MOVEMENT DISORDERS

Dayna Ryan, PT, DPTWinter 2012

Summary• Typically involve dysfunction to the basal ganglia and

cerebellum

• Both influences movement via the thalamus to motor areas of the cerebral cortex

• UMNL or LMNL?• It’s a Upper Lesion (chapter 10 Lundy-E)

Basal Ganglia

The Role of the BG in Movement

BG

Motor Thalamus

Motor Cortex

Corticospinal tracts

LMNs

Voluntary muscles

Pedunculopontine nucleus

Reticulospinal & vestibulospinal tracts

LMNs

Postural and girdle muscles

Basal Ganglia Circuitry

• DIRECT PATHWAY• Striatum -> internal globus pallidus & substantia nigra parts retiulata • These then project to the thalamus VA / VL• Movement results when thalamic cells are released from tonic inhibition• INCREASES excitatory thalamic drive to SMA• TURNS UP motor activity

Normal Basal Ganglia Circuitry• DIRECT PATHWAY

• Straitum -> internal globus pallidus and substantia nigra parts retiulata

• These then project to the thalamus (inhibitory signal)

• Movement results when thalamic cells released from tonic inhibition

• INCREASES excitatory thalamic drive to SMA

• TURNS UP motor activity

Normal Basal Ganglia Circuitry

• INDIRECT PATHWAY• Striatum -> external

globus pallidus -> subthalamic nucleus

• DECREASES excitatory thalamic drive to SMA

• TURNS DOWN motor activity

• Direct pathway TURNS UP motor activity

• Indirect pathway TURNS DOWN motor activity

• Direct and indirect pathways counterbalance each other to maintain normal movement function.

• Basal Ganglia controls the motor commands

Dopaminergic Modulation

• Excitatory effect on D1 receptors in direct pathway

• Inhibitory effect on D2 receptors in indirect pathway

• TURNS UP motor activity

Cholinergic (ACh) Modulation

• Cholinergic (ACh) interneuron: Inhibits the direct pathway and Excites the indirect pathway

• TURNS DOWN motor activity

Parkinson’s Disease• Parkinsonism: a group of rare diseases or syndromes, with signs and symptoms similar to Parkinson’s disease (PD)

• PD: the most common form of parkinsonism; a.k.a. primary parkinsonism or idiopathic PD

• At least 500,000 people currently have Parkinson's disease, ~ 50,000 new cases annually

• Average age of onset = 60 years; Incidence increases incrementally after age 50

• ~ 5-10 % diagnosed before age 50 ("early-onset“)

Parkinson’s Disease: Pathology

• Severe loss of substantia nigra (SN) dopaminergic neurons• Most PD patients have lost 60-80% or more of the dopamine-

producing cells in the substantia nigra by the time symptoms appear

Parkinson’s Disease: Histology• Histology hallmark in PD is

Lewy bodies (abnormal aggregates, clumps composed principally of the protein alpha-synuclein)

• Lewy bodies form primarily in the substantia nigra and brainstem, but can also be elsewhere in the brain

• Researchers do not yet know why Lewy bodies form or what role they play in development of the disease. They may interfere with transmission of nerve signals.

Abnormal Basal Ganglia Circuitry in PD

• Since dopamine cells are lost in PD…• Direct pathway activity ↓ = LESS MOTOR ACTIVITY• Indirect pathway activity ↑ = LESS MOTOR ACTIVITY

Causes of PD• Genetic• Environmental

• Toxins, e.g. MPTP (in heroin), DDT (in pesticides)• Viruses, e.g. 1918 influenza, herpes virus infection

• Interaction of Genetic & Environmental Factors• Even in familial cases, exposure to toxins or other

environmental factors may influence when symptoms of the disease appear or how the disease progresses

• Mitochondrial Dysfunction• Oxidative Stress • Cerebral Inflammation

Parkinson’s Disease Symptoms• Cardinal Symptoms:

• Resting Tremor• “pill rolling”, back-and- forth motion• Rate: 4-6 Hz

• Bradykinesia• Slowing down; less consistent and slow force production• Loss of spontaneous and automatic movements

• Rigidity• Cogwheel• Lead-pipe (when rigidity becomes severe)

• Postural Instability• More likely to use hip instead of ankle strategies, due to

inappropriate scaling of sensory feedback• Hypometric anticipatory postural adjustments

Parkinson’s Disease: Bradykinesia• Slower and less consistent force production

Stelmach, GE 1989

Parkinson’s Disease Symptoms• Other symptoms:

• Difficulty with swallowing and chewing• Speech impairments: Speak too softly, monotone,

hesitant, slurred, repeating words• “Masked” face/Expression-less• Depressed, irritable, other emotional changes • Fatigued-more muscle activity• Sleep problems-when resting they shake• Urinary problems or constipation • Skin problems: very oily, very dry, excessive sweating• Decreased strength in muscles of respiration• Dementia or other cognitive problems• Orthostatic hypotension

Parkinson’s Disease: Postural Changes

• Kyphotic posture with forward-flexed trunk

• Forward head• Crouched legs• Mask-like face

(expression-less)

Parkinson’s Disease: Gait• Difficulty INITIATING gait• Freezing gait

• Patient will report that it feels like their feet are stuck on the ground/heavy and they cannot move

• Festinating gait• Steps too small• Causes COM to get in front of BOS (upper body going faster than

lower body)• Can’t always catch themselves so typically fall forward

• Decreased foot clearance

• Decreased or no trunk rotation• No arm swing

Parkinsons’ Disease: Abnormal Postural Control Strategies

• Abnormal combination of ankle and hip strategies concurrently exhibited

Parkinson’s Disease: Micrographia

• Handwriting is slow and looks cramped or small.

Parkinson’s Disease Progression

• PD is not by itself a fatal disease but it does get worse with time

• PD generally does not affect life expectancy• In the later stages of the disease, PD-related complications can lead to death, such as choking, pneumonia, and falls

• Progression of symptoms may take 20 years or more (In some, PD progresses more quickly)

Parkinson’s Disease Progression: Hoehn & Yahr Staging • Stage One

• Unilateral, one side of the body• Symptoms mild, inconvenient

but not disabling • Usually presents with tremor of

one limb• Friends noticing change in

posture, gait, facial expression

• Stage Two• Bilateral, both sides of the

body• Minimal disability • Posture and gait affected

• Stage Three• Significant slowing of

movement• Early impairment of equilibrium

on gait or standing• Generalized dysfunction that is

moderately severe

• Stage Four• Severe symptoms• Can still walk to a limited

extent• Rigidity and bradykinesia• No longer able to live alone• Tremor may be less than

earlier stages• Stage five

• Cachectic stage • Invalidism complete • Cannot stand or walk • Requires constant nursing

care

Parkinsons Disease:UPDRS (United Parkinson Disease Rating Scale) • Updated version in 2008• Sections include:

• Mentation, Behavior, and Mood• ADL• Motor function

• 199 points total• Higher score indicate increasing disability

UPDRS Example Items

Parkinson’s Disease Diagnosis• No blood or laboratory tests• Medical history & neurological exam• Difficult to diagnose accurately

• early signs and symptoms may be dismissed as the effects of normal aging

• Clinical signs and symptoms• must have 2 or more cardinal signs

• Positive response to dopamine agonist medication

• Unified Parkinson's Disease Rating Scale (UPDRS)

• CT or MRI in PD usually appear normal but may be needed to rule out other diseases

Parkinson’s Disease Medications• Levodopa (L-dopa)

—A dopamine precursor that crosses the blood-brain barrier and then converts to dopamine

—Side effects increase with continued usage, including—Nausea, hypertension (due to activation of peripheral dopamine

receptors)—Dyskinesias (involuntary movements, e.g. twitching, twisting)

—“tolerance” develops with continued usage—Period of effectiveness after each does begins to shorten —Larger doses may be needed to be effective

—“On-Off” effects

• Sinemet (a combination of Carbidopa and Levodopa)—Does not cross the blood brain barrier but prevents peripheral

conversion of levodopa to dopamine and thereby reduces the unwanted peripheral side-effects of levodopa

Parkinson’s Disease Medications

•Dopamine agonists—Mimics the effects of dopamine in the brain—Given alone or in conjunction with L-dopa—Can lengthen the duration of response to L-dopa in patients that are

developing “tolerance” and “on-off” effects—Apomorphone, bromocriptin, pramipexole, ropinirole

•Anticholinergics• Decrease the activity of ACh (Striatum has ACh interneurons, which

oppose the effect of D1 and D2 receptors in the striatum)• Reduce tremors and muscle rigidity• Trihexyphenidl, benztropine

Parkinson’s Disease Medications• MAO-B inhibitors

—Inhibit the enzyme monoamine oxidase B (MAO-B), which breaks down dopamine in the brain

—Delay the need for L-dopa by up to a year or more—Azilect (Rasagiline)

• COMT inhibitors —Inhibit the enzyme Catechol-O-Methyltransferase (COMT), which

breaks down dopamine—Decrease the duration of “off” periods; make it possible to reduce L-

dopa dosage—Entacapone, tolcapone

• Other Medications for non-PD symptoms

Parkinson’s Disease: Surgery• Used if medications no longer effective

• Ablation— Selectively destroying specific cells that contribute to the symptoms— Pallidotomy (reduce tremor, rigidity, and bradykinesia)— Thalamotomy (reduce tremor)

• Deep brain stimulation (DBS)—Electrodes implanted in thalamus, subthalamic nucleus, and

globus pallidus—Electrodes connected to a pulse generator

—The pulse generator and electrodes painless stimulate the brain

—Blocks electrical signals from targeted areas—Reduces the need for medications

• Embryonic stem cell transplant

Recent Research Findings:Implications for Interventions• Paradoxical Kinesia (“motion”)

• A deficit to execute movements can be overcome in the presence of external sensory cues (e.g. visual, auditory, proprioception)

• Rationale: distinct contribution of the cortico-striatal (implicit) and cortico-cerebellar (explicit) systems to motor learning and control

• Provide external sensory cues to bypass the defected cortico-striatal system

Treatment for Freezing Gait in PD

• Visual cue on floor within one step length will stimulate a step

• Can add hand triggered laser light to a walker

• LaserCane™ projects a bright red line across your path

Videos for PD• Before and after L-dopa

• http://www.youtube.com/watch?v=sf1N0Zf5IqA&feature=related

• Michael J. Fox• http://www.youtube.com/watch?v=ECkPVTZlfP8

• What you will likely see• http://www.youtube.com/watch?v=29zHputMEQA&feature=related• http://www.youtube.com/watch?v=oUDDRUtJcgM&feature=related

Huntington’s Disease (HD)

• Huntington’s chorea• Involuntary choreoform movements• Rapid, involuntary, purposeless jerks of irregular and variable location on the body

• Hereditary (autosomal dominant) • 50% inheritance rate in offspring

• No treatment to stop or reverse the progression• Striatum affected.

Huntington’s Disease (HD)

• Pathology• Primarily involved neuronal deaths in the Striatum (= Caudate & Putamen)

• Enlarged ventricles, degenerative cortex & cerebellum• Abnormal Basal Ganglia Circuitry

• Reduction of neurotransmitter, GABA, ACh, metenkephalin due to loss of neurons in the striatum

• Causes relatively higher concentration of dopamine and norepinepherine excessive excitation of thalamocortical pathways choreoform movements

Huntington’s Disease

• Choreiform movements due to:• Direct pathway activity ↑ = MOTOR ACTIVITY ↑• Indirect pathway activity ↓ = MOTOR ACTIVITY ↑

http://www.youtube.com/watch?v=kINXIjs_V3M&feature=related

http://www.youtube.com/watch?v=OveGZdZ_sVs

Abnormal Basal Ganglia Circuitry in HD

Huntington’s ChoreaPrimary Characteristics

• Choreic Movements • Brief• Purposeless• Involuntary• Random

• Personality and Psychiatric Disturbances • Irritable, apathy, depression• Explosive behaviors

• Dementia• Decreased intellect• Decreased memory, attention

Other Signs and Symptoms

• Dysarthria (speaking)• Dysphagia (swallowing)• Cachexia (muscle wasting)• Sleep disorders• Urinary incontinence• Depression• Apraxia

• May become severe• Ideomotor form

Huntington’s Disease: Motor and Sensory Signs

Motor

• DTRs = normal• Strength = normal early in

disease• Tone

• Normal initially• Later become rigid

• Apraxia - ideomotor• Cannot sustain long

muscle contractions

Sensory• Abnormal eye movement

• Impaired saccade• Impaired smooth pursuit • Impaired gaze fixation

• Visuospatial deficits• E.g. may not be able to see a

figure embedded in a picture

HD Movement Patterns• Undershoot targets• Decreased velocity of movement• Latency in initiation (can develop freezing gait)• Wide-based staggering gait• Dysdiadochokinesia (pronate/supinate) • Macrographia

Writing samples from Jan 21 and Nov 13 of same year

HD Disease Progression• Onset

• Juvenile: before age 20• Adult: after age 50

• Juvenile – more severe course

• Suicide• 6% of deaths• 25% attempt suicide

• As disease progresses• More dystonic contractions• May develop rigidity and

bradykinesia• Less choreoform movement

(because more rigid)

• Death• Typically from intercurrent

infection (usually in lungs)• 15-20 years after onset

Huntington’s Disease:Diagnosis and Treatment

Diagnosis

• DNA testing• MRI to show atrophy of

striatum in later stages

Medical Treatment

• Anticonvulsants• Antipsychotic agents• Surgery to remove globus

pallidus• Deep brain stimulation

Dystonia

• Etiology• Unknown, idiopathic in most cases• Defected DYT1 gene in early onset dystonia• Secondary to some other neurologic disorders

• Pathogenesis • Lesions at Caudate, Putamen and Globus pallidus• Overactive direct pathway within the basal

ganglia circuitry increases motor activity

• Definition = abnormal tonicity of muscle with simultaneous contraction of agonist and antagonist

• Involuntary muscle spasms force affected parts of the body into contorted or twisted postures

• Rapid or slow; Rhythmic or un-patterned• Duration varies: < 1 s, a few sec or min, hours or

longer• May be increased with stress, during purposeful

movements, task-specific (Sx only present during specific tasks, e.g. writing, playing instruments)

• Decrease after relaxation and disappear during sleep• Often painful condition

Characteristics of Dystonic Movements

Dystonia• Focal and generalized forms• Focal

• Pharyngeal• Distorted speech; affect vocal cords

• Cervical dystonia • Most common• Hypertrophy of SCM muscle

• Rotation of neck with lateral flexion and flex/ext of neck; typically painful

• Is NOT torticollis (a musculoskeletal disorder with muscle fibrosis)

• Writer’s cramp (task-specific focal dystonia)• Spasm affecting certain muscles of the hand and/or fingers

• Musician’s cramp (task-specific focal dystonia)• Blepharospasm = uncontrollable blinking

• Can be considered legally blind

Dystonia: Disease Progression• Onset

• Generalized ~ 8 y. o.• Focal 30-50 y. o.

• Progression• Dystonia is not fatal, but is chronic and often painful

and debilitating• Generalized begins in legs and progresses to rest of

body• Focal dystonia progresses for about 5 years then

plateau• Spontaneous recovery in 30% of cases

Dystonia• Medications

• BOTOX• Effective for 3-4

months• For focal dystonia

• Common medications for Generalized Dystonia• Baclofen (treats

spasticity)• Artane• Sinemet (parkinson) • Klonopin

• Surgeries• Deep brain stimulation of the

Globus pallidus• Rhizotomy

• Resection of anterior (motor) cervical spinal nerve roots

• Treatment in research phase• RNA interference (RNAi)

therapy• Suppress the expression of

mutated DYT1 gene to prevent further involvement with cell replication

Videos on Dystonia• Generalized Dystonia

• http://www.youtube.com/watch?v=b1yc6YnvrMs&feature=related

• Focal Dystonia• http://www.youtube.com/watch?v=D8_98t74PnQ&feature=related• http://www.youtube.com/watch?v=UzI_4IOw3_8&feature=related

Friedreich’s Ataxia• Lesion:

• Cerebellum• Dorsal root ganglia• Dorsal columns• Spinocerebellar tracts• Some corticospinal tract

involvement

• Etiology: Hereditary (Autosomal recessive)

• Onset• Between 5 to 15 y. o.

(some later)• 25% of offspring have FA

• Course (highly variable)• Generally lose ability to

walk and confined to WC within 10-20 years after onset

• Prognosis• Some survive into their

60’s & 70’s if no heart attack

Friedreich’s Ataxia:Signs and Symptoms

• Ataxia• Most common Sx• Gait ataxia is usually the first

Sx• Ataxia gradually worsens and

spreads to the arms and the trunk

• Clumsiness and intention tremor• Muscle weakness and wasting• Loss of sensation in extremities• + Babinski (esp. if corticospinal

tract involved)• Decreased DTRs• Tone is normal at rest

• May get flexor spasms

• Nystagmus (20% of cases)• Impaired smooth pursuit• Heart disease

• various forms (e.g. cardiomyopathy, dysrhythmia)

• 60% of population• Easily fatigued• Scoliosis• Dysarthria/tongue and oral

motor issues

Videos of FA• http://www.youtube.com/watch?v=CBlrp-Ok38E

• FYI – very long video• http://www.youtube.com/watch?v=pfxPJVryhRE&feature=related

Dyskinesia

= a movement disorder that consists of decreased voluntary movements and increased involuntary movements

• Tic• Chorea

•Tardive Dyskinesia = involuntary movements of the tongue, lips, face, trunk, and extremities that occur in patients treated with long-term dopaminergic antagonist medications

• http://www.youtube.com/watch?v=UbBpt9uCXqc&feature=related• http://www.youtube.com/watch?v=W_3bbpFjI68• http://www.youtube.com/watch?v=R0EbgpyztCA&feature=fvwrel

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