eMedicine Specialties > Neurology > Movement and Neurodegenerative Diseases

Striatonigral Degeneration

Paula K Rauschkolb, DO, Staff Physician, Department of Neurology, Dartmouth-Hitchcock Medical Center
Stephen A Berman, MD, PhD, Professor, Department of Internal Medicine, Section of Neurology, Dartmouth Medical School; Chief, Neurology Service, White River Junction Veterans Medical Center

Updated: Mar 9, 2009

Introduction

Background

Striatonigral degeneration (SND) is a sporadic, progressive neurodegenerative disorder that represents one manifestation of multiple system atrophy (MSA). Other manifestations of multiple system atrophy are Shy-Drager, in which autonomic failure predominates, and sporadic olivopontocerebellar degeneration, which is characterized primarily by cerebellar signs. While symptoms of autonomic failure and cerebellar degeneration may be present in striatonigral degeneration, the predominant finding is parkinsonism.

In many cases, the disease process begins with 1 of the 3 presentations predominating (ie, parkinsonism, autonomic failure, cerebellar signs) and then later converges to include a combination of all 3 plus additional degeneration of the corticospinal system, including tract and motor neuron degeneration as well as cognitive deterioration. However, in some cases, one presentation remains dominant throughout the course of the disease, or it may be that the patient dies before additional symptoms can manifest. This has been most clearly described for the cerebellar form of multiple system atrophy.

In 1933, Sherer described 2 cases that likely represented striatonigral degeneration. However, this condition was first definitively outlined in 1961 and 1964 by Adams et al. In 1969, Graham and Oppenheimer coined the term multiple system atrophy in an effort to emphasize the common features found in all the 3 manifestations.

Thirty years later, the first "Consensus statement on the diagnosis of multiple system atrophy" by Gilman et al recommended that the term striatonigral degeneration be replaced with multiple system atrophy with predominantly parkinsonian features (MSA-P) and the term sporadic olivopontocerebellar degeneration be replaced with multiple system atrophy with predominantly cerebellar features (MSA-C).¹ The term Shy-Drager syndrome was deemed unnecessary and excluded. The consensus group described the clinical features of the disease and set the criteria for diagnosis of possible, probable, and definite multiple system atrophy (see Multiple System Atrophy).

In 2008, the "Second consensus statement on the diagnosis of multiple system atrophy" was published. The purpose of revisiting this topic was to incorporate advances in research, such as the identification of alpha-synuclein as a key pathologic finding, and to simplify the original diagnostic criteria.²

Use of the new nomenclature (MSA-P and MSA-C) has become common in publications subsequent to 1999; however, the term Shy-Drager syndrome is still frequently used. A Medline search can produce numerous papers dated 2000 and later using "Shy-Drager" as a keyword or subject heading, which confirms that this term continues to be used in publications. Many neurologists find this a useful term for the autonomic presentation, but consideration must be given to whether subtle parkinsonian or cerebellar findings are present, in which case the MSA-P or MSA-C classifications, respectively, would be more appropriate. In the event that both parkinsonian and cerebellar signs are present, the term multiple system atrophy can be used without qualification.

Pathophysiology

Striatonigral degeneration is characterized by the presence of glial cytoplasmic inclusions (GCIs) in oligodendroglial cells. These inclusions are widely distributed throughout the brains of affected individuals. Neuronal cytoplasmic inclusions and neuronal nuclear inclusions can also be found, but are far less prominent relative to GCIs. The identification of these inclusion bodies was a unifying factor in the pathological classification of the 3 entities that now fall under the category of multiple system atrophy: striatonigral degeneration (MSA-P), olivopontocerebellar atrophy (MSA-C) and, less formally, Shy-Drager syndrome.

Immunostaining of inclusion bodies has revealed the presence of alpha-synuclein fibrils, which further classifies this group of disorders as synucleinopathies. Other neurodegenerative conditions that fall under this category include Parkinson disease and Lewy body disease.³ Alpha-synuclein, in its soluble form, is found in normal brain tissue. It is the insoluble aggregate that forms the fibrils associated with synucleinopathies that appears to be pathologic. In Parkinson disease, currently a very active area of research, genetic mutations affecting this protein have been identified. This is not the case with multiple system atrophy; it is considered a sporadic disease, without evidence for an underlying genetic alteration.

In addition to inclusion bodies, microscopic evaluation of tissue reveals neuronal loss and gliosis. This is manifested at a macroscopic level as atrophy, primarily of the pons and midbrain. The substantia nigra shows loss of pigmentation, while the putamen, also atrophic, may become grayish-green in color. This pattern of degeneration is consistent with the clinical findings (see Clinical).

Frequency

United States

The prevalence of multiple system atrophy (including all 3 subtypes) is difficult to establish because the disease is frequently misdiagnosed, but it has been estimated at 3-5 per 100,000 in the general population.

International

Data reported show a prevalence of 1.86-4.9 cases per 100,000 people.

Mortality/Morbidity

The prognosis is poor, and all 3 subtypes of multiple system atrophy have a mean survival period of less than a decade from diagnosis. Despite a similar time frame for survival, the most marked clinical deterioration is seen in striatonigral degeneration (MSA-P).

Race

No racial or ethnic predilection is evident.

Sex

Formerly, no gender predominance was observed, but more recent information suggests a male predominance of approximately 2:1. Some reports are of a much greater disparity, with the suggestion that males who seek treatment for autonomic symptoms, such as erectile dysfunction, may be more likely to be diagnosed.

Age

Onset occurs most often in the sixth decade. The mean age at diagnosis is 53 years, with a range of 33-76 years of age.

Clinical

History

Parkinsonism: The vast majority of patients with multiple system atrophy develop parkinsonism at some point, and it is often rapidly progressive.
- Bradykinesia with rigidity, tremor, or postural instability
  - Although presentation can be asymmetric (as is usually the case in Parkinson disease), symmetry of onset is particularly suggestive of MSA-P.
  - Absence of tremor is suggestive of MSA-P (vs Parkinson disease). When present, tremor is usually irregular, postural, and often incorporates myoclonus. While resting tremor can be observed, it is uncommon.
- Patients may have had poor response to a previous trial of levodopa.
Dysautonomia: Autonomic failure to some degree is almost universal and may be the presenting symptom. Genitourinary complaints are common early in the disease.
- Male erectile dysfunction
- Urinary symptoms (frequency, urgency, incomplete bladder emptying, and incontinence)
- Postural or postprandial hypotension (Syncopal events may occur secondary to cerebral hypoperfusion.)
Cerebellar findings
- Gait or limb ataxia
- Cerebellar dysarthria
Affective disorders
- Depression
- Emotional lability
Cognitive impairment
- Difficulty with visuospatial tasks
- Decreased verbal fluency
- Diminished executive function skills
Dysphagia and/or dysphonia
Sleep disturbances (When possible, obtain history from sleeping partner.)
- REM sleep behavior disorder
- Obstructive symptoms (snoring, stridor, obstructive apneas)
- Central symptoms (central apneas, dysrhythmic breathing patterns)
- Insomnia and/or excessive daytime sleepiness
- Restless legs syndrome
Features that suggest an etiology other than multiple system atrophy
- Family history (Multiple system atrophy is a sporadic neurodegenerative disease.)
- Dementia (Cognitive deficits are sometimes present in multiple system atrophy, but dementia is not a predominant feature.)
- Presence of hallucinations (not secondary to medication) (This suggests Lewy body disease.)

Physical

Parkinsonism
- Bradykinesia with rigidity, tremor, or postural instability
  - Symmetric onset is suggestive of multiple system atrophy (vs Parkinson disease).
  - Absence of tremor is suggestive of MSA-P (vs Parkinson disease). When present, tremor is usually irregular, postural, and often incorporates myoclonus. While resting tremor can be observed, it is uncommon.
Dysautonomia
- Urinary retention, elevated postvoid residual
- Orthostatic hypotension (Reduction of systolic blood pressure by more than 30 mm Hg or diastolic blood pressure reduction of more than 15 mm Hg within 3 minutes of standing from a previous period of recumbency greater than 3 minutes.)
Cerebellar findings
- Gait or limb ataxia
- Cerebellar dysarthria
- Cerebellar oculomotor dysfunction - this may include saccadic pursuit movements, gaze-evoked nystagmus, and ocular dysmetria
Dysphagia and/or dysphonia
Stridor: Initially stridor occurs during sleep, but later in the course it may occur during wakefulness.
Corticospinal findings (Hyperreflexia or extensor plantar response is often present.
Raynaud phenomenon or "cold hands sign" (cold, dusky, violaceous hands with poor circulatory return after blanching pressure)⁴
Affective disorders
- Depression
- Emotional lability
Cognitive impairment: Although dementia (as a predominant feature) is a criterion for exclusion, recent studies suggest that some degree of cognitive impairment is common in multiple system atrophy, and particularly so with MSA-P.⁵ The extent of impairment varies significantly. When present, deficits include the following:
- Visuospatial and constructional dysfunction
- Impaired verbal fluency
- Dysexecutive syndrome

Features that suggest an etiology other than multiple system atrophy include the following:

Classic pill-rolling tremor suggests Parkinson disease.
Significant slowing of vertical saccades or vertical supranuclear gaze palsy is a sign of progressive supranuclear palsy.
Dementia: Cognitive deficits are sometimes present in multiple system atrophy, but dementia is not a predominant feature.
Presence of hallucinations (not secondary to medication) suggests Lewy body disease.

Causes

Striatonigral degeneration (MSA-P) is a sporadic, progressive neurodegenerative disorder. Immunohistochemistry techniques have revealed the presence of alpha-synuclein fibrils within the glial cytoplasmic inclusion bodies that are characteristic of this disease; however, as is the case with other synucleinopathies, the significance of this finding remains unclear. Currently, no genetic mutation is associated with any form of multiple system atrophy.

Differential Diagnoses

Cortical Basal Ganglionic Degeneration	Paraneoplastic Cerebellar Degeneration
Essential Tremor	Parkinson Disease
Idiopathic Orthostatic Hypotension and other Autonomic Failure Syndromes	Parkinson-Plus Syndromes
Olivopontocerebellar Atrophy	Progressive Supranuclear Palsy

Workup

Laboratory Studies

No laboratory studies are indicated for striatonigral degeneration (multiple system atrophy with predominantly parkinsonian features [MSA-P]).

Imaging Studies

Positron emission tomography (PET) scan - Decreased postsynaptic D2 receptor density, impaired uptake of fluoro-L-dopa⁶
Single-proton emission computed tomography (SPECT) scan – (A recent study revealed significantly decreased cerebellar and dorsolateral prefrontal perfusion in patients with multiple system atrophy relative to that of control subjects)⁵
MRI may show 1 or more of the following:⁷
- Atrophy of the putamen, best seen on inversion-recovery coronal sequences, and/or putaminal hypointense signal on T2-weighted sequences may, in rare instances, see hyperintense bands lateral to the putamina.
- There may be narrowing and hypointensity of the pars compacta of the substantia nigra, which can give the appearance of fusion between the pars reticularis and the red nucleus.
CT scans may show cerebellar or brainstem atrophy late in the course of the disease.

Other Tests

Autonomic tests for orthostatic vital signs, urodynamic studies
Electromyography: Shows denervation of external sphincter (urethral or anal); however, normal findings do not exclude the disease.
Clonidine Growth Hormone Test⁸: Studies show that after infusion of clonidine, serum growth hormone concentration does not subsequently rise in patients with multiple system atrophy while the normal response, an increase in secretion, is found in Parkinson disease, pure autonomic failure, and control subjects.⁹
Neuropsychiatric evaluation: Recent studies suggest that cognitive impairment is more common than previously thought. Due to the nature of the deficits associated with this disease, the standard mental status examination has been found to be a poor tool for assessment. Neuropsychiatric testing is more sensitive and may be more a more helpful resource in multiple system atrophy.⁵
Sleep studies: Sleep disorders, particularly nocturnal stridor and REM sleep behavior disorder, are common in multiple system atrophy. Formal sleep studies should be considered as research suggests that treatment can improve both survival and quality of life.¹⁰

Histologic Findings

Findings of MSA-P include widespread glial cytoplasmic inclusions (primarily in oligodendrocytes) and, to a lesser degree, neuronal cytoplasmic inclusions and neuronal nuclear inclusions. Immunostaining of inclusion bodies reveals the presence of alpha-synuclein fibrils.

Treatment

Medical Care

Response to anti-parkinsonian medications is sub-optimal at best for treatment of multiple system atrophy; however, it remains the treatment of choice in the absence of better options. Other medical therapies used in multiple system atrophy target associated symptoms (eg, orthostatic hypotension). See Medication and In/Out Patient Meds below.

Surgical Care

Currently, no surgical treatment is appropriate for multiple system atrophy. Because it can be difficult to clinically distinguish multiple system atrophy from Parkinson disease, there are cases of multiple system atrophy patients undergoing placement of deep brain stimulators. The outcomes have generally been poor, even in patients who responded well to levodopa therapy.¹¹

Consultations

Neurology
Sleep medicine
Otolaryngology
Physical and occupational therapy
Speech-language pathology
Psychiatry or counseling

Diet

Unless there are contraindications, patients with symptomatic postural hypotension may benefit from increased salt intake.

Activity

Patients with symptomatic postural hypotension should be advised to avoid activities or environments that produce excessive vagal stimulation or vasodilation (eg, extreme heat, overeating, straining at stool) and to rise slowly and carefully from seated or recumbent positions.

Medication

The drugs in the tables below are specific to treatment of parkinsonism and postural hypotension associated with striatonigral degeneration (multiple system atrophy with predominantly parkinsonian features [MSA-P]). See In/Out Patient Meds for a discussion of adjunct medications.

Antiparkinson agents

Dopaminergic drugs can exacerbate orthostatic hypotension. They must be initiated at low doses and titrated up cautiously.

Levodopa-carbidopa (Sinemet)

Levodopa is a dopamine precursor used to increase CNS dopamine concentration, as it is not possible for dopamine to cross the blood-brain barrier. Carbidopa is a peripheral dopa decarboxylase inhibitor that prevents premature conversion of levodopa to dopamine in the tissues prior to entering the CNS. It increases the efficiency of levodopa therapy, allows for lower dosages, and also decreases the side effects associated with peripheral conversion.
Standard release forms are available in 25/100 mg, 10/100 mg, and 25/250 mg tablets. Controlled-release preparations are available in 50/200 mg and 25/100 mg.

Dosing

Adult

25/100 mg (standard release form) PO tid initially; may titrate upward using a combination of dosage and frequency changes
Carbidopa 70-100 mg PO qd required to completely block peripheral dopa decarboxylase and minimize nausea/vomiting

Pediatric

Not established

Interactions

Hydantoins, pyridoxine, phenothiazine, and hypotensive agents may decrease effects of levodopa; antacids and MAOIs increase levodopa toxicity

Contraindications

Documented hypersensitivity, narrow-angle glaucoma, malignant melanoma or undiagnosed skin lesions, non-selective MAOI use within 2 wk

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in patients with history of cardiac disease, arrhythmia, asthma or other severe pulmonary disease, peptic ulcer disease, endocrine disorders, diabetes (may worsen glucose control), anti-hypertensive therapy (may exacerbate postural hypotension), chronic wide-angle glaucoma, renal insufficiency, depression or psychosis (may increase risk of suicidal ideation); risk of neuroleptic malignant syndrome with abrupt discontinuation of medication

Pramipexole (Mirapex)

Non-ergot dopamine agonist, used with or without concomitant levodopa therapy. Binds D2 and D3 dopamine receptors. Due to high specificity for D3 receptors (relative to other dopamine agonists), it may cause less orthostatic hypotension. It has no significant effect on other adrenergic or serotonergic receptors. Absolute bioavailability is >90%. Peak serum concentration is reached in approximately 2 h and half-life is approximately 8 h. There are no known metabolites; roughly 90% of this drug is renally-excreted in its unchanged form.
Tablets are available in 0.125 mg, 0.25 mg, 0.5 mg, 0.75 mg, 1 mg and 1.5 mg forms.

Dosing

Adult

0.125 mg PO tid initially; may titrate up as tolerated to maximum of 1.5 mg PO tid; when using pramipexole concomitantly with levodopa, the dose of latter can be reduced; dose adjustments are required for patients with renal insufficiency

Pediatric

Not established

Interactions

Cimetidine may increase toxicity (increases levodopa levels)

Contraindications

Documented hypersensitivity, breastfeeding

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May worsen existing orthostatic hypotension; caution advised for patients with renal insufficiency (dose adjustment required); caution when driving or operating machinery (may cause somnolence); may exacerbate underlying psychoses; avoid abrupt withdrawal due to risk of neuroleptic malignant syndrome

Ropinirole (Requip)

Non-ergot dopamine agonist, used with or without concomitant levodopa therapy. Binds to D2 and D3 receptors, with greater affinity for D3. Bioavailability is 55%; peak plasma concentration is reached in 1-2 h and half-life is approximately 6 h. It is extensively metabolized by the liver via P450 CYP1A2. Less than 10% renally excreted; no dosage change required in mild to moderate renal insufficiency. If using as adjunct therapy, may be able to titrate levodopa dosage slowly downward.

Dosing

Adult

0.25 mg PO tid initially; titrate gradually upward as tolerated to maximum dose of 24 mg/d (titrate slowly in patients with hepatic impairment)

Pediatric

Not established

Interactions

Antipsychotics may antagonize effects of ropinirole; antiemetics such as metoclopramide may also decrease effectiveness; amiodarone, cimetidine, ciprofloxacin and other P450 CYP1A2 inhibitors may lead to increased plasma concentrations; carbamazepine, phenobarbital, rifampin and other P450 CYP1A2 inducers may conversely lower plasma levels; estrogens reduce clearance; concomitant use of CNS depressants may potentiate sedative effects; for patients on warfarin, closely monitor INR, dosage adjustment may be required

Contraindications

Documented hypersensitivity, significant orthostatic hypotension, syncope, pregnancy, breastfeeding

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Monitor carefully for signs and symptoms of orthostatic hypotension or dyskinesia; caution in patients with hepatic disease; patients should not drive or operate heavy machinery (due to side effect of somnolence); this drug may exacerbate pre-existing psychoses; avoid abrupt discontinuation

Mineralocorticoids

For treatment of orthostatic hypotension refractory to nonpharmacologic recommendations.

Fludrocortisone (Florinef)

Synthetic steroid with predominantly mineralocorticoid activity. Acts on renal distal tubules to enhance reabsorption of sodium and increase urinary excretion of potassium. The net effect is an increase in plasma volume and elevation of blood pressure. Metabolism is primarily hepatic.

Dosing

Adult

0.1-0.2 mg PO bid/tid; dosages vary among individuals and must be tailored for each patient

Pediatric

Not established

Interactions

Drugs that affect potassium balance may cause or exacerbate hypokalemia; use with fluoroquinolones increases risk of tendon rupture; anti-epileptic medications may decrease effectiveness of this drug; steroid use when vaccines are administered may lead to inadequate immune response

Contraindications

Documented hypersensitivity, systemic fungal infections

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Use caution in patients with heart failure or other cardiac disease, endocrine conditions, electrolyte abnormalities, hepatic failure, diabetes, osteoporosis and GI disorders; monitor electrolytes and glucose during use and taper dose gradually to discontinue

Sympathomimetic agents

For treatment of orthostatic hypotension refractory to non-pharmacologic recommendations.

Midodrine (ProAmatine)

Selective alpha1-adrenergic agonist used for treatment of hypotension.

Dosing

Adult

10 mg PO tid at 3-4h intervals, during daytime hours when patient is upright; not for administering after evening meal or less than 4 h before bedtime; midodrine is also available in IV form but is most commonly administered orally; dose adjustment is required for patients with renal insufficiency

Pediatric

Not established

Interactions

Drugs that stimulate alpha-adrenergic receptors may enhance or potentiate pressor effects (this includes over-the-counter cold remedies and diet aids); certain cardiac medications, (eg, glycosides, beta-blockers) may precipitate or worsen bradycardia, AV block, and arrhythmia; concomitant use of tricyclic antidepressants augments vasoconstriction and other alpha-adrenergic effects which can lead to hypertension, tachycardia, or arrhythmia; drugs such as doxazosin or terazosin directly antagonize alpha-adrenergic effects of midodrine; concomitant use with dihydroergotamine is contraindicated due to potential for severe vasoconstriction

Contraindications

Documented hypersensitivity, acute renal insufficiency, severe organic heart disease, pheochromocytoma, urinary retention, persistent and excessive supine hypertension, thyrotoxicosis, concomitant use with dihydroergotamine

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in cardiovascular disease; monitor for bradycardia or elevated supine blood pressure; dose adjustment and careful monitoring required for patients with renal insufficiency; midodrine can cause or exacerbate pre-existing urinary retention; CNS effects reported by some patients include irritability, excitability, and restlessness

Follow-up

Further Inpatient Care

Striatonigral degeneration (multiple system atrophy with predominantly parkinsonian features [MSA-P]) is unlikely to be the primary cause for hospitalization. Thus, the focus of care would be treatment of the diagnoses that required admission.

Further Outpatient Care

Management of anti-parkinsonian drug regimen (if used)
Patient education regarding orthostatic hypotension (see Patient Education)
Assessment for history or physical signs of falls at each office visit
Assistive devices as needed (cane, walker, wheelchair and household implements)
Teach patient to self-catheterize if urinary retention develops
Referrals as needed (see Consultations)

Inpatient & Outpatient Medications

Also see Medication section.

Anticholinergic medications, such as oxybutynin, are sometimes used for incontinence but often lead to subsequent retention.
Although sildenafil has been used for treatment of erectile dysfunction, it is generally not recommended due to its high potential to provoke or exacerbate hypotension.
Fiber supplement or other bowel regimen may be necessary for constipation.
An SSRI or similar drug may be required for treatment of depression often associated with all subtypes of multiple system atrophy.
For those who suffer from REM sleep behavioral disorder, clonazepam may be beneficial.
Botox injection to the vocal cords has been used for treatment of stridor.

Complications

Vocal fold paresis and glottic airway compromise requiring continuous positive airway pressure support or tracheostomy¹²
Aspiration pneumonia secondary to dysphagia and vocal fold paresis
Sudden death, often occurring at night and associated with sleep-disordered breathing

Prognosis

Multiple system atrophy is a progressive neurodegenerative disorder without remission. Survival time is less than a decade from symptom onset. In a study by Blumin et al, median survival time was 8.6 years for men and 7.3 years for women.¹²

Patient Education

Those with symptomatic postural hypotension should be educated on the following:

Activities or environments that produce excessive vagal stimulation or vasodilation (eg, extreme heat, overeating, alcohol, straining at stool) should be avoided.
Always rise slowly and carefully from seated or recumbent positions.
Sit or lie down as soon as symptoms appear.
Consider pressure stockings, elevating the head of the bed, and increasing sodium intake.
Be aware that there is a risk of fall with associated trauma; always seek medical attention for any but the most minor of falls.

Miscellaneous

Medicolegal Pitfalls

Differentiating multiple system atrophy with predominantly parkinsonian features from Parkinson disease can be challenging but is critical as patients with the former condition should not be considered candidates for placement of deep brain stimulators.
Advance directives should be established, particularly with regard to endotracheal intubation, tracheostomy, and placement of gastrostomy (feeding) tubes.

References

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Keywords

striatonigral degeneration, SND, neurodegenerative disease, multiple system atrophy, MSA, MSA-P, Shy-Drager syndrome, sporadic olivopontocerebellar degeneration, sporadic OPCA, sOPCA, parkinsonism, MSA with predominantly parkinsonian features, MSA with predominantly cerebellar features, MSA-C, parkinsonian MSA, cerebellar MSA, parkinsonian multiple system atrophy, cerebellar multiple system atrophy

Contributor Information and Disclosures

Author

Paula K Rauschkolb, DO, Staff Physician, Department of Neurology, Dartmouth-Hitchcock Medical Center
Paula K Rauschkolb, DO is a member of the following medical societies: American Academy of Neurology and American Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Stephen A Berman, MD, PhD, Professor, Department of Internal Medicine, Section of Neurology, Dartmouth Medical School; Chief, Neurology Service, White River Junction Veterans Medical Center
Stephen A Berman, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Medical Editor

Joseph Quinn, MD, Assistant Professor, Department of Neurology, Portland VA Medical Center, Oregon Health Sciences University
Joseph Quinn, MD is a member of the following medical societies: American Academy of Neurology, Society for Neuroscience, and Society for Pediatric Radiology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

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.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
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: Nothing to disclose.

Chief Editor

Acknowledgments

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors Maritza Arroyo-Muñiz, MD and Syed T Arshad, MD to the development and writing of this article.

Further Reading