically and on MRI. Nerve biopsy showed chronic endoneuritis and perineuritis (indicating leprosy) without visible mycobacteria. His neuropathy continued to deteriorate (lepra reaction) before starting treatment with WHO multidrug therapy, highly active antiretroviral therapy and corticosteroids. There are 10 new cases of leprosy diagnosed annually in the UK. Coinfection with HIV is rare but paradoxically does not usually adversely affect the outcome of leprosy or change treatment. However, permanent nerve damage in leprosy is common despite optimal therapy. Leprosy should be considered in patients from endemic areas who present with mononeuritis multiplex. [ABSTRACT FROM AUTHOR]

We present a diagnostically challenging case of a 61-year-old man presenting with progressive weakness and intermittent low-grade fever. [ABSTRACT FROM AUTHOR]

Compressive lesions of the spinal cord usually cause a syndrome of upper motor neurone weakness, spasticity and sensory loss below the level of the lesion. It has long been recognised that compressive cervical cord lesions may present as isolated lower motor neurone weakness of the upper limbs, a syndrome termed cervical spondylotic amyotrophy. We describe two patients presenting with isolated lower motor neurone weakness of the lower limbs in association with a compressive cord lesion at T11/12, a condition we have termed thoracic spondylotic amyotrophy. [ABSTRACT FROM AUTHOR]

Background: TRPV4 mutations have been identified in Charcot-Marie-Tooth type 2 (CMT2), scapuloperoneal spinal muscular atrophy and distal hereditary motor neuropathy (dHMN).Objective: We aimed to screen the TRPV4 gene in 422 British patients with inherited neuropathy for potentially pathogenic mutations.Methods: We sequenced TRPV4 coding regions and splice junctions in 271 patients with CMT2 and 151 patients with dHMN. Mutations were clinically and genetically characterised and screened in ≥345 matched controls.Results: 13 missense and nonsense variants were identified, of which five were novel and absent from controls (G20R, E218K, N302Y, Y567X and T701I). N302Y and T701I mutations were present in typical CMT2 cases and are potentially pathogenic based on in silico analyses. G20R was detected in a patient with dHMN and her asymptomatic father and is possibly pathogenic with variable expressivity. The Y567X variant segregated with disease in a family with severe CMT2 but also with a MFN2 mutation reported to cause a mild CMT2 phenotype. Although Y567X caused nonsense mediated mRNA decay, the amount of TRPV4 protein on western blotting of patient lymphoblasts was no different to control. Y567X is therefore unlikely to be pathogenic. E218K is unlikely to be pathogenic based on segregation.Conclusions: In this comprehensive analysis of the TRPV4 gene, we identified mutations in <1% of patients with CMT2/dHMN. We found that TRPV4 likely harbours many missense and nonsense non-pathogenic variants that should be analysed in detail to prove pathogenicity before results are given to patients. [ABSTRACT FROM AUTHOR]

The article discusses the author's experience during his visit in Beira, Mozambique, where he had been teaching neurology at the medical faculty of the Universidade Catolica de Mocambique. The author shared that the medical school where he was teaching was set up in 2000 to remedy the desperate shortage of doctors in the country. He stressed that his visit in the place had been fun and seem to have been appreciated.

A sample of 26 HIV seronegative, 59 HIV seropositive asymptomatic and 7 HIV seropositive symptomatic homosexual and bisexual men were assessed over two visits, a mean of 11 months apart, using the BDI, STAI, and CIS. Significant differences emerged between the symptomatic group and the other two groups. Past psychiatric history and the somatic items in the assessments accounted for some of these differences. The seropositive asymptomatic and the seronegative groups did not differ on any of the mood or psychiatric assessments, suggesting minimal effect on psychological well-being of seroconversion in the absence of symptoms. [ABSTRACT FROM AUTHOR]