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Parkinson's disease (PD) is a complex disease, and the treatment is focused on the patient's clinical symptoms. Levodopa continues to be the most effective drug for symptomatic PD treatment. However, chronic levodopa treatment is associated with the development of motor complications in most patients. Add-on therapeutic drugs, such as dopamine agonists and monoamine oxidase B (MAO-B) inhibitors, for example, safinamide and rasagiline, may be a desirable addition to continuously increase the levodopa dose for the optimization of motor control in PD. The scientific literature shows that safinamide significantly alleviated motor fluctuations with no increase in troublesome dyskinesia, thanks to its unique double mechanism, providing further benefits to fluctuating PD patients when compared to a placebo or other drugs. Switching from rasagiline to safinamide has been shown to improve the wearing-off phenomena, which is defined as the recurrent, predictable worsening of symptoms of parkinsonism at the end of the levodopa dose until the next dose reaches a clinical effect. In this situation, safinamide may be helpful for reducing the total daily dose of levodopa, improving the OFF time and ON time without troublesome dyskinesias, and being more effective than other MAO-B inhibitors. In this narrative review, we explore the switch from rasagiline to safinamide in patients with motor complications as a feasible and effective alternative to optimize antiparkinsonian treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The effect of subthalamic deep brain stimulation on balance in Parkinson's disease remains unclear.Objective: To evaluate the effect of subthalamic nucleus stimulation on balance in Parkinson's disease using posturography.Methods: 16 patients (9 women) who underwent subthalamic deep brain stimulation [mean age 59.6 years (46-70); mean disease duration 15.6 years (7-25); mean duration of subthalamic stimulation 32.1 months (3.0-69.6)] and 13 healthy age-matched controls were evaluated using a static posturography analysis. Patients were assessed under four conditions: 1) off medication/off stimulation; 2) off medication/on stimulation; 3) on medication/off stimulation and 4) on medication/on stimulation in ten experimental paradigms, some reproducing common situations of daily living. The displacement of the centre of pressure was analyzed using 14 posturographic parameters. The Mann-Whitney test was used to compare patients with controls. The Wilcoxon signed rank test was used to compare patients under different clinical conditions.Results: Patients off medication/off stimulation showed larger and more rapid displacements of the centre of pressure than controls in most paradigms (p<0.05), particularly when performing a dual task. Subthalamic stimulation alone reduced the lateral excursion and anterior-posterior velocity of the centre of pressure in quite stance paradigms (p<0.05). Subthalamic stimulation combined with antiparkinsonian medication did not induce statistically significant changes in posturagraphic measures in any experimental paradigm.Conclusions: Although subthalamic stimulation alone may induce some positive effect on balance, subthalamic stimulation in addition to antiparkinsonian medication, which is the usual treatment in clinical practice, did not modify balance as assessed by static posturography in patients with Parkinson's disease. [ABSTRACT FROM AUTHOR]

Abstract: Dopamine dysregulation syndrome is a complication of the dopaminergic treatment for Parkinson''s disease, probably related to sensitization of the mesolimbic dopamine system. The relationship between dopamine dysregulation syndrome and deep brain stimulation of the subthalamic nucleus remains unclear. We report three patients with Parkinson''s disease who developed de novo dopamine dysregulation syndrome after deep brain stimulation of the subthalamic nucleus. We hypothesized that the combined effect of dopaminergic replacement therapy and deep brain stimulation on the limbic territory of the subthalamic nucleus could have precipitated the dopamine dysregulation syndrome in these patients, by inducing hyperstimulation of the mesolimbic dopamine system. The outcome of postoperative dopamine dysregulation syndrome is poor despite deep brain stimulation adjustments, attempts to reduce the dose of dopaminergic drugs and the addition of quetiapine or antidepressants. [Copyright &y& Elsevier]

Background: Defects in GNAO1, the gene encoding the major neuronal G‐protein Gαo, are related to neurodevelopmental disorders, epilepsy, and movement disorders. Nevertheless, there is a poor understanding of how molecular mechanisms explain the different phenotypes. Objectives: We aimed to analyze the clinical phenotype and the molecular characterization of GNAO1‐related disorders. Methods: Patients were recruited in collaboration with the Spanish GNAO1 Association. For patient phenotyping, direct clinical evaluation, analysis of homemade‐videos, and an online questionnaire completed by families were analyzed. We studied Gαo cellular expression, the interactions of the partner proteins, and binding to guanosine triphosphate (GTP) and G‐protein‐coupled receptors (GPCRs). Results: Eighteen patients with GNAO1 genetic defects had a complex neurodevelopmental disorder, epilepsy, central hypotonia, and movement disorders. Eleven patients showed neurological deterioration, recurrent hyperkinetic crisis with partial recovery, and secondary complications leading to death in three cases. Deep brain stimulation improved hyperkinetic crisis, but had inconsistent benefits in dystonia. The molecular defects caused by pathogenic Gαo were aberrant GTP binding and hydrolysis activities, an inability to interact with cellular binding partners, and reduced coupling to GPCRs. Decreased localization of Gαo in the plasma membrane was correlated with the phenotype of "developmental and epileptic encephalopathy 17." We observed a genotype–phenotype correlation, pathogenic variants in position 203 were related to developmental and epileptic encephalopathy, whereas those in position 209 were related to neurodevelopmental disorder with involuntary movements. Milder phenotypes were associated with other molecular defects such as del.16q12.2q21 and I344del. Conclusion: We highlight the complexity of the motor phenotype, which is characterized by fluctuations throughout the day, and hyperkinetic crisis with a distinct post‐hyperkinetic crisis state. We confirm a molecular‐based genotype–phenotype correlation for specific variants. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Previous studies have suggested a relationship between the number of CAG triplet repeats in the HTT gene and neurodegenerative diseases not related to Huntington's disease (HD). This study seeks to investigate whether the number of CAG repeats of HTT is associated with the risk of developing certain tauopathies and its influence as a modulator of the clinical and neuropathological phenotype. Additionally, it aims to evaluate the potential of polyglutamine staining as a neuropathological screening. We genotyped the HTT gene CAG repeat number and APOE‐ℰ isoforms in a cohort of patients with neuropathological diagnoses of tauopathies (n=588), including 34 corticobasal degeneration (CBD), 98 progressive supranuclear palsy (PSP) and 456 Alzheimer's disease (AD). Furthermore, we genotyped a control group of 1070 patients, of whom 44 were neuropathologic controls. We identified significant differences in the number of patients with pathological HTT expansions in the CBD group (2.7%) and PSP group (3.2%) compared to control subjects (0.2%). A significant increase in the size of the HTT CAG repeats was found in the AD compared to the control group, influenced by the presence of the Apoliprotein E (APOE)‐ℰ4 isoform. Post‐mortem assessments uncovered tauopathy pathology with positive polyglutamine aggregates, with a slight predominance in the neostriatum for PSP and CBD cases and somewhat greater limbic involvement in the AD case. Our results indicated a link between HTT CAG repeat expansion with other non‐HD pathology, suggesting they could share common neurodegenerative pathways. These findings support that genetic or histological screening for HTT repeat expansions should be considered in tauopathies. [ABSTRACT FROM AUTHOR]

The article discusses the long-term outcomes of deep brain stimulation (DBS) in a 10-year-old boy with Glutaric Aciduria Type 1 (GA1), a rare neurometabolic disorder. The boy experienced significant improvement in choreodystonic movements after DBS surgery, with some persistent symptoms in the left lower limb. DBS has shown effectiveness in treating drug-resistant movement disorders, but outcomes in pediatric patients with GA1 are still being studied due to limited evidence and heterogeneous results. Further research with larger patient cohorts is needed to better understand the impact of DBS on GA1 patients. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

Background The reasons underlying the loss of efficacy of deep brain stimulation ( DBS) of the thalamic nucleus ventralis intermedius ( VIM- DBS) over time in patients with essential tremor are not well understood. Methods Long-term clinical outcome and stimulation parameters were evaluated in 14 patients with essential tremor who underwent VIM- DBS. The mean ± standard deviation postoperative follow-up was 7.7 ± 3.8 years. At each visit (every 3-6 months), tremor was assessed using the Fahn-Tolosa-Marin tremor rating scale ( FTM- TRS) and stimulation parameters were recorded (contacts, voltage, frequency, pulse width, and total electrical energy delivered by the internal generator [ TEED1sec]). Results The mean reduction in FTM- TRS score was 73.4% at 6 months after VIM- DBS surgery ( P < 0.001) and 50.1% at the last visit ( P < 0.001). The gradual worsening of FTM- TRS scores over time fit a linear regression model (coefficient of determination [R2] = 0.887; P < 0.001). Stimulation adjustments to optimize tremor control required a statistically significant increase in voltage ( P = 0.01), pulse width ( P = 0.01), frequency ( P = 0.02), and TEED1sec ( P = 0.008). TEED1sec fit a third-order polynomial curve model throughout the follow-up period (R2 = 0.966; P < 0.001). The initial exponential increase (first 4 years of VIM- DBS) was followed by a plateau and a further increase from the seventh year onward. Conclusions The current findings suggest that the waning effect of VIM- DBS over time in patients with essential tremor may be the consequence of a combination of factors. Superimposed on the progression of the disease, tolerance can occur during the early years of stimulation. [ABSTRACT FROM AUTHOR]

• Two cases of Serotonin syndrome (SS) in COVID-19 patients are presented. • Lopinavir/ritonavir (LPV/r) have been widely used during the COVID-19 pandemic. • LPV/r with duloxetine and lithium triggered SS in patient 1. • LPV/r with risperidone, and probably also morphine, triggered SS in patient 2. • A Video of patient 2 shows myoclonus and ocular clonus in the context of SS. [ABSTRACT FROM AUTHOR]