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.

Unveiling the Unpredictable in Parkinson's Disease: Sensor-Based Monitoring of Dyskinesias and Freezing of Gait in Daily Life.

BACKGROUND: Dyskinesias and freezing of gait are episodic disorders in Parkinson's disease, characterized by a fluctuating and unpredictable nature. This cross-sectional study aims to objectively monitor Parkinsonian patients experiencing dyskinesias and/or freezing of gait during activities of daily living and assess possible changes in spatiotemporal gait parameters. METHODS: Seventy-one patients with Parkinson's disease (40 with dyskinesias and 33 with freezing of gait) were continuously monitored at home for a minimum of 5 days using a single wearable sensor. Dedicated machine-learning algorithms were used to categorize patients based on the occurrence of dyskinesias and freezing of gait. Additionally, specific spatiotemporal gait parameters were compared among patients with and without dyskinesias and/or freezing of gait. RESULTS: The wearable sensor algorithms accurately classified patients with and without dyskinesias as well as those with and without freezing of gait based on the recorded dyskinesias and freezing of gait episodes. Standard spatiotemporal gait parameters did not differ significantly between patients with and without dyskinesias or freezing of gait. Both the time spent with dyskinesias and the number of freezing of gait episodes positively correlated with the disease severity and medication dosage. CONCLUSIONS: A single inertial wearable sensor shows promise in monitoring complex, episodic movement patterns, such as dyskinesias and freezing of gait, during daily activities. This approach may help implement targeted therapeutic and preventive strategies for Parkinson's disease.

The Story behind the Mask: A Narrative Review on Hypomimia in Parkinson's Disease.

Facial movements are crucial for social and emotional interaction and well-being. Reduced facial expressions (i.e., hypomimia) is a common feature in patients with Parkinson's disease (PD) and previous studies linked this manifestation to both motor symptoms of the disease and altered emotion recognition and processing. Nevertheless, research on facial motor impairment in PD has been rather scarce and only a limited number of clinical evaluation tools are available, often suffering from poor validation processes and high inter- and intra-rater variability. In recent years, the availability of technology-enhanced quantification methods of facial movements, such as automated video analysis and machine learning application, led to increasing interest in studying hypomimia in PD. In this narrative review, we summarize the current knowledge on pathophysiological hypotheses at the basis of hypomimia in PD, with particular focus on the association between reduced facial expressions and emotional processing and analyze the current evaluation tools and management strategies for this symptom, as well as future research perspectives.

Incidence and predictors of postural abnormalities in Parkinson's disease: a PPMI cohort study.

BACKGROUND: Axial postural abnormalities (PA) are invalidating symptoms of Parkinson's disease (PD). Risk factors for PA are unknown. OBJECTIVES: We sought to evaluate PA incidence and risk factors over the first 4-6 years of PD. METHODS: We included 441 PD patients from the Parkinson's Progression Markers Initiative (PPMI) cohort with data at diagnosis and after 4-year follow-up. PA was defined according to a posture item ≥ 2 at the Movement Disorder Society-sponsored-revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) in Off therapeutic condition. The Kruskal-Wallis test was used to compare characteristics of patients without PA ('no-PA'), with PA at disease onset ('baseline-PA'), and PA developed during follow-up ('develop-PA'). To identify predictors of PA development, univariate and multivariate Cox regression analyses were performed considering demographic, clinical and therapeutic variables. RESULTS: 10.9% of patients showed PA at baseline and 23.7% developed PA within the first 4-6 years since diagnosis. Older age, malignant phenotype, higher MDS-UPDRS part III, Hoehn & Yahr, and dysautonomia (SCOPA-AUT) score, and lower levels of physical activity were predictors of PA development at the univariate analysis. Older age (Hazard ratio [HR] per year: 1.041) and higher MDS-UPDRS part III score (HR per point: 1.035) survived as PA development predictors in the multivariate analysis. CONCLUSIONS: PPMI cohort data show that > 30% of PD patients present PA within the first 4-6 years of disease. Older age at onset and higher motor burden are associated with a higher risk for PA development. The protective role of physical activity merits to be further investigated.