The Basal Ganglia and Movement Disorders

Brad Cole, M.D.

Overview
The basal ganglia are deeply located neuronal masses that are derived from the telencephalon
(caudate, putamen, and globus pallidus), diencephalon (subthalamic nucleus), and
mesencephalon (substantia nigra). These nuclei are intimately interconnected and communicate
using a multitude of different neurotransmitters. The knowledge of these interconnections and
the neurotransmitters used is clinically relevant in terms of understanding the pathophysiology
and treatment of movement disorders. Diseases or lesions that involve the basal ganglia are
called movement disorders since abnormalities of movement are the primary feature. Unlike
diseases or lesions of the upper or lower motor neurons however, patients with movement
disorders are not generally weak, but rather have difficulties with motor control ranging from
excessive involuntary movements (such as chorea and dyskinesias) to a relative poverty of
movement (bradykinesia). The basal ganglia also contribute to higher mental functions although
this is poorly understood.
Normal Neuroanatomy
The cortex communicates with the basal ganglia via the striatum (caudate and putamen). This
information is processed by the basal ganglia and then output is directed back to the motor cortex
(not to the brain stem or spinal cord nuclei) via the thalamus. Although much is known about the
internal connections of the basal ganglia, little is known about the actual nature of the
information processing.
Striatum - the striatum consists of the caudate and putamen. It receives afferents from the
motor cortex, more widespread cortical areas, the substantia nigra (pars compacta), and the
centromedian nucleus (CM) of the thalamus. The striatum is more than just a relay center since a
substantial amount of information processing occurs. Local processing within the striatum
involves interneurons that use acetylcholine as the primary neurotransmitter. Output from the
striatum is to the internal segment of the globus pallidus and substantia nigra pars reticulata
(using GABA and substance P) and to the external segment of the globus pallidus (using GABA
and enkephalin). Inputs to the striatum from the substantia nigra pars compacta use dopamine
which binds to dopamine receptors in the striatum. The D1 receptor is stimulated by dopamine.
This occurs by activating adenyl cyclase which leads to an increased intracellular level of cAMP.
The D2 receptor is inhibited by dopamine, which inhibits adenyl cyclase activity.
Globus Pallidus - The internal segment of the globus pallidus receives afferents from the
striatum (GABA and substance P) as well as from the subthalamic nucleus (glutamate). The

internal segment of the globus pallidus as well as the substantia nigra (pars reticulata) is the
primary output nucleus of the basal ganglia sending information back to the thalamus (VA > VL)
and eventually the cortex. The external segment of the globus pallidus receives afferents from the
striatum (GABA and enkephalin) and projects to the subthalamic nucleus (GABA).
Efferents from striatum to the internal segment of the globus pallidus and the substantia nigra
(pars reticulata) are called the direct pathway since it is the most direct route to the output
nuclei. Efferents from the striatum to the external segment of the globus pallidus are called the
indirect route since the information first travels through the subthalamic nucleus prior to
arriving in the output nuclei (the internal segment of the globus pallidus and the substantia nigra
pars reticulata).

Substantia Nigra - the pars compacta sends dopamine to the striatum. The pars reticulata
receives input from the striatum (GABA and substance P) and the subthalamic nucleus
(glutamate) before projecting to the thalamus.
Subthalamic Nucleus - serves as a relay between the external segment of the globus pallidus
(GABA) and the internal segment of the globus pallidus (glutamate).

Notice that the decreased production of dopamine by the substantia nigra (pars compacta)
ultimately leads to reduced glutamate stimulation of the motor cortex. This leads to a poverty of
movement (bradykinesia) as will be discussed below. This model is a great oversimplification,
but in general, basal ganglia pathology that leads to under-stimulation of the motor cortex leads
to hypokinetic movement disorders (parkinsonism); basal ganglia pathology that leads to overstimulation of the motor cortex leads to hyperkinetic movement disorders.

Hypokinetic Movement Disorders

1. Primary Parkinsonism (Parkinsons disease)
Parkinsons disease (PD) is the second most common neurodegenerative condition, next to
Alzheimers disease. PD is due to degeneration of the substantia nigra (pars compacta) resulting
in less dopamine production and less dopamine being sent from the substantia nigra to the
striatum. As the disease progresses, however, there is widespread CNS involvement. PD is
characterized by the following:
Tremor This is the most common initial symptom (50-70% of patients). Most prominent at
rest, the tremor is low frequency (4-5 Hz), distal more than proximal, and often lessens during
intentional activity such as reaching for an object. The tremor is asymmetrical and worsens
during stress and when walking. Tremor on top of the rigidity is referred to as cogwheeling or
cogwheel rigidity.
Rigidity - Unlike spasticity in which increased tone is velocity dependent (clasp-knife), the
rigidity of Parkinson's disease is constant regardless of the velocity with which the muscle is
moved.
Akinesia (or bradykinesia) - This refers to the slowness or poverty of movement and
encompasses the most bothersome symptoms for patients. Common complaints in this category
are: difficulty getting out of a deep chair or sofa, loss of facial expression, difficulty doing
buttons and any fine motor task, a softer voice (hypophonia), drooling (sialorrhea), and smaller
handwriting (micrographia). In this category, the examiner will often note a decreased rate of
blinking and facial expression, drooling, difficulty getting out of chairs without pushing off, and
finger tapping that is very slow and of small amplitude. These symptoms are asymmetrical and
usually are worse on the side of the tremor.
Postural Instability - This is usually the last to appear but may progress to the point that patient
may fall multiple times per day. The walking typically consists of a narrow base with very small
shuffled steps and a stooped posture. Freezing of the feet usually occurs with gait initiation and
walking through narrow spaces such as doorways. On exam, a pull test (where the examiner
stands behind the patient and gives a gentle tug on the shoulders) results in the patient taking
multiple steps backward in order to regain balance. Often the examiner must catch the patient.
Other common signs:
Depression and Anxiety 40-50% of patients with P.D.
Dementia 20-30% of patients with P.D., especially in the older population.

Dyskinesias caused by high levodopa blood levels and up-regulation of dopamine receptors.
This finding is suggestive of P.D.
Constipation due to decreased gastrointestinal motility
Sensory symptoms - pain, discomfort, and aching are experienced by 10-15% of patients. For
example, the legs and low back may feel tight. This is often levodopa responsive.
Sweating - an off-manifestation and often levodopa responsive.
Seborrheic dermatitis
Dystonia off dystonia as medication wears off, or can be the presenting sign of P.D. (i.e. foot
inversion or curling in of the toes)
Hyposmia is seen in 90%
REM sleep Behavior Disorder (RBD) acting out dreams is seen in about 60%. A 2013
study followed patients with RBG for 16 years and found that 81% eventually developed
parkinsonism and/or dementia (especially diffuse Lewy body disease).
Pathophysiology:
Parkinsons disease is a neurodegenerative disorder with progressive loss of the pigmented
neurons in the substantia nigra (pars compacta) in the midbrain. The pathologic hallmark is the
presence of cytoplasmic inclusions in the substantia nigra called Lewy bodies. This cell death
results in dopamine deficiency in the substantia nigra cells and at the synaptic endings of nigral
fibers in the striatum (caudate and putamen).
In 1997, the first genetic mutation related to Parkinsons disease was identified involving alphasynuclein (PARK1). Alpha-synuclein is involved at some level in virtually all cases of PD and
the mutant, non-soluble, aggregated form is a major component of Lewy bodies. Alpha-synuclein
accumulation leads to PD from very complex mechanisms. It has also been found that
pathological alpha-synuclein transmission initiates parkinsonian-like neurodegeneration in
nontransgenic mice (Science 2012, Nov. 16; 338). Since 1997, there have been 18 gene locations
(PARK18) related to Parkinsons disease. 30% of Ashkenazi Jews that have PD have an
identifiable genetic cause. The cause of PD goes beyond genetic predisposition, however, and
includes environmental factors and endogenous factors.

Diagnosis:
The diagnosis of PD is based primarily on clinical findings. Patients with PD typically respond
very well to treatment which helps to confirm the diagnosis. Lack of response to dopamine
therapy, symmetrical examination findings, early falling, and the early prominence of other
atypical features (see MSA symptoms below) would suggest the likely possibility of another
form of parkinsonism.
Recently a DaTScan (Dopamine Transporter Scan), which is a SPECT scan that binds to the
dopamine (DA) transporter, can be used to distinguish PD from essential tremor and psychogenic
parkinsonism. It does not distinguish between PD and Multisystem Atrophy (MSA) or
Progressive Supranuclear Palsy (PSP). For now, this scan is being used primarily for research
purposes, but the use of DaTScan is likely to become more readily available in coming years.

Treatment for Early disease: From the time of symptom onset until the symptoms become
troublesome.
Rasagiline (Azilect)
A potent and selective MAO-B inhibitor. Symptomatic benefit can be seen due to slowing the
breakdown of dopamine in the striatum. As to whether or not there is a neuroprotective effect,
this is inconclusive. In theory, reducing the free radical production and decreasing the oxidative
metabolism of dopamine may slow down progressive but there is really no convincing evidence
based on clinical studies.
Amantadine (Symmetrel)
Amantadine is an anti-viral agent which provides symptomatic improvement in P.D. probably by
augmentation of dopamine release and by blocking re-uptake into the presynaptic terminals. The
benefits are modest.
Anticholinergic drugs (muscarinic antagonists)
Trihexyphenydyl (Artane), benztropine (Cogentin) act by blocking cholinergic interneurons in
the striatum. They are most effective for tremor. They are not used frequently however due to
common side effects (anti-muscarinic) such as confusion, blurred vision, dry mouth, urinary
retention, and constipation. For this reason, these medications are not typically used.

Mild disease but symptoms begin to interfere with activities:

If the patient is younger than 60 and the symptoms are not severe enough to require levodopa,
first use dopamine agonist therapy.
WHY?
Dopamine receptor agonists are less likely to prime a patient for dyskinesias and are
recommended for treatment of mild to moderate P.D. or for patients under the age of 60. There is
also a theoretical concern that levodopa may accelerate the loss of dopaminergic neurons through
oxidative stress.
If the patient is older than 70 or has any cognitive difficulties, first use levodopa therapy.
Dopamine receptor agonists
There are four different dopamine agonists approved in the United States: Bromocriptine
(Parlodel), Pramipexole (Mirapex), Ropinirole (Requip) and Rotigotine (Neupro). Dopamine
agonists provide the best symptomatic relief after levodopa. Pramipexole and ropinirole are most
commonly used. Unlike levodopa, dopamine agonists do not require enzymatic conversion in the
striatum and therefore are not dependent on intact nigrostriatal neurons. They are also more
selective in their action than levodopa. Since they have a longer half-live than levodopa, they are
useful in patients with motor fluctuations.
Dopamine receptor agonists are also used to treat restless legs syndrome (especially pramipexole
and ropinirole).
Bromocriptine (Parlodel) an agonist of D2 receptors, but a partial antagonist of D1 receptors. It
has more side effects than the other newer dopamine receptor agonists and is used less
frequently. ***recall that this is the medication used to treat prolactinomas (prolactin inhibitory
factor) ***
Pramipexole (Mirapex) and Ropinirole (Requip) agonists at D2 and D3, with little action at
D1. These 2 medications are the most often used of the dopamine receptor agonists, mainly
because of side effect profile and ability to achieve a therapeutic dose quickly. The most common
side effect of these two medications are:
- Nausea (the most common side effect)
- Hallucinations
- Sudden attacks of sleep this requires discontinuation of the medications
- Gambling and other obsessive behaviors
- Confusion especially in the elderly
In 2012, the rotigotine patch (Neupro) was put back on the market. This has a similar side effect
profile but can be helpful for patients who have difficulty swallowing.

Moderate to severe disease that causes sufficient disability:

Levodopa (Sinemet = carbidopa + levodopa)
Levodopa is a precursor of dopamine and can be taken orally. In contrast to dopamine, levodopa
crosses the blood brain barrier. It is then converted to dopamine in the striatum. Carbidopa
inhibits the peripheral decarboxylation of levodopa to dopamine and, thus, decreases peripheral
side effects such as nausea and hypotension.
Levodopa is available in several different preparations:
Short acting form (10/100, 25/100, 25/250) Since 75 milligrams of carbidopa is often
effective in preventing nausea, 3 of the 25/100 tablets is a commonly prescribed dose.
Long acting form (CR 50/200, 25/100) best for motor fluctuations and wearing off.
Levodopa is clearly the most effective medication and many patients have a dramatic
improvement. A lack of any response to levodopa raises the question as to whether the patient
actually has P.D. or not. Early on, the patient has a big therapeutic window and one dose might
last all day. Slowly, within a few years of beginning levodopa treatment, the patient experiences
motor fluctuations such as wearing off or end-of-dose failure. Finally, the fluctuations may
become so severe, that the patient alternates between dyskinesias and the off state and can
change from one to the other within minutes.
The most common side effects levodopa are:
- Nausea
- Hallucinations
- Dyskinesias (more common than with dopamine agonists)
- Vivid dreams
- Hypotension
- Confusion (less common than dopamine agonists)
COMT inhibitors
Tolcapone (Tasmar) and entacapone (Comtan) inhibit catecholamine-O-methyl-transferase
(COMT), which breaks down dopamine mainly peripherally. This prolongs the effect of
levodopa. COMT-inhibitors are indicated for the wearing-off effect. They should always be
taken with levodopa. Tolcapone is associated with fulminate hepatic failure, thus liver enzymes
must be checked every two weeks. It may cause severe diarrhea. It is therefore not commonly
prescribed. Entacapone is usually given with levodopa since its duration of action is only 2
hours. It is used primarily in patients that have the wearing off phenomenon.

Dopamine agonists
Effective in combination with levodopa to smooth out motor fluctuations.
Low protein diet
Protein competes with the absorption of levodopa in the duodenum and at the blood brain barrier.
In severe disease with rapid motor fluctuations, it is best to take Sinemet 1 hour before or 2 hours
after a meal (if the patient is nauseated, Sinemet should be taken with meals).
Surgical options
Surgical options are occasionally pursued in patients with more severe or refractory PD.
Pallidotomy describes a surgical lesion that is placed in the internal segment of the globus
pallidus. Thalamotomy involves placing a lesion in the thalamus and is more helpful for tremor.
Both of these are rarely done now in favor of deep brain stimulation (DBS). DBS involves
placing a battery-powered neurostimulator (called a brain pacemaker) which is placed into the
globus pallidus or occasionally the subthalamic nucleus. An insulated wire runs from the brain,
down the side of the neck and behind the ear to below the clavicle. DBS has the advantage over
pallidotomy and thalamotomy in that it can be adjusted by the neurologist over time. Patients are
candidates if they have exhausted other medication treatment, but have had a good response to
medications in the past.
2. Multisystem degeneration
This is an important category to remember given that Progressive Supranuclear Palsy (PSP),
Multisystem Atrophy (MSA) and Corticobasal Degeneration (CBD) make up about 15% of
patients with parkinsonism.
A. Progressive Supranuclear Palsy (PSP)
PSP has many overlapping features with typical PD, but has the following unique clinical
features:
Early falling
Vertical supranuclear gaze palsy early on this presents with a diminished velocity of
downward saccades, but eventually involves upward and then horizontal saccades
Frontal subcortical dementia patients often exhibit a withdrawn apathy, a loss of verbal
fluency, and frontal lobe release signs

 Poor response to medications patients may have a transient small clinical improvement with
dopamine therapy, but this generally wears off and patient the steadily deteriorate.
Pseudobulbar palsy (dysarthria, dysphagia, emotional incontinence)
MRI reveals midbrain atrophy without pontine atrophy (hummingbird sign). Pathologically,
PSP demonstrates Tau in the cytoplasms of neurons and glia (Tauopathy is seen in other
neurodegenerative conditions, however)
B. Multisystem Atrophy (MSA)
This category used to be divided into three categories which are listed here since they are still
used by some (including national boards):

Striatonigral degeneration (parkinsonism with little tremor and poor response to therapy)

Shy-Dragar syndrome (parkinsonism with profound autonomic insufficiency)

Olivo-ponto-cerebellar degeneration (early ataxia with parkinsonism).

Since it was found that all 3 of these conditions have glial cytoplasmic inclusions of -synuclein
(which are also seen in PD and dementia with Lewy bodies) these are now lumped together
under the broader term of multisystem atrophy.
Within this category, 80% of patients present with parkinsonism, 20% with ataxia. In addition to
the features of parkinsonism (and sometimes ataxia) patients present with the following clinical
features which suggest that MSA is the more likely diagnosis than Parkinsons disease:
Early falling
Rapid progression
Craniocervical dystonia (especially anterocollis where the head is pulled forward)
Poor response to therapy (although 60% may have some initial mild improvement, very few
have an excellent improvement which is seen in most patients with PD)
Minipolymyoclonus tremor (looks like an irregular hand tremulousness that is more prominent
with hands outstretched and during action. Contrast this with PD which is a regular tremor and is
worse at rest)

 Autonomic instability (orthostatic hypotension, erectile dysfunction) although this can occur
in PD, if it is seen within the first 2 years of parkinsonism, the patient more likely has MSA
Pseudobulbar palsy (dysarthria, dysphagia, emotional incontinence)
Sometimes a high-pitched dysarthria
REM sleep disorder in almost 100% (also common in PD); > 50% also have an obstructive
sleep apnea
MRI reveals putaminal atrophy and with a hyperintense rim around the putamen on T2 weighted
images. In addition, signal changes in the pons and middle cerebellar peduncle are referred to as
the hot cross bun sign.
C. Corticobasal degeneration (CBD) - not asked on this exam
CBD patients have a dramatically asymmetrical rigidity, bradykinesia and dystonia that usually
begins in one arm and then spreads to the leg on the same side. Patients also have the following
unique clinical features which point away from PD as the diagnosis:

Apraxia this refers to an inability to perform a purposeful skilled movement in the

absence of a motor deficit. Eyelid apraxia (difficulty opening the eyes on command) and
ocular motor apraxia (difficulty initiating saccadic eye movements) are two examples of
this.

Cortical hemisensory loss and occasionally cortical motor deficits this presents with a
loss of sensation on one side of the body and sometimes asymmetrical reflexes and other
upper motor neuron findings

Stimulus sensitive myoclonus

Frontal dementia is also common with associated behavioral changes and sometimes a
progressive non-fluent aphasia.

If there is tremor, it is worse with action and is more irregular, jerky and appears
myoclonic.

Typically the symptoms begin in the arm and slowly spread to the leg on the same side,
or occasionally to the other arm.

Alien limb syndrome which is present in < 1/3 of patient at symptom onset is a
distinctive feature of CBD. In this condition, patients fail to recognize the action of the

involved limb as their own. The arm, has a mind of its own and may grope or grab
things involuntarily.

No response to treatment

Mean survival of only 7-9 years from onset

MRI and pathology reveals asymmetrical posterior frontal and parietal atrophy. Tau
accumulations are seen in the cytoplasm of neurons and glia.
3. Heredodegenerative Parkinsonism
Huntingtons and Wilsons disease may present with some overlapping features of PD. Typically,
however, this is not a difficult distinction. In Huntingtons, for example, the early symptoms are
much more likely to be of the hyperkinetic variety with choreiform movements. Only late in the
disease, do patients develop dystonia and features of parkinsonism.
4. Secondary Parkinsonism
A. Vascular (multi-infarct, Binswanger disease)
These patients present with a history of multiple subcortical strokes, typically with focal findings
such as hemiplegia and hemisensory loss in addition to some parkinsonian features. In addition,
pseudobulbar palsy (dysarthria, dysphagia, and emotional incontinence) and a subcortical
dementia are common. Typically the response to medications used to treat P.D. is poor.
B. Normal pressure hydrocephalus (NPH)
Patients with NPH do have some parkinsonian features. Remember though that this is a
remarkably rare condition and that the triad of gait instability, dementia and urinary
incontinence is seen in most patients who have Alzheimers disease. In other words, the triad is
very non-specific and CT/MRI scans are frequently misread as hydrocephalus when in fact
that patient has large appearing ventricles due to atrophy (obstructive hydrocephalus).
NPH typically presents with a gait apraxia. The leg examination is normal, but patients have
difficulty with initiation of gait that often improves after taking a few steps. Later, the cognitive
issues and urinary incontinence may develop. The slowed walking can resemble Parkinsons
disease. Much media attention was given to NPH years ago after a T.V. special suggested that
many patients with NPH had been misdiagnosed with P.D.
C. Drugs (dopamine blockers: antipsychotics, antiemetics)

This is extremely important to consider in the differential of PD and is a very common cause of
parkinsonism. Metoclopromide (reglan) and prochlorperazine (Compazine) are two of the more
common culprits. In addition, most of the first generation antipsychotics (neuroleptics)
commonly cause parkinsonism by blocking dopamine receptors. Haloperidol is a classic example
of this. Recovery after discontinuation of dopamine blocking medications may take months.
Newer generation antipsychotics such as Quetiapine (which has strong histaminic, cholinergic,
and alpha-1-adrenergic binding) or Clozapine do not cause parkinsonism because of their unique
mechanism of action.
D. Infectious (AIDS, Creutzfeldt-Jakob)
These conditions have unique clinical features such that they are rarely confused with typical
PD. They are discussed elsewhere.
E. Toxins (methyl-phenyl-tetrahydropyridine [MPTP], manganese, carbon dioxide)
MPTP is closely related to MPPP, a synthetic opioids drug (similar to morphine). This was
discovered in 1976 when a chemistry graduate student tried to manufacture MPPP but was
instead contaminated with MPTP. Within days he developed features of Parkinsons disease.
MPTP is destructive to neurons in the substantia nigra. Patients with MPTP parkinsonism
respond to Sinemet therapy.
F. Head trauma
It appears that patients with repeated head trauma are more likely to develop PD. In one study,
patients who had frequent head trauma had a 4 times higher risk of developing PD (Neurology,
May 19, 2003).

Hyperkinetic Movement Disorders

1. Essential Tremor (familial tremor, senile tremor)
Essential tremor is probably the most common of all movement disorders. Usually asymmetric, it
begins in the arms as a postural and action tremor and may progress to involve the head, voice,
and legs. It is often inherited in an autosomal dominant manner. In contrast to P.D. the tremor is
bothersome during action and the patient complains of difficulty eating and during most any
activity that involves using the hands. The tremor often improves briefly with alcohol.
As compared to patients with P.D., these patients do very well over a long period of time. Mild

cases often go untreated. If the tremor interferes with the quality of life, primidone (Mysoline)
and propranolol (Inderal) are effective options for reducing the tremor. For more severe cases,
deep brain stimulation may be effective.
2. Dystonia
Dystonia refers to sustained muscle contractions that are typically twisting in nature and result in
abnormal postures.
A. Idiopathic focal dystonias:
1.

Blepharospasm is caused by the contraction of orbicularis oculi muscles

and usually begins with increased blinking which then progresses to
prolonged eyelid closure. If untreated, it can cause functional blindness.
Blepharospasm can be improved by "sensory tricks" such as
humming, or placement of a finger lateral to the orbit.
increased in women over the age of 50.

2.

Torticollis is a sustained turning, tilting, flexing, or extending of the neck.

Symptoms usually begin between the age of 20 60. Patients also
effectively use sensory tricks such as stroking the chin. It is the most
common dystonia seen in movement disorder clinics.

3.

Spasmodic dysphonia is a contraction of the vocalis muscles which

brings the vocal cords together and causes the voice to be strained, coarse,
and constricted (adductor type). A breathy voice can be caused by
dystonic contraction of the posterior cricoarytenoids

talking,
Incidence is

(abductor type).
4.

Writer's cramp is one of a number of task specific dystonias. In the

case of writers cramp, the hand is essentially normal for every function in
life except handwriting. There are several other task specific dystonias
including some notable musicians.

Botulinum toxin is the treatment of choice for most focal dystonias and is very effective for all
types. The effect lasts for about 3 months or more and the procedure is then repeated. Recall that
botulinum toxin acts by cleaving the SNARE proteins that are necessary for fusion of the
acetylcholine containing vesicles with the presynaptic membrane.

3. Other disorders that commonly present with hyperkinetic movement:

1.

Wilson's disease

Wilson's disease is an inborn error of Copper metabolism resulting in abnormal copper

deposition in the liver and in the basal ganglia (hepatolenticular degeneration). Symptoms
develop during the teens or early twenties. Neurologic signs usually present with tremor (often
''wing-beating"), dystonia, dysarthria, and rigidity.
Psychiatric symptoms are also common. Kaiser-Fleischer rings, due to intracorneal deposition of
copper, are an important physical examination finding. Diagnosis is made by the finding of a low
serum ceruloplasmin level and a high 24 hour urine copper level.
Any young patient (< 40) with a movement disorder should be checked for Wilson's disease
since it is treatable if diagnosed.
2.

Huntingtons disease

Huntingtons disease is an autosomal dominant, untreatable and progressive neurodegenerative

disease. The most prominent degeneration is seen in the striatum (especially the caudate nucleus)
as well as the cortical neurons in general. There is a GABA deficit which contributes to the
movement disorder.
HD has three main features:

Dementia and personality disorder: Early in the disease this usually manifests as an
irritability, anxiety, and loss of interest. Depression is also very common Later in the
disease there is clear memory loss and features of dementia.

Choreiform movements: These are brief, irregular contractions of the extremities and
face. Early in the disease this can be confused with insignificant fidgetiness.
Eventually, however, severe chorea may result with uncontrollable flailing of the
extremities. Later in the disease, the excessive choreiform movements are replaced by
dystonia and features of parkinsonism.

A family history of early dementia and choreiform movements.

Onset of symptoms is usually in the early to mid-50s although this can vary. Early onset cases
(juvenile HD under the age of 20) are especially common when a female inherits the gene from
her father. Death usually occurs 10-25 years after the onset of symptoms.
Estimates of the prevalence of HD in the United States range from 4.1-8.4 per 100,000 people.
However, the frequency of HD in different countries varies greatly. The Lake Maracaibo region
in Venezuela has a very high rate of 700 per 100,000 people whereas the prevalence of HD in
Finland and Japan is less than 1 per 100,000 people.
The diagnosis can be confirmed (even prior to the onset of symptoms) by genetics testing which
shows an increased number of CAG repeats on chromosome 4. An MRI of the brain will show
atrophy of the caudate that is out of proportion to other areas of the brain, as well as generalized
brain atrophy.
3.

Hemiballismus

Hemiballismus is due to a stroke in the contralateral subthalamic nucleus. Patients develop acute
onset of wild, flinging, ballistic movement in the contralateral arm and leg. Because this is a
small vessel stroke syndrome, there are no other clinical features and other than the isolated
movement disorder there are no other abnormalities with motor, sensory, language, or vision.

4.

Tourette syndrome

The diagnostic criteria consist of multiple motor tics, one or more vocal tics, onset before age
21, and the presence of tics for more than one year. Onset is most common between the ages
of 5-7. 96% of patients manifest with some clinical symptoms by age 11. In about half of
cases, the tics resolve by age 18. Adult-onset tics can represent TS that resolved and then
recurred later in life.
Tics are intermittent, brief, and include a wide variety of complex movements including
jerking arms, kicking, scratching or even obscene gestures. Patients can suppress these tics
for a period of time but experience tension with prolonged suppression that is relieved by
allowing the tic. Vocalizations including sniffing, grunting, repeating words (echolalia) and

even saying or shouting obscene words (coprolalia).

TS should be distinguished from transient tic disorder of childhood which disappears after 6
months.
Attention deficit hyperactivity disorder and obsessive-compulsive disorder is seen in about
60% and 30% respectively. There is also an increased incidence of learning disorders.
TS is a hereditary condition, usually with bilineal transmission (inheritance from both
parents). Specific genetic mutations have been identified. Disinhibition of the motor and
limbic system result in a disturbance in the striatal-thalamic-cortical pathways. A recent study
showed smaller caudate volumes in children and adults with TS.
Medications that block dopamine are effective but many patients have mild symptoms and do
not desire treatment. Focal motor and vocal tics can respond to botulinum toxin injections
into the affected muscles. There are a wide variety of treatments options that will not be
discussed in this handout.
5.

Tardive Dyskinesia

Chronic treatment with neuroleptic medications (and occasionally those used to treat nausea)
that block dopamine receptors can lead to a hypersensitivity of these receptors. Elderly
women are most susceptible. Since it is often permanent, it is the most feared complication of
these medications. Typical manifestation is repetitive stereotypic movements particularly of
the lower face (orobuccolingual dyskinesias such as chewing movements, flycatcher
tongue, and the bonbon sign). The gait is rarely affected. The drug exposure is usually
present for at least several months.