TRANS NO.

2 NEURO

ILOILO DOCTORS’ COLLEGE OF MEDICINE

Molo, Iloilo City
I L O I L O D O C T O S.Y.
R S2019-2020
’ COLLEGE OF MEDI Basal Ganglia Components and Nomenclature

BATCH 2021 Corpus

Dorsal
striatum,
Ventral Pallidum, Lentinoform
striatum Striatum Paleostriatum Nucles
DISCIMUS SAPIENCIA UT VIRTUS Neostriatum
Caudate + + + - -
BLOCK 2 Putamen + + + - +
LECTURER: DR. HORMILLOSA Globus + - - + +
pallidus
MOVEMENT DISORDER Nucleus - - + - -
accumbens

BASAL GANGLIA FUNCTION Olfactory

tubercle
- - + - -

INTRINSIC CIRCUITS

1. Direct pathway

a. Dopaminergic activation of D1 receptors

b. Direct phasic inhibition of globus pallidus

interna and substantia nigra pars reticulata
(transmitter, GABA; cotransmitters,
substance P and dynorphin) by striatal
projection neurons, which in turn, reduce
inhibition of the thalamus by globus pallidus
interna and substantia nigra pars reticulata

c. Activates thalamocortical excitatory

pathways and promotes movement

d. Net result: augmentation of movement

Motor Function e. HYPERkinetic disorders

 The basal ganglia play a role in the 2. Indirect pathway

automatic execution of learned motor plan
and in the preparation for movement. a. Dopaminergic activation of D2 receptors

 According to Marsden, the basal ganglia b. GABAergic inhibition of globus pallidus

are responsible for the automatic execution
of a learned motor plan.
 As a motor skill is learned, the basal
ganglia take over the role of automatically
executing the learned strategy.
externa (cotransmitter, enkephalin), causing
reduced inhibition of the subthalamic
nucleus and subsequent activation of
subthalamic nucleus excitatory projections
to globus pallidus interna and substantia
nigra pars reticulata

When basal ganglia are damaged, the individual
must revert to a slower, less automatic, and less
accurate cortical mechanism for motor behavior
c. Indirect excitatory stimulation of the globus
pallidus interna and substantia nigra pars
reticulata, increasing inhibition of the
thalamus and subsequent reduction of
excitatory thalamocortical projections

d. Net result: reduction of movement

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e. HYPOkinetic disorders
Direct vs Indirect Projection
Activation of the:
 direct pathway leads to net disinhibitory
(facilitatory) effect on the thalamus and an
increase in motor behavior
 indirect pathway leads to increased
inhibition of the thalamus and decreased
motor activity.
 The two pathways have opposing effects on
the output nuclei and their thalamic targets.
 Enhanced activity of the indirect pathway
may be responsible for the poverty of
movement (hypokinesia) eg: Parkinson's
disease
 Reduced activity in the direct pathway may
result in excessive activity (hyperkinesia) of
some basal ganglia disorders (Huntington's
chorea).
HYPERKINETIC MOVEMENTS
A) Chorea (involuntary, irregular, purposeless,
nonrhythmic, abrupt, rapid, unsustained
movements that seem to flow from one body
part to another)
B) Dystonia (twisting movements that tend to be
sustained at the peak of the movement,
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frequently repetitive and often progress to
prolonged abnormal postures)
C) Myoclonus (sudden, brief, shock-like
involuntary movements caused by muscular
contractions or inhibitions [negative
myoclonus])
D) Hemifacial spasm (unilateral facial muscle
contractions)
E) Hyperekplexia (excessive startle reaction to a
sudden, unexpected stimulus)
F) Ballism (very large amplitude choreic
movements of the proximal parts of the limbs,
causing flinging and flailing of limbs)
G) Athetosis (slow writhing, continuous,
involuntary movement)
H) Akathisia (feeling of inner, general
restlessness, which is reduced or relieved by
walking about)
I) Tremors (an oscillatory, usually rhythmic and
regular movement affecting one or more body
parts)
J) Myokymia (fine persistent quivering or rippling
of muscles)
K) Myorhythmia (slow frequency, prolonged,
rhythmic or repetitive movement without the
sharp wave appearance of a myoclonic jerk)
L) Stereotypy (coordinated movement that
repeats continually and identically)
M) Tics (consist of abnormal movements or
sounds; can be simple or complex)
N) Restless legs (unpleasant crawling sensation
of the legs, particularly when sitting and
relaxing in the evening, which then disappears
on walking)
O) Paroxysmal dyskinesias (choreoathetosis
and dystonia that occur “out of the blue,”
lasting for seconds, minutes, or hours)
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HYPOKINETIC MOVEMENTS
 Parkinsonism
 Hypothyroid slowness
 Stiff muscles
 Catatonia
 Psychomotor depression
 Blocking (holding) tics
PARKINSONISM
A. Idiopathic Parkinsonism
 Parkinson’s disease (PD)
B. Secondary Parkinsonism
 Drug-induced (neuroleptics, antiemetics,
reserpine, tetrabenazine, lithium,
flunarizine, cinnarizine, diltiazem)
 Hydrocephalus
 Hypoxia
 Toxins (1-methyl-4-phenyl-1,2,3,6-
tetrahydropyridine [MPTP], CO,
manganese, cyanide, methanol)
 Infections (fungal, acquired
immunodeficiency syndrome, subacute
sclerosing panencephalitis, postencephalitic
parkinsonism, Creutzfeldt-Jakob disease)
 Metabolic (hypo-/hypercalcemia, chronic
hepatocerebral degeneration, Wilson’s
diseases
 Paraneoplastic parkinsonism
 Psychogenic
 Trauma
 Tumor
 Vascular
C. Parkinson-plus syndromes
 Multiple system atrophy (striatonigral
degeneration, Shy-Drager syndrome,
-olivopontocerebellar atrophy)
 Progressive supranuclear palsy
 Corticobasal ganglionic degeneration
 Progressive pallidal atrophy
 Lytico-Bodig
D. Heredo-degenerative Disease
 Alzheimer’s disease (AD)
 Dementia with Lewy bodies
 Pick’s disease
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 Huntington’s disease
 Machado-Joseph’s disease
 Hallervorden-Spatz disease
 Lubag (X-linked dystonia-parkinsonism)
Parkinson’s Disease
a. Estimated prevalence:
500,000–1 million patients in United States
b. Incidence:
40,000–60,000 new cases per year;
average age of onset is 60 years; affects up
to 0.3% of general population, but 1–3% of
those >65 y/o
c. PD is largely a disease of older adults:
Only 5–10% of patients have symptoms
before 40 y/o (young-onset PD)
d. Cardinal features:
i. Tremor
ii. Rigidity
iii. Bradykinesia
iv. Postural instability and gait disturbance
e. Genetic factors:
Autosomal Dominant (AD) and recessive
patterns of inheritance have been identified:
 PARK1: autosomal dominant (α-
synuclein gene on chromosome 4)
 PARK2: Autosomal recessive (parkin
gene on chromosome 6)
 Both: early parkinsonism and dystonia
f. Many theories on cell death but no firm
conclusions
 apoptosis, mitochondrial dysfunction,
oxidative stress, excitotoxicity, deficient
neurotrophic support, immune mechanisms
g. Loss of pigmentation of the substantia nigra and
locus ceruleus with decreased neuromelanin-
containing neurons affected neurons contain
large homogenous eosinophilic cytoplasmic
inclusions called Lewy bodies, which possess
neurofilament, ubiquitin, and crystalline
immunoreactivity
Tremor
 rest tremor; may also be a postural or
kinetic tremor (rest tremor typically
dampens with posture or action); usually
unilateral onset in an extremity; tremor may
spread to involve contiguous extremities
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Rigidity
 Not velocity-dependent or direction-
dependent;
 “Cogwheeling”: usually indicative of
superimposed tremor
Bradykinesia
 Reduced arm swing; generalized slowness
in movements; slowness and difficulty with
manual dexterity; micrographia; masked
facies (hypomimia); sialorrhea because of
bulbar bradykinesia
Postural instability
 Loss of postural reflexes; retropulsion as
may be found on the “pull test”
Gait disturbance
 Stooped posture: characteristic “shuffling”
festinating gait with short stride, with
tendency to lean forward
 Propulsion: involuntary and unwanted
forward acceleration when patient wants to
stop
 Difficulty initiating gait and gait “freezing”
after gait already initiated (sudden inability
to take another step); difficulty with turns
Associated features
 Hypokinetic speech: characterized by
reduced amplitude and sometimes
acceleration of rate
 Autonomic features: most commonly,
orthostatism, usually not a presenting
feature; other less common features:
urinary symptoms (hesitancy, nocturia,
incontinence), sexual dysfunction,
intermittent increased sweating
Behavioral and cognitive features
 Bradyphrenia (mental slowing), with
difficulty with attention, and poor initiation
and working memory
 Depression in up to 2/3 of patients and
anxiety (especially associated with akinetic
“off” state)
 Dementia may develop after many years:
difficulty with frontal lobe executive and
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visuospatial functions, with some language
deficits; difficulty with attentional tasks and
those involving timed responses
Treatment of PD
1. Amantadine:
Useful for newly diagnosed patients with
mild symptoms and in some patients with
advanced disease; provides mild-to-moderate
benefit by decreasing tremor, rigidity, and
akinesia
2. Anticholinergic agents:
Option for young patients <60 y/o) whose
predominant symptoms are resting tremor and
hypersalivation; available agents
trihexyphenidyl and benztropine
3. Levodopa:
Precursor of Dopamine; advantages—
most efficacious antiparkinsonian drug,
immediate therapeutic benefits (within 1 week),
easily titrated, reduces mortality, lower cost;
disadvantages—no effect on disease course,
no effect on nondopaminergic symptoms (such
as dysautonomia, cognitive disturbances, and
postural instability), motor fluctuations and
dyskinesia develop over time (especially in
younger patients, those with more severe
disease and those requiring higher doses)
4. Dopamine agonists:
Effective for initial monotherapy; also
indicated in combination with levodopa to
smooth clinical response in advanced disease;
directly stimulate postsynaptic dopamine
receptors; effective against key motor
symptoms (tremor, bradykinesia, and rigidity)
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 Apomorphine:
Available in the U.S. as an injectable
(subcutaneous) short acting dopamine
agonist; U.S. Food and Drug Administration
(FDA) approved as a “rescue therapy” for
symptoms of wearing off in advanced PD
patients; benefits take effect as early as 5
minutes from the time of injection, but lasts
for only 1 to 1.5 hours
5. Monoamine oxidase B (MAO-B) inhibitors:
Selegiline, Rasagiline
6. COMT inhibitors:
Used in conjunction with L-dopa therapy to
reduce the peripheral metabolism of L-dopa and
thus increase the efficiency of L-dopa delivery
across the blood-brain barrier.
 This results in the smoothing out of L-dopa
plasma levels and reduction in motor
fluctuations. COMT inhibitors should be
given with carbidopa–L-dopa (Waters,
2002).
 Tolcapone (Tasmar) and
entacapone (Comtan)
Management of Dementia and Hallucinations in
PD:
 Eliminate medical causes of delirium (e.g.,
infection or dehydration)
 Discontinue nonparkinsonian psychotropic
medications, if possible; eliminate
antiparkinsonian drugs in order of their potential
to produce delirium
Anticholinergics > Amantadine > Monoamine
Oxidase-B inhibitors > Dopamine agonists >
Catechol methyl transferase inhibitor >
Levodopa
 Rivastigmine:
For cognitive impairment, the first FDA-
approved medication for Parkinson’s disease
with dementia (PDD); available orally and in
patch form; may also improve mild
hallucinations
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Surgical management of PD:
 lesion vs. deep brain stimulation
 lesion
 Thalamotomy—most effective for
parkinsonian and essential tremor
 Pallidotomy—improves bradykinesia,
tremor, rigidity, dyskinesia in PD
 has the advantage of simplicity, no
technology or adjustments required, no
indwelling device
 Deep brain stimulation surgery of globus
pallidus internus or subthalamic nucleus may
improve most symptoms of PD and has the
advantage of minimal to no cell destruction and
the ability to perform deep brain stimulation on
both sides and to adjust the stimulation settings
as the disease progresses; however, deep brain
stimulation is more expensive, requires
technical expertise
Multiple system atrophy (encompasses three
overlapping entities):
1) Striatonigral degeneration
2) Olivopontocerebellar atrophy/ degeneration
3) Shy-Drager syndrome
Striatonigral degeneration:
 a sporadic disorder with an insidious onset of
neurologic symptoms in the 4th–7th decades of
life
 mean age at onset is 56.6 years, no sex
preference
 Akinetic rigid syndrome, similar to PD; patients
initially present with rigidity, hypokinesia, and
sometimes unexplained falling; may be
symmetric or asymmetric at onset
 course is relentlessly progressive, with a
duration ranging from 2–10 years (mean, 4.5–
6.0 years) eventually, patients are severely
disabled by marked akinesia, rigidity, dysphonia
or dysarthria, postural instability, and autonomic
dysfunction
 mild cognitive and affective changes with
difficulties in executive functions, axial dystonia
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with anterocollis, stimulus-sensitive myoclonus,
and pyramidal signs
 respiratory stridor due to moderate to severe
laryngeal abductor paralysis can sometimes
occur; resting tremor is not common;
cerebellar signs are typically absent
 the majority do not respond to levodopa, except
early in the course
Olivopontocerebellar degeneration:
 essentially a progressive degenerative
cerebellar plus syndrome
 male to female ratio is 1.8:1.0 in familial
olivopontocerebellar atrophy and 1:1 in sporadic
olivopontocerebellar atrophy
 average age of onset is 28 years for familial and
50 years for sporadic olivopontocerebellar
atrophy
 the mean duration of the disease is 16 years in
familial and 6 years in sporadic
olivopontocerebellar atrophy
 cerebellar ataxia, especially involving gait, is the
presenting symptom in 73% of patients
 dysmetria, limb ataxia, and cerebellar dysarthria
are characteristic; other initial symptoms include
rigidity, hypokinesia, fatigue, disequilibrium,
involuntary movements, visual changes,
spasticity, and mental deterioration
Shy-Drager syndrome:
 presence of parkinsonian features with
prominent autonomic dysfunction, such as
orthostatic hypotension, erectile dysfunction,
bladder and bowel disturbance
Pathology:
 there is considerable clinical and pathologic
overlap among the three multiple system
atrophy syndromes
 in olivopontocerebellar atrophy, neuronal loss
with gross atrophy is concentrated in the pons,
medullary olives, and cerebellum
 in Shy-Drager syndrome, the intermediolateral
cell columns of the spinal cord are affected as
well
 striatonigral degeneration is characterized
pathologically by cell loss and gliosis in the
striatum and substantia nigra; macroscopically,
the putamen is most affected with significant
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atrophy; the substantia nigra exhibits
hypopigmentation
Progressive Supranuclear Palsy:
Steele-Richardson-Olszewski syndrome
 Supranuclear ophthalmoparesis (especially
downgaze) and falls within the 1st year of onset
of parkinsonism are mandatory criteria for
probable progressive supranuclear palsy
 60–80% with subcortical form of dementia
 Pathology: widespread diencephalic and
mesencephalic (leading to a Mickey Mouse
midbrain), brain stem and cerebellar nuclear
neuronal loss; with globose neurofibrillary
tangles; marked midbrain atrophy
Corticobasal ganglionic Degeneration
 an asymmetric form of parkinsonism presenting
with unilateral dystonia, myoclonus, alien limb
phenomena plus parkinsonism
 dementia is common
 pathologically with achromatic neuronal
inclusions but no classic Pick bodies
Acute Parkinsonism
Etiology:
 infectious, post infectious, autoimmune
(systemic lupus erythematosus)
 medication (typical side effects of anti-dopamine
drugs, idiosyncratic effects—neuroleptic
malignant syndrome, serotonin syndrome,
chemotherapeutic drugs)
 toxic (carbon monoxide, cadmium, MPTP,
ethanol withdrawal, ethylene oxide, methanol,
disulfiram, bone marrow transplantation)
 structural (stroke, subdural hematoma, central
and extra pontine myelinolysis, tumor,
hydrocephalus)
 psychiatric (catatonia, conversion, malingering)
HUNTINGTON’S DISEASE
 Neurodegenerative disorder
 Combines cognitive (subcortical dementia),
movement disorders (chorea, dystonia, motor
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impersistence, incoordination, gait instability,
and, in the young, parkinsonism: Westphal
variant), and psychiatric disorders
(depression, anxiety, impulsivity, apathy,
obsessive compulsive disorders, etc.)
 commonly manifest by age 20–40 years;
usually progresses relentlessly to death in 10–
15 years
Pathology:
The brain is atrophic, striking atrophy of the
caudate nucleus, and, to a lesser degree, the
putamen is seen
Treatment:
 Chorea: dopamine receptor-blocking agents
(e.g., haloperidol, risperidone, reserpine,
tetrabenazine), clonazepam, amantadine;
tetrabenazine has been recently approved for
the treatment of chorea in HD
 Gait instability: reassess if dopamine-blocking
agents are causing parkinsonism, physical and
occupational therapy
 Depression and anxiety: selective serotonin
reuptake inhibitors, clonazepam
 Speech and swallowing therapy; genetic
counseling; family counseling
SYNDENHAM’S CHOREA
Initial manifestation:
 Usually disturbance in school function,
daydreaming, fidgety, inattentiveness, and
increased emotional lability
 Onset of chorea is rather sudden, lag time
between streptococcal infection and chorea
averages 6 months
 Serologic evidence is absent in one-third of
patients; risk of developing carditis with
Sydenham’s chorea is 30–50%; recurrent
episodes of chorea are most common at the
time of pregnancy in female patients
Lab findings:
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 Elevated erythrocyte sedimentation rate or C-
reactive protein, prolonged PR interval
 Treatment for chorea:
Dopamine receptor-blocking agents, such
as haloperidol, pimozide, phenothiazines, or
amantadine
 For acute rheumatic fever:
Penicillin V, 400,000 U (250 mg) tid for 10
days, followed by prophylaxis (benzathine
penicillin G, 1.2 million U intramuscularly every
3–4 weeks)
TREMOR DISORDERS
1. Rest tremor
 Activation of contralateral limb can
exacerbate tremor and increase its
amplitude
 Classic appearance of pill- rolling
movement of thumb and fingers or
alternating supination-pronation;
 Associated with Parkinsonian syndromes,
including Idiopathic Parkinson’s disease;
 May be seen with severe essential tremor
when action-postural component is severe
2. Action tremor
 Tremor occurring with voluntary muscle
contraction
 Subtypes
 Postural: observed with sustained
posture
 Isometric: muscle contraction against
a rigid object
 Kinetic: goal-oriented or non-goal-
oriented, may be task-specific
 Intention: occurrence and
exacerbation during visually guided
targeted movements; if isolated and
low frequency (<5 Hz), then usually
cerebellar sign
3. Physiologic tremor
 Fine, low-amplitude, high-frequency (7-12
Hz) tremor
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 May be exaggerated and clinically apparent
with stress, anxiety, fear, metabolic
condition (hyperthyroidism, hypocalcemia)
drug-induced (stimulants [e.g., cocaine],
nicotine, corticosteroids, thyroxine, alcohol
withdrawal, caffeine)
4. Essential tremor
a) Sporadic
b) Familial
 Genetic heterogeneity
 Some families follow autosomal
dominant pattern of inheritance
 Possible genetic loci on
chromosomes 2, 3, 4
 Postural and kinetic tremor (4-12 Hz)
involving upper extremities: starts
unilaterally or bilaterally, but eventually
involves both upper extremities
 May be asymmetric: more prominent in
initially affected limb
 Tremor usually noticed with handwriting,
holding objects, or other fine motor
movements
5. Titubation
 Low-frequency oscillation, primarily
involving the axial musculature and
appearance of a tremor involving entire
body
 Usually a cerebellar tremor, associated with
cerebellar disorders
Treatment:
 β-Blockers: propranolol (Inderal) studied most
extensively
 Primidone (Mysoline)
 Second-line agents: carbonic anhydrase
inhibitors (e.g., methazolamide), gabapentin,
benzodiazepines
 Surgical treatment
 Thalamotomy
 Thalamic stimulation: high success rate
(tremor reduced in up to 90% and abolished
in 50% of cases); bilateral procedures have
lower complication rates than thalamotomy
DYSTONIA
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 A movement disorder characterized by
sustained involuntary muscle contractions
causing twisting movements and abnormal
postures
 May affect any body part including the arms,
legs, trunk, neck, head or face
 Features
Such as cognition, strength, and senses
including vision and hearing are normal
 the third most common movement disorder
after Parkinson’s disease and Tremor
Classification (Based on Etiology)
1. Primary Dystonia
 With dystonia alone without any underlying
disorder; no structural abnormality in CNS
 Hereditary (Classic) and sporadic (variant)
forms
 Variant forms are marked by atypical
clinical features
 Heredodegenerative - Underlying brain
degeneration
2. Secondary Dystonia (Acquired)
 Demonstrable exogenous or structural
3. Psychogenic
4. Dystonia plus Syndrome
 Dopa-Responsive Dystonia
 Dystonia-Myoclonus
 Dystonia-Parkinsonism
Primary Dystonia
 “idiopathic”; focal or segmental; involves cranial
– cervical (most common)
 Otherwise neurologically normal but may have
tremors (30%)
 Presumed genetic – 25% have positive family
history; frequently inherited as monogenic traits
and usually lack gross neuropathological
changes
 Heredodegenerative diseases associated with
dystonia including various autosomal dominant
(e.g. Huntington’s disease, some
spinocerebellar ataxias) and autosomal
recessive (e.g. juvenile parkinsonism, Wilson’s
disease, pantothenate kinase associated neuro-
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 TRANS NO. 2 NEURO
degeneration) disorders should be considered a GILLES DE LA TOURETTE’S SYNDROME
subgroup of secondary dystonias

X-linked Dystonia-Parkinsonism (XDP)

 Also known as XDP, or “Lubag”

 A neurodegenerative disorder transmitted as an
X-linked recessive trait
 Gene associated with XDP, called the DYT3
gene, was discovered in 2003.
 Chromosome Xq13.1
 Primarily been reported in young adult males
from the island of Panay, Philippines
 It is also called by Ilonggo name “Lubag”
 This name refers to when the twisting
movements (dystonia) are:
 Intermittent – “wa’eg”
 Sustained – “sud’sud”
 Molecular genetic analysis indicates that  Tic: Sudden, rapid, recurrent, non-rhythmic,
mutation responsible was introduced into the stereotyped motor movement or vocalization
Olongo ethnic group of Panay more than 2,000
years ago  Classification of tics:
 mean age at onset is 35 +/- 8 years (14 years
a. Motor: Brief jerk-like movement(s) such
the youngest reported age at onset)
as blinking, nose twitching, head jerk
 Symptoms may initially include focal dystonia
b. Vocal: Meaningless sounds such as
of the neck; lower limbs; upper limbs; or trunk
sniffing, grunting, blowing, coughing
 Frequently accompanied by Parkinsonism
c. Simple tic: Movement involving one
 Cranial involvement often affects muscles of the
group of muscles or a single meaningless
jaw, mouth, lower face, and tongue
sound
(oromandibular/ lingual dystonia)
d. Complex tic: Coordinated, sequenced,
 The disorder generalizes within 5 years of onset
repetitive groups of tics
(4.7 +/- 2.6 years)
 Signs of parkinsonism may accompany,
 A motor tic
precede, or “replace” symptoms of dystonia
 Stiffness (rigidity) Onset:
 Slowness of movement (bradykinesia)
 Shuffling manner of walking (gait)
 Postural instability

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Usually before age 21; volitional suppression of
tics and immense sense of distress when tics
are suppressed
Criteria:
1. Presence of multiple motor tics and one or
more vocal tics at some time during course
of the illness
2. Tics occurring many times daily intermittently
for at least 1 year, without a period of
absence for 3 months or more
3. Onset before age 21
4. Tics changing over time
5. No other condition to explain the tics
 Major obsessions and compulsions are
observed in half of the patients
 presence of both motor and vocal tics are
required for diagnosis of Tourette’s syndrome
 Can be mild, moderate, or severe; can wax and
wane; may peak at age 8 to 12 and then
diminish in adolescence; gets more severe in
adulthood in <10% of cases
Pharmacological therapy:
Drug therapy is often burdened with dose-limiting
side effects.
 Neuroleptics including D2 receptor blockers
such as haloperidol (Haldol) and pimozide
(Orap) ; Atypical neuroleptic agents such as
risperidone (Risperdal), olanzapine (Zyprexa),
ziprasidone (Geodon), and clozapine; dopamine
receptor agonist pergolide; central muscle
relaxant baclofen; central -agonist clonidine
(Catapres)
 Patients with associated obsessive-compulsive
disorders may benefit from selective serotonin
reuptake inhibitors (SSRIs) such as fluoxetine
(Prozac), paroxetine (Paxil), or sertraline
(Zoloft), or the tricyclic antidepressant
clomipramine (Anafranil)
 Patients with associated attention deficit
hyperactivity disorder may benefit from
stimulants such as methylphenidate (Ritalin),
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pemoline (Cylert), or dextroamphetamine
(Dexedrine).
 Medications being studied experimentally
include but are not limited to botulinum toxin,
mecamylamine, SSRIs, and ondansetron
MYOCLONUS
 Sudden, brief, involuntary movements caused
by contraction (positive) or inhibition of
contraction (negative) of certain muscle groups
 Negative (asterixis):
toxic-metabolic vs. structural, poor
response to treatment
 Positive:
cortical (often stimulus-sensitive),
brainstem, spinal/segmental
 May be classified by localization:
 Cortical myoclonus:
Cortical reflex myoclonus is usually
focal myoclonus activated by active or
passive movements
 Subcortical myoclonus:
Often generalized
 Spinal myoclonus:
Confined to a specific dermatome or
spreads along propriospinal pathways
and involves multiple segments, may
be rhythmic
 Peripheral myoclonus:
Remains in the distribution of irritated
peripheral nerves or roots
Treatment
 Clonazepam: hyperekplexia, postanoxic
myoclonus, essential myoclonus, palatal
myoclonus, spinal myoclonus
 Valproate: cortical, posthypoxic, epileptic,
hiccups
 Levetiracetam, Piracetam, Acetazolamide
(second-line for cortical or epileptic
myoclonus),Zonisamide, Primidone
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DRUG-INDUCED MOVEMENT DISORDERS
Drug-induced Parkinsonism
 Symmetric or asymmetric parkinsonism
clinically indistinguishable from Idiopathic
Parkinson’s Disease
 May be seen with most neuroleptics with D2
receptor blockade and presynaptic dopamine
depletors (D2 receptors most closely associated
with parkinsonian effects)
 Phenothiazines (e.g., chlorpromazine
[Thorazine]
 prochlorperazine [Compazine]
 fluphenazine [Prolixin])
 Thioxanthenes (e.g., thiothixene [Navane])
 Butyrophenones (e.g., haloperidol [Haldol],
droperidol)
 Diphenylbutylpiperidine (e.g. pimozide)
 Thienobenzodiazepine (e.g., olanzapine
[Zyprexa])
 Benzamides (e.g., metoclopramide
[Reglan])
 Presynaptic monoamine depletors (inhibit
reuptake) – Reserpine, Tetrabenazine
(action shorter than reserpine, also may
block dopamine receptors)
 Clozapine and Quetiapine: least propensity to
cause parkinsonism
 Other drugs that may potentially cause
parkinsonism: Valproate, Flunarizine,
Verapamil, Lithium
 Treatment:
Discontinuation of causative drug
Akathisia
 Sensation of inner restlessness and tension and
urge to move
TRANS NO. 2 NEURO
 Usually seen as an acute (possibly very early)
phenomenon, but may also be tardive
 Result of ingestion of typical and atypical
neuroleptics, dopamine depletors such as
Reserpine, and SSRI antidepressants
 Treatment:
Decrease the dose or discontinue offending
agent if possible
Tardive Dyskinesia
 Usually occurs after 3 months to several years
of treatment with a neuroleptic
 Pathophysiology:
Unclear but thought to involve supersensitivity
of the dopamine receptors by chronic blockade
of dopamine receptors; possibly decreased
GABA and glutamic acid decarboxylase (GAD)
activity in pallidum, subthalamic nucleus, and
substantia nigra
 Stereotypic, repetitive involuntary movements
involving mainly oral, buccal, lingual, perioral
muscles; movements may be characterized as
athetosis (slow, writhing) or chorea (rapid and
irregular jerking)
 Treatment:
Pharmacologic treatment often indicated when
movements are not abolished with elimination of
the causative agent
 Atypical antipsychotic agents:
Clozapine and Quetiapine
 Presynaptic dopamine depletors:
Reserpine, Tetrabenazine
 Clonazepam
 Vitamin E
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Tardive Dystonia
 Usually involves repetitive axial twisting,
retrocollis, opisthotonos with elbow extension
and wrist flexion
 May occur within 4 days to 23 years after
exposure to offending agent (usually a
dopamine antagonist)
 Treatment:
As for Tardive Dyskinesia
OTHERS:
Hemifacial Spasms
 Involuntary, episodic synchronous contraction of
the muscles supplied by the ipsilateral facial
nerve
 Usually caused by compression of facial nerve
by an aberrant blood vessel; less commonly, by
other compressive lesions (aneurysms, tumors,
arteriovenous malformations, which may
compress the nerve as it exits from the
brainstem)
 Main component is contraction of orbicularis oris
muscles, eventually may spread to involve other
facial muscles supplied by facial nerve
TRANS NO. 2 NEURO
 Contractions can range from individual muscle
twitches to sustained muscle contraction caused
by series of muscle twitches, producing
sustained eye closure or tonic facial contraction
 Treatment:
 Usually poor response to agents such as
Baclofen or anticonvulsants
 BTX injections usually effective (at least
moderate improvement in up to 92% of
cases)
 Surgery considered for refractory cases:
cranioectomy, microvascular
decompression
Restless leg syndrome
 An underdiagnosed movement disorder in which
patients have an irresistible urge to move their
legs and, less frequently, their arms.
 Patients experience uncomfortable leg
sensations—paresthesias or dysesthesias (e.g.,
aching, motor restlessness, throbbing, or
crawling sensation)—that begin or worsen
during times of inactivity
 Symptoms usually subside with activity or
movement
 Primary RLS (idiopathic RLS) often follows a
slow progressive pattern with daily symptoms
not occurring for many years.
 Secondary RLS is often cured when the
underlying cause is treated.
 RLS is associated with sleep complaints,
chronic sleep deprivation, and wakeful
discomfort of the legs, which has a substantial
negative impact on the patient’s quality of life.
 RLS is a relatively common disorder.
 Incidence is higher if RLS is present in a first-
degree relative; incidence is slightly higher in
women than in men. The mode of inheritance is
unknown; an autosomal dominant inheritance
pattern is suggested
Page 1|of 13
 TRANS NO. 2 NEURO
 Periodic limb movement disorder (PLMD) is
the most frequent coexisting disorder
 80% of RLS patients have PLMD
 Characterized by jerking or flexion of the
toe, knee, hip, or leg that occurs while the
patient sleeps and compounds sleep
disturbances

1. Primary restless leg syndrome

 Positive family history of similar symptoms,
including adolescent “growing pains”;
autosomal dominant inheritance; Onset:
early, before age 45 years, often childhood,
adolescence

2. Secondary restless leg syndrome

 Associated with pregnancy, peripheral
neuropathy, chronic renal failure, iron
deficiency anemia, latent iron deficiency
(correlates with low ferritin levels [<50 μg/L]),
folate deficiency
 Linked to several medications:
antidepressants, neuroleptics, dopamine
antagonists, sedating antihistamines

Treatment:
 First-line agents: dopaminergic agonists
 Pramipexole, Ropinirole, or Pergolide;
Levodopa; Gabapentin, benzodiazepines, or
low-potency opioids if dopaminergic agents are
ineffective or cause side effects
 Iron replacement therapy if serum ferritin level
is less than 50 μg/L

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