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 Disease-4 Cardinal Signs

Tremor

Rigidity

Bradykinesia (slowness of movement)

Postural impairment (comes later in ds)

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 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 “Mask-like” face Widened palpebral

fissures Decreased blinking Seborrhea scalp or

face Dementia 6x nl

population- AD in 40%

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 post-

menopausal 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 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; PD-

micrographia)

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 Drug induced

parkinsonism Progressive

supranuclear palsy Alzheimer’s disease Normal pressure

hydrocephaly Wilson’s Depression

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 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

Anticholinergics 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

MAO-B inhibitor 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

Athetosis- proximal limb writhing

Hemiballismus- violent, proximal limb flinging

Chorea 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

Cognitive disorder 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 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 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 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 Neuralgiaa.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

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 Multiple Sclerosis TMJ dysfunction Dental disturbance Giant cell arteritis Sinusitis Glaucoma Acute otitis

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