Mitochondrial diseases are a diverse group of genetic disorders caused by mutations in nuclear-encoded and mitochondrial DNA (mtDNA)-encoded genes. Disturbance in balance is common in adults with mitochondrial disease and usually attributed to an underlying peripheral neuropathy, skeletal myopathy and/or cerebellar disease, with limited treatment options. The vestibular system is central to balance control, and vestibular dysfunction causes vertigo, dizziness, oscillopsia, unsteadiness, and associated falls. Reports of vestibular dysfunction in mitochondrial disease are confined to small patient cohorts with limited and/or inconsistent use of neuro-otological assessments.1–3 Furthermore, despite the well-recognised association with hearing loss,2 the frequency and underlying pathophysiological basis of vestibular dysfunction in mitochondrial disease is currently unknown. We have undertaken a large-scale, cross-sectional cohort study investigating the prevalence, classification and predictors of vestibular dysfunction in adults with mitochondrial disease. All procedures were conducted as part of routine clinical care. The study was performed under the ethical guidelines issued by our institution, with written informed consent obtained from all participants for genetic studies. We included adults (aged 16 years or older) attending our specialist clinic between May 2016 and August 2017 with clinicopathologically and/or genetically confirmed mitochondrial disease and a suspected balance disorder. This cohort was subsequently evaluated by a specialist neuromuscular physiotherapist (SH) to exclude non-vestibular balance disorders. Patients with suspected vestibulopathy were subsequently referred for neuro-otological investigations (online supplementary table 1). Descriptive analyses were conducted on patient demographics, reported symptoms, neuro-otological and mitochondrial diagnoses, Newcastle Mitochondrial Disease Scale for Adults (NMDAS; a semiquantitative clinical rating scale for mitochondrial disease aimed at providing a …

Positional Manoeuvres for BPPV: Theoretical Approach to Remote Training for Non-specialists

Background and purpose: Identifying vestibular causes of dizziness and unsteadiness in multi‐sensory neurological disease can be challenging, with problems typically attributed to central or peripheral nerve involvement. Acknowledging vestibular dysfunction as part of the presentation provides an opportunity to access targeted vestibular rehabilitation, for which extensive evidence exists. A diagnostic framework was developed and validated to detect vestibular dysfunction, benign paroxysmal positional vertigo or vestibular migraine. The specificity and sensitivity of the diagnostic framework was tested in patients with primary mitochondrial disease.Methods: Adults with a confirmed diagnosis of primary mitochondrial disease were consented, between September 2020 and February 2022. Participants with and without dizziness or unsteadiness underwent remote physiotherapy assessment and had in‐person detailed neuro‐otological assessment. The six framework question responses were compared against objective neuro‐otological assessment or medical notes. The output was binary, with sensitivity and specificity calculated.Results: Seventy‐four adults completed the study: age range 20–81 years (mean 48 years, ±SD 15.05 years); ratio 2:1 female to male. The framework identified a vestibular diagnosis in 35 participants, with seven having two diagnoses. The framework was able to identify vestibular diagnoses in adults with primary mitochondrial disease, with a moderate (40–59) to very high (90–100) sensitivity and positive predictive value, and moderate to high (60–74) to very high (90–100) specificity and negative predictive value.Conclusions: Overall, the clinical framework identified common vestibular diagnoses with a moderate to very high specificity and sensitivity. This presents an opportunity for patients to access effective treatment in a timely manner, to reduce falls and improve quality of life.

Acquired periodic alternating nystagmus (PAN) describes a horizontal jerk nystagmus that reverses its direction with a predictable cycle, and is thought to arise from lesions involving the brainstem and cerebellum. We report a 20-year-old patient with PAN who presented with an acute vertiginous episode and developed an involuntary head movement that initially masked the PAN. The involuntary head movements were abolished with a subtherapeutic dose of botulinum toxin to the neck muscles. We propose that the head movements initially developed as a compensatory movement to the nystagmus, to maintain visual fixation in the presence of the underlying nystagmus, and became an entrained involuntary behavior. This case highlights the importance of disambiguating psychogenic from organic pathology as this may have clinical therapeutic implications, in this case resolution of the most disabling symptom which was her head oscillations, leading to improved day-to-day function despite PAN.