Novel de novo heterozygous CACNA1A gene variant in generalised dystonia: a case report.

Background: Dystonia is a genetic or non-genetic movement disorder with typical patterned and twisting movements due to abnormal muscle contractions that may be associated with tremor. Genetic and phenotypic heterogeneity leads to variable clinical presentation. Methodology: Next-generation sequencing technologies are being currently used in the workup of patients with inherited dystonia to determine the specific cause in the individuals with autosomal dominant, recessive, X-linked or mitochondrial inheritance patterns. Calcium voltage-gated channel subunit alpha1 A (CACNA1A) gene variants are rare in dystonias. Results: We here present a 20-year-old man with a history of delayed milestones, flexor posturing, dysarthria, dysphagia and a negative family history from consanguineous parents. Neurological examination revealed right lateral scoliosis of the neck and generalised dystonic posturing affecting both upper and lower limbs. MRI of the brain was unremarkable. Molecular genetic results revealed a heterozygous variant in the CACNA1A gene (CHR19: NM_023035.2, c. 1602G>A; p. Met534Ile). Segregation analyses in both the parents revealed wild-type CACNA1A gene suggesting de novo nature of the variant with a likely pathogenic classification. Conclusion: Dystonia is one of the clinical phenotypes that can be associated with CACNA1A gene mutations and we recommend that this gene either be included in the dystonia panel offered or tested when the initial primary genetic result is negative.

Neuromodulation Options and Patient Selection for Parkinson's Disease.

Neuromodulation therapies, including deep brain stimulation (DBS) and pump therapies, are currently the standard of care for PD patients with advanced disease and motor complications that are difficult to control with medical management alone. The quest for alternate lesser invasive approaches led to the development of several novel therapies like intrajejunal levodopa infusions (IJLI), continuous subcutaneous apomorphine infusions (CSAI) and Magnetic Resonance guided Focused Ultrasound (MRgFUS) in recent years. To achieve good outcomes with any of these therapeutic modalities, careful patient selection, multidisciplinary evaluation and technical expertise are equally important. In this review, we will provide an overview of the neuromodulation strategies currently available for PD, emphasizing on patient selection and choosing among the various strategies.

Diffusion-Weighted Magnetic Resonance Imaging in Acute Retinal Pathology.

The authors describe diffusion-weighted magnetic resonance imaging (DWI) as an accessible way to screen for acute retinal pathology in emergency setting. They describe three proof-of-principle patients who had abrupt onset of vision loss from acute retinal pathology where DWI was diagnostic. The deficits included central retinal artery occlusion and acute retinitis with retinal necrosis. DWI can be non-specific for aetiology, but it can rapidly localise the retinal pathology and initiate early therapeutic interventions in the emergency room.