Benarroch, Eduardo E.

AbstractBackgroundYoung‐onset multiple system atrophy (YOMSA) is defined as the onset of multiple system atrophy (MSA) before the age of 40 years old. YOMSA is rare and there is much uncertainty of the phenotype and natural history in patients with YOMSA.ObjectiveThe objective is to evaluate the characteristics and disease course of patients with YOMSA.MethodsWe retrospectively reviewed medical records of patients with MSA who were evaluated at all Mayo Clinic sites from 1998 to 2021. We identified patients with YOMSA and evaluated clinical characteristics, autonomic function testing results, and disease course.ResultsOf 1496 patients with a diagnosis of clinically probable or clinically established MSA, 20 patients had YOMSA. The median age of onset was 39.1 (interquartile range [IQR] = 37.1, 40.1) years; 13 patients (65%) were male. MSA‐parkinsonism was the most common subtype (65%). The median duration of symptom onset to YOMSA diagnosis was 4.9 (IQR = 3.7, 9) years. At the time of medical record review, 17 patients were deceased with a median survival of 8.3 (IQR = 7, 10.9) years. Univariate analysis showed that initial onset of autonomic failure predicted unfavorable survival (hazard ratio = 2.89, P = 0.04) compared to those who presented with motor impairment only at onset. At the time of YOMSA diagnosis, composite autonomic severity score was available in 19 patients with a median of 5 (IQR = 4, 6.5).ConclusionsYOMSA resembles MSA in most aspects including phenotype and prognosis, although the diagnosis is usually delayed. The presence of autonomic failure at symptom onset may be a poor predictor for survival.

Abstract Background Restless legs syndrome (RLS) is a prevalent sensorimotor disorder that can dramatically impair sleep quality, daytime function, and quality of life. Although many patients benefit from standard pharmacological therapy, some patients suffer from insufficient treatment response or medication intolerance. Novel treatment approaches are therefore necessary. Objective Given the overlap between RLS and pain syndromes in both pathophysiological mechanisms and certain treatment options, we aimed to perform a scoping review of the available evidence on spinal cord stimulation (SCS) for RLS and discuss potential mechanistic implications. Methods We identified a total of 16 cases of patients with RLS who underwent SCS, all from case reports or case series. Discussion The published evidence is insufficient to assess SCS efficacy in patients with RLS, but SCS remains a promising investigational therapy in RLS on the basis of its potential mitigatory effects in the central hyperexcitability of the sensorimotor cortex through neuromodulation of spinal, subcortical, and cortical areas. A call for further research in this field is presented, with suggestions for future directions and trial designs.

Abstract Objective Advanced Parkinson's Disease (PD) is associated with Parkinson’s Disease gait impairment (PDg), which increases the risk for falls and is often treatment-refractory. Subthalamic nucleus (STN) and globus pallidus pars interna (GPi) deep brain stimulation (DBS) often fails to improve axial symptoms like PDg. Spinal cord stimulation (SCS) has been suggested to improve PDg. SCS may benefit PDg by disrupting pathologic beta-oscillations and hypersynchrony in cortico-striatal-thalamic circuits to override excessive inhibition of brainstem locomotor regions. SCS may potentially improve locomotion by acting at any of these levels, either alone or in combination. Methods We conducted a comprehensive literature search and scoping review, identifying 106 patients in whom SCS was evaluated for PDg. Results Among the identified patients, 63% carried a pain diagnosis. Overall, the most common stimulation location was thoracic (78%), most commonly T9-T10. Burst (sub-perception) was the most common stimulation modality (59%). Prior treatment with DBS was used in 25%. Motor outcomes were assessed by the Unified Parkinson Disease Rating Scale (UPDRS) III-motor, UPDRS, the Timed Up and Go (TUG), and/or 10-/20-meter walking tests. Among these patients, 95 (90%) had PDg amelioration and improved motor outcomes. Conclusions Despite small sample sizes, patient heterogeneity, and unblinded evaluations complicating interpretations of efficacy and safety, SCS may be beneficial for at least a subset of PDg. Further research is required to clarify the role of SCS for PDg and the patients most suitable to benefit from this intervention.