Muscle quality is defined as muscle strength generated per unit muscle mass. If enzyme replacement therapy (ERT) has some effects on type II glycogenosis (GSDII) skeletal muscle pathology, we should be able to measure a change in strength and mass. We conducted a prospective study including 11 patients aged 54.2 ± 11.2 years, referring to a single institution and receiving ERT for ≥2 years. Median Walton score was 3 (2.5-6). Lower limb skeletal muscles were assessed by dynamometry and quantitative muscle MRI. Three segments (anterior thigh, posterior thigh, leg) were analysed separately. Clinical-MRI correlations were searched for at T0, T6/T8, and T18/24. Changes in lean and fat body composition were assessed by bioelectrical impedance analysis. We found that the anterior thigh showed the best therapeutic response, with an improvement in muscle quality (muscle mass: +7.5%, p = 0.035; strength: +45%, p = 0.002). BMI and lean body mass increased (p = 0.007). Patients with low BMI showed a better outcome. Intramuscular fat accumulation significantly progressed in spite of ERT (+3.7%, p = 0.001), especially in the poorly responsive posterior thigh muscles. Both clinical assessment and MRI revealed a definite improvement in the anterior thigh muscles. However, progression of intramuscular fat accumulation during ERT, as well as the limited responsiveness of posterior thigh muscles, suggests the necessity for early treatment intervention. The better outcome of patients with low BMI, if confirmed, may indicate that dietary protocols could be adopted as adjuvant measures to ERT in adult GSDII.

Introduction/Aims Coronavirus disease 2019 (COVID‐19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, has become a global pandemic. Patients with myasthenia gravis (MG), often treated with immunosuppressants, might be at higher risk of developing COVID‐19 and of demonstrating a severe disease course. We aimed to study prevalence and describe features of COVID‐19 in MG patients. Methods In May 2020, we conducted telephonic interviews with MG patients followed at our referral center. We collected structured data regarding MG and COVID‐19, which was diagnosed as probable or confirmed according to the European Centre for Disease Prevention and Control case definition. We compared confirmed‐COVID‐19 prevalence calculated from the beginning of the pandemic in MG patients with that of the overall Pavia district. Results We interviewed 162 MG patients (median age, 66 y; interquartile range 41‐77; males 59.9%), 88 from the Pavia district. Three patients had SARS‐CoV‐2‐confirmed by polymerase chain reaction and eight had probable‐COVID‐19. In the Pavia district, the prevalence of confirmed‐COVID‐19 among MG patients (1/88, 1.14%) and overall population (4777/546 515, 0.87%) did not differ ( P = .538). Higher Myasthenia Gravis Foundation of America clinicalclass and the need for recent rescue treatment, but not ongoing immunosuppressive treatments, were associated with COVID‐19 risk. Of 11 MG patients with probable/confirmed‐COVID‐19, 3 required ventilator support, and 2 elderly patients died of COVID‐19 respiratory insufficiency. Only 1 of11 patients experienced worsening MG symptoms, which improved after increasing their steroid dose. Discussion The risk of COVID‐19 in MG patients seems to be no higher than that of the general population, regardless of immunosuppressive therapies. In our cohort, COVID‐19 barely affected MG course.

Objective Progressive multifocal leukoencephalopathy (PML) is still burdened by high mortality in a subset of patients, such as those affected by hematological malignancies. The aim of this study was to analyze the safety and carry out preliminary evaluation of the efficacy of polyomavirus JC (JCPyV)‐specific T cell therapy in a cohort of hematological patients with PML. Methods Between 2014 and 2019, 9 patients with a diagnosis of “definite PML” according to the 2013 consensus who were showing progressive clinical deterioration received JCPyV‐specific T cells. Cell lines were expanded from autologous or allogenic peripheral blood mononuclear cells by stimulation with JCPyV antigen‐derived peptides. Results None of the patients experienced treatment‐related adverse events. In the evaluable patients, an increase in the frequency of circulating JCPyV‐specific lymphocytes was observed, with a decrease or clearance of JCPyV viral load in cerebrospinal fluid. In responsive patients, transient appearance of punctate areas of contrast enhancement within, or close to, PML lesions was observed, which was interpreted as a sign of immune control and which regressed spontaneously without the need for steroid treatment. Six of 9 patients achieved PML control, with 5 alive and in good clinical condition at their last follow‐up. Interpretation Among other novel treatments, T cell therapy is emerging as a viable treatment option in patients with PML, particularly for those not amenable to restoration of specific immunity. Neurologists should be encouraged to refer PML patients to specialized centers to allow access to this treatment strategy. ANN NEUROL 2021;89:769–779

A 44-year-old previously healthy woman developed acute myelitis in close temporal relationship with ChAdOx1 nCoV-19 vaccine first-dose administration. The neurological involvement was mainly sensory with neuroimaging showing two mono-metameric lesions involving the posterior and lateral cord at dorsal level. Significant improvement was promptly recorded with high-dose intravenous steroids, with complete recovery within one month. The strict temporal relationship between vaccination and myelitis, together with the absence of clues pointing to alternative diagnoses, might suggest a conceivable role for anti-SARS-CoV-2 vaccine as immunological trigger, although a causal relationship has yet to be established and our preliminary observation suggests caution.

In 31 patients with probable Alzheimer's disease (AD), 19 with probable vascular dementia (VaD) and 20 with Possible AD and Possible VaD, cerebrospinal fluid (CSF) tau levels hyperphosphorylated at threonine 181 (Ptau) were measured by ELISA. Thirty-six age-matched subjects were used as controls. The severity of the cognitive decline was assessed at the time of CSF analysis and after a 12-month follow-up. The groups had comparable age, degree of cognitive impairment and disease duration; these parameters were not related to P-tau levels. P-tau discriminated between demented patients and controls, but no significant difference emerged between AD and the other groups. By contrast, higher P-tau values were found to predict, independently of the clinical diagnosis, a more rapid evolution of cognitive decline. Whether these findings are due to a lack of CSF P-tau specificity or to the low reliability of clinical and radiological criteria remains unclear. P-tau may be useful in the evaluation of disease evolution, by predicting the rate of cognitive decline.