Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a progressive late-onset, neurological disease. Recently, a pentanucleotide expansion in intron 2 of RFC1 was identified as the genetic cause of CANVAS. We screened an Asian-Pacific cohort for CANVAS and identified a novel RFC1 repeat expansion motif, (ACAGG)exp, in three affected individuals. This motif was associated with additional clinical features including fasciculations and elevated serum creatine kinase. These features have not previously been described in individuals with genetically-confirmed CANVAS. Haplotype analysis showed our patients shared the same core haplotype as previously published, supporting the possibility of a single origin of the RFC1 disease allele. We analysed data from >26 000 genetically diverse individuals in gnomAD to show enrichment of (ACAGG) in non-European populations.
Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a recently recognized neurodegenerative ganglionopathy. Prompted by the presence of symptomatic postural hypotension in two patients with CANVAS, we hypothesized that autonomic dysfunction may be an associated feature of the syndrome. We assessed symptoms of autonomic dysfunction and performed autonomic nervous system testing among 26 patients from New Zealand. After excluding three patients with diabetes mellitus, 83% had evidence of autonomic dysfunction; all patients had at least one autonomic symptom and 91% had more than two symptoms. We also found a higher rate of downbeat nystagmus (65%) than previously described in CANVAS. We confirmed that sensory findings on nerve conduction tests were consistent with a sensory ganglionopathy and describe two patients with loss of trigeminal sensation consistent with previous pathological descriptions of trigeminal sensory ganglionopathy. Our results suggest that autonomic dysfunction is a major feature of CANVAS. This has implications for the management of patients with CANVAS as the autonomic symptoms may be amenable to treatment. The findings also provide an important differential diagnosis from multiple system atrophy for patients who present with ataxia and autonomic failure.
Objective
To determine the incidence, etiology, and outcome of status epilepticus (SE) in Auckland, New Zealand, using the latest International League Against Epilepsy (ILAE) SE semiological classification.
Methods
We prospectively identified patients presenting to the public or major private hospitals in Auckland (population = 1.61 million) between April 6, 2015 and April 5, 2016 with a seizure lasting 10 minutes or longer, with retrospective review to confirm completeness of data capture. Information was recorded in the EpiNet database.
Results
A total of 477 episodes of SE occurred in 367 patients. Fifty‐one percent of patients were aged <15 years. SE with prominent motor symptoms comprised 81% of episodes (387/477). Eighty‐four episodes (18%) were nonconvulsive SE. Four hundred fifty episodes occurred in 345 patients who were resident in Auckland. The age‐adjusted incidence of 10‐minute SE episodes and patients was 29.25 (95% confidence interval [CI] = 27.34‐31.27) and 22.22 (95% CI = 20.57‐23.99)/100 000/year, respectively. SE lasted 30 minutes or longer in 250 (56%) episodes; age‐adjusted incidence was 15.95 (95% CI = 14.56‐17.45) SE episodes/100 000/year and 12.92 (95% CI = 11.67‐14.27) patients/100 000/year. Age‐adjusted incidence (10‐minute SE) was 25.54 (95% CI = 23.06‐28.24) patients/100 000/year for males and 19.07 (95% CI = 16.91‐21.46) patients/100 000/year for females. The age‐adjusted incidence of 10‐minute SE was higher in Māori (29.31 [95% CI = 23.52‐37.14]/100 000/year) and Pacific Islanders (26.55 [95% CI = 22.05‐31.99]/100 000/year) than in patients of European (19.13 [95% CI = 17.09‐21.37]/100 000/year) or Asian/other descent (17.76 [95% CI = 14.73‐21.38]/100 000/year). Seventeen of 367 patients in the study died within 30 days of the episode of SE; 30‐day mortality was 4.6%.
Significance
In this population‐based study, incidence and mortality of SE in Auckland lie in the lower range when compared to North America and Europe. For pragmatic reasons, we only included convulsive SE if episodes lasted 10 minutes or longer, although the 2015 ILAE SE classification was otherwise practical and easy to use.
BackgroundPoor prognosis after intracerebral haemorrhage (ICH) is related to haemorrhage characteristics. Along with developing therapeutic interventions, we sought to understand the performance of haemorrhage descriptors in large clinical trials.MethodsClinical and neuroimaging data were obtained for 548 participants with ICH from the Efficacy of Nitric Oxide in Stroke (ENOS) trial. Independent observers performed visual categorisation of the largest diameter, measured volume using ABC/2, modified ABC/2, semiautomated segmentation (SAS), fully automatic measurement methods; shape, density and intraventricular haemorrhage were also assessed. Intraobserver and interobserver reliability were determined for these measures.ResultsICH volume was significantly different among standard ABC/2, modified ABC/2 and SAS: (mean) 12.8 (SD 16.3), 8.9 (9.2), 12.8 (13.1) cm3, respectively (p<0.0001). There was excellent agreement for haemorrhage volume (n=193): ABC/2 intraobserver intraclass correlation coefficient (ICC) 0.96–0.97, interobserver ICC 0.88; modified ABC/2 intraobserver ICC 0.95–0.97, interobserver ICC 0.91; SAS intraobserver ICC 0.95–0.99, interobserver ICC 0.93; largest diameter: (visual) interadjudicator ICC 0.82, (visual vs measured) adjudicator vs observer ICC 0.71; shape intraobserver ICC 0.88 interobserver ICC 0.75; density intraobserver ICC 0.86, interobserver ICC 0.73. Graeb score (mean 3.53) and modified Graeb (5.22) scores were highly correlated. Using modified ABC/2, ICH volume was underestimated in regular (by 2.2-2.5 cm3, p<0.0001) and irregular-shaped haemorrhages (by 4.8-4.9 cm3, p<0.0001). Fully automated measurement of haemorrhage volume was possible in only 5% of cases.ConclusionsFormal measurement of haemorrhage characteristics and visual estimates are reproducible. The standard ABC/2 method is superior to the modified ABC/2 method for quantifying ICH volume.Clinical trial registrationISRCTN9941422.
Eleven patients with severe obstructive sleep apnoea syndrome, which was fully reversed by treatment with nasal continuous positive airways pressure, underwent uvulopalatopharyngoplasty. All patients were followed for at least 12 months after surgery. One patient with large tonsils was cured. Of the remaining 10 patients, two showed minimal objective improvement at 12 months and the rest were unchanged. Four patients subsequently developed cardiac failure due to obstructive sleep apnoea. Thus uvulopalatopharyngoplasty was not effective in these patients with severe idiopathic obstructive sleep apnoea syndrome.
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