Transcript Movement Disorders

Movement
Disorders
Tory Davis PA-C
UNE PA Program
Tremor Classification
Rest vs Action
 Body part(s) affected
 Frequency- how fast, measured in
hertz (cycles/second)
 Amplitude- fine or coarse

Resting Tremor
Body part affected is supported
against gravity, no muscle contraction
(hands in lap)
 Amplitude

–  with mental stress
–  with general mvmt (walking)
–  with target directed mvmt (finger to
nose)
Action Tremor

Produced by voluntary muscle
contraction
– 1. Postural- body part maintaining
position against gravity
– 2. Isometric- muscle contraction against
stationary object (finger squeeze)
– 3. Kinetic-with voluntary mvmt
Kinetic subtypes
Simple kinetic tremor- assoc with
mvmt of extremities (pronate/supinate)
 Intention tremor- present during
visually-guided, target-directed motion.
 amplitude fluctuation on
approaching target (finger to nose)

Physiologic tremor
Every “normal” person has a
 High frequency, low amplitude postural
tremor
 Enhanced by hyper-adrenergic states:
hypoglycemia, thyrotoxicosis, drugs
(caffeine), withdrawal, public speaking

Benign Essential
Tremor
aka benign familial tremor
 Most common movement disorder
worldwide
 Prevalence reported up to 5% of
people over 60- BUT, half of people
with mild essential tremor aren’t aware
 FHx reports vary (20-60%)

Essential tremor
Insidious development, slow
progression
 95% start w/ postural distal arm tremor

– Wrist flex/ext , 4-12 Hz frequency
Bimodal onset: teens and 50s
 Unilateral progresses to bilateral
 UE, head (yes or no), palate (rare)

– Legs usually spared
Essential tremor

Amplitude
–  with stress, fatigue, CNS stimulants,
voluntary activity
–  with EtOH, ß-blockade, rest
Pt Ed
Avoid stimulants
 Avoid fatigue
 Avoid stress


…and don’t self-medicate with alcohol
Tx: Primidone
Primidone 50-750 mg/day.
Anticonvulsant. Start at 25mg qhs and
slowly titrate up to avoid sedation.
 Contraindicated in asthma
 SEs: sedation, dizziness, nausea,
mood changes

Tx: Beta blocker
ß- Blockade: Propranolol 40-320
mg/day. Better tolerated, no more
effective than primidone
 Contraindicated in asthma,
bradycardia, cardiac conduction
defects
 SEs: sexual side effects, fatigue,
depression

Parkinson’s
Disease
What it is

Neurodegenerative disorder resulting
from  dopaminergic transmission in
basal ganglia
Parkinson’s Disease4 Cardinal Signs

Tremor

Rigidity

Bradykinesia (slowness of
movement)

Postural impairment (comes later in
PD Tremor
Present in 85%
 4-6 Hz resting tremor
 Distal, unilateral “pill-rolling”
  by voluntary activity,  by stress
 One limb or one side of body for
months to years
 Spares head

PD Rigidity
Increased resistance to passive
movements
 “Cogwheel rigidity”
 No weakness
 No change in DTRs

Bradykinesia
Slowness of movements
 Noticed in speech as well as voluntary
movements
 Start hesitation

Postural impairment

Difficulty with balance and gait

Occurs later in disease course.
– If you see this early, question dx and refer
to neuro
Gait
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Classic “festinating gait”
Flexed trunk. Legs and hips stiff and flexed.
Arms still (not swinging)
Short fast steps- trying to keep up with the
forward center of gravity
Turn “en bloc”
Later in disease, freezing w/ direction
change or when entering small space
(doorway)
Other features
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“Mask-like” face
Widened palpebral
fissures
Decreased blinking
Seborrhea scalp or
face
Dementia 6x nl
population- AD in
40%
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 rapid alt mvmts
“Freezing”/akinesia
Sialorrhea
Depression
Micrographia
Hypophonia
Dystonia
Epidemiology
>1 million in US, 50k new cases yearly
 Estimates of 400% increase in coming
decades
 Peak onset 60 (35-85)
 Course 10-25 years
 Male > female
 Some genetic predisposition

Risk factors
+ FHx (5-10%)
 Male gender
 Pesticide exposure
 Head trauma
 Rural living
 Well water

Reduced Risk
Coffee drinking
 Smoking
 NSAID use
 Estrogen replacement in postmenopausal women

Parkinson’s Dz
Pathophysiology

Loss of melanin-containing,
dopaminergic neurons in substantia
nigra

Lewy bodies- protein lint balls.
Pathological hallmark of PD when in
basal ganglia, but also seen in other
disease states
Diagnosis
Difficult! Clinical!
 No lab test
 No biomarker
 And by the time symptoms appear,
dopamine depleted by 70%

Clinical Dx
Progressive, slow unfolding of
characteristic PD s/s during the first
few years after onset of sx
 Can confirm dx postmortem

– Not helpful

Suspect and refer
Make the case
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Presenting sx: C/o difficulty with dressing,
cutting food, writing, getting in/out of car,
feeling stiff. Spouse notes slowness, blank
face
1st visit- usually after 1-2 years of minor
changes
Check the hx: gradual worsening, fhx of
neuro disorder, drug use, hx encephalitis,
toxic exposure
Office exam I

Tremor- resting, not action. Test it.
– How?
Rigidity- Check passive ROM. Feel
for mechanical, ratchet-like sensation
 Bradykinesia- watch her get out of
chair, write*.

– *(BET- large, shaky scrawl; PDmicrographia)
Office Exam II
Impaired postural reflexes- gait
testing- walk away, pivot and return.
PD will take extra turning steps.
 Pull test. Stand behind and (with
warning) pull back on pt. Nl- stops
potential fall in 1-2 steps. Be braced to
help.

NOT PD?
No response to levodopa
 Symmetrical, bilateral at onset
 Rapid progression, including early falls
 Dysautonomia: incontinence,
orthostatic hypotension, urinary
retention
 Early cognitive defects
 Abnormal eye movements

Differential Dx
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Drug induced
parkinsonism
Progressive
supranuclear palsy
Alzheimer’s disease
Normal pressure
hydrocephaly
Wilson’s
Depression
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Multiple system
atrophy
Dementia with
diffuse Lewy body
disease
Multi-infarct
parkinsonism
Huntington’s
Essential tremor
PD Treatment
No proven clinically neuroprotective
drug. But that’s the goal…
 Start tx when functional disability
starts. Varies based on multiple
factors.
 Goals: maintain function and QOL,
avoid drug-induced complications
 (Do no harm.)

PD Tx- Dopamine
Levodopa- Gold Standard.
Converted to dopamine in brain.
(Dopamine itself can’t cross
blood/brain barrier.)
 Improves all features of PD, but wears
off over time

– Think “Awakenings”
Dopamine

First line for years, but now primarily
second line due to
– Side effects (see next slide)
– Wearing off
– Hypothetical (?) concern that free radicals
generated by the oxidative metabolism of
dopamine contribute further to the
degeneration of dopaminergic neurons
Dopamine Side Effects
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Nausea
Wearing off-when effects of single dose
don’t last as long
Dyskinesias- sudden, uncontrollable, jerky
movements of arms, legs, head, trunk
On/off response- due to fluctuating levels of
dopa
– On-  uncontrolled movements
– Off-  motion, freezing
Add-on meds
 Dopamine
plus….
Carbidopa- (decarboxylase inhibitor)
 Entacapone (COMT inhibitor, inhibits
break down of catecholamines)
 Purpose: decreased levodopa
breakdown/conversion in bloodstream,
maximizes delivery to brain, minimizes
nausea

Dopamine agonists
Maybe some neuroprotection
 Behave like dopamine by stimulating
dopamine receptor directly
 Can be used as initial monotherapy
(first line) to preserve use of dopamine
for later in disease course
 Add-on to dopamine when levodopa
alone no longer effective (or SEs
intolerable)
 Side effect of sudden-onset sleepiness

Dopamine agonists
Bromocriptine (Parlodel)
 Pergolide (Permax)
 Pramipexole (Mirapex)
 Ropinirole (Requip)
 Apomorphine- (Apokyn) injectable,
rapid-acting, “rescue” med for acute
freezing episodes. SE: severe n/v
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Anticholinergics
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Primarily to alleviate tremor. (Balances
acetylcholine and dopamine.)
Trihexylphenidyl (Artane), benztropine
(Cogentin)
SE- dry mouth, nausea, constipation,
palpitations, arrhythmias, urine retention
Contraindications- BPH, narrow angle
glaucoma, obstructive GI disease
Poorly tolerated by elderly
Amantidine
Antiviral flu drug, also anti-dyskinetic
for mild symptoms
 ? MOA
 SEs: restlessness, confusion, rash,
edema, nausea, cardiac arrhythmias
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MAO-B inhibitor
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Monoamine Oxidase type B Inhibitor
Selegiline, rasagiline (also used in
Alzheimer’s)
 dopa breakdown, may  dopamine
reuptake
Modest effect for mild sx, reduces “off” time
May be neuroprotective
SE- confusion, nausea, headache,
insomnia
Antioxidants
Depleted in PD patients. May be
neuroprotective.
 Glutathione
 Coenzyme Q
 Ongoing studies for these relatively
new treatments

DBS

Deep Brain Stimulation
– Surgically implanted neurostimulator in
subthalamic nucleus
– Blocks abnormal signals that cause PD
sx
– Only for pts whose sx are uncontrolled by
medications
Future/Research

Research into causation
– Toxic
– Environmental
– Genetic

Research into treatment
– Neuroprotection
– Meds to delay, prevent, or reverse effects
of disease
Huntington’s
Disease
Definition
Autosomal dominant
neurodegenerative disorder.
 Triad of motor, cognitive and
psychiatric symptoms
 Insidious onset, no cure
 Age of onset of sx 30-50, usually after
people have reproduced
 Fatal in 15-20 years

Movement disorder
Presence of involuntary movements
 Impairment of voluntary movements
 Catch 22: Tx of involuntary can
worsen impairment of voluntary, and
impairment of voluntary movements
is correlated with functional
disability

Involuntary movements

Chorea- “the dance” Primary invol
mvmt in HD
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Athetosis- proximal limb writhing

Hemiballismus- violent, proximal limb
flinging
Chorea
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Involuntary, irregular, rapid, uncontrolled,
excessive movement
Stark contrast to paucity of movement in
Parkinson’s
Seem to move randomly from one body part
to another
Appears to be almost playful, fidgety
Often not noticed by (nor disturbing to) the
pt
Impaired movement
Abnl eye movements
 Slow or uncoordinated fine motor
control
 Dysarthria
 Dysphagia
 Gait disturbance
 Bradykinesia and rigidity late in course
as chorea peaks and wanes

Psych disorder

Under recognized and under treated

Depression- no diff tx from “nl” pt
Mania-tx with mood stabilizers
OCD
Irritability
Perseveration- esp on focus of irritation
Apathy- Can, but won’t. Frontal lobe dysfn
Anxiety- rigid thinking develops, and
departure from routine very upsetting
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Cognitive disorder
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Dysfunction of executive functions:
organization, regulation, perception
Problems with planning, judgment, emotion
regulation, attention, learning, cognitive
speed, decision making
What it looks like: can’t follow recipe, plan
and run errands, work. Temper outbursts.
Difficulty with spatial perception.
 Cognitive
symptoms
usually result in
placement outside home
before psychiatric or
movement symptoms do
Etiology
 GABA
  acetylcholine
  dopamine
 Opposite of PD, so instead of too little,
you have too much dopamine.

Autosomal Dominant
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Autosomal (not sex-linked)
Dominant (expresses itself more strongly
than the normal gene it’s paired with)
Each child of a parent with HD has 50%
chance of inheriting gene.
All or nothing.
– If you do not inherit the abnormal gene, no
chance of passing it on
– A person who inherits the gene defect will
eventually develop the disease
Genetics
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Huntington gene on 4th autosomal
chromosome (IT-15) has excess repeats of
glutamine “CAG” sequence
Normal gene has 10-35 repeats
27-35 repeats may result in nl individual
who transmits increased risk of HD to
offspring
36-39 repeats- abnl but may not have
symptoms in nl lifespan
40+ repeats will have HD
70+ repeats will have juvenile HD
No FHx?
2-5% occur with no known FHx
 Possible causes: early parental death,
adoption, mistaken paternity, or rare
“new mutation” caused by expansion
of high-normal repeats to cause
offspring to be in affected range

Treatment of HD

Directed at symptoms

No cure

No slowing of disease progression
Treatment- Chorea
This isn’t family practice stuff! REFER
 Neuroleptics: haloperidol,
risperdone, fluphenazine

– SEs: sedation, parkinsonism, dystonia,
tardive dyskinesia, dry mouth, weight
gain, akathesia (uncomfortable internal
sense of restlessness, causes pacing,
etc.) **If misinterpret as agitation/anxiety,
you may mistakenly  medication, and
get stuck in a …..
HD Tx

Benzodiazepines clonazepam,
diazepam
– SEs: sedation, ataxia, apathy, withdrawal
seizures

Dopamine depleting agents
reserpine, tetrabenzine
– SEs: hypotension, sedation, depression,
parkinsonism
Your Role
You are a member of an
interprofessional team
 Who else is on your team?

Your Role
Be aware of meds used, possible side
effects…vicious cycles and all
 Treat comorbid conditions, such as
depression, insomnia, in consultation
with neurologist and others

Genetic Counseling
Half of the offspring will be affected
 Refer to specialized center


Testing options:
– Diagnostic
– Predictive
– Prenatal
Future/Research



Into how defective gene affects brain
structures and body chemistry and
metabolism
Into symptoms and progression of disease
Fetal tissue implanted into rodents/primate
brains to try to understand/restore/replace
lost function
Tourette’s
a.k.a.
Gilles de la Tourette Syndrome
What it is
Inherited neurobehavioral disorder
characterized by sudden involuntary,
repetitive muscle movements and
vocalizations
Diagnostic Criteria
Multiple motor and one or more vocal
tics at some time during the disorder
that are NOT explained by another
medical condition and are directly
observed or recorded (ie: video)
 Tic episodes several times a day,
almost every day, or periodically
during period > 1 year

Dx Criteria Continued
Change in type, severity, complexity,
frequency, and anatomical location
during the course of the disorder
 Symptoms before age 18

Epidemiology
Symptom onset age 2-15
 50% have symptoms by age 7
 Four times more common in boys
 Prevalence 0.1-1.0% of population

Motor tics
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Initially simple, located in head and face
Blinking, face twitch, head jerk, shrug, neck
stretch, sniffing
Over time, change in anatomical location,
and get more complex: squatting, jumping,
repetitive touching, deep knee bends,
smelling things, spinning, more complex
hand gestures
Echopraxia- repeating another person’s
actions
Vocal tics
Sudden, involuntary, recurrent, and
often loud
 Onset: Simple tics- grunt, throat
clearing, sigh, bark, hiss, snort, sniff
 More advanced: Repeating word(s) or
phrase(s) out of context

Vocal tics
Palilalia- repeating one’s own words
 Echolalia- repeating heard words- last
words spoken by someone else
 Coprolalia (rarer, but common in
mainstream depictions) -Involuntary,
explosive cursing or compulsive
utterance of obscene word/phrase

More about tics
Often assoc with premonitory “urge to
tic”
  during absorbing activities
  during times of stress and fatigue
 Can be voluntarily suppressed for only
brief periods

Course/Prognosis
Waxing and waning course
 Usually combination of motor and
verbal tics
 Few to many times a day, often in
clusters
 Generally considered lifelong, but
symptoms can  or resolve in
adolescence or adulthood

Associated conditions
Obsessive/compulsive behaviors in
25% (touching, counting, washing)
 Attention deficit in 50-80%
 Rage/poor impulse control 30%
 Anxiety 25%

Pathophys
Genetic predisposition
 Unknown basic underlying defect
 ?Excessive dopamine in basal ganglia
 ?Serotonin abnormality
 ?Other neurotransmitter involvement

Treatment- Purpose
To decrease tics if they present a
problem
 To decrease associated behavioral
problems
 To increase academic, occupational,
social performance

Meds
Dopamine antagonists/antipsychotics
(haloperidol, fluphenazine, risperdone)
 Antianxiety medications
(benzodiazepines, buspirone)
 Antidepressants (SSRIs)

Other Tx
Considerations
Botox injections in small muscle
groups involved in tics- can alleviate
tics and also the premonition of tic
 HRT (habit reversal training)
 Biofeedback and relaxation training
 Vocational, academic, social services

Trigeminal Neuralgia
a.k.a.
“Tic Douloureaux”
NB: This is part movement
disorder, part peripheral
neuropathy.
Classify it how you will, it’s still
neuro.
Qu’est ce que c’est?
Intermittent, progressive chronic
disorder involving aberrant firing of
trigeminal nerve- usually 2nd and 3rd
branches
 Unilateral lancing paroxysmal facial
pain

Epidemiology
Incidence 5 per 100,000
 Prevalence 100-200 per 100,000
 3:2
(female:male)
 Age > 50….younger pts should
make you think MS, other cause

Tell me how you feel…
Stabbing, shocking, “live wire”
 Pain can be quite severe- can be
disabling.
 Pain causes muscle spasm (thus a tic)
 Episodes last a day to several weeks
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Triggers

Light touch and vibration
– Breeze, kiss, shaving, chewing, washing,
talking
– but NOT firm pressure

During an exacerbation, pt will hold
face VERY still to avoid triggering
Por Que?
Increase afferent firing of CN V may be
caused by peripheral injury or disease
of nerve.
 Nerve root irritation by meningeal
inflammation, compression by aberrant
vasculature (ie: cerebellar artery)
 Possible failure of central inhibitory
mechanisms

Physical Exam

NORMAL..
– Except for eliciting pain with soft
touch

Do full CN testing, incl corneal reflex

If abnl findings, suspect pain syndrome
due to another process…
Differential
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Multiple Sclerosis
TMJ dysfunction
Dental disturbance
Giant cell arteritis
Sinusitis
Glaucoma
Acute otitis
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Mass effect (tumor)
Angina (jaw pain)
Atypical face pain
Glossopharyngeal
neuralgia
Herpes Zoster
Postherpetic
neuralgia
Work-up

Classic hx + nl PE = TN
But…not unreasonable to offer elective
MRI to r/o uncommon mass lesion or
correctable aberrant vessel
 If atypical features on hx or PE,
proceed to MRI

Treatment- Drugs

Anticonvulsants-  hyperactivity of
trigeminal nerve nucleus
– Carbamazepine (Tegretol)
– Phenytoin (Dilantin)
– Oxcarbazepine (Trileptal)
– Gabapentin (Neurontin)
Carbamazepine
Usual effective dose 600-1600
mg/day, divided TID or QID
 Effectiveness  over time- incr dose
during exac, decr during remission
 SE: dizzy, sleepy, nausea, confusion,
leukopenia, liver damage
 Monitor WBC, LFT serially

Oxcarbazepine
Start 300 mg BID, incr to max of 2400
mg/day
 Just Carbamazepine with an oxygen
tacked on, solves that pesky
leukopenia problem

Phenytoin

Dose 300-500 mg/day, div TID

SE: Gum hypertrophy, dizzy, drowsy
Gabapentin
Start 300 mg TID, titrate up
  SEs compared to carbamazepine
 No interaction with phenytoin or
carbamazepine, so good for
combination tx

Surgical treatment
For pts who fail or cannot tolerate
medications
 Subcutaneous alcohol- temporary only
 Percutaneous glycerol- thru foramen
ovale, inject glycerol into trigeminal
cistern to cause nerve damage
 Balloon compression of CN V

More surgery
Percutaneous radiofrequency thermal
rhizotomy
 Microvascular decompression- put
Teflon pad between nerve and
offending structures
 Gamma knife radiosurgery
