Biomedical subjects

Elan D Louis

Publications and source records attributed to Elan D Louis.

At least 55 records · Page 3Linked to original sources

PubMed2005

John Adams' essential tremor.

John Adams (1735-1826), one of the signers of the Declaration of Independence, was the second President of the United States. Adams had tremor for many years, about which little has been written. We examined John Adams' penmanship over a 62-year period and studied his correspondence and diaries. It is not clear when Adams' tremor began, although in a diary entry dated 6 December 1760, when Adams was 25 years old, there is evidence of low-amplitude kinetic tremor. The tremor continued in his written correspondence, becoming more persistent over time. Later in life, the clarity of his written correspondence diminished, with greater decomposition of characters and a reduction in the size of individual characters. This finding raises some speculation as to whether Adams could have been developing some parkinsonism, although the evidence in favor of this is not compelling. The most likely diagnosis was essential tremor.

Essential Tremor↗

PubMed2005

Essential tremor: mild olfactory dysfunction in a cerebellar disorder.

Olfactory dysfunction has been reported to occur in patients with cerebellar disorders, including degenerative ataxias and essential tremor (ET). Previous studies have not considered the effects of mild cognitive deficits, which can occur in ET, and could explain the lower olfaction test scores in ET cases. We more than doubled our initial sample (37 ET cases and 37 controls) [Louis ED, Bromley SM, Jurewicz EC, Watner D. Olfactory dysfunction in essential tremor: a deficit unrelated to disease duration or severity. Neurology 2002;59:1631-3. ] and made adjustments for the mini mental status test score. The University of Pennsylvania Smell Identification Test score remained lower in 87 ET cases compared to 92 controls after adjustment for mini mental status test score and other potential confounders (p = 0.04). These findings: suggest that olfactory dysfunction in ET patients occurs independently of mild cognitive deficits and support recent work that the cerebellum may play a role in central olfactory processing.

Aged↗

PubMed2005

Non-motor manifestations in essential tremor: use of a validated instrument to evaluate a wide spectrum of symptoms.

INTRODUCTION: Recent studies suggest an association between non-motor symptoms and essential tremor (ET). Few studies have assessed psychological symptoms in ET. These studies were limited to western white populations and utilized scales that were specific to only one or two psychiatric domains. By contrast, the Symptom Checklist-90R (SCL-90R) is a validated clinical scale to screen for symptoms related to a spectrum of nine different psychological domains. OBJECTIVE: To determine whether a wide spectrum of non-motor manifestations is associated with ET in patients in an Asian cohort. METHODS: Consecutive ET patients and a group of control subjects were evaluated using the SCL-90R, which is comprised of items in nine major symptom dimensions and three global indices, including the positive symptom distress index. RESULTS: ET patients (N = 84) and controls (N = 78) were similar in age (50.0+/-18.0 vs 46.0+/-14.4 years), gender and other demographic variables. ET patients had higher scores in three of nine major symptom dimensions: anxiety, phobic anxiety (p < 0.0005) and psychoticism (p = 0.005). In multivariate analysis, the anxiety (p < 0.0005) and the positive symptom distress index scores (p < 0.0005) were greater in ET patients compared to controls after adjusting for sex, age, marital status and educational level. The severity, but not duration of ET was correlated with the severity of anxiety symptoms. CONCLUSIONS: Utilizing the SCL-90R, we highlighted that ET patients reported more non-motor symptoms than healthy controls. The more frequent occurrence of anxiety symptoms in our Asian cohort extends the observation that such non-motor manifestations should be considered in the clinical management of ET.

Adult↗

PubMed2005

Essential tremor.

Essential tremor (ET) is one of the most common neurological diseases; although it is a disease about which we are only beginning to develop an understanding. Effective treatment options for the disorder are severely limited. The traditional view of ET as a benign, familial, monosymptomatic disorder is being replaced by one of ET as a disease or family of diseases with aetiological, clinical, and pathological heterogeneity. Recent identification of putative environmental toxins linked to ET provide hope for disease prevention through a reduction in exposure to risk factors. Pathological and genetic studies will yield new insights into disease pathogenesis and mechanisms, which may result in the development of more effective symptomatic therapies developed with an understanding of the disease biology. These insights also have the potential to form the basis for neuroprotective therapies.

Essential Tremor↗

PubMed2005

Association between arsenic exposure and a measure of subclinical sensory neuropathy in Bangladesh.

OBJECTIVES: We examined the association between arsenic exposure and peripheral neuropathy in Bangladesh, where the population has been chronically exposed to arsenic in drinking water. METHODS: We conducted a cross-sectional study of 137 subjects derived from a larger cohort. Exposure measures included individual water arsenic concentration, cumulative arsenic index, and urinary arsenic concentration taken at two time points (2001 and 2003). The primary outcome measurement was elevated vibrotactile threshold, as measured by a vibration sensitivity tester (Vibratron II). RESULTS: Arsenic exposure was associated with elevated toe vibration threshold (TVT). Specifically, cumulative arsenic index and urinary arsenic (2001) were both significantly associated with elevated TVT (P = 0.02 and P = 0.009, respectively) after adjustment for age and gender. CONCLUSIONS: Increased arsenic exposure, as measured by both cumulative and urinary measures, was associated with evidence of subclinical sensory neuropathy.

Adult↗

PubMed2005

Benefits and risks of pharmacological and surgical treatments for essential tremor: disease mechanisms and current management.

Essential tremor (ET) is a neurological disease (and possibly a family of diseases) whose most recognisable feature is an action tremor of the hands and occasionally of the voice and head. Current data support the view that CNS gamma-amino-butyric acid (GABA)-ergic mechanisms may underlie ET and that the tremor may be further modulated by peripheral (muscle) adrenoreceptors. Potential pharmacotherapeutic options, targeted to influence the activity of the neurotransmitter GABA within the CNS and the peripheral adrenergic receptors, are part of the current armamentarium to treat ET. As such, primidone and propranolol remain the mainstays of the therapy for ET. Intramuscular injections of botulinum toxin A may play a role in the treatment of voice and head tremor. Surgical options, which are reserved for patients with severe, medically-refractory tremor, provide adequate tremor control in the majority of patients. As with other progressive neurological disorders of late life, the ability to use neuroprotective medications to intervene in the developing disease to either slow or halt the progression of the pathological process, would involve an understanding of underlying disease mechanisms. The understanding of these mechanisms in ET is limited and further study of these mechanisms is critical for the development of such therapies.

Essential Tremor↗

PubMed2005

Behavioral symptoms associated with essential tremor.

As the complexity and heterogeneity of ET emerge, greater interest has been taken in the nonmotor manifestations of this disease. The fact that the motor manifestations reflect widespread anatomic pathology (e.g., cerebellum, basal ganglia) suggests that the nonmotor aspects might be a manifestation of an illness that affects multiple areas of the nervous system. Therefore, nonmotor aspects of the disease might reflect the presence of disease pathology in a particular area of the brain. Alternatively, nonmotor aspects could be the result of the tremor itself and the effects that it has on disability, mood, and personality. Finally, some of the nonmotor aspects could reflect the possibility that individuals with these disorders have a shared predisposition for ET and that a common mechanism underlies both. Further work is needed to define the extent of the nonmotor manifestations, their presence or absence in the predisease state, and their progression over time. These studies will further our insights into the mechanisms and anatomic pathology of ET and help us to develop a broader understanding of issues that are important in treating the individuals with this disease.

Anxiety↗

PubMed2004

Reduced body mass index in patients with essential tremor: a population-based study in the province of Mersin, Turkey.

BACKGROUND: Body mass index (BMI) is an important health indicator. Individuals with a low BMI are more prone to various health problems and have an increased risk of mortality. A reduced BMI in essential tremor (ET) patients who were referred to a tertiary referral center was previously demonstrated. To our knowledge, this has not been confirmed in other groups of ET patients with different demographic characteristics or in a group of unselected ET patients living in the population. OBJECTIVE: To compare BMI in ET case and control subjects in a population-based study in the province of Mersin. INTERVENTIONS: The epidemiological survey used door-to-door examinations to evaluate 2253 residents in Mersin. There were 89 ET cases (mean age, 57.3 years) who were matched to 89 controls based on sex, ward (area of residence), and age. The BMI was calculated as weight in kilograms divided by the square of height in meters. RESULTS: The mean +/- SD BMI in ET cases was 26.0 +/- 4.3 vs 27.5 +/- 5.0 in controls (P =.04), representing, on average, a 5.5% reduction in cases. In a linear regression analysis that adjusted for age, sex, years of education, socioeconomic status, urban vs rural dwelling, cognitive screen score, and Cumulative Illness Rating Scale score, the BMI was lower in cases than in controls (P =.02). CONCLUSIONS: A reduction in BMI is a common accompaniment of neurodegenerative diseases; a mild reduction also seems to be a feature of ET. It is important for physicians to be aware of the potential for a low BMI in their ET patients so that nutrition can be addressed as part of the treatment plan.

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PubMed2004

Lack of familial aggregation of Parkinson disease and Alzheimer disease.

OBJECTIVE: To investigate the risk of Alzheimer disease (AD) in first-degree relatives of patients with Parkinson disease (PD) compared with first-degree relatives of controls. DESIGN: Case-control study, family history method, and reconstructed cohort approach. METHODS: Probands with PD without dementia and control probands, matched by age strata, sex, and ethnicity, were examined in person and enrolled without knowledge of family history of PD and other neurological disorders. Disease status in first-degree relatives of probands with PD and control probands was ascertained through a structured family history interview administered to the proband and a second informant (self-report or another informant). Cox proportional hazards models with double-censoring techniques for missing information on age of onset of AD were used to analyze the risk of AD in first-degree relatives of patients with PD compared with first-degree relatives of controls. RESULTS: Four hundred eighty-seven probands with PD and 409 control probands provided family history information on 4819 first-degree relatives older than 30 years (2534 relatives of probands with PD and 2285 relatives of control probands). One hundred thirteen first-degree relatives (2.3%; 61 relatives [2.4%] of patients with PD and 52 relatives [2.3%] of controls) were diagnosed with AD. The risk of AD was not increased in relatives of patients with PD compared with relatives of controls (hazard ratio, 1.1; 95% confidence interval, 0.7-1.6; P =.65). Similarly, no significantly increased risk of AD was observed when comparing relatives of patients with early-onset (< or =50 years) and late-onset (>50 years) PD with relatives of controls. CONCLUSION: The lack of familial aggregation of PD and AD does not support the hypothesis of major shared genetic contributions to the etiology of the 2 most common neurodegenerative disorders.

Adult↗

PubMed2004

Parkinsonian signs in older people in a community-based study: risk of incident dementia.

BACKGROUND: Mild parkinsonian signs occur in 30% to 40% of community-dwelling older people. In a cross-sectional study, the severity of these signs was greater in people with dementia than in people without dementia. OBJECTIVE: To determine whether baseline mild parkinsonian signs are a predictor of incident dementia. DESIGN: A prospective, longitudinal study of community-dwelling older people who did not have dementia or Parkinson disease at baseline. METHODS: A neurological examination was performed on 1028 residents aged 65 years or older in the Washington Height-Inwood community in northern Manhattan, NY. Parkinsonian signs were rated with an abbreviated Unified Parkinson's Disease Rating Scale, resulting in a parkinsonian sign score (range, 0-40). The risk of incident dementia was assessed using Cox proportional hazards models. In some analyses, data from the modified Unified Parkinson's Disease Rating Scale were divided into 3 domains: rigidity, axial function, and tremor at rest. RESULTS: The mean duration of follow-up was 5.6 years, and 224 participants (21.8%) developed dementia. In a Cox model, the risk of incident dementia was 57% higher in participants with a baseline parkinsonian sign score of 2 vs 0 (relative risk, 1.56; 95% confidence interval, 1.04-2.33; P =.03). In a second Cox model, the baseline parkinsonian sign score was associated with incident dementia (relative risk, 1.08; 95% confidence interval, 1.01-1.16; P =.02) independent of associations with baseline age, education, ethnicity, diabetes mellitus, and stroke. CONCLUSIONS: Baseline mild parkinsonian signs are a predictor of incident dementia. Although these signs are mild, they are not prognostically benign. Brain imaging and postmortem examinations might further our insight into the anatomical and pathological basis for mild parkinsonian signs.

Aged↗

PubMed2004

Late-life action tremor in a southern sea otter (enhydris lutris nereis).

Although tremor is highly prevalent in human beings, there are few reports of tremor occurring in other mammals. Such tremor can further our insight into the mechanisms and anatomical basis of human tremor disorders. We report on a southern sea otter with a slowly progressive 6.5 to 8.5 Hz action tremor of late life that shared several clinical characteristics with essential tremor. The main pathological finding was in the cerebellum, where there was extensive vacuolation of Purkinje cells.

Age Factors↗

PubMed2004

Factor structure of parkinsonian signs in the community-dwelling elderly.

Parkinsonian signs are present in 40% of older people. Factor analysis of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS) in patients with Parkinson's disease (PD) has identified several principal domains, including rigidity, axial function, and rest tremor. We hypothesized that if Parkinsonian signs in the elderly were due to basal ganglia dysfunction that this same constellation of factors (rigidity, axial function, rest tremor) would emerge in a factor analysis. We carried out factor analysis, using the principal component method with orthogonal (varimax) rotation, on motor UPDRS scores in community-dwelling elderly without PD. A modified (10-item) version of the motor portion of the UPDRS was administered to 1,339 older adults living in the Washington Heights-Inwood community and it was found that Parkinsonian signs were present in 537 (40.1%). Three factors (rigidity, axial function. and rest tremor) were obtained from the factor analysis and, together, explained 67.4% of the variance. A second factor analysis was carried out excluding the 26 participants with rest tremor, and two factors (rigidity, axial function) emerged. These data support the view that Parkinsonian signs in older adults might be due to basal ganglia dysfunction, a possibility that requires further exploration.

Adult↗

PubMed2004

Cerebellar metabolic symmetry in essential tremor studied with 1H magnetic resonance spectroscopic imaging: implications for disease pathology.

The pathological basis for essential tremor (ET) is not known; however, metabolic changes in the cerebellum can be observed in positron emission tomography (PET) and (1)H magnetic resonance spectroscopic imaging (MRSI) studies. Tremor is relatively symmetric in ET, suggesting that underlying metabolic changes could be also symmetric. The degree of metabolic asymmetry in the cerebellum, however, has not yet been studied in ET, and knowledge about distribution and laterality of metabolic changes might shed some light on basic disease mechanisms. We measured brain metabolism (N-acetylaspartate[NAA]/creatine [tCR]) to obtain an asymmetry index for cerebellar cortical metabolism ET patients compared with that in controls. This index, a percentage, was calculated as [absolute value (value right - value left)]/(value right + value left) x 100. Multislice (1)H MRSI data were acquired for 20 patients and 11 controls. In ET patients, mean right and left cerebellar cortical NAA/tCR values were 1.61 +/- 0.42 and 1.55 +/- 0.38, respectively, compared with 1.81 +/- 0.62 and 1.87 +/- 0.49 in controls. The difference between right and left cerebellar cortical NAA/tCR was also calculated for each subject. In ET patients, the mean right-left difference was 0.14 +/- 0.11, compared with 0.32 +/- 0.27 in controls (P = 0.016). The mean cerebellar cortical asymmetry index was low in ET (8.8 +/- 6.1%), one-half of that in controls (17.0 +/- 13.7%, P = 0.027). These data suggest that pathological lesions in ET patients, which remain elusive, might be distributed similarly in each cerebellar cortex. Postmortem studies are needed to confirm these preliminary imaging results.

Cerebellum↗

PubMed2004

Semiquantitative study of current coffee, caffeine, and ethanol intake in essential tremor cases and controls.

There are several reasons to study caffeine, coffee, and ethanol intake in essential tremor (ET) patients. ET patients also might modify their use of these beverages because of their effects on tremor. Intake of caffeine, coffee, and ethanol has not been quantified in a group of ET patients. Our objective is to use a semiquantitative food frequency questionnaire to compare current daily intake of coffee, caffeine, and ethanol in ET patients and controls. A total of 130 ET cases were patients at the Neurological Institute of New York, and 175 controls were ascertained by random digit dialing. Caffeine (in milligrams) and ethanol (in grams) intake were calculated from a semiquantitative food-frequency questionnaire. Mean daily caffeine intake in patients was 138.4 versus 246.6 mg in controls; medians were 101.1 versus 175.5 mg (P < 0.001). Mean daily ethanol intake in patients was 8.2 versus 6.2 gm in controls; medians were 2.4 versus 1.9 gm (P = 0.89). Cases drank less coffee than controls, but drank similar amounts of tea, soft drinks, fruit juices, and milk. Daily caffeine intake was not correlated with tremor severity or duration. ET patients consumed less caffeine than did controls, which is likely to be a dietary modification in response to tremor. The observation that caffeine consumption was not correlated with tremor severity raises the additional possibility that lower caffeine consumption in ET patients may not exclusively be a response to tremor. A prospective study is needed to explore whether decreased caffeine consumption is a risk factor for ET.

Aged↗

PubMed2004

Screen for expanded FMR1 alleles in patients with essential tremor.

Fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disorder, was described recently among male carriers of expanded alleles (55-200 CGG repeats; premutation range) of the fragile X mental retardation 1 (FMR1) gene. Major features of the syndrome include intention tremor, gait ataxia, and parkinsonism in men over 50 years of age. This disorder is believed to be relatively common, possibly affecting 1 in 3,000 men over the age of 50 years in the general population. This raises the possibility that some patients presenting with essential tremor (ET) may harbor expanded FMR1 alleles. We screened 81 ET patients (40 males, 41 females) for expanded FMR1 alleles to determine whether ET is associated with such alleles. None of the ET cases had the premutation genotype. CGG repeat sizes ranged from 5 to 47 repeats within this study population, suggesting that expanded FMR1 alleles are uncommon among patients with ET. Screening of movement disorder patients with other clinical features of FXTAS (e.g., ataxia and parkinsonism) may be more likely to yield expanded FMR1 alleles.

Aged↗

PubMed2004

Unusual forehead tremor in a patient with essential tremor.

Voice and head (neck) tremor commonly occur in patients with essential tremor (ET), but involvement of cranial musculature is generally limited to these specific cranial structures, and action tremor of the forehead has not been reported. We describe a patient with ET who had forehead tremor. The tremor seemed to be task-specific, and neurophysiological features suggested that the forehead tremor was dystonic. The presence of forehead tremor in a patient with ET probably indicates an additional pathophysiologic process. The explanation for the specificity of involvement of cranial musculature in ET is not known, but this clinical observation might help guide investigators who are interested in the underlying pathophysiology of this condition.

Electromyography↗

PubMed2004

Increased risk of head tremor in women with essential tremor: longitudinal data from the Rochester Epidemiology Project.

In one cross-sectional study of a community in northern Manhattan, women with essential tremor (ET) were more likely to have head tremor than were men. In that study, patients were seen at one point in time, rather than followed longitudinally. Head tremor often develops after arm tremor, and its appearance in patients with ET may therefore be a function of duration of follow-up. In a second epidemiological study utilizing the Rochester Epidemiology Project, in which ET subjects were followed from disease diagnosis to death, we determined whether there was an association between female gender and head tremor. We utilized the records-linkage system of the Rochester Epidemiology Project to identify ET cases. Records were reviewed and clinical data abstracted by a neurologist specializing in movement disorders. A second neurologist reviewed a subsample of records. There were 107 ET cases (69 women, 38 men) followed for 10.1 +/- 9.1 years from ET diagnosis to death. Head tremor was present in 37 (53.6%) women and 5 (13.2%) men (odds ratio [OR] = 7.6, 95% confidence interval [CI] = 2.7-21.9, P < 0.001). In a multivariate linear regression analysis, women remained at high risk for head tremor (OR = 6.5, 95% CI = 2.2-19.0, P = 0.001) independent of disease duration. We found in this longitudinal epidemiological study that women with ET were six times more likely to develop head tremor over the course of their illness than were men. The reason for the association between gender and head tremor, which has now been demonstrated in several studies, is not known, but it could reflect gender differences in the distribution of disease pathology within the brain.

Aged↗

PubMed2004

Analysis of an early-onset Parkinson's disease cohort for DJ-1 mutations.

The frequency and relative contribution of DJ-1 mutations in early-onset Parkinson's disease (EOPD) is currently unknown. We analyzed a cohort of 89 EOPD patients (mean age at onset of PD +/- SD, 41.5 +/- 7.2 years), ascertained independent of family history, who participated in a study of the genetic epidemiology of PD. This study includes sequence analysis of the DJ-1 gene in addition to assaying the 14,082-bp deletion spanning exons 1 to 5, previously identified in a Dutch kindred, in 89 EOPD cases. A heterozygous missense mutation in exon 5 (A104T) was identified in an EOPD case of Asian ethnicity; this sequence variant was absent in 308 control chromosomes. We identified additional sequence variation in the DJ-1 gene, including a polymorphism in the coding region in exon 5 (R98Q), three polymorphisms in the 5' untranslated region (exon 1A/1B), and two polymorphisms in intronic regions (IVS1 and IVS5). Mutations in the DJ-1 gene are rare in EOPD in both sporadic and familial cases.

Adult↗