Occupational Pesticide Exposure in Parkinson's Disease Related to GBA and LRRK2 Variants.

Background: The penetrance of common genetic risk variants for Parkinson's disease (PD) is low. Pesticide exposure increases PD risk, but how exposure affects penetrance is not well understood. Objective: To determine the relationship between occupational pesticide exposure and PD in people with LRRK2 and GBA risk variants. Methods: Participants of the Parkinson's Progression Markers Initiative (PPMI) with a LRRK2-G2019 S or GBA risk variant provided information about occupational pesticide exposure. We compared exposure in carriers with and without PD. Among carriers with PD, we used Cox proportional hazard models to compare time-to impairment in balance, cognition, and activities of daily living (ADLs) between participants with and without prior occupational pesticide exposure. Results: 378 participants with a risk variant provided exposure information; 176 with LRRK2-G2019 S (54 with and 122 without PD) and 202 with GBA variants (47 with and 155 without PD). Twenty-six participants reported pesticide exposure. People with a GBA variant and occupational pesticide exposure had much higher odds of PD (aOR: 5.4, 95% CI 1.7-18.5, p < 0.01). People with a LRRK2 variant and a history of occupational pesticide exposure had non-significantly elevated odds of PD (aOR 1.3, 95% CI 0.4-4.6, p = 0.7). Among those with PD, pesticide exposure was associated with a higher risk of balance problems and cognitive impairment in LRRK2-PD and functional impairment in GBA-PD, although associations were not statistically significant. Conclusions: Occupational pesticide exposure may increase penetrance of GBA-PD and may be associated with faster symptom progression. Further studies in larger cohorts are necessary.

Dry-Cleaning Chemicals and a Cluster of Parkinson's Disease and Cancer: A Retrospective Investigation.

BACKGROUND: Environmental exposure to trichloroethylene (TCE), a carcinogenic dry-cleaning chemical, may be linked to Parkinson's disease (PD). OBJECTIVE: The objective of this study was to determine whether PD and cancer were elevated among attorneys who worked near a contaminated site. METHODS: We surveyed and evaluated attorneys with possible exposure and assessed a comparison group. RESULTS: Seventy-nine of 82 attorneys (96.3%; mean [SD] age: 69.5 [11.4] years; 89.9% men) completed at least one phase of the study. For comparison, 75 lawyers (64.9 [10.2] years; 65.3% men) underwent clinical evaluations. Four (5.1%) of them who worked near the polluted site reported PD, more than expected based on age and sex (1.7%; P = 0.01) but not significantly higher than the comparison group (n = 1 [1.3%]; P = 0.37). Fifteen (19.0%), compared to four in the comparison group (5.3%; P = 0.049), had a TCE-related cancer. CONCLUSIONS: In a retrospective study, diagnoses of PD and TCE-related cancers appeared to be elevated among attorneys who worked next to a contaminated dry-cleaning site. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Remote telemedicine evaluation of deep brain stimulation candidacy: Retrospective cohort analysis.

OBJECTIVE: To determine whether initial presurgical evaluation of deep brain stimulation (DBS) candidacy with video telemedicine (VTEL) can reliably predict surgical candidacy (patients who will eventually undergo DBS surgery) and decrease resource utilization when compared to an in-person evaluation. METHODS: In this retrospective, cohort analysis, all out-of-state referrals to the San Francisco Veterans Affairs from 2008 to 2013 for DBS therapy were reviewed and their surgical outcomes were assessed until 2017. Patients were designated as good, borderline, or poor surgical candidates after initial evaluation, and their rates of undergoing DBS were recorded. An assessment of patient travel costs was performed. RESULTS: There were 60 out-of-state DBS referrals identified out of the 148 initial presurgical DBS evaluations completed for surgical treatment of dystonia, essential tremor, or Parkinson disease; 24 patients underwent in-person consultation and 36 patients underwent evaluation via VTEL. There was no difference between the rates of undergoing surgical treatment with DBS based on surgical candidacy for patients in the in-person and VTEL cohorts. Patients who underwent initial presurgical screening via VTEL saved time and money. CONCLUSIONS: VTEL can be used to facilitate presurgical screening for DBS and saves costs.

ß-adrenoreceptors and the risk of Parkinson's disease.

BACKGROUND: ß-adrenoceptors are widely expressed in different human organs, mediate important body functions and are targeted by medications for various diseases (such as coronary heart disease and heart attack) and many ß-adrenoceptor acting drugs are listed on the WHO Model List of Essential Medicines. ß-adrenoceptor antagonists are used by billions of patients with neurological disorders, primarily for the treatment of migraine and action tremor (mainly essential tremor), worldwide. RECENT DEVELOPMENTS: An observational study reported a link between the chronic use of the ß-adrenoceptor antagonist propranolol and an increased risk of Parkinson's disease, while the chronic use of the ß-adrenoceptor agonists was associated with a decreased risk. Further support of this association was provided by a dose-dependent decrease in the risk of Parkinson's disease with chronic ß-adrenoceptor agonist (eg, salbutamol) use, and by functional data indicating a possible underlying molecular mechanism. Five additional epidemiological studies have examined the modulation of the risk of Parkinson's disease as a result of the use of ß-adrenoceptor-acting drugs in different populations. Overall, similar estimates but different interpretations of the associations were provided. Several findings suggest that the increase in risk of Parkinson's disease associated with ß-adrenoceptor antagonists use can be explained by reverse causation because prodromal Parkinson's disease is often associated with non-specific action tremor, which is usually treated with propranolol. The lower risk of Parkinson's disease seen in patients receiving ß-adrenoceptor agonists is likely to be indirectly mediated by smoking because smoking has a strong inverse association with Parkinson's disease (people that smoke have a reduced risk of developing Parkinson's disease). Smoking also causes chronic obstructive pulmonary disease, which is treated with ß-adrenoceptor-agonist medications. Even if causal, the effect of ß-adrenoceptor antagonists on the risk of Parkinson's disease would be small compared with other Parkinson's disease risk factors and would be similar to the risk evoked by pesticide exposure. The estimated risk of Parkinson's disease because of ß-adrenoceptor antagonists use corresponds to one case in 10 000 patients after 5 years of propranolol use, and would be considered a very rare adverse effect. Thus, not using ß-adrenoceptor antagonists would severely harm patients with recommended indications, such as heart disease or migraine. Similarly, 50 000 people would have to be treated for 5 years with salbutamol to prevent Parkinson's disease in one patient, suggesting that primary preventive therapy studies on disease modification are not warranted. WHERE NEXT?: Epidemiological evidence for a causal relationship between use of ß2-adrenoceptor antagonists and the increased risk of Parkinson's disease is weak, with other explanations for the association being more probable. Future observational studies are warranted to clarify this association. However, given the very low risk associated with propranolol, most clinicians are unlikely to change their treatment approach.

A specific amino acid motif of HLA-DRB1 mediates risk and interacts with smoking history in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease in which genetic risk has been mapped to HLA, but precise allelic associations have been difficult to infer due to limitations in genotyping methodology. Mapping PD risk at highest possible resolution, we performed sequencing of 11 HLA genes in 1,597 PD cases and 1,606 controls. We found that susceptibility to PD can be explained by a specific combination of amino acids at positions 70-74 on the HLA-DRB1 molecule. Previously identified as the primary risk factor in rheumatoid arthritis and referred to as the "shared epitope" (SE), the residues Q/R-K/R-R-A-A at positions 70-74 in combination with valine at position 11 (11-V) is highly protective in PD, while risk is attributable to the identical epitope in the absence of 11-V. Notably, these effects are modified by history of cigarette smoking, with a strong protective effect mediated by a positive history of smoking in combination with the SE and 11-V (P = 10-4; odds ratio, 0.51; 95% confidence interval, 0.36-0.72) and risk attributable to never smoking in combination with the SE without 11-V (P = 0.01; odds ratio, 1.51; 95% confidence interval, 1.08-2.12). The association of specific combinations of amino acids that participate in critical peptide-binding pockets of the HLA class II molecule implicates antigen presentation in PD pathogenesis and provides further support for genetic control of neuroinflammation in disease. The interaction of HLA-DRB1 with smoking history in disease predisposition, along with predicted patterns of peptide binding to HLA, provide a molecular model that explains the unique epidemiology of smoking in PD.

Parkinson's disease research in a prospective cohort in China.

INTRODUCTION: China has the largest population of Parkinson's disease (PD) patients; however few etiological studies of PD have been conducted in China. METHODS: The Shanghai Women's Health Study recruited 74,941 women in urban Shanghai, aged 40 to 70, from 1996 to 2000. Self-reported PD cases were invited for a neurological examination and diagnoses were made by a movement disorder specialist. RESULTS: This cohort had very few smokers (2.7%), alcohol drinkers (2.3%), and post-menopausal hormone users (4.3%); however, tea drinking (29.9%) and exposure to tobacco smoke from husbands (61.8%) were common. A total of 301 participants reported PD diagnosis during the follow-up. The diagnosis was confirmed in 76 (57%) of the 133 clinically examined patients. An additional 19 (53%) PD cases were identified out of 36 participants who self-confirmed the diagnosis and provided a history on PD symptoms and treatments. As expected, increasing age was strongly associated with PD risk. Further, PD risk appears to be inversely associated with exposures to second-hand tobacco smoke from husbands and tea drinking, and positively with education, although none of these reached statistical significance. The age-adjusted odds ratio (OR) was 0.7 (95% confidence interval: 0.4-1.1) for participants whose husbands were current smokers at baseline and 0.8 (0.5-1.3) for ever tea-drinkers. Compared with primary education or lower, the age-adjusted OR was 1.3 (0.7-2.4) for middle school and 1.6 (1.0-2.7) for high school or above. CONCLUSION: PD research in this unique cohort is feasible and, with extended follow-up, will allow for prospective PD etiological research in China.

Protective glove use and hygiene habits modify the associations of specific pesticides with Parkinson's disease.

Pesticides have been associated with Parkinson's disease (PD), and protective gloves and workplace hygiene can reduce pesticide exposure. We assessed whether use of gloves and workplace hygiene modified associations between pesticides and PD. The Farming and Movement Evaluation (FAME) study is a nested case-control study within the Agricultural Health Study. Use of protective gloves, other PPE, and hygiene practices were determined by questionnaire (69 cases and 237 controls were included). We considered interactions of gloves and hygiene with ever-use of pesticides for all pesticides with ≥5 exposed and unexposed cases and controls in each glove-use stratum (paraquat, permethrin, rotenone, and trifluralin). 61% of respondents consistently used protective gloves and 87% consistently used ≥2 hygiene practices. Protective glove use modified the associations of paraquat and permethrin with PD: neither pesticide was associated with PD among protective glove users, while both pesticides were associated with PD among non-users (paraquat OR 3.9 [95% CI 1.3, 11.7], interaction p=0.15; permethrin OR 4.3 [95% CI 1.2, 15.6] interaction p=0.05). Rotenone was associated with PD regardless of glove use. Trifluralin was associated with PD among participants who used <2 hygiene practices (OR 5.5 [95% CI 1.1, 27.1]) but was not associated with PD among participants who used 2 or more practices (interaction p=0.02). Although sample size was limited in the FAME study, protective glove use and hygiene practices appeared to be important modifiers of the association between pesticides and PD and may reduce risk of PD associated with certain pesticides.

Caffeine consumption and risk of dyskinesia in CALM-PD.

BACKGROUND: Adenosine A2A receptor antagonists reduce or prevent the development of dyskinesia in animal models of levodopa-induced dyskinesia. METHODS: We examined the association between self-reported intake of the A2A receptor antagonist caffeine and time to dyskinesia in the Comparison of the Agonist Pramipexole with Levodopa on Motor Complications of Parkinson's Disease (CALM-PD) and CALM Cohort extension studies, using a Cox proportional hazards model adjusting for age, baseline Parkinson's severity, site, and initial treatment with pramipexole or levodopa. RESULTS: For subjects who consumed >12 ounces of coffee/day, the adjusted hazard ratio for the development of dyskinesia was 0.61 (95% CI, 0.37-1.01) compared with subjects who consumed <4 ounces/day. For subjects who consumed between 4 and 12 ounces/day, the adjusted hazard ratio was 0.73 (95% CI, 0.46-1.15; test for trend, P = .05). CONCLUSIONS: These results support the possibility that caffeine may reduce the likelihood of developing dyskinesia.

Brain organochlorines and Lewy pathology: the Honolulu-Asia Aging Study.

Although organochlorines have been reported more frequently in Parkinson's disease (PD) brains than in controls, the association with brain Lewy pathology is unknown. Honolulu-Asia Aging Study (HAAS) participants, exposed to organochlorines from a variety of sources during midlife, represent a population well suited to determining the relationship of brain organochlorines with Lewy pathology in decedents from the longitudinal HAAS. The study design included the measurement of 21 organochlorine levels in frozen occipital lobe samples from HAAS decedents. Alpha-synuclein immunostaining performed on 225 brains was used to identify Lewy bodies and Lewy neurites. With the potential for spurious associations to appear between Lewy pathology and 17 organochlorine compounds found in at least 1 brain, initial assessments identified heptachlor epoxide isomer b, methoxychlor, and benzene hexachloride b as being most important. The prevalence of Lewy pathology was 75% (6 of 8) among brains with any 2 of the 3 compounds, 48.8% (79 of 162) among those with 1, and 32.7% (18 of 55) for those with neither (P = .007 test for trend). Although findings persisted after removing cases with PD and dementia with Lewy bodies and after adjustment for age at death, body mass index, pack-years of cigarette smoking, and coffee intake (P = .013), the results were insignificant when correcting for multiple testing. Although consistent with earlier accounts of an association between organochlorines and clinical PD, associations with Lewy pathology warrant further study.

Predictors of time to requiring dopaminergic treatment in 2 Parkinson's disease cohorts.

The rate of progression of Parkinson's disease (PD) is highly variable. Knowledge of factors associated with disease milestones and commonly used research outcome measures helps with patient counseling and guides the design and interpretation of clinical studies. The objective of the study was to identify prognostic factors for time to acquiring disability requiring dopaminergic therapy that are reproducible within 2 large prospectively followed cohorts. Potential prognostic factors were identified using data from the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) trial, and their reproducibility was examined using data from the Parkinson Research Examination of CEP-1347 trial (PRECEPT). In multivariable analyses of the DATATOP cohort, higher baseline Unified Parkinson's Disease Rating Scale (UPDRS) scores, full-time employment, a lesser smoking history, and onset on the left side were associated with a shorter time to disability requiring dopaminergic therapy. PRECEPT data confirmed the associations of higher baseline UPDRS scores and full-time employment with shorter time to requiring treatment. Any clinical trial using the end point of time to disability requiring dopaminergic therapy should ensure that groups are well balanced with respect to baseline UPDRS scores and the proportion of subjects employed full time and should consider including these variables as covariates in the statistical model for primary analysis of treatment effects. We suspect that individuals employed full time may have a lower threshold for requiring dopaminergic therapy because of occupational demands.

Comorbid cancer in Parkinson's disease.

The aim of this article was to evaluate cancer occurrence before and after diagnosis of Parkinson's disease (PD). We investigated 692 patients newly diagnosed with PD and 761 age- and sex-matched control subjects identified during two periods (1994-1995 and 2000-2003) within Kaiser Permanente Medical Care Program of Northern California. Primary cancers were searched and dated, and all participants were followed up until the end of membership, death, or December 31, 2008. We used unconditional logistic regression to evaluate the PD-cancer association before the date of PD diagnosis or the index date and Cox proportional hazards regression to evaluate the PD-cancer association after the index date. Nearly 20% (140 of 692) of the PD patients and 25% (188 of 761) of the non-PD controls had ever had a cancer diagnosis. Before the index date, the prevalence of cancer was not significantly lower in patients with PD (8.1% PD vs. 9.2% controls; OR = 0.83; 95% CI 0.54-1.3). After the index date, the risk of developing a cancer did not differ between PD cases and controls (relative risk [RR] = 0.94; 95% CI 0.70-1.3). Among specific cancers, melanoma was more common among PD cases (before PD, OR = 1.5; 95% CI 0.40-5.2; after PD, RR = 1.6; 95% CI 0.71-3.6), but independent of dopaminergic therapy. Cancer occurrence is not significantly lower among patients with PD. The positive association between PD and subsequent melanoma merits further investigation, as it does not seem to be attributable to dopaminergic therapy, pigmentation, or confounding by smoking.

Advances in environmental epidemiology.

Parkinson's disease (PD) is likely due to the combined effects of environment and genes in most cases. Environmental factors inversely associated with PD (or, putative protective factors) include cigarette smoking, use of coffee/caffeine, higher uric acid levels, and anti-inflammatory drug use. Less well-established inverse associations with PD include higher cholesterol levels, statin use, higher dietary vitamin B6, and night shift work. Putative risk factors are pesticide exposure, head trauma, certain occupations, and milk consumption. The pathogenesis of PD may begin decades before motor symptoms. PD may have shared determinants with other neurodegenerative disorders involving abnormal protein aggregation.

Occupation and risk of parkinsonism: a multicenter case-control study.

BACKGROUND: We examined risk of parkinsonism in occupations (agriculture, education, health care, welding, and mining) and toxicant exposures (solvents and pesticides) putatively associated with parkinsonism. OBJECTIVE: To investigate occupations, specific job tasks, or exposures and risk of parkinsonism and clinical subtypes. DESIGN: Case-control. SETTING: Eight movement disorders centers in North America. PARTICIPANTS: Inclusion criteria were parkinsonism (>or=2 cardinal signs), diagnosis within 8 years of recruitment (to minimize survival bias), and ability to participate in detailed telephone interviews. Control subjects were primarily nonblood relatives or acquaintances of patients. MAIN OUTCOME MEASURES: This multicenter case-control study compared lifelong occupational and job task histories to determine associations with parkinsonism and certain clinical subtypes (postural instability and gait difficulty and age at diagnosis

Meeting report: consensus statement-Parkinson's disease and the environment: collaborative on health and the environment and Parkinson's Action Network (CHE PAN) conference 26-28 June 2007.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder. People with PD, their families, scientists, health care providers, and the general public are increasingly interested in identifying environmental contributors to PD risk. METHODS: In June 2007, a multidisciplinary group of experts gathered in Sunnyvale, California, USA, to assess what is known about the contribution of environmental factors to PD. RESULTS: We describe the conclusions around which they came to consensus with respect to environmental contributors to PD risk. We conclude with a brief summary of research needs. CONCLUSIONS: PD is a complex disorder, and multiple different pathogenic pathways and mechanisms can ultimately lead to PD. Within the individual there are many determinants of PD risk, and within populations, the causes of PD are heterogeneous. Although rare recognized genetic mutations are sufficient to cause PD, these account for < 10% of PD in the U.S. population, and incomplete penetrance suggests that environmental factors may be involved. Indeed, interplay among environmental factors and genetic makeup likely influences the risk of developing PD. There is a need for further understanding of how risk factors interact, and studying PD is likely to increase understanding of other neurodegenerative disorders.

Research priorities in spasmodic dysphonia.

OBJECTIVE: To identify research priorities to increase understanding of the pathogenesis, diagnosis, and improved treatment of spasmodic dysphonia. STUDY DESIGN AND SETTING: A multidisciplinary working group was formed that included both scientists and clinicians from multiple disciplines (otolaryngology, neurology, speech pathology, genetics, and neuroscience) to review currently available information on spasmodic dysphonia and to identify research priorities. RESULTS: Operational definitions for spasmodic dysphonia at different levels of certainty were recommended for diagnosis and recommendations made for a multicenter multidisciplinary validation study. CONCLUSIONS: The highest priority is to characterize the disorder and identify risk factors that may contribute to its onset. Future research should compare and contrast spasmodic dysphonia with other forms of focal dystonia. Development of animal models is recommended to explore hypotheses related to pathogenesis. Improved understanding of the pathophysiology of spasmodic dysphonia should provide the basis for developing new treatment options and exploratory clinical trials. SIGNIFICANCE: This document should foster future research to improve the care of patients with this chronic debilitating voice and speech disorder by otolaryngology, neurology, and speech pathology.

Nicotine and Parkinson's disease: implications for therapy.

Accumulating evidence suggests that nicotine, a drug that stimulates nicotinic acetylcholine receptors, may be of therapeutic value in Parkinson's disease. Beneficial effects may be several-fold. One of these is a protective action against nigrostriatal damage. This possibility stems from the results of epidemiological studies that consistently demonstrate an inverse correlation between tobacco use and Parkinson's disease. This reduced incidence of Parkinson's disease has been attributed to the nicotine in tobacco products, at least in part, based on experimental work showing a protective effect of nicotine against toxic insults. Second, several studies suggest a symptomatic effect of nicotine in Parkinson's disease, although effects are small and somewhat variable. Third, recent data in nonhuman primates show that nicotine attenuates levodopa-induced dyskinesias, a debilitating side effect that develops in the majority of patients on levodopa therapy. Collectively, these observations suggest that nicotine or CNS selective nicotinic receptor ligands hold promise for Parkinson's disease therapy to reduce disease progression, improve symptoms, and/or decrease levodopa-induced dyskinesias.

Association of olfactory dysfunction with risk for future Parkinson's disease.

OBJECTIVE: Although olfactory dysfunction is commonly associated with Parkinson's disease (PD), it is not known whether such dysfunction can predate the onset of clinical PD in a community-based population. This study examines the association of olfactory dysfunction with future development of PD in Honolulu-Asia Aging Study cohort members METHODS: Olfaction was assessed from 1991 to 1996 in 2,267 men in the Honolulu-Asia Aging Study aged 71 to 95 years who were free of clinical PD and dementia at the time of olfaction testing. Participants were followed for up to 8 years for incident PD RESULTS: In the course of follow-up, 35 men were diagnosed with PD (24.6/10,000 person-years). The average age at the time of diagnosis was 82.9 +/- 3.8 (range, 76-93) years, and the average time to a diagnosis was 4.0 +/- 1.9 (range, 1-8) years. During the first 4 years of follow-up, age-adjusted incidence of PD declined from 54.5/10,000 person-years in the lowest quartile of odor identification to 26.6, 8.2, and 8.4/10,000 person-years in the second, third, and fourth quartiles, respectively (p < 0.001 for trend). After adjustment for age and other potential confounders, the odds ratios for PD in the lowest quartile was 5.2 (95% confidence interval, 1.5-25.6) compared with the top two quartiles. This relation was not evident beyond 4 years of follow-up. INTERPRETATION: Impaired olfaction can predate clinical PD in men by at least 4 years and may be a useful screening tool to detect those at high risk for development of PD in later life.

Bowel movement frequency in late-life and incidental Lewy bodies.

It is not known if constipation is associated with the preclinical phase of Parkinson's disease (PD), often characterized by the presence of incidental Lewy bodies (ILB). Such an association could provide evidence that constipation is an early symptom of PD. The purpose of this report is to examine the association between late-life bowel movement frequency and ILB. Bowel movement frequency was assessed from 1991 to 1993 in 245 men aged 71 to 93 years in the Honolulu-Asia Aging Study who later received postmortem examinations. All were without clinical PD and dementia. Brains were examined for ILB in the substantia nigra and locus ceruleus. Among the decedents, 30 men had ILB (12.2%). After age-adjustment, the percent of brains with ILB declined with increasing bowel movement frequency (P=0.013). For men with <1, 1, and >1 bowel movement/day, corresponding percents were 24.1, 13.5, and 6.5%. Findings persisted after additional adjustment for time to death, mid-life pack-years of smoking and coffee intake, physical activity, and cognitive function. Infrequent bowel movements are associated with ILB. Findings provide evidence that constipation can predate the extrapyramidal signs of PD. Constipation could be one of the earliest markers of the beginning of PD processes.

Benefits and risks of pharmacological treatments for essential tremor.

Essential tremor can cause significant functional disability in some patients. The arms are the most common body part affected and cause the most functional disability. The treatment of essential tremor includes medications, surgical options and other forms of therapy. Presently there is no cure for essential tremor nor are there any medications that can slow the progression of tremor. Treatment for essential tremor is recommended if the tremor causes functional disability. If the tremor is disabling only during periods of stress and anxiety, propranolol and benzodiazepines can be used during those periods when the tremor causes functional disability. The currently available medications can improve tremor in approximately 50% of the patients. If the tremor is disabling, treatment should be initiated with either primidone or propranolol. If either primidone or propranolol do not provide adequate control of the tremor, then the medications can be used in combination. If patients experience adverse effects with propranolol, occasionally other beta-adrenoceptor antagonists (such as atenolol or metoprolol) can be used. If primidone and propranolol do not provide adequate control of tremor, occasionally the use of benzodiazepines (such as clonazepam) can provide benefit. Other medications that may be helpful include gabapentin or topiramate. If a patient has disabling head or voice tremor, botulinum toxin injections into the muscles may provide relief from the tremor. Botulinum toxin in the hand muscles for hand tremor can result in bothersome hand weakness and is not widely used. There are other medications that have been tried in essential tremor and have questionable efficacy. These drugs include carbonic anhydrase inhibitors (e.g. methazolamide), phenobarbital, calcium channel antagonists (e.g. nimodipine), isoniazid, clonidine, clozapine and mirtazapine. If the patient still has disabling tremor after medication trials, surgical options are usually considered. Surgical options include thalamotomy and deep brain stimulation of the thalamus. These surgical options provide adequate tremor control in approximately 90% of the patients. Surgical morbidity and mortality for these procedures is low. Deep brain stimulation and thalamotomy have been shown to have comparable efficacy but fewer complications have been reported with deep brain stimulation. In patients undergoing bilateral procedures deep brain stimulation of the thalamus is the procedure of choice to avoid adverse effects seen with bilateral ablative procedures. The use of medication and/or surgery can provide adequate tremor control in the majority of the patients.