spatial neglect_ overview, etiology, mechanisms and morbidities in spatial neglect

Spatial Neglect

Author: A M Barrett, MD; Chief Editor: Michael Hoffmann, MBBCh, MD more...

Updated: May 27, 2014

Overview

Spatial neglect is a behavioral syndrome occurring after brain injury. Spatial neglect

involves the inability to report, respond, or orient to stimuli, generally in the

contralesional space.[1] Because symptoms can vary depending on which spatial

brain systems are affected, the authors suggest that a uniform, patient-centered

definition of spatial neglect should be defined by spatial bias causing functional

disability.[2] The deficit must not be fully attributable to primary sensory deficits (eg,

hemianopia) or motor disturbance (eg, hemiparesis).Treatment for spatial neglect

focuses on visuomotor, cognitive, and behavioral training, in a rehabilitation program

including specific exercises. Management of spatial neglect is also tremendously

important, including alterations to the patient's environment and caregiver

counseling.

Despite the fact that speech and language, memory, and other mental abilities may

be spared in brain-injured patients with spatial neglect, the prognosis for recovery of

independent function in patients with persisting spatial neglect is significantly worse

than in those with seemingly more disabling deficits in these other abilities.[3] Even

global aphasia and right hemiparesis may not have as great an effect on the ability

to become independent.[4] It is particularly troubling that most people with spatial

neglect may not be identified, even when evaluated by stroke specialists.[5]

Although patients may recover from spatial neglect, they often remain severely

disabled. The reasons for the persistent disability are poorly understood, although

this dissociation might be explained by an overly narrow clinical definition for the

presence of spatial neglect. Daily life functions are often performed under more

challenging conditions than is the case for formal neuropsychological testing (eg,

distractions, need for dual or multitasking, continuous dynamic computations using

output from previous operations, need for self-initiation and self-organization) and

may involve larger areas of space than a paper-and-pencil task on a tabletop (eg,

navigating in an airport or mall, playing baseball, driving).

Spatial neglect also encompasses a cluster of symptoms affecting several areas of

vital importance in daily life and is associated with other cognitive dysfunction, such

as emotional processing dysfunction and abnormal awareness of deficits

(anosognosia for hemiplegia [may occur in the hyperacute phase of right

hemispheric stroke in as many as 32% of patients, about 18% after 1 week and 5%

after 6 months[6] ] and anosodiaphoria), which may affect independence.[1]

Patient education

Family members involved in patient care should be well educated in the various

aspects of neglect and its implications for day-to-day functioning. Family members

and patients should be made aware that even after seeming recovery of spatial

neglect, some patients may have functional problems, including difficulty with

complex navigating in familiar and unfamiliar environments and safe driving.

Etiology

Causes of spatial neglect include stroke, traumatic brain injury, brain tumors, and

aneurysm. Rarely, neurodegenerative diseases can cause neglect symptoms.[7, 8]

People with injury to either side of the brain may experience spatial neglect, but

neglect occurs more commonly in persons with brain injury affecting the right cortical

hemisphere, which often causes left hemiparesis.[9]

Spatial neglect is more commonly associated with lesions of the inferior parietal

lobule or temporoparietal region, superior temporal cortex, or frontal lobe. Less

common are lesions of the subcortical regions, including the basal ganglia,

thalamus, and cingulate cortex.[1, 10, 11] Spatial neglect may be more common and

persistent after cortical, rather than subcortical, lesions.[9]

Mechanisms and Morbidities in Spatial Neglect

Because different neuroanatomic systems may be dysfunctional with spatial neglect,

different neuropsychological mechanisms, as follow, may explain the process of this

disorder:

Perception-attention - In the absence of primary sensory deficits, people with

spatial neglect may have disordered awareness of events occurring on the

neglected side [1]

Imagery/representation - Even when no external stimuli are present, people

with spatial neglect may have difficulty maintaining an internal map or image

or other spatial knowledge pertaining to the environment, objects, body, or

other reference frames

Additional dysfunctions that may be found in individuals with spatial neglect include

Spatial Neglect: Overview, Etiology, Mechanisms and Morbidities in S... http://emedicine.medscape.com/article/1136474-overview#a11

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the following:

Self-monitoring - People with spatial neglect may be unaware of their deficit

(anosognosia) or may be unconcerned about it (anosodiaphoria)

Emotional processing - After a right-hemisphere stroke, individuals may have

difficulty making appropriate emotional facial expressions and may lack

normal affect or vocal intonation (at times, these signs can be mistaken for

poststroke depression); patients may also have difficulty representing

emotional knowledge (disordered emotional semantics) or understanding

emotional information presented via others' vocal prosody or facial

expressions

Arousal - Hypoarousal may be associated with spatial neglect

Motor intentional deficits - These deficits include motor neglect and premotor

neglect; people with spatial neglect may have trouble with activating or

directing actions into portions of space; they may also be slow to act and may

not persist

Personal neglect - Individuals may not normally attend to the left side of their

body

Epidemiology

Reported overall frequency of spatial neglect in the United States is estimated to be

anywhere from 13-81% in people who have had a right-hemisphere stroke, although

2 studies reported an overall rate of approximately 50%.[9, 12] The frequency of

spatial neglect may increase with the size of the lesion at presentation and at 3

months after injury.[9] International frequency of spatial neglect is not known.

No evidence currently indicates that spatial neglect is more common in either

gender.[13] Spatial neglect may be more common in older individuals after stroke

than it is in younger individuals, according to some preliminary evidence.[9, 14, 15]

Prognosis

Although neglect may be seen at baseline, obvious symptoms improve rapidly within

the first few days.[9] The potential mechanisms include reperfusion of the penumbral

area and resolution of cytotoxic edema and other factors.

Most patients with neglect show early recovery, particularly within the first month,[16]

and marked improvement may be seen within 3 months[9] .

Patients who demonstrate symptoms of spatial neglect would be expected to benefit

from referral for outpatient treatment with speech therapy, occupational and physical

therapy,[17] neuropsychological therapy, or a combination of these referrals, even if

obvious signs of spatial neglect appear to have abated, because spatial bias may be

present in functional tasks that cannot be detected by interacting with the patient

briefly at the bedside.

In approximately 10% of patients, classic (more severe) symptoms of spatial neglect

persist after 6 months or longer. In these individuals, the deficit may be regarded as

chronic neglect. Patients demonstrating persistent symptoms, when present with

other impairments or disabilities, may benefit from intensive inpatient rehabilitation

and may need to live under supervision if the patient will otherwise not be safe.

Whether people with spatial neglect fully recover is controversial. Although

symptoms abate in most patients in weeks to months,[14] patients are not usually

evaluated on dynamic tasks in the presence of distraction; functionally important

bias, for example limiting community mobility,[18] may persist.

When persistent, spatial neglect is an unfavorable sign for overall improved

prognosis.[3] Neglect syndrome predicts a poor outcome in persons with right-

hemisphere stroke.[12]

Spatial neglect may greatly increase morbidity and the risk of acute and chronic

complications of stroke (eg, hip fracture). It is associated with a longer acute hospital

stay.[19]

Patients with neglect need to be monitored because they may be more prone to falls

or left-sided wheelchair collisions.[20] Patients may require sitters, vest restraints,

gait belts, or other interventions to prevent falling out of bed, for which they are at

high risk.

Whether any acute stroke management strategies can decrease the risk of

poststroke spatial neglect is currently unknown, although animal studies suggest

that factors as fundamental as ambient room light may affect the development of

spatial neglect symptoms.[21]

History and Physical Examination

Spatial neglect is commonly observed after cerebral infarction or hemorrhage.

Because of associated abnormal self-monitoring (anosognosia), individuals usually

do not report attention or perceptual problems. Thus, the disorder is usually detected

via clinical observation and testing. A complete neurologic evaluation by a thorough

and knowledgeable clinician may be needed to document the presence of the

syndrome and even of the underlying stroke that caused it; a cursory examination in

a nonaphasic patient would be unlikely to demonstrate the neglect syndrome.

Spatial neglect symptoms are often first observed by caregivers or therapists, who

may note personal neglect (failure to groom or clothe the contralesional side) or

motor neglect (may not use the contralesional limb despite adequate motor strength

or may not explore left space). The most severe cases of spatial neglect may be


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diagnosed by simple bedside observation, and more moderate cases may be

diagnosed based on findings from a complete neurologic examination that includes

neurobehavioral testing. The following observations may be made:

In acute care settings, the position of the patient in bed or in a wheelchair

(lying with the head and eyes turned to the extreme ipsilesional side, usually

the right) may first arouse suspicion of the presence of spatial neglect

A patient may have difficulty maintaining a normal posture (may be tilted or

crooked in the bed); the contralesional leg may dangle off the bed

When approached from the left, patients may bizarrely orient and reply to the

right, away from the person addressing them (allesthesia)

People with spatial neglect may navigate their wheelchairs or ambulate in a

rightward-biased manner; alternately, they may collide with doorways or

objects on the left

Spatial neglect of perceptual-attentional, representational, or motor-

intentional types may affect several regions of contralesional space; patients

may have problems with near space, within reaching distance (peripersonal

neglect), or space beyond reaching distance (extrapersonal neglect)

Patients with spatial neglect may deny ownership of their contralateral limb,

stating that it belongs to someone else (asomatognosia); they may express

dislike of their paralyzed limb (misoplegia)

Patients may deny a neurologic problem (anosognosia), underestimate the

severity or implications of their deficit, or fail to express sadness or anger

about their difficulties and losses (anosodiaphoria); anosognosia particularly

impairs participation in rehabilitation

Differential Diagnosis

Conditions to consider in the differential diagnosis of spatial neglect include the

following:

Complex partial seizures

Cortical basal ganglionic degeneration

Multiple sclerosis

Wallenberg (lateral medullary stroke) syndrome - Lateropulsion may produce

an abnormal bed posture

Other stroke syndromes

Primary visual or motor systems abnormality - Such as cortical blindness or

spinal cord abnormality

Vestibular abnormality

Posterior cortical atrophy - A neurodegenerative disorder that can be

associated with spatial neglect

Conversion disorder

Migraine accompaniment

Lab Studies

Laboratory tests are determined based on the neurologic disorder causing the

cortical or subcortical-cortical deficit (eg, stroke, tumor, aneurysm) and vary

accordingly.

Check vitamin B-12 levels, thyrotropin levels, and total thyroxine levels if memory

impairment accompanies spatial neglect; perform these tests for all patients, even if

diagnosed with an acute neurologic syndrome. Elevated homocysteine levels should

not be interpreted as idiopathic in stroke patients unless vitamin B-12 deficiency has

been excluded as a possible cause.

Check rapid plasma reagent values in patients with memory disorder, especially

when associated with stroke, to evaluate for potentially treatable secondary

conditions. Although false-negative and false-positive results occur, false-positive

results may also be clinically relevant (eg, for connective-tissue disease).

Imaging Studies

Computed tomography (CT) scanning or magnetic resonance imaging (MRI) is

indicated even if the clinical picture is otherwise entirely consistent with a right-

middle cerebral artery stroke syndrome, because subdural hematomas, brain

tumors, or other mass lesions occasionally mimic a stroke.

Contrast-enhanced MRI is generally nontoxic and increases the sensitivity of the

technique for detecting the above diagnostic confounds. CT scanning alone is

adequate to detect hemorrhage, but it is insufficiently sensitive to detect some other

lesions seen with MRI. Diffusion-weighted MRI distinguishes acute ischemia from

chronic infarction.

Magnetic resonance angiography, conventional angiography, or functional imaging,

such as single-photon emission CT or positron emission tomography (PET)

scanning, may be required for the management of stroke, brain tumor, or another

primary brain disorder causing spatial neglect.

Neurologic Exams

A complete neurologic examination needs to be performed. This must include a

complete test of higher cortical function at the bedside. Tests of right and left

hemisphere function should be performed. Specific tests for neglect often include

the following:

Line bisection test

Letter cancellation test

Drawing and copying


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Reading and writing

Sensory tests - Involving double-simultaneous stimulation for extinction in the

visual, auditory, somatosensory, or motor modalities

Important to note is that paper-and-pencil tests, which were once the standard, have

been demonstrated to be potentially less sensitive to disability than structured,

semiquantitative observation of functional tasks.[22] This kind of assessment can be

trained like the NIH Stroke Scale, but it usually must be performed by a therapist

who is able to challenge the patient to dress, eat, and transfer, among other tasks,

during the examination.[23]

If paper-and-pencil tests are used, more than one screening behavioral test is

recommended to increase the sensitivity of detecting neglect. Because patients may

have deficits in either spatial "where," perceptual-attentional systems,"where"

representational systems, or "aiming” motor-intentional systems,[24] those who

perform abnormally on one test but who do not show abnormal performance on

other tasks may still have functional impairment as a result of neglect-related

symptoms.[25]

Line bisection test

Line bisection tests are easy, universally available bedside tests to screen for the

presence of hemispatial neglect that take 15 seconds or less to perform. (See the

image below.)

Line bisection task. A male patient is asked to "mark the center of the line," which the

examiner presents centered with respect to his head and body. The patient writes "good" on

the sheet when asked "How did you do?", reflecting unawareness of his significant rightward

bias. (Patient without left hemianopia.)

Detailed assessment of a patient's ability to bisect lines is ideally accomplished

using several trials with different line lengths greater than 22 cm. In the motor line

bisection task, use also vertical lines and radial lines.[26]

Neglect is also more apparent when the lines are placed in the contralesional body

or head space.[26]

The lines should be as long as possible (eg, the entire span of a page) because

neglect is more apparent when longer lines are used.[27]

Cancellation task

The ability to cancel an array of lines or other stimuli may be used.[28] Letter

cancellation, symbol cancellation, or other target cancellation from an array can be

tested. (See the image below.)

Cancellation task (Albert, 1973). The patient is presented with an array of lines scattered on a

piece of paper centered with respect to head and body space and is asked to "cross out all of

them." When the patient stops canceling, he or she is prompted "Did you get all the lines?"

Patient neglects to cancel stimuli in left space.

Double-simultaneous stimulation

Testing for extinction using double-simultaneous stimulation is performed because

patients may be able to detect single stimuli on the right and left hemifields but not

double-simultaneous stimuli in both hemifields.

Patients with spatial neglect may not perceive a contralesional stimulus when it is

simultaneously presented with an ipsilesional stimulus. This may occur

simultaneously with visual, tactile, or auditory modalities.[1]

At the bedside, this can be tested by asking the patient to count fingers presented to


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both hemifields, snapping fingers at both ears, or touching both hands. Extinction

cannot be tested if a patient's ability to detect a single stimulus is impaired.

Drawing

Although time consuming, testing the ability of the patient to draw, either by having

him or her draw from memory (eg, draw-a-person task) or by having the patient copy

the examiner's production (see the image below), may be one of the most sensitive

means of detecting spatial neglect.

Copying a drawing. The examiner draws a simple scene with a house and 2 trees (top of

picture) and asks a female patient to "copy my drawing exactly." The sample for copying is

presented centered in the patient's body space, but her attempt to copy (bottom) includes only

the right side of the rightward-most parts of the scene. Note that the left neglect affects not

only the left side of the page (the house is omitted), but also the left side of objects within the

page. (The round tree is to the left of the pine tree, but the left side of the pine tree is still

missing.)

Additional tests

Other bedside tests may be carried out. For example, the patient can be observed to

see if he or she has evidence of personal (body) neglect (eg, symmetrical shaving,

grooming).

Reading assessment can be useful, particularly for planning occupational and

vocational rehabilitation. When reading English, patients with spatial neglect may not

begin reading at the left margin; rather, they may start in the middle of the page.

When asked to identify single words, they may omit left-sided letters so that

"blueberry" may be read as "berry" (neglect dyslexia).

Informal anosognosia testing is performed by asking the patient about his or her

presentation to the hospital and the symptoms. For example, questions may include

the following: "Are you weak anywhere?" or "Do you have any problems with your

vision or with detecting objects?"

Distinguish neglect and hemianopia (which may coexist) by directing the patient's

gaze into the preferred (eg, right) hemispace. In many people with spatial neglect,

the ability to detect visual stimuli in the contralesional retinal hemifield improves

when gaze is directed into the non-neglected hemispace (eg, when the patient looks

to the extreme right and a stimulus is presented a few degrees to the right of the

body midline, in the left retinal hemifield). These patients are less likely to have true

hemianopia.[29]

Perceptual-Motor Rehabilitation Techniques

Treatment of spatial neglect ideally includes specific rehabilitation interventions that

target each type of deficit.[24] However, although geriatric individuals may be at

higher risk for spatial neglect, behavioral treatments may not be as effective for

these patients. Unfortunately, special management strategies for people older than

65 years with spatial neglect are not yet available.

Motor bias rehabilitation

Motor-intentional "aiming" spatial bias is a tremendous problem for functional

performance and may be uniquely disabling.[22]

An extremely promising neglect therapy, prism adaptation,[30, 31, 32, 33, 34] appears to

target the motor-intentional aiming systems and may be particularly effective in

people with this type of spatial neglect. Other motor bias rehabilitation is performed

by having patients use their extremity in the left hemispace. A form of constraint-

induced therapy, in which the nonparetic limb is restrained and motor cueing is used

for the left hand, may also address motor bias.

Perceptual deficit rehabilitation

Environmental modification

Perceptual deficit rehabilitation may be performed via environmental modification.


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The patient's bedside environment may be oriented leftwards and hence make the

patient perceive his or her left side.

Interventions used to attempt to shift the representation of space rightward include

the following:

Caloric stimulation [35, 36]

Trunk rotation treatment [37]

Optokinetic stimulation [38]

Vibration of left posterior neck muscles [37]

These may act at a representational level, shifting the representation of space to the

neglected side. Eye patching to increase leftward orientation has also been

attempted as a treatment for neglect.[39, 2]

Cueing

Perceptual deficit rehabilitation may be performed via cueing. Scanning training

attempts to encourage patients to direct their gaze to the neglected side and to scan

their environment to the left with verbal cueing. Other methods of scanning training

to improve awareness of the neglected side include cueing patients to find a red line

or other stimulus placed by therapists on the left margin of a page.[40]

Unawareness rehabilitation

Unawareness rehabilitation may be performed via environmental modification and

family education. For example, one modification might include positioning the

patient's chair or bed asymmetrically in the room. (It is not known whether the chair

or bed should be positioned so that the room is in the preferred or neglected

space—both may be theoretically helpful.)

Family members may simplify the visual environment by setting the table with as few

items as possible to improve attention to food and utensils.

Emotional processing rehabilitation

Emotional processing rehabilitation may be performed through the careful education

of the caregivers or family. When present, underlying depression needs to be

treated.

Hypoarousal therapy

Hypoarousal treatment using dopaminergic drugs (eg, bromocriptine) has been used

to treat neglect as part of a treatment strategy that targets arousal and attention

deficits associated with neglect.[41] Patients should be reevaluated while they are on

medication, because paradoxical effects have been reported.[42]

The dopamine agonist apomorphine improved neglect in one study.[43] Other

dopaminergic agents or stimulants may be useful but have not been well studied.

Hypoarousal rehabilitation has been attempted by training patients to sustain

attention by self-alerting.[44]

Poststroke patients with severe hypoarousal accompanying spatial neglect, or

severe anosognosia, may require transfer to subacute care, because they may be

unable to tolerate or cooperate with the usual recommendation of intensive acute

rehabilitation.

Personal neglect rehabilitation

Personal neglect rehabilitation is addressed mainly by occupational therapists in the

course of addressing the activities of daily living and may involve direct verbal,

visual, or tactile cueing.

Consultations

Consultation with a skilled neuro-optometrist may be considered in the presence of

hemianopia. A detailed bedside examination is preferred over automated methods of

assessing visual-field deficits.

Consultation with a neuropsychologist can be helpful for family and caregiver

counseling and for transition to long-term stages of recovery and potential

community reintegration, as well as for dealing with issues of psychological

adjustment by the patient, who may have intact emotional reactions but an impaired

ability to communicate emotionally.

Transitions to postacute and chronic stages of recovery can be particularly

challenging for stroke survivors with spatial neglect. It is difficult for their families to

anticipate the difficulties they will have, purely as a result of their stroke, in taking

medications accurately, managing transfers and ambulation safely, and reintegrating

into their social and community roles. Focusing planned postacute follow-up on

avoiding these care transition problems may mean transitional consultation with a

case manager, nurse, occupational therapist or speech-language pathologist, or

psychologist, depending on which professionals are available and most skilled in

particular communities.

Medications

The use of dopaminergic or other medications for spatial neglect, although an

exciting and developing area,[42] has not yet become standard care for this disorder.

An established practice, however, is to withhold anticholinergic medications,


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antidopaminergic medication (eg, for gastrointestinal indications), sedatives, and

hypnotics in these patients unless absolutely necessary, because these agents may

adversely affect the symptoms of spatial neglect and eventual functional recovery.

Similarly, phenytoin is relatively contraindicated. Patients taking the above

medications should be carefully monitored and their spatial neglect symptoms

should be periodically reevaluated.

No current clinical literature supports a benefit related to the use of modafinil or

cholinesterase inhibitors in patients with spatial neglect. Neither treatment would be

expected to specifically remediate attentional asymmetry, and improving attention

and orienting of intact brain systems might actually worsen behavioral

asymmetry.[42]

Safety Issues

The most important issue that may have legal implications in cases of spatial neglect

is driving. Patients with spatial neglect may not be allowed to drive, for their safety

and the safety of the others. Unfortunately, how people with driving disability can be

identified is not clear, short of an on-road standard driving evaluation by consultation

through a clinical driving program.

Patients who have had acute spatial neglect, even if the symptoms appear to have

resolved, should undergo this evaluation before returning to driving.

Patients should undergo an occupational/vocational rehabilitation evaluation before

returning to work that involves handling machines or tools that may cause injury to

self or others.

Dangerous tools, firearms, and other environmental risks should be removed from

the homes of patients with more severe deficits who are homebound but are not

constantly supervised. The authors have observed a number of accidents in the

home and workplace when patients and families were not compliant with

management recommendations.

Vocational disability in spatial neglect may extend to other, non–safety-related

issues. Difficulty reading left-sided material (neglect dyslexia) may lead to

embarrassing errors in financial, academic, or other detail-oriented work. Spatial

bias may also affect social behavior (effective audience interaction during

presentations), and social-emotional changes are, of course, common after right

brain stroke. A cognitive remediation program assessment may be extremely

valuable if a legal dispute arises between a stroke survivor and his or her employer

about job fitness. If it is hard to locate a cognitive remediation program program, one

can sometimes be identified among resources primarily intended for individuals with

traumatic brain injury or even developmental disabilities and may offer referral

resources to a job coach specialized in right brain neurorehabilitative challenges.

Contributor Information and Disclosures

Author

A M Barrett, MD Director, Stroke Rehabilitation Research Program, Kessler Foundation; Chief,

Neurorehabilitation Program Innovation, Kessler Institute of Rehabilitation; Professor of Physical Medicine and

Rehabilitation, Rutgers New Jersey Medical School

A M Barrett, MD is a member of the following medical societies: American Academy of Neurology, International

Neuropsychological Society, American Society of Neurorehabilitation

Disclosure: Received grant/research funds from Wallerstein Foundation for Geriatric Improvement for research;

Received salary from Kessler Foundation for employment; Received grant/research funds from National Institutes

of Health for research; Received grant/research funds from Healthcare Foundation of NJ for research; Received

grant/research funds from National Institute on Disability, Independent Living & Rehab. Research for research.

Coauthor(s)

Sylvia T John, MBBS Consulting Staff, Brain Injury Unit, Rehabilitation Medicine Associates, Southside Hospital

Sylvia T John, MBBS is a member of the following medical societies: American Academy of Physical Medicine

and Rehabilitation

Disclosure: Nothing to disclose.

Chief Editor

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 is a member of the following medical societies: American Academy of Neurology,

American Heart Association, American Society of Neuroimaging, American Headache Society



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Acknowledgements

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


Daniel H Jacobs, MD, FAAN Associate Professor of Neurology, University of Florida College of Medicine

Daniel H Jacobs, MD, FAAN 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

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College

of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

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