Biomedical subjects

B Ford

Publications and source records attributed to B Ford.

At least 19 recordsLinked to original sources

PubMed2006

Frequency of LRRK2 mutations in early- and late-onset Parkinson disease.

OBJECTIVE: To evaluate the frequency of leucine-rich repeat kinase gene (LRRK2) mutations and single nucleotide polymorphisms (SNPs) in early-onset Parkinson disease (EOPD) and late-onset Parkinson disease (LOPD). METHODS: We genotyped five previously reported LRRK2 mutations (G2019S, L1114L, I1122V, R1441C, and Y1699C) and 17 coding SNPs for haplotype analysis in 504 cases with PD and 314 controls enrolled in the Genetic Epidemiology of PD Study. Cases and controls were recruited without knowledge of family history of PD and cases were oversampled in the < or =50 age at onset (AAO) category. RESULTS: The LRRK2 G2019S mutation was present in 28 cases with PD (5.6%) and two controls (0.6%) (chi(2) = 13.25; p < 0.01; odds ratio 9.18, 95% CI: 2.17 to 38.8). The mutations L1114L, I1122V, R1441C, and Y1699C were not identified. The frequency of the LRRK2 G2019S mutation was 4.9% in 245 cases with AAO < or =50 years vs 6.2% in 259 cases with AAO >50 (p = 0.56). All cases with PD with the G2019S mutation shared the same disease-associated haplotype. The frequency of the LRRK2 G2019S mutation was higher in the subset of 181 cases reporting four Jewish grandparents (9.9%) than in other cases (3.1%) (p < 0.01). Age-specific penetrance to age 80 was 24% and was similar in Jewish and non-Jewish cases. CONCLUSIONS: The G2019S mutation is a risk factor in both early- and late-onset Parkinson disease and confirms the previous report of a greater frequency of the G2019S mutation in Jewish than in non-Jewish cases with Parkinson disease.

Adult↗

PubMed2006

Operative techniques and morbidity with subthalamic nucleus deep brain stimulation in 100 consecutive patients with advanced Parkinson's disease.

OBJECTIVE: Subthalamic nucleus (STN) stimulation for patients with medically refractory Parkinson disease (PD) is expanding. Reported experience has provided some indication of techniques, efficacy, and morbidity, but few centres have reported more than 50 patients. To expand this knowledge, we reviewed our experience with a large series of consecutive patients. METHODS: From March 1999 to September 2003, 191 subthalamic stimulator devices (19 unilateral) were implanted in 100 patients with PD at New York Presbyterian Hospital/Columbia University Medical Center. Sixteen patients had undergone a prior surgery for PD (pallidotomy, thalamotomy, or fetal transplant). Microelectrode guided implantations were performed using techniques similar to those described previously. Electrode implantation occurred 1-2 weeks before outpatient pulse generator implantation. RESULTS: Reductions of dyskinesias and off severity/duration were similar to prior published reports. Morbidity included: 7 device infections (3.7%), 1 cerebral infarct, 1 intracerebral haematoma, 1 subdural haematoma, 1 air embolism, 2 wound haematomas requiring drainage (1.0%), 2 skin erosions over implanted hardware (1.0%), 3 periprocedural seizures (1.6%), 6 brain electrode revisions (3.1%), postoperative confusion in 13 patients (6.8%), and 16 battery failures (8.4%). Of the 100 patients, there were no surgical deaths or permanent new neurological deficits. The average hospital stay for all 100 patients was 3.1 days. CONCLUSION: Subthalamic stimulator implantation in a large consecutive series of patients with PD produced significant clinical improvement without mortality or major neurological morbidity. Morbidity primarily involved device infections and hardware/wound revisions.

Adult↗

PubMed2005

Simple enumerations of peripheral blood natural killer (CD56+ NK) cells, B cells and T cells have no predictive value in IVF treatment outcome.

BACKGROUND: To evaluate the association between the absolute counts of the peripheral natural killer (NK) cells (including total CD56(+) NK cells, CD56(dim) NK cells and CD56(bright) NK cells), B cells and T cells on the implantation rate and miscarriage rate after IVF treatment. METHODS: This was a prospective observation study. A total of 138 patients who underwent IVF treatment from December 2002 to July 2003 were recruited to the study. Blood samples were obtained on the day of vaginal oocyte retrieval prior to the procedure. The absolute counts of lymphocytes, NK cells, B cells and T cells were identified by flow cytometry. These absolute counts and their relationships to IVF treatment outcome and miscarriage rate were analysed. RESULTS: There were no significant differences with regard the mean values of absolute lymphocyte count, T cell count, B cell count and NK cell count (including total CD56(+) NK, CD56(dim) NK and CD56(bright) NK cells) between the pregnant and non-pregnant groups and also between the ongoing pregnancy and miscarriage groups. The cause of infertility, duration of infertility, basal FSH levels, number of previous failed IVF treatments, number of previous miscarriages and stimulation characteristics were not significantly different between the pregnant and non-pregnant groups. Previous studies have suggested that women with a history of recurrent miscarriage and those with infertility accompanied by recurrent failed IVF treatments are associated with a peripheral blood NK cell percentage >12%, therefore further analysis of peripheral CD56(+) NK cell levels <12% (group A) and >12% (group B) was performed. There was no significant difference in implantation rate (group A: 17.0%; group B: 23.2%), pregnancy rate (group A: 36.6%; group B: 47.7%) or miscarriage rate (group A: 23.3%; group B: 28.6%). CONCLUSION: There were no significant differences between simple enumerations of peripheral blood NK cells (including total CD56(+) NK, CD56(dim) NK and CD56(bright) NK cells), B cells and T cells with IVF treatment outcome and pregnancy outcome. Women who had a peripheral NK cell level >12% did not have higher number of previous pregnancy losses. Importantly their pregnancy rate was not reduced and their miscarriages were not increased compared to women who had a peripheral NK cells level <12%.

Abortion, Habitual↗

PubMed2004

An increase in the absolute count of CD56dimCD16+CD69+ NK cells in the peripheral blood is associated with a poorer IVF treatment and pregnancy outcome.

BACKGROUND: Our aim was to evaluate the effect of the absolute count of the activation marker (CD69), IgG Fc receptor (CD16) and inhibitor marker (CD94) expression on peripheral blood natural killer (NK) cells on implantation and miscarriage rates after IVF treatment. METHODS: Prospective observational study of 138 randomly selected women who underwent IVF treatment from December 2002 to September 2003. NK cells were identified as CD56(+) (dim + bright) and CD3(-) by flow cytometry. The absolute counts of the CD69(+), CD16(+) and CD94(+)expressing NK cells were recorded and their relation to IVF treatment outcome and miscarriage rate was analysed. RESULTS: The mean (+/-SD) absolute count of the CD56(dim)CD16(+)CD69(+) NK cells for women who had a successful ongoing pregnancy was 0.61 x 10(6)/l (+/-0.31). For those women who failed to achieve a pregnancy, the mean value of the absolute count of CD56(dim)CD16(+)D69(+) NK cells was significantly (P=0.003) higher at 1.66 x 10(6)/l (+/-0.52). The absolute count of CD56(dim)CD16(+)CD94(+) and CD56(dim)CD16(+) NK cells did not show any statistically significant differences between those women with successful and failed IVF treatment. Receiver operating characteristic (ROC) curve analysis was performed to select a CD69 threshold for further statistical analysis. The implantation rate (IR) was significantly lower (13.1%) and miscarriage rate (MR) was significantly higher (66.7%) for women with an absolute CD56(dim)CD16(+)CD69(+) NK cell count of >1.0 x 10(6)/l compared to women with count below this value (IR 28.2% and MR 16.7%). Further analysis of the absolute count of CD56(bright)CD69(+) and CD56(bright)CD94(+) NK cells did not show any significant difference between those women with successful and failed IVF treatment. CONCLUSIONS: An increase in the absolute count of activated NK cells (CD56(dim)CD16(+)CD69(+)) in the peripheral blood is associated with a reduced rate of embryo implantation in IVF treatment. Furthermore, women with high CD56(dim)CD16(+)CD69(+) peripheral blood NK cell absolute count, who are able to achieve pregnancy, have a significantly higher miscarriage rate.

Abortion, Spontaneous↗

PubMed2004

Aromatic L-amino acid decarboxylase deficiency: clinical features, treatment, and prognosis.

BACKGROUND: Deficiency of aromatic L-amino acid decarboxylase (AADC) is associated with severe developmental delay, oculogyric crises (OGC), and autonomic dysfunction. Treatment with dopamine agonists and MAO inhibitors is beneficial, yet long-term prognosis is unclear. OBJECTIVE: To delineate the clinical and molecular spectrum of AADC deficiency, its management, and long-term follow-up. RESULTS: The authors present six patients with AADC deficiency and review seven cases from the literature. All patients showed reduced catecholamine metabolites and elevation of 3-O-methyldopa in CSF. Residual plasma AADC activity ranged from undetectable to 8% of normal. Mutational spectrum was heterogeneous. All patients presented with hypotonia, hypokinesia, OGC, and signs of autonomic dysfunction since early life. Diurnal fluctuation or improvement of symptoms after sleep were noted in half of the patients. Treatment response was variable. Two groups of patients were detected: Group I (five males) responded to treatment and made developmental progress. Group II (one male, five females) responded poorly to treatment, and often developed drug-induced dyskinesias. CONCLUSIONS: The molecular and clinical spectrum of AADC deficiency is heterogeneous. Two groups, one with predominant male sex and favorable response to treatment, and the other with predominant female sex and poor response to treatment, can be discerned.

Adolescent↗

PubMed2004

Phenylalanine loading as a diagnostic test for DRD: interpreting the utility of the test.

Phenylalanine loading has been proposed as a diagnostic test for autosomal dominant DRD (dopa-responsive dystonia), and recently, a phenylalanine/tyrosine (phe/tyr) ratio of 7.5 after 4 h was reported as diagnostic of DRD. To test the utility of this test in another sample with DRD, we administered an oral challenge of phenylalanine (100 mg/kg) to 11 individuals with DRD and one non-manifesting gene carrier. Only 6/12 had a 4 h phe/tyr ratio of greater than 7.5, suggesting that additional parameters must be set to avoid missing the diagnosis of DRD, including the need for the plasma phenylalanine to reach a minimum level 600 in order for the test to be valid. We propose that in cases where this minimum plasma phenylalanine level is not reached, plasma tetrahydrobiopterin should be measured or alternatively other symptomatic family members should be screened.

Adolescent↗

PubMed2004

Subthalamic nucleus stimulation in advanced Parkinson's disease: blinded assessments at one year follow up.

OBJECTIVE: To measure the effect of deep brain stimulation (DBS) of the subthalamic nucleus in patients with advanced Parkinson's disease. DESIGN: Open label follow up using blinded ratings of videotaped neurological examinations. PATIENTS: 30 patients with advanced Parkinson's disease (19 male, 11 female; mean age 58.8 years; mean disease duration 12.8 years), complicated by intractable wearing off motor fluctuations and dopaminergic dyskinesias. MAIN OUTCOME MEASURES: Unified Parkinson's disease rating scale (UPDRS), part III (motor), score at one year, from blinded reviews of videotaped neurological examinations. Secondary outcomes included the other UPDRS subscales, Hoehn and Yahr scale, activities of daily living (ADL) scale, mini-mental state examination (MMSE), estimates of motor fluctuations and dyskinesia severity, drug intake, and patient satisfaction questionnaire. RESULTS: Subthalamic nucleus stimulation was associated with a 29.5% reduction in motor scores at one year (p<0.0001). The only important predictors of improvement in UPDRS part III motor scores were the baseline response to dopaminergic drugs (p = 0.015) and the presence of tremor (p = 0.027). Hoehn and Yahr scores and ADL scores in the "on" and "off" states did not change, nor did the mean MMSE score. Weight gain occurred in the year after surgery, from (mean) 75.8 kg to 78.5 kg (p = 0.028). Duration of daily wearing off episodes was reduced by 69%. Dyskinesia severity was reduced by 60%. Drug requirements (in levodopa equivalents) declined by 30%. CONCLUSIONS: The 30% improvement in UPDRS motor scores was a more modest result than previously reported. DBS did not improve functional capacity independent of drug use. Its chief benefits were reduction in wearing off duration and dyskinesia severity.

Activities of Daily Living↗

PubMed2003

Risk of action tremor in relatives of tremor-dominant and postural instability gait disorder PD.

BACKGROUND: Action tremor may be more prevalent in relatives of patients with Parkinson's disease (PD) than in relatives of control subjects. This tremor could represent mild PD or essential tremor. An estimate of the risk of this condition in families of patients with PD is important when studying the genetics of PD. OBJECTIVE: S: To determine the risk of action tremor in first-degree relatives of probands with tremor-dominant PD (TD-PD) and postural instability gait disorder PD (PIGD-PD) compared with first-degree relatives of control probands. METHODS: PD and control probands participated in a familial aggregation study of PD. The presence of action tremor in their relatives was ascertained from reports of one or more informants. Relatives who met diagnostic criteria for PD were excluded. Cox proportional hazards models adjusting for gender, education, race, and vital status (dead vs alive) of the relatives were used to assess the relative risk (RR) of action tremor in first-degree relatives of PD probands vs first-degree relatives of control probands. RESULTS: There were 487 PD probands, 409 control probands, and 5,563 relatives. The risk of action tremor was higher in the relatives of TD-PD probands than in the relatives of control probands (RR = 2.14; 95% CI = 1.53 to 2.98) but not in the relatives of PIGD-PD probands compared with the relatives of control probands (RR = 1.81; 95% CI = 0.66 to 5.02). CONCLUSION: The risk of action tremor was increased in the relatives of PD probands, particularly when they had TD-PD. Whether the tremor in these relatives represents essential tremor or an isolated manifestation of PD requires further investigation.

Comorbidity↗

PubMed2003

Accuracy of family history data on Parkinson's disease.

BACKGROUND: Genetic studies of PD frequently rely on family history interviews (FHI), yet the accuracy of data obtained in this way is unclear. OBJECTIVE: To assess the interinformant reliability and validity of family history information on PD in first-degree relatives of PD cases and controls. METHODS: A structured FHI was administered to nondemented PD cases and controls and to a second informant (self-report, sibling or child of the subject) for each relative. Interinformant agreement was assessed on four algorithm-derived diagnostic categories of PD: definite, definite or probable, definite, probable or possible ("conservative diagnosis"); or definite, probable, possible, or uncertain ("liberal diagnosis"). The sensitivity and specificity of each diagnostic category were assessed, using as the gold standard diagnoses based on either in-person examination or medical record review. RESULTS: Five hundred thirty-six families containing 2,225 first-degree relatives were included in the interinformant reliability study. Agreement between informants was excellent for definite or probable PD for all three pairwise comparisons: proband vs self-report (kappa = 0.92), proband vs sibling of subject (kappa = 0.80), and proband vs child of subject (kappa = 0.87). Agreement was also good to excellent for the conservative diagnosis (kappa = 0.66, 0.49, and 0.79). In the validity analysis (141 individuals in 96 families), the conservative diagnosis provided the best combination of sensitivity (95.5%) and specificity (96.2%) for the proband's family history report. No difference was apparent across categories defined by case or control status, relationship to the proband, or gender or age at onset of the proband. However, specificity was lower for deceased relatives than for living relatives. CONCLUSION: The FHI can be used to obtain reliable and valid family history information on PD in first-degree relatives when a conservative diagnostic algorithm is applied.

Algorithms↗

PubMed2003

ET-1- and NO-mediated signal transduction pathway in human brain capillary endothelial cells.

Previous studies have demonstrated that functional interaction between endothelin (ET)-1 and nitric oxide (NO) involves changes in Ca(2+) mobilization and cytoskeleton in human brain microvascular endothelial cells. The focus of this investigation was to examine the possible existence of analogous interplay between these vasoactive substances and elucidate their signal transduction pathways in human brain capillary endothelial cells. The results indicate that ET-1-stimulated Ca(2+) mobilization in these cells is dose-dependently inhibited by NOR-1 (an NO donor). This inhibition was prevented by ODQ (an inhibitor of guanylyl cyclase) or Rp-8-CPT-cGMPS (an inhibitor of protein kinase G). Treatment of endothelial cells with 8-bromo-cGMP reduced ET-1-induced Ca(2+) mobilization in a manner similar to that observed with NOR-1 treatment. In addition, NOR-1 or cGMP reduced Ca(2+) mobilization induced by mastoparan (an activator of G protein), inositol 1,4,5-trisphosphate, or thapsigargin (an inhibitor of Ca(2+)-ATPase). Interestingly, alterations in endothelial cytoskeleton (actin and vimentin) were associated with these effects. The data indicate for the first time that the cGMP-dependent protein kinase colocalizes with actin. These changes were accompanied by altered levels of phosphorylated vasodilator-stimulated phosphoprotein, which were elevated in endothelial cells incubated with NOR-1 and significantly reduced by ODQ or Rp-8-CPT-cGMPS. The findings indicate a potential mechanism by which the functional interrelationship between ET-1 and NO plays a role in regulating capillary tone, microcirculation, and blood-brain barrier function.

Actins↗

PubMed2001

Neuregulins increase alpha7 nicotinic acetylcholine receptors and enhance excitatory synaptic transmission in GABAergic interneurons of the hippocampus.

Neuregulins are highly expressed in the CNS, especially in cholinergic neurons. We have examined the effect of neuregulin on nicotinic acetylcholine receptors (nAChRs) in neurons dissociated from the rat hippocampus. Rapid application of acetylcholine (ACh) induced a rapidly rising and decaying inward current in some of the neurons, which was completely blocked by methyllycaconitine, a specific antagonist of the alpha7 subunit of the nAChR. When the cells were treated with 5 nm neuregulin (NRG1-beta1) for 2-4 d, a twofold increase in amplitude of the peak ACh-induced current was observed, and there was a comparable increase in (125)I-alpha-bungarotoxin binding. The fast ACh-induced peak current was prominent in large neurons that also contained GABA immunoreactivity. These presumptive GABAergic neurons constituted approximately 10% of neurons present in 7- to 9-d-old cultures. In addition to the large inward peak current, ACh also evoked transmitter release from presynaptic nerve terminals. Pharmacologic experiments indicated that the shower of PSCs was mediated by glutamate, with a small minority caused by the action of GABA. Chronic exposure to NRG1-beta1 increased the amplitude of ACh-evoked PSCs but not the minimum "quantal" PSC. NRG1-beta1 also increased the percentage of neurons that exhibited ACh-evoked PSCs.

Acetylcholine↗

PubMed2001

Evidence for familial aggregation of tremor in normal individuals.

BACKGROUND: Tremor occurs in most normal individuals, and this tremor may offer basic clues about the mechanisms of neuromuscular control. It is not known whether genetic factors influence the magnitude of tremor in normal families. OBJECTIVE: To assess the familial aggregation of tremor in normal families. METHODS: Control subjects from the Washington Heights-Inwood community in northern Manhattan, NY, were enrolled in a family study. These subjects and their first- and second-degree relatives underwent a videotaped tremor examination. Two neurologists rated the severity of tremor on the videotaped examination, assigning a total tremor score (0 to 36 [maximum]). Associations between the control subjects' and their relatives' total tremor scores were assessed using correlation coefficients and linear regression analysis. In addition, maximum likelihood methods were used to fit a linear mixed-effects model to the total tremor scores of probands and their siblings, after excluding any relatives with essential tremor. RESULTS: There were 56 control subjects and 226 relatives. Tremor was clinically detectable in 221 (97.8%) of 226 relatives. There was an association between the control subjects' total tremor scores and those of their siblings (r = 0.40; p = 0.018), those of all of their first-degree relatives (siblings and children combined, r = 0.20; p = 0.037), but not those of their second-degree relatives (r = 0.002; p = 0.99). In analyses of probands and normal siblings, the estimate of the variance of the family-specific component of the age-adjusted total tremor score was different from zero (p < 0.005), and the family specific component was estimated to account for 52% of the variability in the scores. CONCLUSIONS: Tremor aggregates in normal families, suggesting that genetic factors may contribute to its etiology. Other studies might be designed by investigators to identify these genes through genetic linkage or association analysis. Identification of such genes would help to elucidate the mechanisms underlying this ubiquitous condition.

Adult↗

PubMed2001

Renal-coloboma syndrome: prenatal detection and clinical spectrum in a large family.

Renal-coloboma syndrome includes abnormalities in the urogenital and ocular systems as its primary manifestations, although it can be associated with abnormalities in other systems as well. This syndrome is caused by mutations in the PAX2 gene and is transmitted as an autosomal dominant trait. We report a family in which at least 7 members have manifestations of renal-coloboma syndrome, including two in whom renal disease was diagnosed prenatally by ultrasound examination. A pathogenic frame-shift mutation (619insG) was found in the PAX2 gene in affected family members, who show remarkable variability in both the ocular and renal manifestations of the syndrome.

Adolescent↗

PubMed2001

A randomized, controlled trial of remacemide for motor fluctuations in Parkinson's disease.

BACKGROUND: Preclinical studies suggest that glutamate antagonists help ameliorate motor fluctuations in patients with PD treated with levodopa. METHODS: In a multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study, the authors assessed the safety, tolerability, and efficacy of the glutamate receptor blocker remacemide hydrochloride in 279 patients with motor fluctuations treated with levodopa. The primary objective was to assess the short-term tolerability and safety of four dosage levels of remacemide during 7 weeks of treatment. Patients were also monitored with home diaries and the Unified PD Rating Scale (UPDRS) to collect preliminary data on treatment efficacy. RESULTS: Remacemide was well tolerated up to a dosage of 300 mg/d on a twice daily schedule and 600 mg/d on a four times daily schedule. The most common dosage-related adverse events were dizziness and nausea, as observed in previous studies of remacemide. The percent "on" time and motor UPDRS scores showed trends toward improvement in the patients treated with 150 and 300 mg/d remacemide compared with placebo-treated patients, although these improvements were not significant. CONCLUSION: Remacemide is a safe and tolerable adjunct to dopaminergic therapy for patients with PD and motor fluctuations. Although this study had limited power to detect therapeutic effects, the observed improvement is consistent with studies of non-human primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian signs and symptoms. Additional studies are warranted to confirm these results over an extended period of observation, and to explore the potential neuroprotective effects of remacemide in slowing the progression of PD.

Acetamides↗

PubMed2001

Mild tremor in relatives of patients with essential tremor: what does this tell us about the penetrance of the disease?

BACKGROUND: Mild tremor may occur in relatives of patients with essential tremor (ET). However, this phenomenon has not been studied quantitatively or with a comparison group. Such a study may provide information on the penetrance of ET. OBJECTIVE: To obtain data on the magnitude of tremor in case and control relatives who did not meet diagnostic criteria for ET. METHODS: Cases with ET and control subjects from the Washington Heights-Inwood community in northern Manhattan, NY, were enrolled in a family study. Their first- and second-degree relatives underwent a videotaped tremor examination. Two neurologists rated the severity of tremor, assigning a total tremor score (0-36 [maximum]). Data were analyzed on 201 case relatives and 212 control relatives who did not meet diagnostic criteria for ET. RESULTS: The mean total tremor score of first-degree case relatives was higher than that of first-degree control relatives (4.9 vs 3.9; P<.003). Total tremor scores for second-degree relatives did not differ (4.1 vs 4.2; P =.68). A larger percentage (55.2% vs 36.6%; P =.01) of first-degree case relatives had total tremor scores of 4 or more. Among first-degree relatives who were older than 60 years, 13 case relatives (59.1%) and 18 control relatives (45.0%) had total tremor scores of 4 or more. CONCLUSIONS: A considerable number of seemingly normal case relatives may have a genetic predisposition for tremor. Even among older case relatives (> or =60 years of age), there was an increased prevalence of higher tremor scores, suggesting that in that age group, subclinical ET may be present and penetrance still may not be complete.

Adult↗

PubMed2001

A teaching videotape for the assessment of essential tremor.

UNLABELLED: Teaching videotapes, developed to aid in the evaluation of several movement disorders, have not been used in essential tremor research. As part of the Washington Heights-Inwood Genetic Study of Essential Tremor (WHIGET), we developed a reliable and valid tremor rating scale. Because this rating scale is currently being used by investigators at other centers, we developed a teaching videotape to aid in the consistent application of this scale. OBJECTIVE: To develop a teaching videotape for a revised version of the WHIGET Tremor Rating Scale and to assess the interrater agreement among raters who used this videotape to rate tremor. METHODS: The revised WHIGET Tremor Rating Scale was used to rate action tremor from 0 to 4 during six tests: arm extension, pouring, drinking, using a spoon, finger-to-nose, and drawing spirals. A 22-minute teaching videotape was developed that includes a 29-item educational section and a self-assessment section consisting of 20 examples of tremor ratings chosen by the two WHIGET study neurologists. Eight raters, including senior movement disorder specialists, movement disorder fellows, general neurologists, and a movement disorder nurse practitioner, independently viewed the videotape and rated tremor during the self-assessment section. Interobserver reliability was assessed with weighted kappa statistics (kappa(w)). RESULTS: Eight raters each rated 20 items (160 ratings total). Total kappa(w) was 0.97 (nearly perfect agreement). Interrater reliability was as follows: kappa(w) = 0.99 (movement disorder specialists), kappa(w) = 0.98 (movement disorder fellows), and kappa(w) = 0.97 (general neurologists); all kappa(w) were nearly perfect. CONCLUSIONS: This teaching videotape may be used to improve the uniform application of the revised WHIGET Tremor Rating Scale by raters with various levels of experience in movement disorders.

Essential Tremor↗

PubMed2001

Risk of tremor and impairment from tremor in relatives of patients with essential tremor: a community-based family study.

Essential tremor (ET) is a common condition that is present in as many as 23% of elderly individuals. Our objective was to determine the risk of ET and to study the impairment resulting from ET among relatives of ET cases compared to relatives of controls. ET cases and matched controls from the Washington Heights-Inwood community, New York, and their first- and second-degree relatives underwent a standardized tremor examination. The risk of having ET in relatives of cases vs relatives of controls was compared using Cox proportional hazards models. Five hundred ninety-one subjects were examined (59 ET cases, 72 controls, 234 case relatives, and 226 control relatives). ET was present in 25 (22.5%) of the 111 first-degree relatives of cases compared to 6 (5.6%) of 107 first-degree relatives of controls [relative risk (RR) = 4.67, 95% confidence interval (CI) = 1.90-11.49, p = 0.0008]. RRs were higher in relatives of cases with onset < or =50 years than in those with later onset (RR = 10.38 vs 4.82). Sixteen (64%) of twenty-five affected first-degree case relatives exhibited moderate tremor while performing tasks such as writing, drinking, or pouring. Relatives of ET patients are five times more likely to develop the disease than are members of the population and ten times more likely if the proband's tremor began at an early age. The majority of the affected relatives can expect to experience impairment resulting from tremor.

Adolescent↗

PubMed2001

Family history information on essential tremor: potential biases related to the source of the cases.

The proportion of essential tremor (ET) cases that can be attributed to genetic factors is unknown; estimates range from 17--100%. One possible reason for this variability is that clinic and community cases may differ with regard to family history of ET. This is because clinic patients are self-selected and represent as few as 0.5% of all ET cases. Our goal was to determine whether ET cases ascertained from a clinic differed from those ascertained from a community in terms of the family history information that they provided. Subjects (57 clinic, 64 community) underwent a family history interview. Clinic cases were 4.73 times more likely to report an affected relative than were community cases. We conclude that there was a substantial difference between our clinic and community ET cases in terms of the information they provided regarding their family history. Selection and reporting biases could have accounted for this difference. Because of these biases, the source of the cases must be taken into consideration when investigators are trying to synthesize the widely variable results of studies that have estimated the genetic contribution to ET.

Aged↗