Parkinson Disease Workup

  • Author: Robert A Hauser, MD, MBA; Chief Editor: Selim R Benbadis, MD   more...
 
Updated: May 10, 2012
 

Approach Considerations

Parkinson disease is a clinical diagnosis. No laboratory biomarkers exist for the condition, and findings on routine magnetic resonance imaging (MRI) and computed tomography (CT) scan are unremarkable. Positron emission tomography (PET) and single-photon emission CT (SPECT) may show findings consistent with Parkinson disease, and olfactory testing may provide evidence pointing toward Parkinson disease, but these studies are not routinely needed. (Olfactory testing can reveal hyposmia, which may precede the motor signs of Parkinson disease by several years.[24] However, olfactory loss is not specific and can also occur in Alzheimer disease.)

No laboratory or imaging study is required in patients with a typical presentation. Such patients are aged 55 years or older and have a slowly progressive and asymmetric parkinsonism with resting tremor and bradykinesia or rigidity. Patients who do not have tremor should generally be considered for MRI evaluation to exclude brain lesions such as stroke, tumor, or demyelination.

In patients with an unusual presentation, diagnostic testing may be indicated to exclude other disorders in the differential diagnosis. Such tests may include serum ceruloplasmin, sphincter electromyography, or lumbar puncture.

Serum ceruloplasmin concentration is obtained as a screening test for Wilson disease in patients younger than 40 years who present with parkinsonian signs. If the ceruloplasmin level is low, measurement of 24-hour urinary copper excretion and slit-lamp examination for Kayser-Fleischer rings must be performed. Abnormal results on urinary sphincter electromyography have been noted in patients with multiple system atrophy (MSA).

A substantial and sustained response to dopamine medications (dopamine agonists or levodopa) helps confirm a diagnosis of Parkinson disease. It is unclear whether acute levodopa or apomorphine challenge has any advantage over clinical diagnostic criteria.[15] Over time, diagnostic accuracy improves as the progression of signs and symptoms and response to medications unfolds.

In the general community, there is a high diagnosis error rate between Parkinson disease and essential tremor. For movement disorder neurologists, when an erroneous diagnosis of Parkinson disease is made, the most likely correct diagnoses are the atypical parkinsonisms (MSA, progressive supranuclear palsy [PSP], corticobasal ganglionic degeneration [CBD]). Early in the disease course, it may be very difficult to distinguish between Parkinson disease and the atypical parkinsonisms. These disorders also do not have laboratory biomarkers, and, therefore, distinguishing among them is based on clinical criteria. Olfactory testing may help differentiate Parkinson disease from PSP and CBD, but olfaction is also reduced in MSA.

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Radiologic Studies

Magnetic resonance imaging

Magnetic resonance imaging (MRI) is useful to exclude strokes, tumors, multi-infarct state, hydrocephalus, and the lesions of Wilson disease. MRI should be obtained in patients whose clinical presentation does not allow a high degree of diagnostic certainty, including those who lack tremor, have an acute or stepwise progression, or are younger than 55 years.

The following MRI indicates where a thalamic stimulator is typically placed.

Axial, fast spin-echo inversion recovery magnetic Axial, fast spin-echo inversion recovery magnetic resonance image at the level of the posterior commissure. The typical target for placing a thalamic stimulator is demonstrated (cross-hairs).

Below is a coronal MRI following bilateral subthalamic nuclei deep brain stimulation.

Postoperative coronal magnetic resonance image (MRPostoperative coronal magnetic resonance image (MRI) demonstrating desired placement of bilateral subthalamic nuclei-deep brain stimulation (STN-DBS) leads.

PET and SPECT scanning

Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) scanning are useful diagnostic imaging studies, but these are not routinely required. Different radioligands permit imaging of different components or abnormalities within the brain.

At the onset of motor signs, patients with Parkinson disease show an approximately 30% decrease in18 F-dopa (fluorodopa) uptake on PET imaging in the contralateral putamen.18 F-Dopa is taken up by the terminals of dopamine neurons and converted to18 F-dopamine. The rate of striatal18 F accumulation reflects transport of18 F-dopa into dopamine neurons and its decarboxylation to18 F-dopamine, which is stored in dopamine nerve terminals in the striatum. Thus,18 F-dopa PET imaging provides an index of remaining dopamine neurons. However, this study is not widely available, is usually not covered by insurance, and is currently generally considered a research tool.

Carbon-11 (11 C)-nomifensine and cocaine analogues such as123 I-beta-CIT (iodine-123-labeled carboxymethoxy-3beta-4-iodophenyl-nortropane) and123 I-FP-CIT (fluoropropyl-CIT) bind to dopamine reuptake sites on nigrostriatal terminals and provide an index of the remaining dopamine neurons. Ioflupane (123 I) (DaTscan) is a radiopharmaceutical agent that is indicated for striatal dopamine transporter visualization using SPECT brain imaging to assist in the evaluation of adults with suspected Parkinsonian syndromes (PSs). This agent may be used to help differentiate essential tremor from tremor due to PSs (idiopathic Parkinson disease [IPD] and Parkinson-plus syndromes [PPS]).[1]

Deficits on123 I SPECT scans indicate a dopamine deficiency syndrome but do not differentiate Parkinson disease from atypical parkinsonisms, including multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Ioflupane SPECT imaging reveals a dopamine deficiency in Parkinson disease, MSA, PSP, corticobasal ganglionic degeneration, and Lewy body disease. This study is normal in essential tremor, dystonic tremor, medication-induced parkinsonism or tremor, psychogenic disorders, and in normal individuals.

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Histologic Findings

Classic pathologic findings in Parkinson disease include degeneration of the neurons containing neuromelanin, especially in the substantia nigra and the locus ceruleus. Surviving neurons often contain eosinophilic cytoplasmic inclusions called Lewy bodies (see the following image). The primary biochemical defects are loss of striatal dopamine, which results from degeneration of dopamine-producing cells in the substantia nigra, as well as hyperactivity of the cholinergic neurons in the caudate nucleus.

Lewy bodies are intracytoplasmic eosinophilic inclLewy bodies are intracytoplasmic eosinophilic inclusions, often with halos, that are easily seen in pigmented neurons, as shown in this histologic slide. They contain polymerized alpha-synuclein; therefore, Parkinson disease is a synucleinopathy. Lewy bodies in the locus coeruleus from a patient Lewy bodies in the locus coeruleus from a patient with Parkinson disease.

Alpha-synuclein is a major structural component of Lewy bodies; all Lewy bodies stain for alpha-synuclein, and most also stain for ubiquitin. Lewy bodies are concentric, eosinophilic, cytoplasmic inclusions with peripheral halos and dense cores. The presence of Lewy bodies within pigmented neurons of the substantia nigra is characteristic, but not pathognomonic, of Parkinson disease. Lewy bodies are also found in the cortex, nucleus basalis, locus ceruleus, intermediolateral column of the spinal cord, and other areas.

According to the Braak hypothesis, Lewy body pathology in the brain begins in the olfactory bulb and lower brainstem and slowly ascends to affect dopamine neurons in the substantia nigra and, ultimately, the cerebral cortex.[25] Lewy body pathology is also observed in autonomic nerves of the gut and heart.

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Lumbar Puncture

Lumbar puncture should be considered if signs of normal-pressure hydrocephalus (NPH) are observed (eg, incontinence, ataxia, dementia). In NPH, clinical signs characteristically improve after removal of about 20 mL of cerebrospinal fluid.

Dopa-responsive dystonia should be considered in patients with juvenile-onset dystonia and parkinsonism, particularly with diurnal fluctuations in symptoms. In such patients, a trial of levodopa is critical. Additional tests for this condition include measurement of CSF concentrations of biopterin, neopterin, and the neurotransmitter metabolites homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG). In both forms of dopa-responsive dystonia, an altered pattern of decreases in these compounds is observed.

See Lumbar Puncture for detailed information on indications for the procedure, contraindications, and a step-by-step discussion containing images and video on how to perform the procedure.

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Contributor Information and Disclosures
Author

Robert A Hauser, MD, MBA  Professor of Neurology, Molecular Pharmacology and Physiology, Director, Parkinson's Disease and Movement Disorders Center, University of South Florida College of Medicine; Clinical Chair, Signature Interdisciplinary Program in Neuroscience

Robert A Hauser, MD, MBA is a member of the following medical societies: American Academy of Neurology, American Medical Association, American Society of Neuroimaging, and Movement Disorders Society

Disclosure: Ingelheim Pharmaceuticals, Inc Honoraria Advisory Board; Teva Neuroscience Honoraria Advisory Board; Impax Pharmaceuticals Honoraria Advisory Board; UCB, Inc Honoraria Advisory Board; GE Healthcare Honoraria Advisory Board; IPSEN Pharmaceuticals Honoraria Advisory Board; Novartis Pharmaceuticals Advisory Board; Parkinson Study Group Honoraria Advisory Board; Solvay Pharmaceuticals Honoraria Advisory Board; Quintiles Honoraria Advisory Board

Coauthor(s)

Kelly E Lyons, PhD  Research Associate 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 and Movement Disorders Society

Disclosure: Novartis Honoraria Speaking and teaching; Teva Neuroscience Honoraria Speaking and teaching; St Jude Medical Honoraria 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: Teva Consulting fee Consulting; GSK Consulting fee Consulting; Valeant Pharm Consulting fee Consulting; Solvay Consulting fee Consulting; Shering Plough Consulting fee 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 and Movement Disorders Society

Disclosure: Nothing to disclose.

Chief Editor

Selim R Benbadis, MD  Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida 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, and American Medical Association

Disclosure: UCB Pharma Honoraria Speaking, consulting; Lundbeck Honoraria Speaking, consulting; Cyberonics Honoraria Speaking, consulting; Glaxo Smith Kline Honoraria Speaking, consulting; Pfizer Honoraria Speaking, consulting; Sleepmed/DigiTrace Honoraria Speaking, consulting

Additional Contributors

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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Schematic representation of the basal ganglia - thalamocortical motor circuit and its neurotransmitters in the normal state. From Vitek J. Stereotaxic surgery and deep brain stimulation for Parkinson disease and movement disorders. In: Watts RL, Koller WC, eds. Movement Disorders: Neurologic Principles and Practice. New York: McGraw-Hill, 1997:240. Copyright, McGraw-Hill Companies, Inc. Used with permission.
Schematic representation of the basal ganglia - thalamocortical motor circuit and the relative change in neuronal activity in Parkinson disease. From Vitek J. Stereotaxic surgery and deep brain stimulation for Parkinson disease and movement disorders. In: Watts RL, Koller WC, eds. Movement Disorders: Neurologic Principles and Practice. New York: McGraw-Hill, 1997:241. Used with kind permission. Copyright, McGraw-Hill Companies, Inc.
Parkinson disease diary. The patient or caregiver should place 1 check mark in each half-hour time slot to indicate the patient's predominant response during most of that period. The goal of therapeutic management is to minimize off time and on time with troublesome dyskinesia. Copyright Robert Hauser, 1996. Used with permission.
Stages in the development of Parkinson disease (PD)-related pathology (path.). Adapted from Braak H, Ghebremedhin E, Rub U, Bratzke H, Del Tredici K. Stages in the development of Parkinson's disease-related pathology. Cell Tissue Res. 2004 Oct;318(1):121-34.
Schematic diagram of the basal ganglia circuitry. Represented are the following: inhibitory (red arrows) and excitatory (green arrows) projections between the motor cortex, the putamen, the globus pallidus pars externa (GPe) and globus pallidus pars interna (GPi), the subthalamic nucleus (STN), the substantia nigra pars reticulata (SNr) and substantia nigra pars compacta (SNc), and the ventrolateral thalamus (VL). D1 and D2 indicate the direct (regulated by dopamine D1 receptors) and indirect (regulated by dopamine D2 receptors) pathways, respectively.
Sagittal section, 12 mm lateral of the midline, demonstrating the subthalamic nucleus (STN) (lavender). The STN is one of the preferred surgical targets for deep brain stimulation to treat symptoms of advanced Parkinson disease.
The deep brain stimulating lead is equipped with 4 electrode contacts, each of which may be used, alone or in combination, for therapeutic stimulation.
Axial, fast spin-echo inversion recovery magnetic resonance image at the level of the posterior commissure. The typical target for placing a thalamic stimulator is demonstrated (cross-hairs).
Implantation of the deep brain stimulation (DBS) lead.
Insertion of an electrode during deep brain stimulation for Parkinson disease.
Postoperative coronal magnetic resonance image (MRI) demonstrating desired placement of bilateral subthalamic nuclei-deep brain stimulation (STN-DBS) leads.
Radiograph of the skull depicting a deep brain stimulator and leads in a patient with Parkinson disease.
Lewy bodies in the locus coeruleus from a patient with Parkinson disease.
A: Schematic initial progression of Lewy body deposits in the first stages of Parkinson disease (PD), as proposed by Braak and colleagues. B: Localization of the cluster of significant volume reduction in PD compared with health control subjects. The significant cluster located in the medulla oblongata/pons is superimposed as a red blob on the mean normalized anatomic scan of all participants. The axial and sagittal sections are centered on the peak of significance (–1; –36; –49). This image using voxel-based morphometry (VBM), which searched for regional atrophy in idiopathic PD by comparing a group of subjects with the disease and a group of healthy controls. Jubault T, Brambati SM, Degroot C, et al. Regional brain stem atrophy in idiopathic Parkinson's disease detected by anatomical MRI. PLoS ONE. 2009;4(12):e8247.
Gross comparison of the appearance of the substantia nigra between a normal brain and a brain affected by Parkinson disease. Note the well-pigmented substantia nigra in the normal brain specimen on the left. In the brain of a Parkinson disease patient on the right, loss of pigmented substantia nigra due to depopulation of pigmented neurons is observed.
Lewy bodies are intracytoplasmic eosinophilic inclusions, often with halos, that are easily seen in pigmented neurons, as shown in this histologic slide. They contain polymerized alpha-synuclein; therefore, Parkinson disease is a synucleinopathy.
 
 
 
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