NOTES

NOTES
MOVEMENT DISORDERS

GENERALLY, WHAT ARE THEY?

▪ Motor abnormality
PATHOLOGY & CAUSES ▫ Hypokinesia: ↓ amplitude
▪ Disorders causing abnormal movement ▫ Bradykinesia: ↓ speed
▫ Increased voluntary/involuntary ▫ Dyskinesia: unwanted, characterized
movement (hyperkinetic disorders); motor movement
reduced movement (hypokinetic ▫ Tremor: rhythmic motor movement;
disorders) resting, action, postural
▫ Rigidity: abnormal, uncoordinated
muscle tone across joint
TYPES
Acute fulminant episodes
▪ Reaction to trigger, medication (neuroleptic
DIAGNOSIS
malignant syndrome)
OTHER DIAGNOSTICS
Benign chronic conditions ▪ Neurologic examination
▪ Restless legs syndrome (RLS), essential ▫ Observation of spontaneous movement,
tremor strength testing, tone evaluation, reflex
exam
Progressive chronic syndromes
▪ Parkinson’s disease (PD), Friedreich’s ataxia
TREATMENT
CAUSES
MEDICATIONS
▪ Often idiopathic; genetic mutations,
medication ▪ Beta blockers, anti-epileptics,
benzodiazepines; dopamine replacement,
agonists
SIGNS & SYMPTOMS
OTHER INTERVENTIONS
▪ Mild, unpleasant sensations, intention/ ▪ Avoid caffeine, nicotine, etc.
action tremors; rigidity, catatonia ▪ Educational, supportive therapy

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ESSENTIAL TREMOR
[Link]/essential-tremor

PATHOLOGY & CAUSES DIAGNOSIS

▪ Most common movement disorder; OTHER DIAGNOSTICS
involuntary, rhythmic shaking ▪ Postural/action tremor of hands/head;
▪ Usually affects hands, fingers; sometimes duration ≥ three year
head, vocal cords ▪ Alleviation with alcohol intake
▪ Action tremor (occurs during muscle effort)
Physical examination
▫ Postural/intention tremor
▪ Fine postural, action tremor in hands, head/
voice
CAUSES ▪ Asymmetric/symmetric: cogwheel rigidity,
▪ Unknown; may be familial with autosomal resting tremor, dystonia (esp. head)
dominant inheritance pattern

RISK FACTORS TREATMENT

▪ Meat consumption
MEDICATIONS
▫ Exposure to heterocyclic amines (e.g.
▪ If disabling, symptomatic treatment
harmane, harmaline)
▫ Beta blockers
▪ Associated with dystonia (cervical,
spasmodic, cranial dystonia, writer's ▫ Anti-epileptics
cramp), parkinsonism ▫ Benzodiazepines
▫ Botulinum toxin (head tremors not
responsive to medication)
SIGNS & SYMPTOMS
OTHER INTERVENTONS
▪ Rhythmic, symmetrical tremor
▪ Avoid caffeine, nicotine, etc.
▫ Hands, head, vocal cords, neck, face,
leg, tongue, trunk ▪ Get enough sleep
▪ High frequency tremor (4–12Hz)
exacerbated by muscle contraction
▪ Inability to perform precise tasks
▪ Intention tremor
▫ Intensifies upon touching nose with
finger
▪ Postural tremor
▫ During outstretched arms
▪ Walking difficulties
▪ ↓ tremor with alcohol intake

[Link] 639
 FRIEDREICH'S ATAXIA
[Link]/friedreichs-ataxia
▫ 600–1200 trinucleotide repeats →
PATHOLOGY & CAUSES Friedreich’s ataxia

▪ Genetic disorder; causes progressive

central nervous system (CNS) damage, COMPLICATIONS
movement problems
Progressive loss of cells
▪ Predominantly affects CNS; also affects
▪ In CNS, heart, pancreas
heart, pancreas
▪ Limb, gait ataxia → wheelchair bound →
▪ ↓ frataxin → ↓ mitochondrial oxidative
bedridden
phosphorylation → cell damage, death
▪ Dysphagia, dysarthria → aspiration →
▪ ↓ frataxin → ↑ free iron → ↑ oxidative stress
gastric bacteria insult to respiratory
→ cell damage, death
parenchyma
▪ Neuronal cell death affects posterior
▪ Hypertrophic cardiomyopathy (secondary
columns of spinal cord, distal corticospinal
to myocardial cell death)
tracts, spinocerebellar tracts, brain stem,
cerebellum ▫ Fibrosis → arrhythmia, hypertrophic
cardiomyopathy → heart failure
▪ Gene silencing → no frataxin synthesized
→ iron accumulates in cell, reacts with ▫ Most common cause of death in
oxygen → unstable oxygen radicals → cell affected individuals (age 40–50)
death ▪ Diabetes mellitus
▫ Loss of beta cells of pancreas
CAUSES ▪ 25% of affected individuals
▪ Trinucleotide repeat GAA expansion ▪ Musculoskeletal abnormalities
(chromosome 9q13) → ↓ production of ▫ Muscle denervation → abnormal forces
mitochondrial inner membrane protein, about joints → abnormalities
frataxin ▪ Kyphoscoliosis
▫ Autosomal recessive inheritance pattern ▫ Severe → ↓ total lung capacity →
▫ ↑ repeats → ↑ severity, ↓ age of onset restrictive lung disease

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▪ Pes cavus OTHER DIAGNOSTICS

▫ Similar restrictive lung disease in severe ▪ Symptom progression, family history
cases ▪ Neurological exam
▪ Hammer toes ▫ Ataxia (gait, hand); ↓ vibratory
sensation, proprioception; ↓ deep
tendon reflexes, nystagmus
SIGNS & SYMPTOMS
Electromyogram
▪ Ataxia ▪ Absent/reduced sensory nerve action
▫ Falling/staggering while walking, wide- potentials
based gait ▪ Normal/only slightly decreased motor nerve
▫ Gait ataxia most common (age 0–10); conduction velocities
most individuals progress to wheelchair ▪ Abnormal auditory, visual, somatosensory-
dependence within 11–25 years evoked responses
▪ Loss of vibratory sense, proprioception
▪ Muscle weakness, chest pain,
dyspnea, heart palpitations, absence TREATMENT
of tendon reflexes in legs, involuntary
eye movements, action tremor, hand OTHER INTERVENTIONS
clumsiness, dysarthria, fatigue ▪ Occupational, physical therapy
▫ Balance, ataxic progression
▪ Cardiology
DIAGNOSIS ▫ Annual electrocardiogram,
echocardiogram
LAB RESULTS ▪ Severe scoliosis
Genetic testing ▫ Orthopedic referral
▪ Confirms diagnosis ▪ Annual diabetes screening
▪ GAA repeats; examine first intron in frataxin ▪ Genetic, psychological counseling services
gene

[Link] 641
 NEUROLEPTIC MALIGNANT
SYNDROME
[Link]/neuroleptic-malignant-syndrome
▪ Lithium/alcohol/psychoactive substance use
PATHOLOGY & CAUSES ▪ Previous episode of neuroleptic malignant
syndrome
▪ Life-threatening idiosyncratic reaction
to antipsychotic drugs; muscle rigidity, ▪ Acute injury (e.g. trauma, surgery, infection)
fever, altered mental status, autonomic ▪ Psychiatric conditions (e.g. acute catatonia,
dysfunction severe agitation)
▪ Dopamine blockade theory ▪ Lewy body dementia
▫ Central dopamine blockade →
hypothalamus → hyperthermia, COMPLICATIONS
dysautonomia ▪ Rhabdomyolysis, renal failure
▫ Nigrostriatal dopamine blockade → ▪ Seizures
tremor, rigidity
▫ Due to hyperthermia, metabolic
▪ Peripheral muscle theory imbalances
▫ Direct toxic effect of neuroleptics → ▪ Encephalopathy, stupor, coma
mitochondria of skeletal muscle →
▪ Cardiac arrhythmias (e.g. torsades de
rigidity, fever
pointes, cardiac arrest)
▪ Sympathetic nervous system theory
▪ Disseminated intravascular coagulation
▫ ↓ dopamine inhibitors → ↑ sympathetic
output
▫ ↑ sudomotor, vasomotor activity → fever SIGNS & SYMPTOMS

CAUSES Altered mental status

▪ Agitated delirium with confusion (initial
Reaction to medications symptom); coma
▪ First-generation neuroleptic (most
common) Muscular abnormalities
▫ Haloperidol, fluphenazine, ▪ Generalized muscular rigidity (“lead-pipe
chlorpromazine rigidity”)
▪ Second-generation neuroleptic medication ▫ Associated dysphonia, dysarthria
▫ Clozapine, risperidone, olanzapine ▪ Catatonic signs
▪ Antiemetic ▪ Extrapyramidal symptoms
▫ Metoclopramide, promethazine, ▫ Tremor, chorea, akinesia
droperidol ▪ Less common
▪ Withdrawal of L-Dopa/dopamine agonist ▫ Dystonic movements (e.g. opisthotonos,
therapy (Parkinson disease) trismus, blepharospasm), mutism,
dysarthria, dysphagia
RISK FACTORS Hyperthermia
▪ Increase in dose/change of neuroleptic ▪ Temperatures > 38–40°C/100.4–104°F
medication
▪ Abrupt cessation/reduction of dopaminergic
medication

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Autonomic dysfunction
▪ Tachycardia, labile/elevated blood pressure,
TREATMENT
tachypnea, sialorrhea, profuse diaphoresis
(sweating), flushing, incontinence
MEDICATIONS
▪ Discontinue offending neuroleptic agent
▪ Dantrolene (skeletal muscle relaxant),
DIAGNOSIS bromocriptine (dopamine agonist); both
(if severe) to reduce muscle rigidity,
LAB RESULTS hyperthermia
▪ Severe ↑ creatine kinase (CK)
▫ Correlates with rigidity severity → OTHER INTERVENTIONS
1–100k international units/L ▪ Maintain cardiorespiratory stability
▪ Mild ↑ lactate dehydrogenase, alkaline ▫ Intubation, mechanical ventilation
phosphatase, liver transaminases ▪ Temperature reduction
▪ Electrolyte imbalances ▫ Cooling blankets, ice water
▫ ↓ Ca2+, ↓ Mg2+, ↓ Na+/↑ Na+, ↑ K+, gastric lavage, ice packs in axilla;
metabolic acidosis acetaminophen/aspirin
▪ ↑ white blood cell count (leukocytosis) ▪ Correct fluid, electrolyte imbalance
10–40k ▫ ↓ CK damage/accumulation; replete
▪ Myoglobinuria insensible losses from diaphoresis
▪ ↓ serum iron concentration ▫ Benzodiazepines: ↓ uncontrollable
agitations
OTHER DIAGNOSTICS ▪ Electroconvulsive therapy
▪ Clinical presentation ▫ If not responsive to medical therapy in
▫ Altered mental status → hyperthermia, first week; if severe/lethal catatonia
rigidity → autonomic dysfunction

[Link] 643
 PARKINSON'S DISEASE
[Link]/parkinsons-disease
COMPLICATIONS
PATHOLOGY & CAUSES
▪ Freezing phenomenon
▪ Degeneration of dopaminergic neurons in ▫ Progressive hypokinesia, bradykinesia
substantia nigra → tremor, rigidity, akinesia, → (akinetic) pauses in movement;
postural instability common when walking; tend to occur at
thresholds (e.g. door frames)
▪ Most common neurological disorder; onset
after age 50 ▪ Falls
▪ Degeneration of neurons in substantia nigra ▫ Secondary to postural instability, poor
→ dopamine depletion from basal ganglia movement amplitude
→ disruption of connection to thalamus, ▪ Dystonia
motor cortex → Parkinsonism ▫ Abnormal tone across joints →
▪ Exact mechanism unknown; build-up disfiguring, painful posturing; universal
of abnormal proteins into Lewy bodies flexion of joints → severely kyphotic
in neurons; accompanied by death of posturing → poor ability to ambulate,
astrocytes, significant increase in microglia ventilate
of substantia nigra ▪ Dementia
▪ Protein (e.g. alpha-synuclein) accumulation ▫ Common after prolonged, primarily
in neuron → abnormal intracellular transit motor disease (in contrast to Lewy body
→ neuronal damage, death → motor dementia); psychosis, hallucinations
symptoms (severe)
▫ Asymptomatic neuronal degeneration:
brainstem (locus coeruleus)
▫ Symptomatic neuronal degeneration: SIGNS & SYMPTOMS
basal ganglia; dopaminergic substantia
nigra pars compacta neurons diseased, ▪ Psychiatric
die → dennervate striatum → ▫ Depression, anxiety, mood disturbances;
dysfunctional basal ganglia → hypo/ impairment of cognitive function,
bradykinetic motor output dementia (advanced stages)
▫ Late degeneration: cerebral cortex; ▪ Sleep disturbances
leads to cognitive impairment ▫ Wild dreams
▪ Autonomic dysfunction
CAUSES ▫ Orthostatic hypotension, constipation,
▪ Usually idiopathic increased sweating
▪ Mutation of PINK1, parkin, alpha synuclein ▪ ↓ olfactory sense
genes ▫ Common first symptom; history of ↓ /
▪ Toxicity in recreational drug MPPP changed sense of taste, smell prior to
(synthetic opioid); rare motor symptoms
▪ Micrographia
RISK FACTORS
▪ Family history, previous head injuries,
pesticides exposure
▪ Protective factors
▫ Caffeine, nicotine

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MNEMONIC: TRAPS MNEMONIC: SALAD

Parkinson’s disease Common Parkinsonism
symptoms treatments
Tremor (resting tremor) Selegiline
Rigidity Anticholinergics:
Akinesia trihexyphenidyl, benzhexol,
Postural changes (stooped) orphenadrine
Stare (serpentine stare) L-Dopa + peripheral
decarboxylase inhibitor:
carbidopa, benserazide
Amantadine
Dopamine postsynaptic
receptor agonists:
bromocriptine, lisuride,
pergolide

Dopamine replacement
▪ Precursor to dopamine → ↑ dopamine
synthesis → ↑ synaptic dopamine → ↓
motor symptoms
▪ Commonly formulated with carbidopa
(peripheral decarboxylase inhibitor)
▫ Carbidopa-mediated inhibition of liver,
DIAGNOSIS systemic carboxylation → levodopa
cross blood brain barrier (BBB) → ↑
dopamine formation
OTHER DIAGNOSTICS
▪ Adverse effects
▪ Clinical presentation
▫ On/off phenomena: return of symptoms
▫ Resting tremor, rigidity, bradykinesia
prior to next dose; due to half life of
▫ Dopaminergic medication response levodopa (approx. 90 minutes)
▪ Postmortem autopsy ▫ Dyskinesia, dystonia: abnormal,
▫ Loss of pigmented dopaminergic repetitive movement (dyskinesia),
neurons of substantia nigra pars abnormal sustained muscle contraction
compacta (dystonia); head, neck (e.g. tardive
▫ Lewy bodies (intracytoplasmic dyskinesia of tongue, cervical torticollis);
eosinophilic inclusions), neurites ↑ incidence with ↑ dosing, duration of
disease
▫ Neuroleptic malignant syndrome: when
TREATMENT discontinued abruptly/high, multiple
doses missed
MEDICATIONS
▪ Symptomatic treatment; see mnemonic Dopamine agonists
▪ ↑ dopaminergic stimulation of postsynaptic
receptors → ↓ motor symptoms
▪ Adverse effects
▫ Dyskinesia
▫ Impulse control disorder: ↑ risk-taking
behavior (e.g. pathologic gambling;
compulsive sexual behavior, shopping)

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 Monoamine oxidase B (MAO-B) inhibitors SURGERY
▪ ↓ MAO-B-related dopamine metabolism → ▪ Deep brain stimulation (DBS)
↑ synaptic dopamine → ↓ motor symptoms ▫ Direct neural stimulation of basal
▪ Most effective for mild-moderate symptoms ganglia (either subthalamic nucleus
of globus pallidus interna) → ↑ motor
Anticholinergic output of basal ganglia → ↓ motor
▪ Improves neurochemical imbalance in basal symptoms
ganglia ▫ Severe/medication nonresponsive
▪ Most useful in young (< 70) individuals with disease
tremor as primary symptom; less useful for
rigidity, bradykinesia
OTHER INTERVENTIONS
▪ Anticholinergic side effects common
▪ Education, support
Amantadine ▫ Physical, emotional aspect of
▪ Antiviral drug degenerative, debilitating disease
▫ Known NMDA receptor agonist; ↓ ▪ Physical therapy
neurotransmitter imbalance i ▫ Exercise → ↓ incidence of falls
▪ Most useful in mild disease

Catechol-O-methyltransferase (COMT)
inhibitors
▪ ↓ dopamine, levodopa metabolism → ↑
synaptic dopamine → ↓ motor symptoms
▪ Rarely used as monotherapy

RESTLESS LEG SYNDROME

[Link]/restless-legs-syndrome
TYPES
PATHOLOGY & CAUSES
Primary RLS
▪ Uncontrollable urge to move legs, relieved ▪ Idiopathic; runs in families; onset < 45 years
by movement old; progressive, worsens over time
▪ Affects legs, feet bilaterally; less commonly
affects arms Secondary RLS
▪ Associated with underlying medical
conditions, medications; onset > 45 years
CAUSES
▪ Unknown
▪ CNS
RISK FACTORS
▪ Pregnancy, iron deficiency/anemia,
▫ ↓ iron, dopamine
smoking, caffeine, Parkinson’s disease,
▪ Peripheral nervous system family history, renal failure, obesity
▫ Abnormal A fibers, peripheral nerve ▪ Peripheral neuropathy (due to diabetes,
microvasculature alcoholism, rheumatoid arthritis, etc.)

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▪ Medications
▫ Antidepressants, antiemetics,
TREATMENT
antipsychotics, antihistamines, calcium
channel blockers
MEDICATIONS
▪ If other interventions not effective
▪ More common in individuals who are
biologically female ▪ Dopamine agonists (e.g. pramipexole,
ropinirole)
▪ Alpha-2-delta calcium channel ligands (e.g.
COMPLICATIONS pregabalin, gabapentin)
▪ Insomnia → daytime drowsiness ▪ Benzodiazepine
▫ Individuals with intermittent symptoms
SIGNS & SYMPTOMS ▪ Iron replacement
▫ ↓ symptom severity when low (< 75ng/
▪ Strong urge to move legs while resting; ml) serum iron levels repleted
unpleasant sensations (e.g. tingling,
burning, crawling, itching, aching) OTHER INTERVENTIONS
▪ Relief by movement; worsening of ▪ Lifestyle changes
symptoms in evening/night → insomnia
▫ Avoid aggravating factors/situations, ↓
▪ Nighttime leg twitching while asleep caffeine intake
Aggravating factors ▪ Mental alert activities
▪ Antihistamines ▫ Distract individual in times of symptoms
▫ Commonly used for sleep assistance
▪ Dopamine antagonists
▪ Psychiatric medications
▫ Selective serotonin reuptake inhibitors
(SSRIs), serotonin norepinephrine
reuptake inhibitors (SNRIs), tricyclic
antidepressants (TCAs)

DIAGNOSIS
OTHER DIAGNOSTICS
Clinical Presentation
▪ Urge to move limbs with/without
unpleasant sensations
▪ Improvement with activity
▪ Worsening at rest/in evening

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