Phenotypic commonalities in familial and sporadic Parkinson disease.

Background: Parkinson disease (PD) is a clinically well-documented neurodegenerative disorder. However, the mechanism or mechanisms of its phenotypic expressions are still unknown.

Objective: To compare phenotypes by examining demographic and clinical features of patients with familial PD and sporadic PD and with or without a family history of PD.

Hereditary diffuse leukoencephalopathy with spheroids: clinical, pathologic and genetic studies of a new kindred.

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a rare autosomal dominant disorder characterized by cerebral white matter degeneration with axonal spheroids leading to progressive cognitive and motor dysfunction. We report clinical and pathological features, as well as molecular genetic analysis, of a family with HDLS. A pedigree consisting of 27 persons in 5 generations contained 6 affected individuals.

Coexistence of PSP and MSA: a case report and review of the literature.

Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy characterized by Parkinsonism, vertical gaze palsy, and early falls. The neuropathology is characterized by neurofibrillary tangles, tufted astrocytes, and coiled bodies, but some brains show other pathologic processes. To investigate the frequency of alpha-synuclein pathology in PSP with immunohistochemistry and to report the clinical and pathological features of a case of PSP with concomitant Multiple system atrophy (MSA) (PSP/MSA), 290 cases of PSP were screened for alpha-synuclein pathology with immunohistochemistry.

Genetics of restless legs syndrome.

Restless legs syndrome (RLS) is a common disorder, although under-diagnosed, with a prevalence of up to 15% depending on the population sampled. Familial aggregation has been widely shown since Ekbom formerly described the condition in 1960; twin studies support a genetic contribution in the development of this disorder. Molecular genetic approaches have identified three genomic regions in RLS susceptibility, however no specific mutations have yet been identified.

Progressive supranuclear palsy: phenotypic sex differences in a clinical cohort.

We examined sex-based differences in phenotypic expression among a consecutive clinical series of 121 individuals diagnosed with probable progressive supranuclear palsy (PSP). For both men (44%) and women (56%), the age at symptomatic onset (66.2 and 68.

Comprehensive analysis of the LRRK2 gene in sixty families with Parkinson's disease.

Mutations in the gene leucine-rich repeat kinase 2 (LRRK2) have been recently identified in families with Parkinson's disease (PD). However, the prevalence and nature of LRRK2 mutations, the polymorphism content of the gene, and the associated phenotypes remain poorly understood. We performed a comprehensive study of this gene in a large sample of families with Parkinson's disease compatible with autosomal dominant inheritance (ADPD).

Alterations of T-lymphocyte populations in Parkinson disease.

Immune reaction-related inflammation may be important in the pathogenesis of Parkinson disease (PD). To elucidate peripheral immunologic alterations in PD, we characterized extended peripheral T-lymphocyte populations in 33 patients with PD and 34 normal subjects. Patients with PD had significantly decreased CD4+:CD8(+)T-cell ratios (P<0.

Gender and the Parkinson's disease phenotype.

Objectives: To determine whether there are gender differences in the Parkinson's disease (PD) phenotype using a large clinic-based cohort.

Methods: We examined gender differences in demographic, historical and clinical characteristics in a consecutive clinical series of 1,264 individuals diagnosed with PD.

Results: The majority of individuals in the sample were male (67 %).

PET in LRRK2 mutations: comparison to sporadic Parkinson's disease and evidence for presymptomatic compensation.

Parkinson's disease may arise from multiple aetiologies, including genetic mutations that are for the most part uncommon. We describe here the positron emission tomography (PET) findings in clinically affected and asymptomatic, high-risk members of two autosomal dominantly inherited Parkinson's disease kindreds with recently described mutations at the PARK8 locus, in a novel gene encoding a leucine-rich repeat kinase (LRRK2). Affected family members have L-dopa-responsive parkinsonism with loss of dopaminergic nigral neurons and pleomorphic subcellular pathology.

Deep brain stimulation lead fixation: a comparative study of the Navigus and Medtronic burr hole fixation device.

Objectives: To determine the extent of lead movement based on the type of burr hole fixation device used to secure the lead (Image-Guided Neurologics [IGN], Navigus versus Medtronic [Model 7495-51]). A randomized, blinded design of lead movement measurement was used.

Methods: A clinical series of 58 individuals undergoing placement of a deep brain stimulation (DBS) system with a total of 71 operative sides were examined.

Fragile X-associated tremor/ataxia syndrome and movements disorders.

Purpose Of Review: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a multiple-system neurologic disorder caused by expansion of 55-200 CGG repeats in the FMR1 (fragile site mental retardation 1) gene. The presence of both hyperkinetic and hypokinetic movement disorders such as ataxia, tremor, and parkinsonism are clinical features of FXTAS. The purpose of this review is to summarize the description of movement disorders associated with FXTAS and to discuss recent observations regarding the relationship between abnormal expansion in the FMR1 gene and development of neurodegenerative disorders.

Parkinson disease: handedness predicts asymmetry.

Objective: To determine the proportion of individuals in a clinic-based setting that present with asymmetric Parkinson disease (PD) and identify predictive factors associated with asymmetric symptoms.

Methods: The authors examined right vs left difference scores on the Unified Parkinson Disease Rating Scale motor subscale in a consecutive clinical series of 1,277 individuals diagnosed with PD. Predictors of asymmetry included sex, symptomatic disease duration, age at onset, initial motor symptom laterality, handedness, and medical history variables (e.

Heredofamilial brain calcinosis syndrome.

Brain calcinosis syndrome (BCS) usually is defined as bilateral calcium accumulation in the brain parenchyma, primarily in the basal ganglia. More than 50 reported clinical conditions have been associated with BCS. We reviewed clinical, radiological, and genetic features of heredofamilial BCS accompanying all conditions associated with calcium accumulation in the brain reported in English between 1962 and 2003 in MEDLINE.

The effect of tau genotype on clinical features in FTDP-17.

The clinical phenotype of frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) varies. This variability is seen not only between kindreds with different mutations but also in families sharing the same mutation. Inheritance of tau haplotype (H1) and genotype (H1/H1) has been established as a risk factor for some neurodegenerative disorders with parkinsonism.

Increased tau burden in the cortices of progressive supranuclear palsy presenting with corticobasal syndrome.

The objective of this study is to better define the pathological characteristics of pathologically proven progressive supranuclear palsy (PSP) presenting with the corticobasal syndrome (CBS). PSP is characterized by early falls, vertical supranuclear ophthalmoplegia, and axial rigidity, whereas asymmetric limb features, including rigidity, bradykinesia, apraxia, alien limb phenomena, and cortical sensory loss are characteristic of CBS. We investigated clinicopathological characteristics of 5 cases of PSP that presented with CBS (CBS-PSP).

Bilateral thalamic deep brain stimulation: midline tremor control.

Objectives: To determine the efficacy of bilateral deep brain stimulation (DBS) for management of midline tremor (head, voice, tongue, trunk) in patients with essential tremor.

Design: Prospective assessment of tremor at baseline (presurgical), and postoperatively at 1, 3, and 12 months, and annually thereafter.

Methods: A clinical series of 22 individuals undergoing staged, bilateral DBS for treatment of essential tremor.

Sporadic SCA8 mutation resembling corticobasal degeneration.

Spinocerebellar ataxia type 8 (SCA8) is caused by the expansion of CTA/CTG triplet repeats on 13q21. Cases can be familial or sporadic. The clinical findings include cerebellar ataxia with upper motor neuron dysfunction, dysphagia, peripheral sensory disturbances, or cognitive and psychiatric impairments, indicating phenotypic variability in SCA8.

Defining the Parkinson's disease phenotype: initial symptoms and baseline characteristics in a clinical cohort.

Objectives: Examine the demographic and historical characteristics of a large Parkinson's disease (PD) clinical cohort and determine the pattern and relationship between initial symptoms of PD and physical examination ratings at the initial subspecialty clinic visit.

Methods: A clinical series of 1244 consecutive individuals diagnosed with PD. Baseline characteristics were examined.

Is the neuropathological 'gold standard' diagnosis dead? Implications of clinicopathological findings in an autosomal dominant neurodegenerative disorder.

Genetically-derived neurodegenerative disorders offer a rare opportunity to test validity of neuropathological criteria for diagnosis. Implications regarding an autosomal dominant neurodegenerative disorder (PARK 8) in which four different neuropathological diagnoses were found at autopsy are discussed. We suggest that just as there is currently no clinical 'gold standard' for Parkinson's disease, there is no pathological 'gold standard.

Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology.

We have previously linked families with autosomal-dominant, late-onset parkinsonism to chromosome 12p11.2-q13.1 (PARK8).

Parkinsonism, FXTAS, and FMR1 premutations.

The presence of late-onset neurological symptoms in male carriers of premutation expansions of the fragile X mental retardation 1 (FMR1) gene has been described recently. One of the clinical symptoms in this fragile X-associated tremor/ataxia syndrome (FXTAS) is parkinsonism. To test the possible association between expanded FMR1 alleles and Parkinson's disease (PD), we determined the size of the FMR1 CGG repeat in 414 male cases of clinically diagnosed parkinsonism, the majority of whom had PD.

Thalamic deep brain stimulation for essential tremor: recommendations for long-term outcome analysis.

Objectives: Determine the efficacy of thalamic deep brain stimulation (DBS) for tremor control among individuals with essential tremor (ET).

Methods: A clinical series of 52 consecutive individuals undergoing placement of a DBS system for treatment of ET completed an unblinded battery of subjective and objective measures at postoperative intervals of one, three, and 12 months, and annually thereafter up to three years. The assessment battery included measures of tremor and activities of daily living.

Autosomal dominant parkinsonism associated with variable synuclein and tau pathology.

Since the original 1995 report of a parkinsonian kindred, four individuals have been affected (mean age at onset, 65 years). All four had cardinal signs of Parkinson disease (PD) and good response to levodopa. Four autopsies showed neuronal loss and gliosis in the substantia nigra.

The PARK8 locus in autosomal dominant parkinsonism: confirmation of linkage and further delineation of the disease-containing interval.

Recently, a new locus (PARK8) for autosomal dominant parkinsonism has been identified in one large Japanese family. Linkage has been shown to a 16-cM centromeric region of chromosome 12, between markers D12S1631 and D12S339. We tested 21 white families with Parkinson disease and an inheritance pattern compatible with autosomal dominant transmission for linkage in this region.