Objective GM2 gangliosidoses are lysosomal diseases due to biallelic mutations in the HEXA (Tay–Sachs disease [TS]) or HEXB (Sandhoff disease [SD]) genes, with subsequent low hexosaminidase(s) activity. Most patients have childhood onset, but some experience the first symptoms during adolescence/adulthood. This study aims to clarify the natural history of adult patients with GM2 gangliosidosis. Methods We retrospectively described 12 patients from a French cohort and 45 patients from the literature. Results We observed 4 typical presentations: (1) lower motoneuron disorder responsible for proximal lower limb weakness that subsequently expanded to the upper limbs, (2) cerebellar ataxia, (3) psychosis and/or severe mood disorder (only in the TS patients), and (4) a complex phenotype mixing the above 3 manifestations. The psoas was the first and most affected muscle in the lower limbs, whereas the triceps and interosseous were predominantly involved in the upper limbs. A longitudinal study of compound motor action potentials showed a progressive decrease in all nerves, with different kinetics. Sensory potentials were sometimes abnormally low, mainly in the SD patients. The main brain magnetic resonance imaging feature was cerebellar atrophy, even in patients without cerebellar symptoms. The prognosis was mainly related to gait disorder, as we showed that beyond 20 years of disease evolution, half of the patients were wheelchair users. Interpretation Improved knowledge of GM2 gangliosidosis in adults will help clinicians achieve correct diagnoses and better inform patients on the evolution and prognosis. It may also contribute to defining proper outcome measures when testing emerging therapies. ANN NEUROL 2020;87:609–617

Growing evidence suggests that environmental factors play a key role in the onset of multiple sclerosis (MS). This study was conducted to examine whether environmental factors may also be associated with the evolution of the disease. We collected data on smoking habits, sunlight exposure and diet (particularly consumption of vitamin D-rich foods) from a sample of 131 MS patients. We also measured their serum vitamin D concentration. The clinical impact of MS was quantified using the Multiple Sclerosis Severity Score (MSSS); MS was considered “severe” in patients with MSSS ≥ 6, and “mild” in patients with MSSS ≤ 1. The results showed a strong association between serum vitamin D concentration and both sunlight exposure (26.4 ± 11.9 ng/mL vs. 16.5 ± 12.1 ng/mL, p = 0.0004) and a fish-rich diet (23.5 ± 12.1 ng/mL vs. 16.1 ± 12.4 ng/mL, p = 0.005). Patients reporting frequent sunlight exposure had a lower MSSS (2.6 ± 2.4 h vs. 4.6 ± 2.6 h, p < 0.001). The mild MS patients reported much more frequent sunlight exposure (75% mild MS vs. 25% severe MS p = 0.004, Chi square test). A higher serum vitamin D concentration determined a lower risk of developing severe MS, adjusted for sunlight exposure (OR = 0.92 for one unit increase in vitamin D, 95% CI: 0.86–0.97, p = 0.005). A stronger inverse association emerged between frequent sunlight exposure and the risk of severe MS (OR = 0.26, 95% CI: 0.09–0.71, p = 0.009). Our data show that an appropriate diet and adequate expose to sunlight are associated with less aggressive MS.

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To evaluate the utility of different outcome measures to monitor dose adjustment of intravenous immunoglobulin (IVIg) therapy in patients with chronic inflammatory neuropathy (CIN). We assessed the adjustment of IVIg maintenance therapy in 20 patients (10 CIDP and 10 MMN) by regularly monitoring grip strength (GS) using a Martin Vigorimeter, RODS, and quality of life using the SF‐36 questionnaire. These measures were regularly performed by the patient at home. We also assessed the extended MRC sumscore (eMRC sumscore) at each outpatient visit for IVIg infusion. We also enrolled 30 healthy controls to measure any possible training effect of GS with time and to analyze random fluctuation of GS. Clinically relevant change was detected by eMRC sumscore in 14 (93%) patients, by RODS in 11 (73%) patients, and by GS in 8 (53%) patients. Early sensitivity was greatest for RODS (73%), followed by GS (53%), and eMRC sumscore (27%). This differed from CIDP, with an early change in RODS in 100% of patients, and MMN with an early change in GS in 75%. None of the outcome measures alone was sufficient to detect clinically significant changes in all patients. Home monitoring of outcome measures objectively assisted clinical decision during individualization of IVIg treatment. We recommend a multimodal approach using different outcome measures to monitor the individual patient with CIN.