DNMT1-associated sensory neuropathy and cerebellar ataxia: A novel variant and review of genotype-phenotype correlation.

AIM: Hereditary sensory neuropathy (HSN) 1E is a neurodegenerative disorder caused by pathogenic variants in DNA methyltransferase 1 (DNMT1). It is characterised by sensorineural deafness, sensory neuropathy and cognitive decline. Variants in DNMT1 are also associated with autosomal dominant cerebellar ataxia, deafness and narcolepsy. METHODS: A 42-year-old man presented with imbalance, lancinating pain, numerous paucisymptomatic injuries, progressive deafness since his mid-20s, mild cognitive decline and apathy. Examination revealed abnormalities of eye movements, distal sensory loss to all modalities, areflexia without weakness and lower limb ataxia. MRI brain and FDG-PET scan demonstrated biparietal and cerebellar atrophy/hypometabolism. Whole exome sequencing detected a heterozygous likely pathogenic missense variant in DNMT1, c.1289G > A, p.Cys430Tyr. Cochlear implant was performed at 44 years for the bilateral high frequency sensorineural hearing loss with improvement in hearing and day-to-day function. RESULTS AND CONCLUSION: We describe a novel variant in DNMT1 and confirm that an overlapping HSN1E-cerebellar phenotype can occur. Only one prior case of cochlear implant in HSN1E has been reported to date but this case adds to that literature, suggesting that cochlear implant can be successful in such patients. We further explore the clinical and radiological signature of the cognitive syndrome associated with this disorder.

Misdiagnosis of myasthenia gravis presenting with tongue and palatal weakness.

We discuss the case of an elderly male who presented with a history of dysphagia, dysphonia, palatal weakness and a sensation of tongue swelling, each symptom of varying time duration. Myasthenia gravis may have a variety of presentations that include ocular fatigability, respiratory muscle weakness and bulbar symptoms. The variety of these myasthenic syndromes can serve as a barrier to diagnosis and can often result in delayed or incorrect diagnosis. In this report, we present an atypical presentation of a relatively rare condition.

Delayed Diagnosis of Atypical Presentation of Myasthenia Gravis.

Myasthenia gravis is an autoimmune disorder affecting the neuromuscular junction, resulting in muscle fatiguability and weakness. The pathological characteristics of the disorder include ocular weakness resulting in diplopia and/or ptosis. More generally, the disease can result in fluctuant weakness of skeletal muscle, predominantly affecting ocular, bulbar and respiratory muscles. Autoimmunity in this instance is mediated by IgG anti-acetylcholine receptor antibodies that results in an impaired structure of postsynaptic neurotransmission. Approximately 15% of patients with myasthenia gravis present with bulbar symptoms, of which isolated bulbar symptoms are seen only on occasion. As with our patient, this presentation is most commonly seen in men with late-onset myasthenia gravis. We present a case of an 83-year-old male who presented with a 1 year history of dysphagia for solids and fatigable dysarthria. Following a diagnosis of myasthenia gravis, he was initiated on corticosteroid treatment. He later descended into myasthenic crisis, requiring invasive ventilation measures due to a failure of both non-invasive ventilation and intravenous immunoglobulin G (IVIG) to achieve therapeutic goals. LEARNING POINTS: Isolated bulbar symptoms in an elderly man warrants consideration of myasthenia gravis to be included in the differential diagnosis.There is possibly an increased risk of myasthenic crisis in late-onset isolated bulbar myasthenia gravis.Empirical treatment for myasthenia gravis must be administered within a hospital setting, paying attention to respiratory tract infection and corticosteroid treatment as triggers for myasthenic crisis.

Guillain-Barre syndrome associated with Norovirus infection.

The authors describe a case of Guillain-Barre syndrome after the diarrhoeal infection due to Norovirus. Many infections have been described most notably Campylobacter jejuni. To our knowledge a connection to Norovirus has not been described in the world literature. The authors speculate on why this may be so.

Manipulated stress and dispositional reinvestment in a wall-volley task: an investigation into controlled processing.

This field-based study examined the action of reinvesting in controlled processing on 14 university soccer players to assess skill breakdown under pressure. Based on scores on the Reinvestment Scale of Masters, Polman, and Hammond, two experimental groups of participants were inferred to be dispositionally High or Low in Reinvestment. They performed a wall-volley soccer task, which involved kicking a ball repeatedly against a wall target zone for 90 sec. as defined by McMorris, Gibbs, Palmer, Payne, and Torpey in a High and Low Stress environment. Prior to each condition performers were required to complete the Anxiety Rating Scale. A series of two-way (reinvestment x stress) analyses of variance with repeated measures on stress were conducted on the Anxiety and soccer scores. Players scoring High on the Reinvestment Scale reported significantly greater Intensity for Somatic Anxiety and lower Self-confidence than players who scored Low in the High Stress condition. Anxiety Direction scores indicated players scoring High on the Reinvestment Scale reported their increase in Somatic Anxiety and reduction in Self-confidence in the High Stress condition to be significantly more debilitating of performance than players who scored Low on the Reinvestment Scale. Soccer scores indicated players scoring High on the Reinvestment Scale were more prone to reinvesting in controlled processing and essentially experiencing greater decreases in performance under pressure than those Low in Reinvestment. Therefore, these findings support the predictive power of the Reinvestment Scale.