Rare mutations in NADH:ubiquinone oxidoreductase complex assembly factor 5 (NDUFAF5) are linked to Leigh syndrome.

Early-onset Parkinson's disease (EOPD) commonly recognizes a genetic basis; thus, patients with EOPD are often addressed to diagnostic testing based on next-generation sequencing (NGS) of PD-associated multigene panels. However, NGS interpretation can be challenging in a diagnostic setting, and few studies have addressed this issue so far.

A recent article by Ortega et al1 reported sex-specific differences in GBA1-related Parkinson's disease (PD), with an excess of females in carriers of severe variants and of males in carriers of mild variants, although these differences were not confirmed in subsequent reports.2, 3 They hypothesized that this difference might be because of a higher risk of male carriers of GBA1 severe variants developing

Spinocerebellar ataxia type 12 (SCA12) is a neurodegenerative disease caused by expansion of a CAG repeat in the PPP2R2B gene.

In movement disorders, phenomenology refers to the science and art of classifying abnormal movements. Traditional clinical practice has been based on phenotype-driven investigation, diagnosis, and management. However, many have questioned our continued reliance on phenotype. Phenotype has been repeatedly demonstrated to be an unreliable guide to the precise lower-level pathophysiological process. After

There is a growing body of evidence suggesting that botulinum toxin can alter proprioceptive feedback and modulate the muscle-spindle output for the treatment of dystonia. However, the mechanism for this modulation remains unclear.

Excessive glutamatergic transmission in the striatum is implicated in Parkinson's disease (PD) progression. Astrocytes maintain glutamate homeostasis, protecting from excitotoxicity through the glutamate–aspartate transporter (GLAST), whose alterations have been reported in PD. Noninvasive brain stimulation using intermittent theta-burst stimulation (iTBS) acts on striatal neurons and glia, inducing

Metals have been postulated as environmental concerns in the etiology of Parkinson's disease (PD), but metal levels are typically measured after diagnosis, which might be subject to reverse causality.

Preliminary studies suggested seasonality of dopaminergic functioning, but it is unknown whether dopamine transporter (DAT) expression in humans is also dependent on the seasons. We, therefore, investigated seasonal and sunlight-dependent effects on DAT availability in early Parkinson's disease (PD) patients and healthy controls.

Similar molecular processes have been identified in the development of Parkinson's disease (PD) and type 2 diabetes mellitus (T2DM).1 Insulin resistance is a central feature of T2DM pathology, and recent evidence supports its occurrence in the brain and its contribution in neurodegeneration.2 Insulin receptor substrate (IRS)-1 is the initial node in the pathway of insulin signaling and its activity

Vacuolar protein sorting 13 homolog A (VPS13A) disease, historically known as chorea-acanthocytosis, is a rare neurodegenerative disorder caused by biallelic mutations in VPS13A, usually resulting in reduced or absent levels of its protein product, VPS13A. VPS13A localizes to contact sites between subcellular organelles, consistent with its recently identified role in lipid transfer between membranes

Schirinzi T, Maftei D, Grillo P, et al., Olfactory Neuron Substance P is Overexpressed in Parkinson's Disease Reflecting Gut Dysfunction. Mov Disord 2023;38:1364–1366. In the ‘Funding agencies’ and ‘Acknowledgments’ sections of the above article, the grant from Sapienza University Intramural Grant “Grandi Progetti” lacks the number: RG12117A7779E023. We apologize for this error.

To date, studies on positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in progressive supranuclear palsy (PSP) usually included PSP cohorts overrepresenting patients with Richardson's syndrome (PSP-RS).

The aim of our study is to analyze sex-specific patterns of Parkinson's disease dementia (PDD) incidence. We are investigating the extent to which sex differences in survival after initial Parkinson's disease (PD) diagnosis influence differences in PDD risk among PD patients.

Dysfunction of the primary motor cortex, participating in regulation of posture and gait, is implicated in freezing of gait (FOG) in Parkinson's disease (PD).

In recent years, cervical dystonia (CD) has been recognized as a network disorder that involves not only the basal ganglia but other brain regions, such as the primary motor and somatosensory cortex, brainstem, and cerebellum. So far, the role of the cerebellum in the pathophysiology of dystonia is only poorly understood.

Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder characterized by motor and nonmotor symptoms. Several features have prognostic importance and have been used as key indicators for identifying clinical subtypes. However, the symptom-based classification approach has limitations with respect to the stability of the obtained subtypes.

GNAO1 variants are typically associated with severe, early-onset movement disorders (MDs) with life-threatening and drug-resistant paroxysmal exacerbations, neurodevelopmental disorders, and epilepsy. Recently, the phenotypic spectrum has broadened to include milder phenotypes with late-onset dystonia, minor cognitive impairment, and other neurological signs, including parkinsonism and myoclonus. GNAO1

Patients with Parkinson's disease (PD) carrying GBA gene mutations (GBA-PD) have a more aggressive disease course than those with idiopathic PD (iPD).

Mitochondrial membrane protein-associated neurodegeneration (MPAN) is caused by mutations in the C19orf12 gene. MPAN typically appears in the first two decades of life and presents with progressive dystonia-parkinsonism, lower motor neuron signs, optic atrophy, and abnormal iron deposits predominantly in the basal ganglia. MPAN, initially considered as a strictly autosomal recessive disease (AR), turned

Plant-based diets have been associated with a lower risk of several chronic diseases, but the relationship with PD is unknown.

Whether bone mineral density (BMD) is related to the risk of Parkinson's disease (PD) is unclear.

The accumulation and aggregation of α-synuclein (α-Syn) are characteristic of Parkinson's disease (PD). Epidemiological evidence indicates that hyperlipidemia is associated with an increased risk of PD. The levels of 27-hydroxycholesterol (27-OHC), a cholesterol oxidation derivative, are increased in the brain and cerebrospinal fluid of patients with PD. However, whether 27-OHC plays a role in α-Syn

To investigate whether mild motor signs (MMS) in old age correlate with synaptic density in the brain.

We read with great interest the article by Zou and colleagues titled “Summing MDS-UPDRS Parts 1 + 2 (Nonmotor and Motor Experience of Daily Living): The Patient's Voice.”1 In the past few years, the Movement Disorder Society–sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS),2 developed according to clinimetric guidelines and validated in several languages,3 has become an

In a recent article, Martino and colleagues1 describe the results of a systematic literature review of scales for measuring drug-induced movement disorders in people with severe mental illness (SMI). The article takes the starting point of the neurologist, and the lack of experiential knowledge about the conditions under which the scales are used provides quite a few misses. For example, the plea to

In their recent publication, Kühnel et al1 described the progression of multiple system atrophy (MSA) in the European MSA study group (EMSA-SG) cohort via an innovative disease progression model (DPM). DPMs are valuable longitudinal methods to describe MSA natural history while accounting for data uncertainty (delayed diagnosis, uncertain timing, heterogeneous staging).2 The mean trajectories of clinical

We are pleased to read the letter by Saulnier and colleagues related to our article “Disease Progression in Multiple System Atrophy—Novel Modeling Framework and Predictive Factors,”1 and we thank the authors for the impressive work they have done to replicate and expand on our research in a larger and more contemporary cohort. As Saulnier and colleagues rightly point out, our study relied on a cohort

We read with interest the updated review of the epidemiology of Huntington's disease (HD) by Medina et al.1 In their article, the authors present results from a series of meta-analyses of prevalence and incidence studies conducted in populations in Africa, Asia, Europe, and the Americas between 2011 and 2022. Worldwide pooled estimates are reported for prevalence and incidence, along with separate

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease that predominantly impacts a Caucasian population, but few efforts have explored racial differences in presentation and progression.

Cognitive deficits in Parkinson's disease (PD) patients are well described, however, their underlying neural mechanisms as assessed by electrophysiology are not clear.

Epigenetic clocks using DNA methylation (DNAm) to estimate biological age have become popular tools in the study of neurodegenerative diseases. Notably, several recent reports have shown a strikingly similar inverse relationship between accelerated biological aging, as measured by DNAm, and the age of onset of several neurodegenerative disorders, including Parkinson's disease (PD). Common to all of

Multiple system atrophy with parkinsonism (MSA-P) is a progressive condition with no effective treatment.

Brain magnetic resonance imaging (MRI) is used to support the diagnosis of progressive supranuclear palsy (PSP). However, the value of visual descriptive, manual planimetric, automatic volumetric MRI markers and fully automatic categorization is unclear, particularly regarding PSP predominance types other than Richardson's syndrome (RS).

Neurturin is a member of the glial cell line-derived neurotrophic factor family of neurotrophic factors and has the potential to protectdegenerating dopaminergic neurons.

Magnetic resonance guided focused ultrasound (MRgFUS) is United States Food and Drug Administration approved for the treatment of tremor-dominant Parkinson's disease (TdPD), but only limited studies have been described in practice.

Amyloid-β, phosphorylated tau (p-tau), and total tau (t-tau) in cerebrospinal fluid are established biomarkers for Alzheimer's disease (AD). In other neurodegenerative diseases, such as Parkinson's disease (PD), these biomarkers have also been found to be altered, and the molecular mechanisms responsible for these alterations are still under investigation. Moreover, the interplay between these mechanisms

Comorbidity exists between amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD), but the role of genetic factors is unclear.

Deep brain stimulation (DBS) has been part of the Parkinson's Disease (PD) toolkit for more than 20 years.1 Since then, an increasing number of patients have received DBS for management of PD motor fluctuations, parkinsonian tremor, and dyskinesias.2 As clinical experience with DBS for PD has deepened and more results such as the 2013 publication of the EARLYSTIM trial have supported earlier use of

Intronic GAA repeat expansions in the fibroblast growth factor 14 gene (FGF14) have recently been shown to be a common cause of adult-onset degenerative ataxia (spinocerebellar ataxia 27B [SCA27B], MIM: 620174),1, 2 but frequencies in strictly consecutive SCA cohorts are unknown. Here we studied the relative frequencies of SCA27B in a cohort of genetically undetermined autosomal dominant cerebellar

Glycoprotein nonmetastatic melanoma protein B (GPNMB) has been demonstrated to mediate pathogenicity in Parkinson's disease (PD) through interactions with α-synuclein, and plasma GPNMB tended to be a novel biomarker for PD.

Degeneration of the cortically-projecting cholinergic basal forebrain (cBF) is a well-established pathologic correlate of cognitive decline in Parkinson's disease (PD). In Alzheimer's disease (AD) the effect of cBF degeneration on cognitive decline was found to be mediated by parallel atrophy of denervated cortical areas.

Patients with Parkinson's disease (PD) exhibit widespread brain perfusion changes.

Laryngeal dystonia (LD) is focal task-specific dystonia, predominantly affecting speech but not whispering or emotional vocalizations. Prior neuroimaging studies identified brain regions forming a dystonic neural network and contributing to LD pathophysiology. However, the underlying temporal dynamics of these alterations and their contribution to the task-specificity of LD remain largely unknown.

Protein synthesis is a tightly controlled process, involving a host of translation-initiation factors and microRNA-associated repressors. Variants in the translational regulator EIF2AK2 were first linked to neurodevelopmental-delay phenotypes, followed by their implication in dystonia. Recently, de novo variants in EIF4A2, encoding eukaryotic translation initiation factor 4A isoform 2 (eIF4A2), have

A mitochondrial polygenic score (MGS) is composed of genes related to mitochondrial function and found to be associated with Parkinson's disease (PD) risk.

Adaptor protein complex 4-associated hereditary spastic paraplegia (AP-4-HSP) is caused by pathogenic biallelic variants in AP4B1, AP4M1, AP4E1, and AP4S1.

We read with interest the recent article by Weill et al.1 The authors collected local field potential (LFP) activity during implantation of subthalamic nucleus (STN) electrodes. They compared β-activity in genetic subtypes and idiopathic PD (iPD). No differences were found in β-activity, and the authors conclude that, in the future, similar adaptive deep brain stimulation (DBS) algorithms would be

Intracerebral administration of glial cell line–derived neurotrophic factor (GDNF) as a disease-modifying therapy has been trialed in Parkinson's disease (PD)1, 2; however, the potent effects seen in animal models have not been reproduced clinically. One reason proposed for this lack of efficacy in humans is downregulation of the GDNF receptor RET by α-synuclein (αSyn) in the PD substantia nigra (SN)

Heterozygous GAA expansions in the FGF14 gene have been related to autosomal dominant cerebellar ataxia (SCA27B-MIM:620174). Whether they represent a common cause of sporadic late-onset cerebellar ataxia (SLOCA) remains to be established.

Sex differences in Parkinson's disease (PD) risk are well-known. However, the role of sex chromosomes in the development and progression of PD is still unclear.

Alternating hemiplegia of childhood (AHC) (OMIM No. 614820) is an early-onset neurodevelopmental encephalopathy frequently caused by mutations in the ATP1A3 gene (OMIM *182350) encoding for the α3 subunit of the Na+/K+-ATPase.1 It is typically characterized by intellectual disability, motor dysfunction, and various paroxysmal events.1 The occurrence of plegic or dystonic attacks is an important determinant

Long-term use of levodopa for Parkinson's disease (PD) treatment is often hindered by development of motor complications, including levodopa-induced dyskinesia (LID). The substantia nigra pars reticulata (SNr) and globus pallidus internal segment (GPi) are the output nuclei of the basal ganglia. Dysregulation of SNr and GPi activity contributes to PD pathophysiology and LID.

It is generally believed that the pathogenesis of PINK1/parkin-related Parkinson's disease (PD) is due to a disturbance in mitochondrial quality control. However, recent studies have found that PINK1 and Parkin play a significant role in mitochondrial calcium homeostasis and are involved in the regulation of mitochondria–endoplasmic reticulum contact sites (MERCSs).

Essential tremor of voice (ETv) is characterized by involuntary oscillations of laryngeal and upper airway muscles, causing rhythmic alterations in pitch and loudness during both passive breathing and active laryngeal tasks, such as speaking and singing. Treatment of ETv is challenging and typically less effective compared with treatment of ET affecting extremities.

Parkinson's disease (PD) biomarkers are needed by both clinicians and researchers (for diagnosis, identifying study populations, and monitoring therapeutic response). Imaging, genetic, and biochemical biomarkers have been widely studied. In recent years, extracellular vesicles (EVs) have become a promising material for biomarker development. Proteins and molecular material from any organ, including