Background Pathogenic variants in the spastic paraplegia type 7 gene cause a complicated hereditary spastic paraplegia phenotype associated with classical features of mitochondrial diseases, including ataxia, progressive external ophthalmoplegia, and deletions of mitochondrial DNA. Objectives To better characterize spastic paraplegia type 7 disease with a clinical, genetic, and functional analysis of a Spanish cohort of spastic paraplegia type 7 patients. Methods Genetic analysis was performed in patients suspecting hereditary spastic paraplegia and in 1 patient with parkinsonism and Pisa syndrome, through next‐generation sequencing, whole‐exome sequencing, targeted Sanger sequencing, and multiplex ligation‐dependent probe analysis, and blood mitochondrial DNA levels determined by quantitative polymerase chain reaction. Results Thirty‐five patients were found to carry homozygous or compound heterozygous pathogenic variants in the spastic paraplegia type 7 gene. Mean age at onset was 40 years (range, 12–63); 63% of spastic paraplegia type 7 patients were male, and three‐quarters of all patients had at least one allele with the c.1529C>T (p.Ala510Val) mutation. Eighty percent of the cohort showed a complicated phenotype, combining ataxia and progressive external ophthalmoplegia (65% and 26%, respectively). Parkinsonism was observed in 21% of cases. Analysis of blood mitochondrial DNA indicated that both patients and carriers of spastic paraplegia type 7 pathogenic variants had markedly lower levels of mitochondrial DNA than control subjects (228 per haploid nuclear DNA vs. 176 vs. 573, respectively; P < 0.001). Conclusions Parkinsonism is a frequent finding in spastic paraplegia type 7 patients. Spastic paraplegia type 7 pathogenic variants impair mitochondrial DNA homeostasis irrespective of the number of mutant alleles, type of variant, and patient or carrier status. Thus, spastic paraplegia type 7 supports mitochondrial DNA maintenance, and variants in the gene may cause parkinsonism owing to mitochondrial DNA abnormalities. Moreover, mitochondrial DNA blood analysis could be a useful biomarker to detect at risk families. © 2019 International Parkinson and Movement Disorder Society

Serotonin syndrome (SS) is a potentially life-threatening drug-induced disorder mediated by serotoninergic over-activity at synapses of the central and peripheral nervous system [1]. The fixed combination of lopinavir/ritonavir (LPV/r) has been widely used during the present Coronavirus Disease 2019 (COVID-19) pandemic [2]. Ritonavir has, however, been shown to trigger SS in HIV-infected individuals [3]. We here provide the first report of two COVID-19 patients who developed SS.

Objective To describe the spectrum of neurological complications observed in a hospital‐based cohort of COVID‐19 patients who required a neurological assessment. Methods We conducted an observational, monocentric, prospective study of patients with a COVID‐19 diagnosis hospitalized during the 3‐month period of the first wave of the COVID‐19 pandemic in a tertiary hospital in Madrid (Spain). We describe the neurological diagnoses that arose after the onset of COVID‐19 symptoms. These diagnoses could be divided into different groups. Results Only 71 (2.6%) of 2750 hospitalized patients suffered at least one neurological complication (77 different neurological diagnoses in total) during the timeframe of the study. The most common diagnoses were neuromuscular disorders (33.7%), cerebrovascular diseases (CVDs) (27.3%), acute encephalopathy (19.4%), seizures (7.8%), and miscellanea (11.6%) comprising hiccups, myoclonic tremor, Horner syndrome and transverse myelitis. CVDs and encephalopathy were common in the early phase of the COVID‐19 pandemic compared to neuromuscular disorders, which usually appeared later on ( p = 0.005). Cerebrospinal fluid severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) polymerase chain reaction was negative in 15/15 samples. The mortality was higher in the CVD group (38.1% vs. 8.9%; p = 0.05). Conclusions The prevalence of neurological complications is low in patients hospitalized for COVID‐19. Different mechanisms appear to be involved in these complications, and there was no evidence of direct invasion of the nervous system in our cohort. Some of the neurological complications can be classified into early and late neurological complications of COVID‐19, as they occurred at different times following the onset of COVID‐19 symptoms.

Background The aim of this study was to determine the frequency of intermediate alleles (IAs) in ATXN1, ATXN2 and HTT in patients with neurodegenerative diseases. Methods This is a multicentric study that included 1126 Alzheimer disease (AD) , 433 frontotemporal dementia (FTD) and 610 Parkinson´s disease (PD) patients. In all cohorts, we genotyped CAG repeats in ATXN1 and ATXN2 genes. Additionally, in FTD cohort we genotyped CAG repeats in HTT gene. Results In the overall FTD cohort, the frequency of HTT IAs was significantly higher in cases comparatively to controls (6.9% vs. 2.9%; p=0.007.; OR:2.45 (1.30-4.62). The frequency was even higher for c9orf72 expansion negative individuals (7.4% vs. 2.9%; p=0.

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