Analysis of Fine Motor Skills in Essential Tremor: Combining Neuroimaging and Handwriting Biomarkers for Early Management.

Essential tremor (ET) is a highly prevalent neurological disorder characterized by action-induced tremors involving the hand, voice, head, and/or face. Importantly, hand tremor is present in nearly all forms of ET, resulting in impaired fine motor skills and diminished quality of life. To advance early diagnostic approaches for ET, automated handwriting tasks and magnetic resonance imaging (MRI) offer an opportunity to develop early essential clinical biomarkers.

The unexpected co-occurrence of GRN and MAPT p.A152T in Basque families: Clinical and pathological characteristics.

Background: The co-occurrence of the c.709-1G>A GRN mutation and the p.A152T MAPT variant has been identified in 18 Basque families affected by frontotemporal dementia (FTD).

Tau/α-synuclein ratio and inflammatory proteins in Parkinson's disease: An exploratory study.

Background: No CSF or plasma biomarker has been validated for diagnosis or progression of PD.

Objectives: To assess whether the CSF and plasma levels of proteins associated with PD neuropathological inclusions and with neuroinflammation might have value in the diagnosis of PD or in relation to disease severity.

Methods: CSF levels of α-synuclein, amyloid-ß1-42, total tau, and threonine-181 phosphorylated tau, as well as CSF and plasma levels of cytokines (interleukin-1ß, interleukin-2, interleukin, interferon-γ, and tumor necrosis factor α) were studied in 40 PD patients and 40 healthy controls.

Genetic Mutation Analysis of Parkinson's Disease Patients Using Multigene Next-Generation Sequencing Panels.

Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting millions of people. Genome-wide association studies (GWAS) have found >25 genetic risk factors and at least 15 loci directly associated with PD. Recent advances in new next-generation DNA sequencing technologies, such as the semiconductor-based Ion Torrent platform, make multigene sequencing cheaper, faster, and more reliable.

Inflammatory profile in LRRK2-associated prodromal and clinical PD.

Background: There is evidence for a relevant role of inflammation in the pathogenesis of Parkinson's disease (PD). Mutations in the LRRK2 gene represent the most frequent genetic cause for autosomal dominant PD. LRRK2 is highly expressed in macrophages and microglia suggesting an involvement in inflammatory pathways.

DAT imaging and clinical biomarkers in relatives at genetic risk for LRRK2 R1441G Parkinson's disease.

Background: The objective of this study was to study motor and nonmotor symptoms and striatal dopaminergic denervation, as well as the relationship between them, in a cohort of asymptomatic relatives of patients with Parkinson's disease (PD) with the R1441G-leucine-rich repeat kinase 2 mutation.

Methods: Asymptomatic relatives of patients with PD and this mutation were tested for the presence of the mutation and evaluated for striatal, putamenal, and caudate dopaminergic transporters using (123)I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single-photon emission computed tomography binding ratios. Clinical and neuropsychological evaluations including timed motor tests, a smell identification test, and global cognition, attention, executive, visuospatial, and memory functions as well as depression, constipation, and rapid eye movement sleep behavior disorder were also assessed.

Congenital Spinal Malformation and Stroke: Aneurysmal Dilatations and Bilateral Rotational Vertebral Artery Occlusion.

A 30-year-old woman suffered from acute vertebrobasilar stroke. Cranial tomography (CT) scans showed multiple vertebral abnormalities suggestive of congenital spine malformation, and angiographic CT revealed aneurysmal dilatations (ADs) at segment V2 of both vertebral arteries (VAs). Dynamic neuroimaging tests including angiography and angio-CT were performed and showed occlusion of both VAs at the point of the ADs with contralateral rotation of the neck.

SCN4A pore mutation pathogenetically contributes to autosomal dominant essential tremor and may increase susceptibility to epilepsy.

Essential tremor (ET) is the most prevalent movement disorder, affecting millions of people in the USA. Although a positive family history is one of the most important risk factors for ET, the genetic causes of ET remain unknown. In an attempt to identify genetic causes for ET, we performed whole-exome sequencing analyses in a large Spanish family with ET, in which two patients also developed epilepsy.

SORT1 Mutation Resulting in Sortilin Deficiency and p75(NTR) Upregulation in a Family With Essential Tremor.

*These authors contributed equally to this work.Essential tremor (ET) is the most prevalent movement disorder affecting millions of people in the United States. Although a positive family history is one of the most important risk factors for ET, the genetic causes of ET remain unknown.

GIGYF2 mutation in late-onset Parkinson's disease with cognitive impairment.

Although in the last two decades there has been considerable progress in understanding the genetic basis of Parkinson's disease (PD), the majority of PD is sporadic and its genetic causes are largely unknown. In an attempt to identify novel genetic causes of PD, whole-exome sequencing and subsequent analyses were performed in a family featuring late-onset PD with cognitive impairment. A novel genetic variant (p.

Autonomic involvement in Parkinsonian carriers of PARK2 gene mutations.

Background And Objectives: The objective of this study was to assess the presence of autonomic nervous system dysfunction in PARK2 mutation carriers.

Patients And Methods: We performed a cross-sectional analysis of 8 PARK2 carriers (age: 60.1 ± 12.

Neurogenetic disorders in the Basque population.

In the molecular era, the study of neurogenetic disorders in relict populations provides an opportunity to discover new genes by linkage studies and to establish clearer genotype-phenotype correlations in large cohorts of individuals carrying the same mutation. The Basque people are one of the most ancient populations living in Europe and represent an excellent resource for this type of analysis in certain genetic conditions. Our objective was to describe neurogenetic disorders reported in the Basque population due to the presence of ancestral mutations or an accumulation of cases or both.

Higher frequency of certain cancers in LRRK2 G2019S mutation carriers with Parkinson disease: a pooled analysis.

Importance: Patients with Parkinson disease (PD) who harbor LRRK2 G2019S mutations may have increased risks of nonskin cancers. However, the results have been inconsistent across studies.

Objectives: To analyze pooled data from 5 centers to further examine the association between LRRK2 G2019S mutation and cancer among patients with PD and to explore factors that could explain discrepancies.

Clinical correlations with Lewy body pathology in LRRK2-related Parkinson disease.

Importance: Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of genetic Parkinson disease (PD) known to date. The clinical features of manifesting LRRK2 mutation carriers are generally indistinguishable from those of patients with sporadic PD. However, some PD cases associated with LRRK2 mutations lack Lewy bodies (LBs), a neuropathological hallmark of PD.

Prevalence of cancer in Parkinson's disease related to R1441G and G2019S mutations in LRRK2.

An inverse relationship between Parkinson's disease (PD) and cancer has been described. However, the association between cancers and genetic forms of PD, in particular the R1441G mutation in the LRRK2 gene, is not well known. The objective of this work was to analyze cancer prevalence in PD patients with R1441G or G2019S mutations in LRRK2, and in idiopathic PD (iPD).

The ACMSD gene, involved in tryptophan metabolism, is mutated in a family with cortical myoclonus, epilepsy, and parkinsonism.

Unlabelled: Familial cortical myoclonic tremor and epilepsy is a phenotypically and genetically heterogeneous autosomal dominant disorder characterized by the presence of cortical myoclonic tremor and epilepsy that is often accompanied by additional neurological features. Despite the numerous familial studies performed and the number of loci identified, there is no gene associated with this syndrome. It is expected that through the application of novel genomic technologies, such as whole exome sequencing and whole genome sequencing, a substantial number of novel genes will come to light in the coming years.

The effect of visual cues on the number and duration of freezing episodes in Parkinson's patients.

Freezing of gait is a phenomenon common in Parkinson's patients and significantly affects quality of life. Sensory cues have been known to improve walking performance and reduce freezing of gait. Visual cues are reported to be particularly effective for this purpose.

The LRRK2 G2019S mutation in a series of Argentinean patients with Parkinson's disease: clinical and demographic characteristics.

Objectives: To determine clinical characteristics and frequency of leucine-rich repeat kinase 2 gene (LRRK2) mutations in a cohort of patients with Parkinson's disease (PD) from Argentina.

Background: Variation in the LRRK2 gene represents the most common genetic determinant of PD, only few data are available from Latin-America.

Design/methods: Informed consent was obtained and all studies were approved by the Institutional Review Boards.

Αlpha-synuclein levels in blood plasma from LRRK2 mutation carriers.

The diagnosis of Parkinson's disease (PD) remains primarily a clinical issue, based mainly on phenotypic patterns. The identification of biomarkers capable of permitting the preclinical detection of PD is critically needed. α-Synuclein is a key protein in PD, with missense and multiplication mutations in the gene encoding α-synuclein (SNCA) having been reported in familial cases of PD, and accumulation of the protein identified in Lewy bodies (LBs) and Lewy neurites (LNs) in affected brain regions.

Distinctive age-related temporal cortical thinning in asymptomatic granulin gene mutation carriers.

Studies in asymptomatic granulin gene (GRN) mutation carriers are essential to improve our understanding of the pattern and timing of early morphologic brain changes in frontotemporal lobar degeneration. The main objectives of this study were to assess the effect of age in cortical thickness changes (CTh) in preclinical GRN mutation carriers and to study the relationship of CTh with cognitive performance in GRN mutation carriers. We calculated CTh maps in 13 asymptomatic carriers of the c.

Neuropsychological features of asymptomatic c.709-1G>A progranulin mutation carriers.

Mutations in the progranulin (PGRN) gene have been identified as a cause of frontotemporal dementia (FTD). However, little is known about the neuropsychological abilities of asymptomatic carriers of these mutations. The aim of the study was to assess cognitive functioning in asymptomatic c.