Burden, Anxiety, and Depression Among Caregivers of Parkinson's Disease Patients.

Background: Parkinson's disease (PD) is a disabling neurodegenerative movement disorder. Most PD patients are looked after by caregivers who are close to them regardless of their relationship. Caregivers may experience a notable impact on their mental health as they dedicate a significant amount of time to the patient while observing the progression of the disease. Objective: The aim of this study was to evaluate the level of burden, depression, anxiety, and stress among caregivers of PD patients. Methods: We conducted a cross-sectional analysis between July and September 2023 among caregivers of PD patients following in the Movement Disorders Clinic at King Khalid University Hospital in Riyadh, Saudi Arabia, and through the Saudi Parkinson's Society. The data collection was done anonymously through an electronic self-administered questionnaire. Caregiver burden was assessed by using the validated Arabic version of the Zarit Burden Interview (ZBI) scale, and the Depression Anxiety Stress Scale (DASS) was used to assess the presence and level of anxiety and depression. Results: There were 118 caregivers (53.39% female, 33.9% aged between 35- 45 years, and 73.73% were sons/daughters) caring for 118 patients (57.63%, male, 38.98% aged between 66- 76). The ZBI score was highest among sibling caregivers. Moreover, burden scores were higher among those who provided care more frequently than others. Conclusions: Our study revealed that PD caregivers face a high risk of care burden, especially those who are siblings and spend longer periods in patient care. Additionally, female caregivers reported higher rates of depression, anxiety, and stress.

Parkinson's disease (PD) is a serious condition that affects movement, and most PD patients are cared for by someone close to them, such as a family member. This caregiving can significantly impact the mental health of the caregiver, who often spends a lot of time caring for the patient and witnessing the disease's progression. We studied caregivers of PD patients at the Movement Disorders Clinic at King Khalid University Hospital and through the Saudi Parkinson's Society from July to September 2023. Caregivers completed an anonymous electronic questionnaire, and we measured caregiver burden using the Zarit Burden Interview (ZBI) and assessed anxiety and depression using the Depression Anxiety Stress Scale (DASS). Our study included 118 caregivers (53.39% female, most aged 35­ 45 years, and 73.73% were sons or daughters) caring for 118 PD patients (57.63% male, most aged 66­ 76 years). Caregivers who were siblings or cared for the patient daily had higher burden scores, and female caregivers had higher levels of depression, anxiety, and stress compared to males. Our study revealed that PD caregivers face a high risk of care burden, especially those who are siblings and spend longer periods in patient care, and that female caregivers exhibited an elevated risk of experiencing depression, anxiety, or stress.

Opinions and experience of neurologists and neurology trainees in Saudi Arabia on functional neurological disorders: a survey based study.

BACKGROUND: Functional Neurological Disorder (FND) is commonly encountered in clinical practice, causing functional impairment and poor quality of life. As there is limited data from Saudi Arabia, our study aims to explore the experience and opinions of Saudi neurologists and neurology trainees regarding FND. METHODS: In our cross-sectional observational study, we included 100 neurology consultants and trainees. Data was collected using an online questionnaire from March to August 2023. RESULTS: A total of one hundred neurologists participated in the survey. Although 41% of physicians encountered FND patients on a weekly basis or more frequently, only 41.7% of trainees reported receiving dedicated lectures on FND. Furthermore, only 46% of respondents felt comfortable providing a clear explanation of the FND diagnosis to their patients. While the majority (64%) used the term "Functional Neurological Disorder" in medical documentation, only 43% used this term when communicating the diagnosis to patients, with the terminology varying widely. Clinicians emphasized that inconsistent and variable neurological examinations were key indicators raising diagnostic suspicion, which aligns with the recommended reliance on detailed clinical history and neurological examination. Lastly, 61% of physicians stated that their approach to patients with FND lacked a structured management plan. CONCLUSION: Our study findings emphasize that FND is commonly encountered in clinical practice and reveal a significant lack of targeted education on FND for neurology trainees. Enhancing educational programs for both trainees and practicing neurologists on this prevalent neurological condition is essential for improving patient care and outcomes.

Alpha-synuclein pathology in isolated rapid eye movement sleep behaviour disorder: a meta-analysis.

Accumulating evidence indicates that patients with isolated rapid eye movement sleep behaviour disorder (iRBD), a prodromal stage of synucleinopathies, show abnormal deposition of misfolded alpha-synuclein (a-Syn) in peripheral tissues. The clinical utility of testing for a-Syn in iRBD is unclear. This meta-analysis focused on the utility of testing for the abnormal a-Syn phosphorylated at Ser129 (p-syn) and a-Syn seeding activity (a-Syn seed amplification assays [aSyn-SAA]). Following an electronic database search, 15 studies were included that provided at a minimum data on test positivity in participants with iRBD. Test positivity from cerebrospinal fluid (CSF) was 80% (95% confidence interval [CI] 68-88%, I2 = 71%) and for skin was 74.8% (95% CI 53.2-88.5%, I2 = 64%) for aSyn-SAA and 78.5% (95% CI 70.4-84.9%, I2 = 14%) for p-syn. The phenoconversion rate ratio of biopsy-positive versus biopsy-negative iRBD was 1.28 (95% CI 0.68-2.41, I2 = 0%). Skin as a source had a specificity of 99% (95% CI 95-100%, I2 = 0%; p = 0.01 compared to CSF). As a test, p-syn, had a specificity of 100% (95% CI 93-100%, I2 = 0%; p < 0.001) compared to aSyn-SAA. The odds ratio of a-Syn test positivity in iRBD versus other RBDs was 112 (95% CI 20-629, I2 = 0%). These results demonstrate clinically significant test positivity in iRBD and favour skin over CSF as the source of a-Syn pathological analysis, and p-syn over aSyn-SAA as the testing method. Overall, these findings indicate that testing for a-Syn could help in differentiating iRBD from RBD secondary to other conditions.

Study of Rivaroxaban for Cerebral Venous Thrombosis: A Randomized Controlled Feasibility Trial Comparing Anticoagulation With Rivaroxaban to Standard-of-Care in Symptomatic Cerebral Venous Thrombosis.

BACKGROUND: Emerging data suggest that direct oral anticoagulants may be a suitable choice for anticoagulation for cerebral venous thrombosis (CVT). However, conducting high-quality trials in CVT is challenging as it is a rare disease with low rates of adverse outcomes such as major bleeding and functional dependence. To facilitate the design of future CVT trials, SECRET (Study of Rivaroxaban for Cerebral Venous Thrombosis) assessed (1) the feasibility of recruitment, (2) the safety of rivaroxaban compared with standard-of-care anticoagulation, and (3) patient-centered functional outcomes. METHODS: This was a phase II, prospective, open-label blinded-end point 1:1 randomized trial conducted at 12 Canadian centers. Participants were aged ≥18 years, within 14 days of a new diagnosis of symptomatic CVT, and suitable for oral anticoagulation; they were randomized to receive rivaroxaban 20 mg daily, or standard-of-care anticoagulation (warfarin, target international normalized ratio, 2.0-3.0, or low-molecular-weight heparin) for 180 days, with optional extension up to 365 days. Primary outcomes were annual rate of recruitment (feasibility); and a composite of symptomatic intracranial hemorrhage, major extracranial hemorrhage, or mortality at 180 days (safety). Secondary outcomes included recurrent venous thromboembolism, recanalization, clinically relevant nonmajor bleeding, and functional and patient-reported outcomes (modified Rankin Scale, quality of life, headache, mood, fatigue, and cognition) at days 180 and 365. RESULTS: Fifty-five participants were randomized. The rate of recruitment was 21.3 participants/year; 57% of eligible candidates consented. Median age was 48.0 years (interquartile range, 38.5-73.2); 66% were female. There was 1 primary event (symptomatic intracranial hemorrhage), 2 clinically relevant nonmajor bleeding events, and 1 recurrent CVT by day 180, all in the rivaroxaban group. All participants in both arms had at least partial recanalization by day 180. At enrollment, both groups on average reported reduced quality of life, low mood, fatigue, and headache with impaired cognitive performance. All metrics improved markedly by day 180. CONCLUSIONS: Recruitment targets were reached, but many eligible participants declined randomization. There were numerically more bleeding events in patients taking rivaroxaban compared with control, but rates of bleeding and recurrent venous thromboembolism were low overall and in keeping with previous studies. Participants had symptoms affecting their well-being at enrollment but improved over time. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03178864.

Clinical Reasoning: A Young Woman With Rapidly Progressive Weakness and Paresthesia.

A 24-year-old Middle Eastern woman presented with a 2-month history of rapidly progressive asymmetric weakness and paresthesia that began in her left lower extremity and progressed to involve both legs and arms. It was associated with overflow urinary incontinence and significant weight loss. In addition, she complained of a constant occipital headache that worsened in the supine position and was associated with photophobia, tinnitus, nausea, vomiting, and horizontal binocular diplopia. She also had signs of meningismus, decreased left facial sensation, and right sensorineural hearing loss. Because multifocal localization suggests a wide variety of possible differential diagnoses, this study expands on the differential of a subacute multifocal process while highlighting the importance of identifying appropriate risk factors and performing a relevant yet focused diagnostic workup.

Demographics and Clinical Characteristics of Autosomal Dominant Spinocerebellar Ataxia in Canada.

Background: Autosomal dominant (AD) spinocerebellar ataxias (SCAs) encompass a large group of rare disorders, which occurs in individuals of different ethnic backgrounds. To date, demographics, and clinical descriptions of AD SCA in Canada are lacking. Methods: A retrospective chart review of patients with a genetically confirmed diagnosis of AD SCAs was performed at five tertiary centers across Canada in the provinces of Quebec, Alberta, and Ontario. Demographic, genetic, and clinical information were collected and analyzed. Results: A total of 203 patients with AD SCA were identified. Weighted estimated prevalence of AD SCA in three large Canadian provinces was calculated (2.25 cases per 100.000) which is in keeping with the figures documented worldwide. We found that the distribution of the most common SCA differed when comparing provinces. The most prevalent SCA diagnosis in Ontario was SCA3 (49%), while the most prevalent SCA diagnosis in Alberta and Quebec was SCA2 in 26% and 47%, respectively. SCA6 was the third most prevalent SCA subtype in Quebec (14%), which was not seen as commonly in other provinces. SCA1 was uncommonly seen in both Alberta and Quebec, despite being common in Ontario. Conclusions: In this largest Canadian study, we describe the prevalence, distribution, and clinical characteristics of AD SCA. We found that the distribution of the most common SCA differed in the three provinces studied. This finding reflects the heterogenous nature of the Canadian population.

Periodic Limb Movements while Awake (PLMA) as a Manifestation of Wearing-Off in Parkinson's Disease: A Case Series and Review of the Literature.

Background: Periodic limb movements while awake (PLMA) are similar to Periodic limb movements in sleep (PLMS) but occurring during wakefulness and seen in association with restless leg syndrome (RLS). Objectives: To describe PLMA as a wearing-off phenomenon in Parkinson's Disease (PD). Methods: We describe four individuals with PD and PLMS, who had associated similar periodic and stereotypic lower extremity movements during wakefulness, thought to be secondary to PLMA, and were highly responsive to dopaminergic treatment. Results: Despite the prevalence of RLS and PLMS in individuals with PD, the presence of similar movements during wakefulness has not been well characterized. The lack of a specific diagnostic criteria poses a significant diagnostic challenge. Conclusions: We describe, for the first time to our knowledge, PLMA as a wearing-off phenomenon in PD. This entity could be classified in the spectrum of "low-dose dyskinesia," as we found that it was highly responsive to dopaminergic treatment.

Functional tremor developing after successful MRI-guided focused ultrasound thalamotomy for essential tremor.

OBJECTIVE: To describe a case of functional tremor occurring after a successful MR-guided focused ultrasound thalamotomy (MRgFUS) for essential tremor. METHODS: A 71-year-old right-handed man with essential tremor was referred to us for consideration of deep brain stimulation surgery for worsening bilateral upper limb tremor after a successful left MRgFUS for essential tremor. RESULTS: On clinical exam, signs compatible with a functional tremor were noted, including entertainability and suppressibility. Electrophysiological studies were consistent with essential tremor and superimposed tremor fulfilling the laboratory-supported criteria for functional tremor. DISCUSSION: We describe the first reported case of a functional movement disorder occurring after successful MRgFUS procedure for essential tremor. Recognising this entity and its development after such therapeutic interventions is essential to avoid further unnecessary invasive therapies.

Alpha-synuclein seeding shows a wide heterogeneity in multiple system atrophy.

BACKGROUND: Multiple system atrophy (MSA) is a neurodegenerative condition characterized by variable combinations of parkinsonism, autonomic failure, cerebellar ataxia and pyramidal features. Although the distribution of synucleinopathy correlates with the predominant clinical features, the burden of pathology does not fully explain observed differences in clinical presentation and rate of disease progression. We hypothesized that the clinical heterogeneity in MSA is a consequence of variability in the seeding activity of α-synuclein both between different patients and between different brain regions. METHODS: The reliable detection of α-synuclein seeding activity derived from MSA using cell-free amplification assays remains challenging. Therefore, we conducted a systematic evaluation of 168 different reaction buffers, using an array of pH and salts, seeded with fully characterized brain homogenates from one MSA and one PD patient. We then validated the two conditions that conferred the optimal ability to discriminate between PD- and MSA-derived samples in a larger cohort of 40 neuropathologically confirmed cases, including 15 MSA. Finally, in a subset of brains, we conducted the first multi-region analysis of seeding behaviour in MSA. RESULTS: Using our novel buffer conditions, we show that the physicochemical factors that govern the in vitro amplification of α-synuclein can be tailored to generate strain-specific reaction buffers that can be used to reliably study the seeding capacity from MSA-derived α-synuclein. Using this novel approach, we were able to sub-categorize the 15 MSA brains into 3 groups: high, intermediate and low seeders. To further demonstrate heterogeneity in α-synuclein seeding in MSA, we conducted a comprehensive multi-regional evaluation of α-synuclein seeding in 13 different regions from 2 high seeders, 2 intermediate seeders and 2 low seeders. CONCLUSIONS: We have identified unexpected differences in seed-competent α-synuclein across a cohort of neuropathologically comparable MSA brains. Furthermore, our work has revealed a substantial heterogeneity in seeding activity, driven by the PBS-soluble α-synuclein, between different brain regions of a given individual that goes beyond immunohistochemical observations. Our observations pave the way for future subclassification of MSA, which exceeds conventional clinical and neuropathological phenotyping and considers the structural and biochemical heterogeneity of α-synuclein present. Finally, our methods provide an experimental framework for the development of vitally needed, rapid and sensitive diagnostic assays for MSA.

Emerging drugs for the treatment of L-DOPA-induced dyskinesia: an update.

INTRODUCTION: Prolonged treatment with L-3,4-dihydroxyphenylalanine (L-DOPA) leads to the development of uncontrolled movements (L-DOPA-induced dyskinesias (LID)) in Parkinson's disease (PD). There is currently only a single approved drug for the treatment of LID, a long-acting preparation of the NMDA antagonist, amantadine, that has variable benefits and side-effects. Therefore, new treatments for LID remain an unmet in PD. AREAS COVERED: We review the current strategies for the management of LID; the pathogenic mechanisms underlying the development of LID, which provides the rationale for clinical trials of novel targets for LID and provide a review of phase II/III trials for emerging drugs for LID, with either positive results, or ongoing studies, reported between January 2014 and December 2019. EXPERT OPINION: There are several ongoing studies for agents that showed possible benefit at phase Ib/IIa for reducing LID. However, there are no new positive phase III double-blind randomized controlled clinical trials (DBRCT) for emerging treatments for LID. Generating better preclinical models, more precise recruitment tools and better outcome measures remain a priority. The pharmacology of drugs investigated for LID may be too selective; therefore, evaluating combinations of drugs is worthy of consideration as is the repurposing of existing drugs with multiple pharmacological targets.