Parkinson Disease
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Parkinson disease (PD) is one of the most common neurologic disorders, affecting approximately 1% of individuals older than 60 years and causing progressive disability that can be slowed, but not halted, by treatment. The 2 major neuropathologic findings in Parkinson disease are loss of pigmented dopaminergic neurons of the substantia nigra pars compacta and the presence of Lewy bodies and Lewy neurites. See the images below.
Initial clinical symptoms of Parkinson disease include the following:
Tremor
Subtle decrease in dexterity
Decreased arm swing on the first-involved side
Soft voice
Decreased facial expression
Sleep disturbances
Rapid eye movement (REM) behavior disorder (RBD; a loss of normal atonia during REM sleep)
Decreased sense of smell
Symptoms of autonomic dysfunction (eg, constipation, sweating abnormalities, sexual dysfunction, seborrheic dermatitis)
A general feeling of weakness, malaise, or lassitude
Depression or anhedonia
Slowness in thinking
Onset of motor signs include the following:
Typically asymmetric
The most common initial finding is a resting tremor in an upper extremity
Over time, patients experience progressive bradykinesia, rigidity, and gait difficulty
Axial posture becomes progressively flexed and strides become shorter
Postural instability (balance impairment) is a late phenomenon
Nonmotor symptoms
Nonmotor symptoms are common in early Parkinson disease. Recognition of the combination of nonmotor and motor symptoms can promote early diagnosis and thus early intervention, which often results in a better quality of life.
See Clinical Presentation for more detail.
Parkinson disease is a clinical diagnosis. No laboratory biomarkers exist for the condition, and findings on routine magnetic resonance imaging and computed tomography scans are unremarkable.
Clinical diagnosis requires the presence of 2 of 3 cardinal signs:
Resting tremor
Rigidity
Bradykinesia
See Workup for more detail.
The goal of medical management of Parkinson disease is to provide control of signs and symptoms for as long as possible while minimizing adverse effects.
Symptomatic drug therapy
Usually provides good control of motor signs of Parkinson disease for 4-6 years
Levodopa/carbidopa: The gold standard of symptomatic treatment
Monoamine oxidase (MAO)–B inhibitors: Can be considered for initial treatment of early disease
Other dopamine agonists (eg, ropinirole, pramipexole): Monotherapy in early disease and adjunctive therapy in moderate to advanced disease
Anticholinergic agents (eg, trihexyphenidyl, benztropine): Second-line drugs for tremor only
Treatment for nonmotor symptoms
Sildenafil citrate (Viagra): For erectile dysfunction
Polyethylene glycol: For constipation
Modafinil: For excessive daytime somnolence
Methylphenidate: For fatigue (potential for abuse and addiction)
Deep brain stimulation
Surgical procedure of choice for Parkinson disease
Does not involve destruction of brain tissue
Reversible
Can be adjusted as the disease progresses or adverse events occur
Bilateral procedures can be performed without a significant increase in adverse events
See Treatment and Medication for more detail.
Parkinson disease is recognized as one of the most common neurologic disorders, affecting approximately 1% of individuals older than 60 years. There are 2 major neuropathologic findings: the loss of pigmented dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of Lewy bodies (see the following image). Most cases of Parkinson disease (idiopathic Parkinson disease [IPD]) are hypothesized to be due to a combination of genetic and environmental factors. However, no environmental cause of Parkinson disease has yet been proven. A known genetic cause can be identified in approximately 10% of cases, and these are more common in younger-onset patients.
The classic motor features of Parkinson disease typically start insidiously and emerge slowly over weeks or months, with tremor being the most common initial symptom. The 3 cardinal signs of Parkinson disease are resting tremor, rigidity, and bradykinesia. Postural instability (balance impairment) is sometimes listed as the fourth cardinal feature. However, balance impairment in Parkinson disease is a late phenomenon, and in fact, prominent balance impairment in the first few years suggests that Parkinson disease is not the correct diagnosis. (See Presentation.)
When a patient presents with tremor, the clinician evaluates the patient’s history and physical examination findings to differentiate Parkinson disease tremor from other types of tremor. In patients with parkinsonism, careful attention to the history is necessary to exclude causes such as drugs, toxins, or trauma. (See Differential Diagnosis.) Other common causes of tremor include essential tremor, physiologic tremor, and dystonic tremor.
No laboratory or imaging study is required in patients with a typical presentation of Parkinson disease. Such patients are aged 55 years or older and have a slowly progressive and asymmetric parkinsonism with resting tremor and bradykinesia or rigidity. There are no red flags such as prominent autonomic dysfunction, balance impairment, dementia, or eye-movement abnormalities. In such cases, the diagnosis is ultimately considered confirmed once the patient goes on dopaminergic therapy (levodopa or a dopamine agonist) as needed for motor symptom control and exhibits a robust and sustained benefit. (See Workup.)
Imaging studies can be considered, depending on the differential diagnosis. Magnetic resonance imaging (MRI) of the brain can be considered to evaluate possible cerebrovascular disease (including multi-infarct state), space-occupying lesions, normal-pressure hydrocephalus, and other disorders.
Iodine-123–labeled fluoropropyl-2beta-carbomethoxy-3beta-4-iodophenyl-nortroptane (FP-CIT I123) (Ioflupane, DaTscan) single-photon emission computed tomography (SPECT) can be considered in cases of uncertain parkinsonism to help differentiate disorders associated with a loss of dopamine neurons (Parkinson disease and atypical parkinsonisms, including multiple system atrophy [MSA] and progressive supranuclear palsy [PSP]) from those disorders not associated with a loss of dopamine neurons (eg, essential tremor, dystonic tremor, vascular parkinsonism, medication-induced parkinsonism or tremor, psychogenic conditions). [1]
Levodopa coupled with a peripheral decarboxylase inhibitor (PDI), such as carbidopa, remains the gold standard of symptomatic treatment of motor features of Parkinson disease. It provides the greatest antiparkinsonian benefit with the fewest adverse effects in the short term. However, its long-term use is associated with the development of fluctuations and dyskinesias. Moreover, the disease continues to progress, and patients accumulate long-term disability. (See Treatment.)
Dopamine agonists such as pramipexole (Mirapex) and ropinirole (Requip) can be used as monotherapy to improve symptoms in early Parkinson disease or as adjuncts to levodopa in patients who are experiencing motor fluctuations. Monoamine oxidase (MAO)-B inhibitors, such as selegiline (Eldepryl) and rasagiline (Azilect) provide mild benefit as monotherapy in early disease and as adjuncts to levodopa in patients with motor fluctuations. (See Medication.) Entacapone (Comtan), a catechol-o-methyltransferase (COMT) inhibitor, reduces the peripheral metabolism of levodopa, thereby making more levodopa available to enter the brain over a longer period; this agent is used as an adjunct to levodopa in patients with motor fluctuations.
Parkinson disease is predominantly a disorder of the basal ganglia, which are a group of nuclei situated at the base of the forebrain. The striatum, composed of the caudate and putamen, is the largest nuclear complex of the basal ganglia. The striatum receives excitatory input from several areas of the cerebral cortex, as well as inhibitory and excitatory input from the dopaminergic cells of the substantia nigra pars compacta (SNc). These cortical and nigral inputs are received by the spiny projection neurons, which are of 2 types: those that project directly to the internal segment of the globus pallidus (GPi), the major output site of the basal ganglia; and those that project to the external segment of the globus pallidus (GPe), establishing an indirect pathway to the GPi via the subthalamic nucleus (STN).
For an illustration of the subthalamic nucleus, see the image below.
The actions of the direct and indirect pathways regulate the neuronal output from the GPi, which provides tonic inhibitory input to the thalamic nuclei that project to the primary and supplementary motor areas.
No specific, standard criteria exist for the neuropathologic diagnosis of Parkinson disease, as the specificity and sensitivity of its characteristic findings have not been clearly established. However, the following are the 2 major neuropathologic findings in Parkinson disease:
Loss of pigmented dopaminergic neurons of the substantia nigra pars compacta
The presence of Lewy bodies and Lewy neurites
The loss of dopamine neurons occurs most prominently in the ventral lateral substantia nigra. Approximately 60-80% of dopaminergic neurons are lost before the motor signs of Parkinson disease emerge.
Some individuals who were thought to be normal neurologically at the time of their deaths are found to have Lewy bodies on autopsy examination. These incidental Lewy bodies have been hypothesized to represent the presymptomatic phase of Parkinson disease. The prevalence of incidental Lewy bodies increases with age. Note that Lewy bodies are not specific to Parkinson disease, as they are found in some cases of atypical parkinsonism, Hallervorden-Spatz disease, and other disorders. Nonetheless, they are a characteristic pathology finding of Parkinson disease.
The basal ganglia motor circuit modulates the cortical output necessary for normal movement (see the following image).
Signals from the cerebral cortex are processed through the basal ganglia-thalamocortical motor circuit and return to the same area via a feedback pathway. Output from the motor circuit is directed through the internal segment of the globus pallidus (GPi) and the substantia nigra pars reticulata (SNr). This inhibitory output is directed to the thalamocortical pathway and suppresses movement.
Two pathways exist within the basal ganglia circuit, the direct and indirect pathways, as follows:
In the direct pathway, outflow from the striatum directly inhibits the GPi and SNr; striatal neurons containing D1 receptors constitute the direct pathway and project to the GPi/SNr
The indirect pathway contains inhibitory connections between the striatum and the external segment of the globus pallidus (GPe) and between the GPe and the subthalamic nucleus (STN); striatal neurons with D2 receptors are part of the indirect pathway and project to the GPe
The STN exerts an excitatory influence on the GPi and SNr. The GPi/SNr sends inhibitory output to the ventral lateral nucleus (VL) of the thalamus. Dopamine is released from nigrostriatal (substantia nigra pars compacta [SNpc]) neurons to activate the direct pathway and inhibit the indirect pathway. In Parkinson disease, decreased striatal dopamine causes increased inhibitory output from the GPi/SNr via both the direct and indirect pathways (see the following image).
The increased inhibition of the thalamocortical pathway suppresses movement. Via the direct pathway, decreased striatal dopamine stimulation causes decreased inhibition of the GPi/SNr. Via the indirect pathway, decreased dopamine inhibition causes increased inhibition of the GPe, resulting in disinhibition of the STN. Increased STN output increases GPi/SNr inhibitory output to the thalamus.
Although the etiology of Parkinson disease is still unclear, most cases are hypothesized to be due to a combination of genetic and environmental factors. Currently known genetic causes of Parkinson disease account for approximately 10% of cases.
Environmental risk factors commonly associated with the development of Parkinson disease include use of pesticides, living in a rural environment, consumption of well water, exposure to herbicides, and proximity to industrial plants or quarries. [2]
A meta-analysis of 89 studies, including 6 prospective and 83 case-control studies, found that exposure to pesticides may increase the risk for PD by as much as 80%. [3, 4] Exposure to the weed killer paraquat or to the fungicides maneb or mancozeb is particularly toxic, increasing the risk for PD about 2-fold. Many of the agents studied are no longer used in the United States and Europe; however, some are still found in developing parts of the world. [3, 4]
In case-control studies, PD was associated with exposure to any type of pesticide, herbicide, insecticide, and solvent, with risks ranging from 33% to 80%. [3, 4] Increased PD risk was also associated with proxy conditions of exposure to organic pollutants, such as farming, well-water drinking, and rural living. In addition, risk seemed to increase with length of exposure. [3, 4]
The National Institutes of Health-AARP Diet and Health Study, as well as a meta-analysis of prospective studies, found that higher caffeine intake was associated with lower risk of Parkinson disease in both men and women. A similar association was found for smoking and Parkinson disease risk. [5] The biological mechanisms underlying the inverse relationship between caffeine or smoking and Parkinson disease risk are not well elucidated.
MPTP interference with mitochondrial function
Several individuals were identified who developed parkinsonism after self-injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). These patients developed bradykinesia, rigidity, and tremor, which progressed over several weeks and improved with dopamine replacement therapy. MPTP crosses the blood-brain barrier and is oxidized to 1-methyl-4-phenylpyridinium (MPP+) by monoamine oxidase (MAO)-B. [6]
MPP+ accumulates in mitochondria and interferes with the function of complex I of the respiratory chain. A chemical resemblance between MPTP and some herbicides and pesticides suggested that an MPTP-like environmental toxin might be a cause of Parkinson disease, but no specific agent has been identified. Nonetheless, mitochondrial complex I activity is reduced in Parkinson disease, suggesting a common pathway with MPTP-induced parkinsonism.
The oxidation hypothesis suggests that free radical damage, resulting from dopamine’s oxidative metabolism, plays a role in the development or progression of Parkinson disease. The oxidative metabolism of dopamine by MAO leads to the formation of hydrogen peroxide. Normally, hydrogen peroxide is cleared rapidly by glutathione, but if hydrogen peroxide is not cleared adequately, it may lead to the formation of highly reactive hydroxyl radicals that can react with cell membrane lipids to cause lipid peroxidation and cell damage. In Parkinson disease, levels of reduced glutathione are decreased, suggesting a loss of protection against formation of free radicals. Iron is increased in the substantia nigra and may serve as a source of donor electrons, thereby promoting the formation of free radicals.
Parkinson disease is associated with increased dopamine turnover, decreased protective mechanisms (glutathione), increased iron (a pro-oxidation molecule), and evidence of increased lipid peroxidation. This hypothesis has raised concern that increased dopamine turnover due to levodopa administration could increase oxidative damage and accelerate loss of dopamine neurons. However, there is no clear evidence that levodopa accelerates disease progression.
If genetic factors are important in a particular disease, concordance in genetically identical monozygotic (MZ) twins will be greater than in dizygotic (DZ) twins, who share only about 50% of genes. Early Parkinson disease twin studies generally found low and similar concordance rates for MZ and DZ pairs.
However, genetic factors in Parkinson disease appear to be very important when the disease begins at or before age 50 years. In a study of 193 twins, overall concordance for MZ and DZ pairs was similar, but in 16 pairs of twins in whom Parkinson disease was diagnosed at or before age 50 years, all 4 MZ pairs, but only 2 of 12 DZ pairs, were concordant. [7]
The identification of a few families with familial Parkinson disease sparked further interest in the genetics of the disease. In one large family in Salerno, Italy, 50 of 592 members had Parkinson disease; linkage analysis incriminated a region in bands 4q21-23, and sequencing revealed an A-for-G substitution at base 209 of the alpha-synuclein gene. [8] Termed PD-1, this mutation codes for a substitution of threonine for alanine at amino acid 53. These individuals were characterized by early age of disease onset (mean age, 47.5 years), rapid progression (mean age at death, 56.1 years), lack of tremor, and good response to levodopa therapy. [8] Five small Greek kindreds were also found to have the PD-1 mutation.
In a German family, a different point mutation in the alpha-synuclein gene (a substitution of C for G at base 88, producing a substitution of proline for alanine at amino acid 30) confirmed that mutations in the alpha-synuclein gene can cause Parkinson disease. [9] A few additional familial mutations in the alpha-synuclein gene have been identified and are collectively called PARK1. It is now clear that these mutations are an exceedingly rare cause of Parkinson disease.
A total of 18 loci in various genes have now been proposed for Parkinson disease. Mutations within 6 of these loci (SNCA, LRRK2, PRKN, DJ1, PINK1, and ATP 13A2) are well-validated causes of familial parkinsonism. [10] Inheritance is autosomal dominant for SNCA and LRRK2 (although LRRK2 mutations exhibit variable penetrance). Inheritance is autosomal recessive for PRKN, DJ1, PINK1, and ATP13A2. In addition, polymorphisms within SNCA and LRRK2, as well as variations in MAPT and GBA, are risk factors for Parkinson disease. [10]
(For more information on genes/loci underlying monogenic parkinsonism and susceptibility genes/loci for Parkinson disease, see Tables 1 and 2, respectively, in The Genetics of Parkinson Disease. [10] )
In one study of 953 patients with Parkinson disease with age at onset of 50 years or younger, 64 patients (6.7%) had a PRKN mutation, 1 patient (0.2%) had a DJ1 mutation, 35 patients (3.6%) had an LRRK2 mutation, and 64 patients (6.7%) had a GBA mutation. [11] . Mutations were more common in patients with age at onset of 30 years or younger (40.6%) than in those with age at onset between 31 and 50 years (14.6%); more common in patients of Jewish ancestry (32.4%) than in non-Jewish patients (13.7%); and more common in patients reporting a first-degree family history of Parkinson disease (23.9%) than in those without such a family history (15.1%). [11]
Although the mechanisms by which genetic mutations cause Parkinson disease is not known, evidence to date converges on mechanisms related to abnormal protein aggregation, defective ubiquitin-mediated protein degradation, mitochondrial dysfunction, and oxidative damage.
Abnormally aggregated alpha-synuclein is the major component of Lewy bodies and Lewy neurites, which are characteristic pathologic findings in Parkinson disease. Missense mutations and multiplications in the SNCA gene that encodes alpha-synuclein, although rare, cause autosomal dominant Parkinson disease. However, genome-wide association studies have also demonstrated a link between SNCA and sporadic Parkinson disease.
Dysfunction of alpha-synuclein appears to play a central role in the pathogenesis of Parkinson disease, and understanding its relationship to the disease process holds major promise for the development of a cure.
Alpha-synuclein is a 140-amino-acid protein that is unfolded at neutral pH. However, when bound to membranes or vesicles containing acidic phospholipids, it takes on an alpha-helical structure. Normally, alpha-synuclein is found mainly in neuronal presynaptic terminals and may play a role in assembly and function of SNARE (soluble N-ethylmaleimide-sensitive factor activating protein receptor) proteins that are involved in neurotransmitter release.
Under certain conditions, alpha-synuclein aggregates into oligomers that are gradually converted to the beta–sheet-rich fibrillary structures that form Lewy bodies and neurites in Parkinson disease. Most evidence currently suggests that it is the intermediate soluble oligomers that are toxic to neurons.
Multiple mechanisms have been suggested as to how abnormally aggregated alpha-synuclein could exert neurotoxicity. [12] One hypothesis suggests that oligomeric alpha-synuclein can promote formation of ion-permeable pores on neuronal membranes, leading to increased calcium influx. Aberrant pore formation could also lead to neurotransmitter leaks from synaptic vesicles into the cytosol. In addition, overexpression of alpha-synuclein has been demonstrated to impair mitochondrial complex I activity, and oligomeric alpha-synuclein may have a direct effect on mitochondrial membranes. Other lines of evidence suggest that oligomerization of alpha-synuclein could cause cytoskeletal disruption, possibly by an effect on the microtubule-stabilizing protein, tau. [13]
Elevated levels of alpha-synuclein promote abnormal aggregation. levels are normally regulated by a balance between synthesis and degradation. SNCA multiplications lead to increased synthesis of alpha-synuclein and can cause Parkinson disease. Alpha-synuclein appears to be degraded by the ubiquitin proteasome system and the autophagy-lysosome pathway. Several genetic mutations associated with Parkinson disease may lead to decreased alpha-synuclein degradation. For example, increased risk of Parkinson disease in carriers of GBA (beta-glucocerebrosidase gene) mutations, which encode for the lysosomal enzyme glucocerebrosidase, may be due to lysosomal dysfunction and consequent alpha-synuclein accumulation and oligomerization.
How the Parkinson disease process begins is not known. Once it is initiated, however, it may propagate by a prionlike process in which misconformed proteins induce the templated misfolding of other protein molecules. In Parkinson disease, synuclein pathology begins in the lower brainstem and olfactory bulb, ascends up the midbrain, and eventually affects the neocortex. One set of observations in support of a prionlike process comes from experience with fetal dopaminergic grafts transplanted into the striata of patients with Parkinson disease, because these grafts develop Lewy bodies, suggesting host-graft transmission of disease. [14]
Preventing the propagation of abnormal alpha-synuclein aggregation may be the key to slowing or stopping Parkinson disease progression.
For years, there has been speculation about a relationship between PD and melanoma. Initially, it was theorized that the drug levodopa led to an increased risk of skin cancer, but studies did not confirm this. However, subsequent trials have since found an increased risk for melanoma in patients with PD. One particular study conducted in 2017 found that Parkinson patients have about a 4-fold increased risk of having preexisting melanoma. [15, 16] Another study found the risk to be 7-fold. [17]
In a large cohort study, researchers found that individuals with type 2 diabetes had a 32% increased risk of developing later Parkinson’s disease than those without diabetes. The study involved 2 million people with type 2 diabetes and compared them to a reference cohort of 6,173,208 people without diabetes and results showed significantly elevated rates of Parkinson’s disease in the type 2 diabetes cohort (hazard ratio [HR], 1.32, 95% confidence interval [CI], 1.29 – 1.35; P < .001). The relative increase was greater in patients with diabetic complications and in younger individuals with type 2 diabetes aged 25 to 44 years. [18]
Parkinson disease is recognized as one of the most common neurologic disorders, affecting approximately 1% of individuals older than 60 years. The incidence of Parkinson disease has been estimated to be 4.5-21 cases per 100,000 population per year, and estimates of prevalence range from 18 to 328 cases per 100,000 population, with most studies yielding a prevalence of approximately 120 cases per 100,000 population. The wide variation in reported global incidence and prevalence estimates may be the result of a number of factors, including the way data are collected, differences in population structures and patient survival, case ascertainment, and the methodology used to define cases. [19]
The incidence and prevalence of Parkinson disease increase with age, and the average age of onset is approximately 60 years. Onset in persons younger than 40 years is relatively uncommon. Parkinson disease is about 1.5 times more common in men than in women.
Before the introduction of levodopa, Parkinson disease caused severe disability or death in 25% of patients within 5 years of onset, 65% within 10 years, and 89% within 15 years. The mortality rate from Parkinson disease was 3 times that of the general population matched for age, sex, and racial origin. With the introduction of levodopa, the mortality rate dropped approximately 50%, and longevity was extended by many years. This is thought to be due to the symptomatic effects of levodopa, as no clear evidence suggests that levodopa stems the progressive nature of the disease. [20, 21]
The American Academy of Neurology notes that the following clinical features may help predict the rate of progression of Parkinson disease [22] :
Older age at onset and initial rigidity/hypokinesia can be used to predict (1) a more rapid rate of motor progression in those with newly diagnosed Parkinson disease and (2) earlier development of cognitive decline and dementia; however, initially presenting with tremor may predict a more benign disease course and longer therapeutic benefit from levodopa
A faster rate of motor progression may also be predicted if the patient is male, has associated comorbidities, and has postural instability/gait difficulty (PIGD)
Older age at onset, dementia, and decreased responsiveness to dopaminergic therapy may predict earlier nursing home placement and decreased survival
Patients with Parkinson disease should be encouraged to participate in decision making regarding their condition. [23] In addition, individuals and their caregivers should be provided with information that is appropriate for their disease state and expected or ongoing challenges. [21] Psychosocial support and concerns should be addressed and/or referred to a social worker or psychologist as needed.
Prevention of falls should be discussed. The UK National Institute for Health and Clinical Excellence has several guidance documents including those for patients and caregivers.
Other issues that commonly need to be addressed at appropriate times in the disease course include cognitive decline, personality changes, depression, dysphagia, sleepiness and fatigue, and impulse control disorders. Additional information is also often needed for financial planning, insurance issues, disability application, and placement (assisted living facility, nursing home).
For patient education information, see the Brain & Nervous System Center, as well as Parkinson’s Disease Dementia.
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Robert A Hauser, MD, MBA Professor of Neurology, Molecular Pharmacology and Physiology, Director, USF Parkinson’s Disease and Movement Disorders Center, National Parkinson Foundation Center of Excellence, Byrd Institute, Clinical Chair, Signature Interdisciplinary Program in Neuroscience, University of South Florida College of Medicine
Robert A Hauser, MD, MBA is a member of the following medical societies: American Academy of Neurology, American Medical Association, American Society of Neuroimaging, International Parkinson and Movement Disorder Society
Disclosure: Received consulting fee from Cerecor for consulting; Received consulting fee from L&M Healthcare for consulting; Received consulting fee from Cleveland Clinic for consulting; Received consulting fee from Heptares for consulting; Received consulting fee from Gerrson Lehrman Group for consulting; Received consulting fee from Indus for consulting; Received consulting fee from University of Houston for consulting; Received consulting fee from AbbVie for consulting; Received consulting fee from Adama.
Kelly E Lyons, PhD Research Professor of Neurology, Director of Research and Education, Parkinson’s Disease and Movement Disorder Center, University of Kansas Medical Center
Kelly E Lyons, PhD is a member of the following medical societies: American Academy of Neurology, International Parkinson and Movement Disorder Society
Disclosure: Received honoraria from Novartis for speaking and teaching; Received honoraria from Teva Neuroscience for speaking and teaching; Received honoraria from St Jude Medical for board membership.
Theresa A McClain, RN, MSN, ARNP-BC Advanced Registered Nurse Practitioner and Investigator, Parkinson’s Disease and Movement Disorders Center, University of South Florida College of Medicine
Theresa A McClain, RN, MSN, ARNP-BC is a member of the following medical societies: Sigma Theta Tau International
Disclosure: Received consulting fee from Teva for consulting; Received consulting fee from Schering Plough for consulting; Received consulting fee from Biotie for consulting; Received consulting fee from Novartis for consulting.
Rajesh Pahwa, MD Professor of Neurology, Director, Parkinson Disease and Movement Disorder Center, Department of Neurology, University of Kansas Medical Center
Rajesh Pahwa, MD is a member of the following medical societies: American Academy of Neurology, International Parkinson and Movement Disorder Society
Disclosure: Nothing to disclose.
Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida Morsani College of Medicine
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, American Medical Association
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Acorda, Livanova, Eisai, Greenwich, Lundbeck, Neuropace, Sunovion, Upsher-Smith.<br/>Serve(d) as a speaker or a member of a speakers bureau for: Livanova, Eisai, Greenwich, Lundbeck, Neuropace, Sunovion.<br/>Received research grant from: Acorda, Livanova, Greenwich, Lundbeck, Sepracor, Sunovion, UCB, Upsher-Smith.
Ron L Alterman, MD Associate Professor of Neurosurgery, Mount Sinai School of Medicine; Consulting Surgeon, Department of Neurosurgery, Mount Sinai School of Medicine, Elmhurst Hospital, and Walter Reed Army Medical Center
Ron L Alterman, MD is a member of the following medical societies: Alpha Omega Alpha, American Association of Neurological Surgeons, Congress of Neurological Surgeons, Medical Society of the State of New York, and New York County Medical Society
Disclosure: Nothing to disclose.
Heather S Anderson, MD Assistant Professor, Staff Neurologist, Department of Neurology, Alzheimer and Memory Center, University of Kansas Medical Center
Heather S Anderson, MD is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.
Jeff Blackmer, MD, FRCP(C) Associate Professor, Medical Director, Neurospinal Service, Division of Physical Medicine and Rehabilitation, The Rehabilitation Centre, University of Ottawa Faculty of Medicine; Executive Director, Office of Ethics, Canadian Medical Association
Jeff Blackmer, MD, FRCP(C) is a member of the following medical societies: American Paraplegia Society, Canadian Association of Physical Medicine and Rehabilitation, Canadian Medical Association, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.
Thomas L Carroll, MD Assistant Professor, Department of Otolaryngology-Head and Neck Surgery, Tufts University School of Medicine and Director, The Center for Voice and Swallowing, Tufts Medical Center
Thomas L Carroll, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Otolaryngology-Head and Neck Surgery, American Bronchoesophagological Association, American Laryngological Association, and American Medical Association
Disclosure: Merz aesthetics inc. Consulting fee Speaking and teaching
Richard J Caselli, MD Professor, Department of Neurology, Mayo Medical School, Rochester, MN; Chair, Department of Neurology, Mayo Clinic of Scottsdale
Richard J Caselli, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Medical Association, American Neurological Association, and Sigma Xi
Disclosure: Nothing to disclose.
Arif I Dalvi, MD Director, Movement Disorders Center, NorthShore University HealthSystem, Clinical Associate Professor of Neurology, University of Chicago Pritzker Medical School
Arif I Dalvi, MD is a member of the following medical societies: European Neurological Society and Movement Disorders Society
Disclosure: Nothing to disclose.
Nestor Galvez-Jimenez, MD, MSc, MHA Chairman, Department of Neurology, Program Director, Movement Disorders, Department of Neurology, Division of Medicine, Cleveland Clinic Florida
Nestor Galvez-Jimenez, MD, MSc, MHA is a member of the following medical societies: American Academy of Neurology, American College of Physicians, and Movement Disorders Society
Disclosure: Nothing to disclose.
Stephen T Gancher, MD Adjunct Associate Professor, Department of Neurology, Oregon Health Sciences University
Stephen T Gancher, MD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, and Movement Disorders Society
Disclosure: Nothing to disclose.
Michael Hoffmann, MBBCh, MD, FCP(SA), FAAN, FAHA Professor of Neurology, University of Central Florida College of Medicine; Director of Cognitive Neurology, Director of Stroke Program, James A Haley Veterans Affairs Hospital
Michael Hoffmann, MBBCh, MD, FCP(SA), FAAN, FAHA is a member of the following medical societies: American Academy of Neurology, American Headache Society, American Heart Association, and American Society of Neuroimaging
Disclosure: Nothing to disclose.
Daniel H Jacobs MD, FAAN, Associate Professor of Neurology, University of Florida College of Medicine; Director for Stroke Services, Orlando Regional Medical Center
Daniel H Jacobs is a member of the following medical societies: American Academy of Neurology, American Society of Neurorehabilitation, and Society for Neuroscience
Disclosure: Teva Pharmaceutical Grant/research funds Consulting; Biogen Idex Grant/research funds Independent contractor; Serono EMD Royalty Speaking and teaching; Pfizer Royalty Speaking and teaching; Berlex Royalty Speaking and teaching
Robert M Kellman, MD Professor and Chair, Department of Otolaryngology and Communication Sciences, State University of New York Upstate Medical University
Robert M Kellman, MD is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, American Medical Association, American Neurotology Society, American Rhinologic Society, American Society for Head and Neck Surgery, Medical Society of the State of New York, and Triological Society
Disclosure: GE Healthcare Honoraria Review panel membership; Revent Medical Honoraria Review panel membership
Milton J Klein, DO, MBA Consulting Physiatrist, Heritage Valley Health System-Sewickley Hospital and Ohio Valley General Hospital
Milton J Klein, DO, MBA is a member of the following medical societies: American Academy of Disability Evaluating Physicians, American Academy of Medical Acupuncture, American Academy of Osteopathy, American Academy of Physical Medicine and Rehabilitation, American Medical Association, American Osteopathic Association, American Osteopathic College of Physical Medicine and Rehabilitation, American Pain Society, and Pennsylvania Medical Society
Disclosure: Nothing to disclose.
Kat Kolaski, MD Assistant Professor, Departments of Orthopedic Surgery and Pediatrics, Wake Forest University School of Medicine
Kat Kolaski, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine and American Academy of Physical Medicine and Rehabilitation
Disclosure: Nothing to disclose.
Jose G Merino, MD Medical Director, Suburban Hospital Stroke Program
Jose G Merino, MD is a member of the following medical societies: American Heart Association and American Stroke Association
Disclosure: Nothing to disclose.
Arlen D Meyers, MD, MBA Professor, Department of Otolaryngology-Head and Neck Surgery, University of Colorado School of Medicine
Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, and American Head and Neck Society
Disclosure: Covidien Corp Consulting fee Consulting; US Tobacco Corporation Unrestricted gift Unknown; Axis Three Corporation Ownership interest Consulting; Omni Biosciences Ownership interest Consulting; Sentegra Ownership interest Board membership; Syndicom Ownership interest Consulting; Oxlo Consulting; Medvoy Ownership interest Management position; Cerescan Imaging Honoraria Consulting; GYRUS ACMI Honoraria Consulting
Lorraine Ramig, PhD Professor, Department of Speech Language Hearing Sciences, University of Colorado at Boulder; Senior Scientist, National Center for Voice and Speech (NCVS); Adjunct Professor, Department of Biobehavior, Columbia University Teacher’s College
Disclosure: Nothing to disclose.
Alan D Schmetzer, MD Professor Emeritus, Interim Chairman, Vice-Chair for Education, Associate Residency Training Director in General Psychiatry, Fellowship Training Director in Addiction Psychiatry, Department of Psychiatry, Indiana University School of Medicine; Addiction Psychiatrist, Midtown Mental Health Cener at Wishard Health Services
Alan D Schmetzer, MD is a member of the following medical societies: American Academy of Addiction Psychiatry, American Academy of Clinical Psychiatrists, American Academy of Psychiatry and the Law, American College of Physician Executives, American Medical Association, American Neuropsychiatric Association, American Psychiatric Association, and Association for Convulsive Therapy
Disclosure: Eli Lilly & Co. Grant/research funds Other
Roy Sucholeiki, MD Director, Comprehensive Seizure and Epilepsy Program, The Neurosciences Institute at Central DuPage Hospital
Roy Sucholeiki, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, and American Neuropsychiatric Association
Disclosure: Nothing to disclose.
Margaret M Swanberg, DO Assistant Professor of Neurology, Uniformed Services University; Chief of Neurobehavior Service, Walter Reed Army Medical Center; Assistant Chief, Department of Neurology, Walter Reed Army Medical Center
Margaret M Swanberg, DO is a member of the following medical societies: American Academy of Neurology and American Neuropsychiatric Association
Disclosure: Nothing to disclose.
Michele Tagliati, MD Associate Professor, Department of Neurology, Mount Sinai School of Medicine; Division Chief of Movement Disorders, Mount Sinai Medical Center
Michele Tagliati, MD is a member of the following medical societies: American Academy of Neurology, American Medical Association, and Movement Disorders Society
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Medscape Salary Employment
B Viswanatha, MBBS, MS, DLO Professor of Otolaryngology (ENT), Chief of ENT III Unit, Sri Venkateshwara ENT Institute, Victoria Hospital, Bangalore Medical College and Research Institute; PG and UG Examiner, Manipal University, India and Annamalai University, India
B Viswanatha, MBBS, MS, DLO is a member of the following medical societies: Association of Otolaryngologists of India, Indian Medical Association, and Indian Society of Otology
Disclosure: Nothing to disclose.
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