Parkinson Disease & other Movement Disorders

OU NeurologyOU Neurology

Parkinson Disease & other Movement Disorders

Cherian Abraham Karunapuzha, M.D.Assistant Professor

Movement Disorders DivisionDepartment of Neurology

The University of Oklahoma Health Sciences Center


DISCLOSURES

FINANCIAL DISCLOSUREThe speaker is on the speaker bureau

for Teva neuroscience and UCB.

UNLABELED/UNAPPROVED USES DISCLOSUREThe speaker has nothing to disclose


LEARNING OBJECTIVES

Learn to recognize the phenomenology of various abnormal movements

Learn about common movement disorders associated with such abnormal movements


What is a “movement disorder” ?

Most diseases of BG are not “fixable” but can be alleviated, eg. Parkinson’s, essential tremors, Huntington’s, torticollis, Tourette’s

Light Blue – ventriclesRed – Caudate nucleusGreen – PutamenDark Blue – Globus PallidusBlack – Substantia NigraBrown - Thalamus

Not “weakness” - more like a switchbox with different On and Off switches or programs.

Depending on locus of BG damage, the signs can be bradykinesia, rigidity, tremor, chorea, dystonia, tic, myoclonus…

Conditions arising from a dysfunction of the extrapyramidal system (basal ganglia) – extrapyramidal diseases


Basal Ganglia Circuit

Cortex

StriatumDirectPathway

StriatumIndirectPathway

GPe STN

GPi

Thalamus

Substantia Nigra

D1

D2

GPe – Globus Pallidus externa /lateralGPi – Globus Pallidus interna /medialSTN – Subthalamic NucleusD1, D2 – types of dopamine receptors


Common phenomenonology and associated symptoms

BradykinesiaBradykinesia FreezingFreezing RigidityRigidity Tremor – Tremor – restingresting

Tremor – Tremor – action/posturalaction/postural

Chorea, ballismChorea, ballism StereotypyStereotypy DystoniaDystonia TicTic MyoclonusMyoclonus

Parkinsonism Parkinsonism Parkinson diseaseParkinson disease Multiple System atrophyMultiple System atrophy PSPPSP Drug induced Drug induced

parkinsonismparkinsonism NPHNPH

Essential TremorEssential Tremor Drug induced tremorDrug induced tremor Huntington diseaseHuntington disease Sydenham choreaSydenham chorea Levodopa dyskinesiasLevodopa dyskinesias Tardive dyskinesiasTardive dyskinesias Torticollis, Torticollis,

blepharospasmblepharospasm Tourette syndromeTourette syndrome Metabolic, CJDMetabolic, CJD


Tremor

Oscillatory, rhythmic and regular movement that affects one or more body parts, such as the limbs, neck, tongue, chin, or vocal cords.

Distribution : Arms, head, legs, larynx… Unilateral or asymmetric or symmetric Context : Resting – 3-6 Hz Postural – 5-10 Hz Action (kinetic) – 5-10 Hz Terminal (intention) – 2-4 Hz


Postural/Action Tremor


Essential Tremor

Action or postural tremor of arms, sometimes head and voice, occasionally legs

Family history common Improves with alcohol. Worsens with

Caffeine. Mild tremor may first appear in teens or

young adulthoodGradually worsen over decades


Essential Tremor (Contd.)

Check for hyperthyroidismCheck for drug induced – albuterol, SSRI,

Depakote, antipsychoticsMRI brain for mimics - white matter

lesions brainstem & cerebellumRx: Propranolol 10 mg tid -> 60mg tid or

Primidone 25 mg qhs -> 250 mg tidSurgery: deep brain stimulation (DBS) in

thalamus for refractory tremors


Cerebellar Tremor – associated findings of dysmetria, dysdiadokinesia , ataxia etc.


Psychogenic tremor ?? – improves with distraction - Counseling/clinical psychology


Resting Tremor

present in the distal parts of the extremities and the lips while the involved body part is “at rest” & ceases on active movement of the limb

“Pill-rolling” tremor of the fingersflexion-extension or pronation-

supination tremor of the hands


Brady/hypokinesia – slowness or decreased amplitude of movementa loss of automatic movements slowness in initiating movement on

command reduction in amplitude of the

voluntary movementmasked facies, decreased frequency

of blinking, soft speech, drooling, small handwriting, shuffling gait, decreased armswing


Rigidity - Increased resistance to passive motion ....present equally in all directions of the

passive movement, equally in flexors and extensors & throughout the range of motion – extrapyramidal lesions

Stiffness, heaviness, or aching muscle Cogwheel and Leadpipe rigidity Spasticity – Another hypertonic state –

Damage to the primary motor cortex or the corticospinal tract - velocity dependent, clasp knife phenomenon


Parkinson Disease

A clinical syndrome resulting from degeneration of nigro-striatal dopaminergic neurons

Asymmetric onsetTRAP : Tremor (resting), Rigidity,

Akinesia (bradykinesia), Postural instability

Diagnosis – clinical exam & response to levodopa (L-dopa) supplementation


Parkinson disease (contd.)

MRI brain to look for mimics - enlarged ventricles, subdural hemorrhage, tumor, multiple subcortical strokes



Incidence: 4.5-21 cases/100,000 per year

Cause: combination of genetic and environmental factors

Pathology: Lewy body – abnormal aggregates of protein (alpha synuclein)



slow progression - 10-25 yearsindependence usually not reduced in

first 5-10 yearslater: postural instability, freezing,

levodopa induced dyskinesia, fluctuating response to meds, dysphagia, incontinence, postural hypotension, dementia


Freezing = arrest in initiation or continuation of movement



MAO B inhibitors – Rasagiline, Selegiline – mild symptomatic effect, increase ON time,?disease modifying

Dopamine agonists – Ropinirole, Pramipexole, Rotigotine – moderate symptomatic effect

Dopamine – Carbidopa/Levodopa (Sinemet) 25/100 one tablet TID to 1200mg/day – Robust symptomatic effect

COMT inhibitors – Entacapone – increase ON time NMDA antagonist – Amantadine - dyskinesias DBS (deep brain stimulation) or Surgical ablation PT/OT , speech therapy – Lee silverman voice therapy


Choreioform Movements

Chorea - involuntary, irregular, purposeless, nonrhythmic, abrupt, rapid, unsustained movements that seem to move unpredictably from one body part to another

Ballism – larger amplitude and rapid-proximal parts of limb

Athetosis - more sinuous slow, writhing


Sydenham Chorea


Sydenham Chorea

Post-strep reactionDemographics: teens, female > maleChorea; sometimes behavioral (OCD-

like) Testing of limited use: ASOT false pos

and neg, infection usually resolvedTends to subside even without Rx in

weeks or monthsValproate can reduce the chorea


Huntington’s Disease


Huntington’s Disease

Neurodegeneration, initially of striatal ‘medium spiny’ neurons to GPe

Caused by expanded CAG repeat in Huntingtin Gene (autosomal dominant), normal < 35 repeats

Onset young adult, though can be any agePresents with gradually worsening chorea,

cognitive, mood & behavioral changesManagement: antipsychotics,

antidepressant, tetrabenazine, behavioral


Hemiballismus – Subthalamic Nucleus lesion


L-Dopa induced Dyskinesias – usually peak dose about 40 minutes after ingestion of L-Dopa


Stereotypy

‘Coordinated’ movements that repeat continually and identically

When they occur at irregular intervals, stereotypies may not always be easily distinguished from motor tics, compulsions, gestures & mannerisms

Tics - occur paroxysmally out of a background of normal motor behavior and usually associated with an urge


Tardive Dyskinesia

Dopamine Antagonists (D2):

Typical > atypical antipsychotics

metoclopramide (Reglan), promethazine (Phenergan)

? D2 receptor hypersensitivity

Appears after years of use (sometimes even months)

Risk factors: dose, older age, female sex

Classic - Oro-Bucco-Lingual stereotypy (lipsmacking).

Anticholinergics - Artane, Cogentin or even Benadryl worsen it.

Rx - Tetrabenazine 12.5 mg tid Remove offending drug, or

switch to a more atypical antipsychotic


Tics

Brief, Stereotyped abnormal movements or sounds

In response to urge (psychic/physical)Can be complex (sequence, muscles)The diversity of motor tics is one

feature that sets their phenomenology apart from stereotypies


Tourette Syndome

Onset < 18 . For > 1 yearMultiple motor tics and vocal tics –

coprolalia. Tics evolves over time.Comorbidities: ADHD, OCD, impulse

control disorderM > F (female relatives may have

OCD)


Tourette Syndome (contd.)

Adrenergic - Guanfacine, Clonidine (0.1 - 0.3mg tid)

Antipsychotics - Pimozide, Haloperidol, Risperidone (1-16 mg/day div qd-bid)

Dopamine Depletor –Tetrabenazine

Stimulants – Adderall, Ritalin SR (20 – 60 mg/day div qd-bid)

Antidepressants Behavioral therapy ? DBS


Dystonia

Twisting movements that tend to be sustained at the peak of the movement

Frequently repetitive in the same group of muscles (patterned – unlike Chorea)

Often progresses to prolonged abnormal postures

Can be focal, segmental or generalizedOften induced by action, sometimes

task-specific such as writing etc.


Adult onset focal dystonia (more common)

Cervical dystonia (torticollis)

Blepharospasm (forced eyelid closure)

Usually idiopathic but sometimes a triggering insult (eg. injury)


Primary Torsion Dystonia

Generalized - gradual onset, usually starts in the foot

Juvenile Onset CAG deletion in

DYT1 gene resulting in Torsin A mutation


Dystonia (contd.)

Anticholinergic: Cogentin, Artane(2 -16mg per day div. TID titrated gradually over 2-3 months).

Muscle relaxants – Benzos, Baclofen Botulinum toxin injection – focal

dystonias – last 3-4 monthsDBS - “Humanitarian Device

Exemption”


Myoclonus

Sudden lightning-like movementCan be repetitive but Not rhythmic (if

it was, it would be a tremor!)Can be focal or regional or multifocoal

or generalized; epileptic and non epileptic.

Like tremor, myoclonus can arise from disease of many parts of CNS, not just basal ganglia


Myoclonus (contd.)

Physiologic (Hypneic, Hiccups)

Serotonin Syndrome

Dementias – Creutzfeld Jakob Disease (CJD)

Multiple Sclerosis JME (epilepsy) Rx: clonazepam (0.25-0.5 mg PO bid-tid) or

valproic acid or levetiracitam


Thank You

Questions and Comments

Contact or Refer - OU Movement disorders clinic or the Medicaid movement disorders

clinic

www.wemove.org

Documents

Parkinson Disease & other Movement Disorders