CACNA1A variant associated with generalized dystonia.

INTRODUCTION: CACNA1A gene variants are correlated with different disorders, including episodic ataxia type 2, spinocerebellar ataxia type 6, and familial hemiplegic migraine type 1. Despite dystonia not being a typical manifestation of CACNA1A variants, there are reports indicating a link between this gene mutation and dystonic features. METHODS: We report the case of a patient with a novel missense variant of the CACNA1A gene presenting headache, head and arm tremor, dystonia, episodic painful focal dystonic attacks, and unexplained falls. RESULTS:  A 57-year-old woman presented with a history of neck dystonia, head and arm tremor, and headaches since age 15. In 2017, she progressively developed dystonic tremor of the head and arms with an unremarkable brain MRI. In 2018 she experienced worsening of tremor and developed painful dystonic attacks, resistant to treatments including clonazepam, trihexyphenidyl, baclofen, and levodopa/benserazide. Botulinum toxin injections for neck dystonia provided limited benefit. The next-generation sequencing exam revealed a CACNA1A gene missense variant (NM_023035.2:c.1630C > T; p.Arg544Trp). In 2021 we observed a worsening of dystonia, accompanied by weight loss, mood changes, and unexplained falls. Deep brain stimulation was considered but ruled out due to cortical atrophy and mild cognitive deficits revealed by the neuropsychological examination. DISCUSSION: Only a few studies reported dystonia as part of the clinical features in carriers of CACNA1A mutations. This case points out the relevance of a need to expand the literature on voltage-dependent P/Q-type Ca2 + channels' role in dystonia's pathogenesis and stresses the complex phenotype-genotype presentation of CACNA1A mutation.

Hypotensive episodes at 24-h ambulatory blood pressure monitoring predict adverse outcomes in Parkinson's disease.

PURPOSE: Neurogenic orthostatic hypotension (nOH) is a frequent nonmotor feature of Parkinson's disease (PD), associated with adverse outcomes. Recently, 24-h ambulatory blood pressure monitoring (ABPM) showed good accuracy in diagnosing nOH. This study aims at evaluating the prognostic role of ABPM-hypotensive episodes in predicting PD disability milestones and mortality and comparing it to the well-defined prognostic role of bedside nOH. METHODS: Patients with PD who underwent ABPM from January 2012 to December 2014 were retrospectively enrolled and assessed for the development of falls, fractures, dementia, bed/wheelchair confinement, hospitalization, and mortality, during an up-to-10-year follow-up. Significant ABPM-hypotensive episodes were identified when greater than or equal to two episodes of systolic BP drop ≥ 15 mmHg (compared with the average 24 h) were recorded during the awakening-to-lunch period. RESULTS: A total of 99 patients (74% male, age 64.0 ± 10.1 years, and PD duration 6.4 ± 4.0 years) were enrolled. At baseline, 38.4% of patients had ABPM-hypotensive episodes and 46.5% had bedside nOH. On Kaplan-Meier analysis, patients with ABPM-hypotensive episodes showed earlier onset of falls (p = 0.001), fractures (p = 0.004), hospitalizations (p = 0.009), bed/wheelchair confinement (p = 0.032), dementia (p = 0.001), and shorter survival (8.0 versus 9.5 years; p = 0.009). At Cox regression analysis (adjusted for age, disease duration, Charlson Comorbidity Index, and Hoehn and Yahr stage) a significant association was confirmed between ABPM-hypotensive episodes and falls [odds ratio (OR) 3.626; p = 0.001), hospitalizations (OR 2.016; p = 0.038), and dementia (OR 2.926; p = 0.008), while bedside nOH was only associated with falls (OR 2.022; p = 0.039) and dementia (OR 1.908; p = 0.048). CONCLUSIONS: The presence of at least two ABPM-hypotensive episodes independently predicted the development of falls, dementia, and hospitalization, showing a stronger prognostic value than the simple bedside assessment.

Hypotensive episodes at 24-h Ambulatory Blood Pressure Monitoring predict adverse outcomes in Parkinson's Disease.

Purpose: Neurogenic orthostatic hypotension (nOH) is a frequent non-motor feature of Parkinson's disease (PD), associated with adverse outcomes. Recently, 24-hour ambulatory BP monitoring (ABPM) has been shown to diagnose nOH with good accuracy (in the presence of at least 2 episodes of systolic BP drop ≥ 15 mmHg compared to the average 24-h). This study aims at evaluating the prognostic role of ABPM-hypotensive episodes in predicting PD disability milestones and mortality and comparing it to well-defined prognostic role of nOH. Methods: PD patients who underwent ABPM from January 2012 to December 2014 were retrospectively enrolled and assessed for the development of falls, fractures, dementia, bed/wheelchair confinement, hospitalization, mortality, during an up-to-10-year follow-up. Results: Ninety-nine patients (male 74%; age: 64.0 ± 10.1 years; PD duration: 6.4 ± 4.0 years) were enrolled. At baseline, 38.4% of patients had ABPM-hypotensive episodes and 46.5% had bedside nOH.At Kaplan-Meier analysis patients with ABPM-hypotensive episodes had an earlier onset of falls (p = 0.001), fractures (p = 0.004), hospitalizations (p = 0.009), bed/wheelchair confinement (p = 0.032), dementia (p = 0.001), and showed a shorter survival (8.0vs9.5 years; p = 0.009). At Cox regression analysis (adjusted for age, disease duration, Charlson Comorbidity Index, and H&Y stage at baseline) a significant association was confirmed between ABPM-hypotensive episodes and falls (OR:3.626; p = 0.001), hospitalizations (OR:2.016; p = 0.038), and dementia (OR:2.926; p = 0.008), while bedside nOH was only associated with falls (OR 2.022; p = 0.039) and dementia (OR:1.908; p = 0.048). Conclusion: The presence of at least two ABPM-hypotensive episodes independently predicted the development of falls, dementia, and hospitalization, showing a stronger prognostic value than the simple bedside assessment.