Novel genetic variant in hereditary spastic paraparesis.

A man in his 30s was referred to neurology with right-sided paraesthesia, tremors, chest pain and lower urinary tract and erectile dysfunction. He had a medical history of left acetabular dysplasia, and subjective memory impairment, the latter being in the context of depression and chronic pain with opioid use. There was no notable family history. On examination, he had a spastic paraparesis. Imaging revealed atrophy of the thoracic spine. Lumbar puncture demonstrated a raised protein but other constituents were normal, including no presence of oligoclonal bands. Genetic testing revealed a novel heterozygous likely pathogenic SPAST variant c. 1643A>T p.(Asp548Val), confirming the diagnosis of hereditary spastic paraparesis. Symptomatic treatment with physiotherapy and antispasmodic therapy was initiated. This is the first study reporting a patient with this SPAST variant. Ensembl variant effect predictor was used, with the application of computational variant prediction tools providing support that the variant we have identified is likely deleterious and damaging. Our variant CADD score was high, indicating that our identified variant was a highly deleterious substitution.

Acute Inflammatory Diseases of the Central Nervous System After SARS-CoV-2 Vaccination.

BACKGROUND AND OBJECTIVES: Acute inflammatory CNS diseases include neuromyelitis optica spectrum disorders (NMOSDs) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Both MOGAD and acute disseminated encephalomyelitis (ADEM) have been reported after vaccination. Consequently, the mass SARS-CoV-2 vaccination program could result in increased rates of these conditions. We described the features of patients presenting with new acute CNS demyelination resembling NMOSDs or MOGAD within 8 weeks of SARS-CoV-2 vaccination. METHODS: The study included a prospective case series of patients referred to highly specialized NMOSD services in the UK from the introduction of SARS-CoV-2 vaccination program up to May 2022. Twenty-five patients presented with new optic neuritis (ON) and/or transverse myelitis (TM) ± other CNS inflammation within 8 weeks of vaccination with either AstraZeneca (ChAdOx1S) or Pfizer (BNT162b2) vaccines. Their clinical records and paraclinical investigations including MRI scans were reviewed. Serologic testing for antibodies to myelin oligodendrocyte glycoprotein (MOG) and aquaporin 4 (AQP4) was performed using live cell-based assays. Patients' outcomes were graded good, moderate, or poor based on the last clinical assessment. RESULTS: Of 25 patients identified (median age 38 years, 14 female), 12 (48%) had MOG antibodies (MOGIgG+), 2 (8%) had aquaporin 4 antibodies (AQP4IgG+), and 11 (44%) had neither. Twelve of 14 (86%) antibody-positive patients received the ChAdOx1S vaccine. MOGIgG+ patients presented most commonly with TM (10/12, 83%), frequently in combination with ADEM-like brain/brainstem lesions (6/12, 50%). Transverse myelitis was longitudinally extensive in 7 of the 10 patients. A peak in new MOGAD cases in Spring 2021 was attributable to postvaccine cases. Both AQP4IgG+ patients presented with brain lesions and TM. Four of 6 (67%) seronegative ChAdOx1S recipients experienced longitudinally extensive TM (LETM) compared with 1 of 5 (20%) of the BNT162b2 group, and facial nerve inflammation was reported only in ChAdOx1S recipients (2/5, 40%). Guillain-Barre syndrome was confirmed in 1 seronegative ChAdOx1S recipient and suspected in another. DISCUSSION: ChAdOx1S was associated with 12/14 antibody-positive cases, the majority MOGAD. MOGAD patients presented atypically, only 2 with isolated ON (1 after BNT162b2 vaccine) but with frequent ADEM-like brain lesions and LETM. Within the seronegative group, phenotypic differences were observed between ChAdOx1S and BNT162b2 recipients. These observations might support a causative role of the ChAdOx1S vaccine in inflammatory CNS disease and particularly MOGAD. Further study of this cohort could provide insights into vaccine-associated immunopathology.

Let's talk about sex(ual) wellbeing! Staff perceptions of implementing a novel service for people with Multiple Sclerosis.

BACKGROUND: In people with multiple sclerosis (PwMS), a complex interplay of neurological dysfunction, polypharmacy and psychological issues, contrive to impair their sexual and reproductive wellbeing. Realising an unmet need, the Tayside MS service in collaboration with a sexual health clinician (LJ), established a 'Pelvic Health Clinic' to improve quality of life for PwMS. OBJECTIVE: To explore clinician's perceptions of implementing an MS Pelvic Health service with a view to establishing future outcomes for health care professionals about the utility in such a service. METHOD: In this small-scale qualitative case study, we explored clinician's perceptions of such a clinic adjunct. Semi-structured interviews were conducted, transcribed, and thematically analysed in a reflexive manner. RESULTS: Five participants consented. Ten sub-themes emerged, which were organised into three main themes: service tensions, patient needs and practitioner feelings. CONCLUSION: Clinicians highly valued the new MS 'pelvic health clinic'. Knowing that there was a service available empowered clinicians to ask patients about sexual health needs. Specific referral criteria may help further develop the service and improve patient care. Staff welcome training and support in this area or the option to signpost onwards; either mechanism lends itself to enhancing MS patient needs.

Paraneoplastic ataxia and dystonia secondary to a malignant fibrous histiocytoma.

Paraneoplastic movement disorders are part of the spectrum of paraneoplastic syndromes caused by the production of onconeural antibodies such as anti-Hu by underlying tumours. These attack specific neurons depending on receptor aetiology. We report the case of a 53-year-old man who presented 8 years previously with symptoms of upper limb weakness, light headedness, dizziness and falls. His condition followed a progressive course. Two years after onset he had right-sided weakness, diplopia and generalised dystonia. Initial investigations identified a positive anti-Hu antibody, but an extensive search for a primary tumour was negative. A malignant fibrous histiocytoma in his right gluteal fold was subsequently identified. At this stage he was bed bound with severe ataxia, dystonia and spasticity. Following surgical excision and treatment with high dose steroids and pulse immunoglobulin, further progression was arrested and minor improvements occurred. He can now ambulate with bilateral assistance but remains severely disabled.