Evidente, Virgilio Gerald H.

ABSTRACT Objective To determine the test performance of cutaneous phosphorylated alpha‐synuclein (P‐SYN) in dementia with Lewy bodies (DLB), individuals with reduced Montreal Cognitive Assessment (MoCA) and healthy controls. Methods This is the first subgroup analysis of the Synuclein‐One study, a prospective, blinded study evaluating P‐SYN detection from skin biopsies in 218 subjects with a referral diagnosis of control ( N = 151) and DLB ( N = 67). All subjects completed detailed examinations, questionnaires, and had skin biopsies for detection of P‐SYN. DLB patients were included if meeting the 4th DLB consensus probable criteria. Control subjects, aged 40–99, had no history, examination findings, or symptoms suggestive of a synucleinopathy or neurodegenerative disease. An expert review panel, blinded to pathological data, determined the final diagnosis. Controls with reduced MoCA (MoCA < 26, N = 26) at screening were analyzed separately. Results After expert panel review, only 50/67 patients met consensus criteria for DLB, 26/151 controls had a reduced MoCA, and 120/151 controls had a normal MoCA. The proportions of subjects with cutaneous P‐SYN detected by skin biopsy were 96.0% (48 of 50) of the DLB group, 31% (8 of 26) of the controls with reduced MoCA, and 3.3% (4 of 120) of the controls with normal MoCA. Interpretation In this prospective, blinded, cross‐sectional study, a high proportion of subjects meeting clinical consensus criteria for DLB had P‐SYN detected in skin biopsies. Almost 1/3 of subjects with reduced MoCA testing also had P‐SYN detected. These results support a role for skin biopsy detection of P‐SYN in patients with DLB. Trial Registration NCT04700722

ImportanceFinding a reliable diagnostic biomarker for the disorders collectively known as synucleinopathies (Parkinson disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA], and pure autonomic failure [PAF]) is an urgent unmet need. Immunohistochemical detection of cutaneous phosphorylated α-synuclein may be a sensitive and specific clinical test for the diagnosis of synucleinopathies.ObjectiveTo evaluate the positivity rate of cutaneous α-synuclein deposition in patients with PD, DLB, MSA, and PAF.Design, Setting, and ParticipantsThis blinded, 30-site, cross-sectional study of academic and community-based neurology practices conducted from February 2021 through March 2023 included patients aged 40 to 99 years with a clinical diagnosis of PD, DLB, MSA, or PAF based on clinical consensus criteria and confirmed by an expert review panel and control participants aged 40 to 99 years with no history of examination findings or symptoms suggestive of a synucleinopathy or neurodegenerative disease. All participants completed detailed neurologic examinations and disease-specific questionnaires and underwent skin biopsy for detection of phosphorylated α-synuclein. An expert review panel blinded to pathologic data determined the final participant diagnosis.ExposureSkin biopsy for detection of phosphorylated α-synuclein.Main OutcomesRates of detection of cutaneous α-synuclein in patients with PD, MSA, DLB, and PAF and controls without synucleinopathy.ResultsOf 428 enrolled participants, 343 were included in the primary analysis (mean [SD] age, 69.5 [9.1] years; 175 [51.0%] male); 223 met the consensus criteria for a synucleinopathy and 120 met criteria as controls after expert panel review. The proportions of individuals with cutaneous phosphorylated α-synuclein detected by skin biopsy were 92.7% (89 of 96) with PD, 98.2% (54 of 55) with MSA, 96.0% (48 of 50) with DLB, and 100% (22 of 22) with PAF; 3.3% (4 of 120) of controls had cutaneous phosphorylated α-synuclein detected.Conclusions and RelevanceIn this cross-sectional study, a high proportion of individuals meeting clinical consensus criteria for PD, DLB, MSA, and PAF had phosphorylated α-synuclein detected by skin biopsy. Further research is needed in unselected clinical populations to externally validate the findings and fully characterize the potential role of skin biopsy detection of phosphorylated α-synuclein in clinical care.

Object Meige syndrome is characterized by blepharospasm, cervical dystonia, and facial oromandibular dystonia. The medical treatment of this condition is largely unsuccessful over time and is a major source of decreased quality of life in those patients suffering from this disease. Recent advances in the application of deep brain stimulation (DBS) surgery techniques for many disorders have prompted several recent reports of DBS for medically refractory cases of Meige syndrome. While the etiology for this disorder is unknown, it is considered by many investigators to be a form of idiopathic torsion dystonia. Pallidal stimulation is widely considered to be effective for dystonia. Methods The authors report the long-term results of bilateral globus pallidus internus (GPi) or subthalamic nucleus (STN) stimulation in 3 patients with Meige syndrome and 1 patient with Parkinson disease and associated craniofacial dystonia treated at their center. Results Initial 12-month and long-term follow-up Burke-Fahn-Marsden scores were substantially improved in all 4 patients compared with preoperative scores. Conclusions Bilateral GPi DBS may be an effective and safe treatment for medically refractory Meige syndrome. The results are comparable with those reported in the literature. Sustained and long-term improvement in symptoms does appear to be reproducible across reports. The authors' patient with Parkinson disease and associated craniofacial dystonia syndrome undergoing bilateral STN DBS noted immediate and sustained improvement in his symptoms. Further study is required, but these results, along with the other reports, suggest that bilateral GPi DBS is an effective treatment for medically refractory Meige syndrome.

PurposeCorticomuscular electroencephalographic-electromyographic (EEG-EMG) coherence elicited by speech and nonspeech oromotor tasks in healthy participants and those with Parkinson’s disease (PD) was examined. Hypotheses were the following: (a) corticomuscular coherence is demonstrable between orbicularis oris (OO) muscles' EMG and scalp EEG recording; (b) the presence, location, and magnitude of coherence is task specific; (c) differences in corticomuscular coherence patterns exist between healthy and PD participants; and (d) differences will manifest as either increased or decreased coherence values in certain frequency bands, with EEG localization at primary sensorimotor cortex and/or supplementary motor area (SMA).MethodSimultaneous EEG, EMG (OO), and speech samples were recorded on 20 healthy and 20 PD participants during speech and nonspeech tasks. Fast Fourier transform and coherence analysis was performed with Neuroscan software on 1,000 randomly generated epochs per task per group. Corticomuscular coherence was analyzed between each EEG electrode and right and left superior and inferior OO muscles up to 200 Hz. Significant coherence peaks exceeded 95% confidence limits (.003).ResultsCorticomuscular coherence existed for both groups and for all tasks, but to varying degrees in primary sensorimotor cortex and SMA.ConclusionsResults support task specificity for both groups and, in PD, a diminished modulation flexibility linked to the sensorimotor area and reduced corticomuscular coherence at the SMA.

Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) is a severe primary headache disorder that is often refractory to medical therapy. Although the pathogenesis of this and other trigeminal autonomic cephalalgias is not completely understood, ipsilateral activation of the posterior and inferior hypothalamus has been identified on functional imaging studies during attacks. The authors report on a case of SUNCT syndrome successfully treated with hypothalamic deep brain stimulation and discuss the current literature.