Does limited EMG denervation in early primary lateral sclerosis predict amyotrophic lateral sclerosis?

Objective: We assessed whether a cohort of patients with primary lateral sclerosis (PLS) and limited electromyography (EMG) motor unit denervation changes evolve into amyotrophic lateral sclerosis (ALS) with prolonged follow-up. Methods: We initially ascertained all PLS patients diagnosed at Mayo Clinic-Rochester (1990-2016). Of 64 total cases, 43 had normal EMGs ("pure" PLS) during the first 4 years after symptom onset and were the focus of a prior publication, documenting absence of evolution to ALS. The remaining 21 patients had limited motor unit changes on EMG needle examination (denervation and most with fibrillation or fasciculation potentials) but insufficient to raise a strong suspicion of ALS; these 21 patients were followed to determine whether they evolved into ALS. Results: Of these 21 patients, the median follow-up was 7 years' disease duration (range: 4-27 years; IQR 5-8.5). They included 11 females (52%) with median onset-age of 57 years (range: 42-72 years). Two patients (10%) subsequently met revised El Escorial criteria for ALS after 7 and 13 years, respectively. The remainder had stable EMG changes with a persistent PLS phenotype. Among these remaining 19 patients, the PLS course was somewhat more aggressive than our previously reported series of 43 patients devoid of EMG denervation. The paraparetic variant was more common than the hemiparetic and bulbar variants, similar to "pure" PLS. Conclusions: Among PLS patients with definite but limited EMG denervation, 2/21 (10%) later developed ALS. The patients in this series had a more progressive clinical course compared to our previously reported pure PLS cases.

Motor and non-motor features of Parkinson's disease in LRRK2 G2019S carriers versus matched controls.

INTRODUCTION: LRRK2 G2019S mutation carriers with Parkinson's disease (PD) have been generally indistinguishable from those with idiopathic PD, with the exception of variable differences in some motor and non-motor domains, including cognition, gait, and balance. LRRK2 G2019S is amongst the most common genetic etiologies for PD, particularly in Ashkenazi Jewish (AJ) populations. METHODS: This cross-sectional data collection study sought to clarify the phenotype of LRRK2 G2019S mutation carriers with PD. Primary endpoints were the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) and Montreal Cognitive Assessment (MoCA). Other motor and non-motor data were also assessed. The Mann-Whitney U Test was utilized to compare LRRK2 G2019S carriers with PD (LRRK2+) with non-carrier PD controls who were matched for age, gender, education, and PD duration. Survival analyses and log rank tests were utilized to compare interval from onset of PD to development of motor and non-motor complications. RESULTS: We screened 251 subjects and 231 completed the study, of whom 9 were LRRK2+, including 7 AJ subjects. 22.73% of AJ subjects with a family history of PD (FH) and 12.96% of AJ subjects without a FH were LRRK2+. There were no significant differences between the 9 LRRK2+ subjects and 19 matched PD controls in MDS-UPDRS, MoCA, or other motor and non-motor endpoints. CONCLUSION: Prevalence of the LRRK2 G2019S mutation in AJ and non-AJ subjects in our study population in Cleveland, Ohio was comparable to other clinical studies. There were no significant motor or non-motor differences between LRRK2+ PD and matched PD controls.