Isolated gluteal and paravertebral muscle weakness due to anti-3-hydroxy-3-methylglutaryl-coenzyme a reductase antibody-associated necrotizing autoimmune myopathy.

INTRODUCTION: A 56-year-old man with a distant history of statin use presented with progressive isolated very proximal lower limb and truncal weakness. Electromyogram (EMG) showed isolated gluteal and lumbar paraspinal muscle involvement. METHODS: Gluteus medius muscle biopsy was performed under general anesthesia. RESULTS: The biopsy showed a pauci-inflammatory necrotizing myopathy. Serum antibodies to 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) were positive. He has since partially responded to corticosteroids and methotrexate. CONCLUSIONS: Anti-HMGCR-associated necrotizing autoimmune myopathy (NAM) can present in a restricted form after cessation of a statin. Biopsy of a symptomatic but uncommonly studied muscle is worthwhile. Muscle Nerve 54: 150-152, 2016.

Defects of mutant DNMT1 are linked to a spectrum of neurological disorders.

We report a broader than previously appreciated clinical spectrum for hereditary sensory and autonomic neuropathy type 1E (HSAN1E) and a potential pathogenic mechanism for DNA methyltransferase (DNMT1) mutations. The clinical presentations and genetic characteristics of nine newly identified HSAN1E kinships (45 affected subjects) were investigated. Five novel mutations of DNMT1 were discovered; p.C353F, p.T481P, p.P491L, p.Y524D and p.I531N, all within the target-sequence domain, and two mutations (p.T481P, p.P491L) arising de novo. Recently, HSAN1E has been suggested as an allelic disorder of autosomal dominant cerebellar ataxia, deafness and narcolepsy. Our results indicate that all the mutations causal for HSAN1E are located in the middle part or N-terminus end of the TS domain, whereas all the mutations causal for autosomal dominant cerebellar ataxia, deafness and narcolepsy are located in the C-terminus end of the TS domain. The impact of the seven causal mutations in this cohort was studied by cellular localization experiments. The binding efficiency of the mutant DNMT proteins at the replication foci and heterochromatin were evaluated. Phenotypic characterizations included electromyography, brain magnetic resonance and nuclear imaging, electroencephalography, sural nerve biopsies, sleep evaluation and neuropsychometric testing. The average survival of HSAN1E was 53.6 years. [standard deviation = 7.7, range 43-75 years], and mean onset age was 37.7 years. (standard deviation = 8.6, range 18-51 years). Expanded phenotypes include myoclonic seizures, auditory or visual hallucinations, and renal failure. Hypersomnia, rapid eye movement sleep disorder and/or narcolepsy were identified in 11 subjects. Global brain atrophy was found in 12 of 14 who had brain MRI. EEGs showed low frequency (delta waves) frontal-predominant abnormality in five of six patients. Marked variability in cognitive deficits was observed, but the majority of patients (89%) developed significant cognitive deficit by the age of 45 years. Cognitive function decline often started with personality changes and psychiatric manifestations. A triad of hearing loss, sensory neuropathy and cognitive decline remains as the stereotypic presentation of HSAN1E. Moreover, we show that mutant DNMT1 proteins translocate to the cytoplasm and are prone to form aggresomes while losing their binding ability to heterochromatin during the G2 cell cycle. Our results suggest mutations in DNMT1 result in imbalanced protein homeostasis through aggresome-induced autophagy. This mechanism may explain why mutations in the sole DNA maintenance methyltransferase lead to selective central and peripheral neurodegeneration.

Diabetes mellitus prevalence in Northland New Zealand schizophrenia patients on clozapine.

AIMS: Clozapine is a unique atypical anti-psychotic agent with best efficacy for treatment resistant schizophrenia compared to other agents, but with increased metabolic adverse effects. We sought to audit the prevalence of diabetes and pre-diabetes in Northland, New Zealand patients on clozapine. METHOD: We captured all 287 patients in Northland, New Zealand who were prescribed clozapine in September 2021 and obtained demographic, clinical and laboratory data. RESULTS: We discovered that 26.48% had diabetes (one patient type one, 75 type two diabetes) and 14.63% had pre-diabetes that developed after a median of six years' clozapine treatment. Diabetes prevalence is approximately 6% in the general population. NZ Maori made up 65.85% of the entire cohort (35.8% of the general population) and 85.53% of the diabetes patients. NZ Europeans represented most of the remaining 30.66% on clozapine, consistent with the largely bicultural ethnic mix of our region. Maori on clozapine were younger: mean age 42 years, compared to NZ Europeans, mean age 49 years. The average BMI was 37kg/m2 for Maori, 32 for Europeans (range 21-63, SD 8); there was a moderate relationship between clozapine use and increasing BMI (correlation coefficient of 0.74). For the diabetes patients, glycaemic control was overall suboptimal with a mean Hba1c of 66mmol/mol (range 41-117). CONCLUSIONS: Culturally appropriate, flexible and accessible services which integrate both the mental and physical health needs of Northland, New Zealand people with treatment-resistant schizophrenia on clozapine are required to reduce the 41% rate of dysglycaemia in this predominantly Maori group.

Gastric bypass for insulin resistance due to lipodystrophy.

We report a 41-year-old woman with severe insulin resistance due to partial lipodystrophy, who was successfully treated with gastric bypass surgery.

The incidence of atrial fibrillation and the use of warfarin in Northland, New Zealand stroke patients.

AIM: To identify the number of Northland stroke patients with atrial fibrillation (AF) and to assess the effective use of warfarin anticoagulation in this group METHOD: A retrospective study of patients admitted with stroke or transient ischaemic attack (TIA) to Whangarei Hospital between 1 Jan 2010 and 1 Sept 2010. RESULTS: Of 198 stroke/TIA patients identified, 47 (24%) had confirmed persistent or paroxysmal AF (PAF) or flutter. Only 12 (31%) patients with pre existing PAF or AF were on warfarin and only 1 patient had an ischaemic stroke while in the therapeutic INR range of 2.0-3.0. The commonest reason cited for no anticoagulation was patients' wishes. CONCLUSION: In our region, effective warfarin use for stroke prevention in AF patients is lower than recommended. This may be improved with increased awareness of efficacy and safety of warfarin and more thorough monitoring of INR.

Reversible optic neuropathy due to metronidazole.

Metronidazole is a little known cause of drug-induced optic neuropathy. We report a patient who developed progressive visual loss after an 8-month course of Metronidazole. Electrophysiology confirmed a bilateral optic neuropathy. Her vision improved dramatically with cessation of the drug.