Movement Disorders Update

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Movement Disorders Update

• Colleen Peach, RN, MSN, FNP
• Movement Disorders Clinic
• Emory University School of Medicine

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Movement Disorders

• Clinically, divided into 2 categories
• Poverty of movement (Akinesia)
• Associated with an increase in muscle tone
• Excessive abnormal involuntary movements
  (Dyskinesia)
• Classified as tremor, chorea, ballism, dystonia,
  athetosis, myoclonus, and tic

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Movement Disorders

• Dystonia
• Tourettes Syndrome
• Restless Leg Syndrome
• Huntingtons Disease
• Essential Tremor
• Parkinsons Disease

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Dystonia

• Characterized by sustained muscle contractions
  that frequently cause twisting or repetitive
  movements and abnormal, sometimes painful,
  postures or positions
• May affect any part of the body

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Dystonia (cont.)

• Primary Dystonia
• may be due to DYT1 mutation
• Secondary Dystonia
• Most common cause is neuroleptic administration
• Dystonia assoc. with parkinsonism
• Psychogenic causes

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Dystonia (cont.)

• Treatment
• Medications
• Klonopin
• Baclofen
• Levodopa
• Botulinum toxin injections (Botox)
• Surgery
• Deep Brain Stimulator

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Dystonia (cont.)

• Diagnostic Challenge Frequent Misdiagnoses
• Blepharospasm
• Dry eye syndrome or tics
• Cervical dystonia
• Stiff neck, arthritis, subluxation of the
  cervical vertebrae, posterior fossa tumors
• Writers cramp
• Carpal tunnel, strain, tennis elbow

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Dystonia (cont.)

• Frequent Misdiagnoses (cont.)
• Laryngeal dystonia
• Sore throat, laryngitis, vocal abuse
• Oromandibular dystonia
• TMD (temporomandibular joint disorder)
• All dystonia
• Psychogenic, stress, nervousness

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Tourettes Syndrome

• Characterized by sudden, involuntary, repetitive
  muscle movements (motor tics) and vocalizations
  (verbal tics) such as repeated eye blinking,
  facial twitching, head jerking, grunting,
  snorting, barking, sniffing, echolalia,
  palilalia, coprolalia, etc.

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Tourettes Syndrome (cont.)

• Motor Spectrum Tics
• Behavior Spectrum
• Obsessive Compulsive Disorder
• Attention Deficit Hyperactivity Disorder
• Other behaviors such as aggressiveness,
  immaturity, anxiety and depression

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Tics

• Repetitive, irregular stereotypic movements or
  vocalizations that can be mimicked by the
  observer and often can be willfully held in check
  by the patient, usually at the expense of
  mounting inner tension which is then relieved
  when the tic is expressed
• Resemble myoclonis when they are rapid and
  shocklike but can also be prolonged or complex
  motor acts

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Tourettes Syndrome (cont.)

• Treatment
• Tics Orap, antipsychotics, Effexor,
• clonidine, Klonopin, Haldol
• OCD Klonopin, SSRIs
• ADHD Stimulants, clonidine
• Behavior Modification
• Therapy/Counseling

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Restless Leg Syndrome

• Characterized by sensory and motor abnormalities
  such as the desire to move the legs in
  association with unusual or uncomfortable
  sensations motor restlessness symptoms are
  worse at rest and occur most frequently in the
  evening or early part of night

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Restless Leg Syndrome (cont.)

• Treatment
• None may be needed
• Medications
• Dopamine agonists Requip, Mirapex, Permax
• Levodopa

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Huntingtons Disease

• Hereditary progressive neurodegenerative disorder
• Characterized by emotional, behavioral, and
  psychiatric abnormalities
• Loss of previously acquired intellectual or
  cognitive functioning
• Motor disturbances

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Huntingtons Disease (cont.)

• Treatment
• Motor symptoms (chorea)
• Dopamine depleters
• Dopamine blocking agents
• Prefer atypicals risk of drug induced PD
• Psychiatric symptoms
• SSRIs
• Antipsychotics

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Huntingtons Disease (cont.)

• Treatment
• Safety Considerations
• PT
• OT
• Nutrition support- encourage high protein/high
  fat diet
• Support system for caregivers

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Tremor

• An involuntary movement of a body part resulting
  from alternate contractions of opposing muscles.

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Essential Tremor

• Characterized by a rhythmic back and forth or
  to and fro movement produced by involuntary
  contractions of the muscle
• ET may be asymmetric at onset and have a kinetic
  component (action-postural tremor of the hands,
  arms, and head)

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Essential Tremor (cont.)

• Supportive Criteria for Diagnosis
• History and Physical/Neuro Exam
• Tremor assessment
• Improvement with use of alcohol
• Family history but not definite

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Essential Tremor (cont.)

• Goals for treatment
• Reduce tremor severity
• Improve ability to function
• Decrease social handicap

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Essential Tremor (cont.)

• Treatment (depending on severity, there may be no
  treatment)
• Medications
• propanolol (Inderal)
• primadone (Mysoline)
• trihexphenidyl (Artane)
• clonazepam (Klonopin)
• diazepam (Valium)
• alprazolam (Ativan)

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Essential Tremor (cont.)

• Treatment (cont.)
• Botox injections
• Surgical Interventions
• Thalamotomy
• Deep Brain Stimulation (DBS)

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Parkinsons Disease

• Progressive, chronic, neurodegenerative disease
• Slow, selective loss of substantia nigra
  dopaminergic neurons
• Clinical features due to severe loss of striatal
  dopamine

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Epidemiology of Parkinsons Disease

• 1 million patients diagnosed in US
• Approximately 60,000 new cases/year
• Average age of onset is 60 years
• 5 to 10 of PD patients have symptoms before age
  40 (young-onset PD)
• Prevalence in population gt80 years old is 10

Lang AE et al. N Engl J Med. 1998339(15)1044,
1049-50. Olanow CW et al. Neurology.
200156(suppl 5)S1.
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Parkinsons Disease (cont.)

• Age is single most consistent risk factor
• Onset is insidious
• Male predominance 3/2
• Affects all ethnic and socioeconomic groups
• James Parkinson first described shaking palsy
  in 1817

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Pathophysiology

• PD occurs when neurons in the substantia nigra
  die or become impaired
• Substantia nigra is located in the midbrain.
  Dopamine pathways are also connected to the
  frontal and limbic (emotional) regions of the
  brain

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Pathophysiology (cont.)

• Dopamine is the chemical messenger responsible
  for transmitting signals between the substantia
  nigra and the relay station of the brain, the
  corpus striatum, to produce smooth, purposeful
  muscle activity
• Loss of dopamine in the striatum leaves the
  patient unable to direct or control their
  movements in a normal matter

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Classification of PD

• Primary, Degenerative form
• Idiopathic Parkinsonism
• Secondary
• Toxins
• Drugs
• Trauma, Vascular, and Post-Encephalitic

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Classification (cont.)

• Parkinson-Plus Syndromes
• Multi-system atrophy (MSA)
• Progressive Supranuclear Palsy (PSP)
• Cortical-basal Ganglionic Degeneration (CBGD)
• Dementia Syndromes
• Alzheimers with PD symptoms
• Lewy Body Disease

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Potential Causes of PD

• Genes
• ?-synuclein
• Parkin
• UCH-L1
• Susceptibility genes

• Environment
• Pesticides
• Rural living
• Other (?)

• Pathogenic Mechanisms
• Protein aggregation
• Mitochondrial dysfunction
• Oxidative stress
• Inflammation
• Excitotoxicity

Apoptosis (cell death)
UCH-L1 ubiquitin hydrolase L1.
McNaught K St P et al. Ann Neurol. 200353(suppl
3)S73-S86 Olanow CW, Tatton WG. Annu Rev
Neurosci. 199922123-124 Steece-Collier K et
al. Proc Natl Acad Sci USA. 20029913972-13974.
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Characteristic Motor Symptoms

• Tremor
• Bradykinesia/akinesia
• Rigidity
• Postural instability

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PD Symptoms

• Micrographia
• Masked Facies/Hypomimia
• Hypophonia
• Decreased Arm Swing
• Shuffling Gait
• Truncal Flexion
• Fatigue

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PD Symptoms (cont.)

• Dysphagia
• Sialorrhea
• Decreased Gastric Emptying
• Dry Eyes
• Seborrhea

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Non-Motor Symptoms in PD

• Mental Changes
• Dementia
• Depression
• Sleep Disturbance
• Fragmented Sleep
• REM behavioral sleep disorder

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Non-Motor Symptoms in PD

• Dysautonomia
• Constipation
• Sexual dysfunction
• Bladder dysfunction
• Sweating
• Orthostasis
• Pain
• Untreated patients
• Shoulder and back pain
• Treated patients
• Off dystonia (foot pain)

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Diagnosing PD

• Requires at least 2 of the 4 cardinal features,
  without other neurologic deficits and a clear-cut
  response to L-dopa therapy
• Almost all patients with idiopathic PD will
  improve with L-dopa therapy
• Parkinson-Plus syndromes will not improve as
  dramatically

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Diagnosing PD (cont.)

• No abnormalities of routine x-rays, labs, EEG, or
  EKG
• CT/MRI
• PET scan
• SPECT scan

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Treating PD

• When considering treatment, ask the patient..
• What symptoms bother you most?
• How much do these symptoms interfere with daily
  function and lifestyle?

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Management of PD
Disease Progression
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Medication Management

• Mainstay of therapy is dopaminergic medication
• Dopamine replacement
• Activate dopamine receptors
• Stimulation of dopamine release
• Inhibit dopamine uptake

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Medication Management (cont.)
Anticholinergic Medications (Reduce relative
excess acetylcholine) Trihexiphenidyl
(Artane) Benztropine (Cogentin ) MAO Inhibitor,
Other Selegiline (Eldepryl ) Amantadine
(Symmetrel) Zydis Selegiline (Zelapar) Rasagilin
e (Azilect)
Levodopa (L-dopa) (? Dopamine) Give with
carbidopa (reduces nausea) Carbidopa/Levodopa
(Sinemet ) Dopamine Agonists (Mimic
dopamine) Pergolide (Permax) Pramipexole
(Mirapex ) Ropinerole (Requip) Apomorphine
(Apokyn ) Rotigitine (Neupro patch
) COMT-Inhibitors (?Slow dopamine
breakdown) Entacapone (Comtan) Tolcapone
(Tasmar )
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Levodopa

• Most effective drug for parkinsonian symptoms
• First developed in the late 1960s rapidly
  became the drug of choice for PD
• Large neutral amino acid requires active
  transport across the gut-blood and blood-brain
  barriers
• Side effects nausea, postural hypotension,
  dyskinesias, motor fluctuations

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Levodopa (cont.)

• Motor fluctuations
• Up to 50 of patients after 5 years of treatment
• 70 of patients after 15 years of treatment
• End-of-dose wearing off phenomenon
• Unpredictable on-off fluctuations
• Dyskinesias
• Peak dose or diphasic
• Neuropsychiatric disturbances
• Hallucinations
• Confusion

Lang AE et al. N Engl J Med. 1998339(16)1134-36.
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Response to Levodopa and Progression of
Parkinsons Disease
Moderate PD
Early PD
Advanced PD
Dyskinesia Threshold
Dyskinesia Threshold
Dyskinesia Threshold
Response Threshold
Clinical Effect
Clinical Effect
Clinical Effect
Clinical Effect
Clinical Effect
Response Threshold
Response Threshold
Levodopa
2
4
6
Levodopa
Levodopa
2
4
6
2
4
6
Time (h)
Time (h)
Time (h)

• Shorter duration motor response
• Increased incidence of dyskinesias

• Short durationmotor response
• On time consistently associated with dyskinesias

• Long duration motor response
• Low incidence of dyskinesias

Olanow CW, Agid Y. http//www.medscape.com/viewpro
grm/1847-pnt.
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Dopamine Agonists

• Ergot-derived dopamine agonists-First generation
• pergolide (Permax )
• bromocriptine (Parlodel )
• Nonergot-derived dopamine agonists-Second
  generation
• ropinirole HCl (Requip )
• pramipexole (Mirapex )
• apokyn injection
• rotigitine (Neupro patch )

Olanow CW et al. Neurology. 200156(suppl 5)S14.
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MAO-B Inhibitors

• Inhibit monoamine oxidase B enzyme, which breaks
  down dopamine following its action in synaptic
  cleft
• Selegiline is an irreversible MAO-B inhibitor
• DATATOP study
• Provided slight symptomatic benefit
• delayed the need to begin levodopa therapy by 9
  months
• Inconclusive evidence in humans that selegiline
  slows progression in PD

Olanow CW et al. Neurology. 200156(suppl
5)S6-S7. Parkinson Study Group. Ann Neurol.
19963937-38.
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Rasagiline

• An irreversible selective MAO-B inhibitor
• Administered orally once per day
• No amphetamine or amphetamine-like metabolites
• FDA approved for the treatment of PD as both
  initial therapy and adjunctive therapy

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Amantadine

• Provides mild-to-moderate benefit
• Neuropsychiatric adverse effects limit use in
  older patients or those with dementia
• Other adverse events
• Anticholinergic Livedo reticularis
• Antidyskinetic effect can reduce dyskinesia by
  about 45, but benefit lasts less than 8 months

Mendis T et al. Can J Neurol Sci.
19992691. Lang AE et al. N Engl J Med.
1998339(16)1134. Olanow CW et al. Neurology.
200156(suppl 5)S24-S25. Thomas, A et al. JNNP.
200475141-143.
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Anticholinergics

• Option for young patients (lt60 years) whose
  predominant symptom is resting tremor
• Available agents
• trihexyphenidyl (Artane)
• benztropine
• Adverse effects often limit use due to
• Memory impairment Dysphoria
• Confusion Antimuscarinic effects
• Hallucinations Dry mouth
• Sedation Blurred vision

Olanow CW et al. Neurology. 200156(suppl
5)S24-S25.
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Parcopa(Carbidopa/levodopa Orally
Disintegrating Tablets)

• RapiTab technology dissolves rapidly on the
  tongue without need for water
• Same strength and dosage schedule as conventional
  carbidopa/levodopa
• Equivalent benefit and side effects
• Rapid access to medication, convenient

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Apomorphine (Apokyn)

• The only injectable DA available
• Apomorphine sc has been shown in controlled
  clinical trials to effectively abort OFF
  episodes in patients already on maximal oral
  therapies
• Apomorphine is a highly potent DA

Dewey RB Jr, et al. Arch Neurol.
2001581385-1392.
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COMT Inhibitors

• Only used in combination with levodopa
• Inhibit levodopa catabolism/extend duration of
  levodopa effect
• Indicated for treatment of patients with PD
  experiencing end-of-dose wearing off with
  levodopa
• COMT inhibitors available
• entacapone (Comtan)
• tolcapone (Tasmar) may cause hepatic toxicity
• Stalevo

Olanow CW et al. Neurology. 200156(suppl
5)S21-S22. Tasmar (tolcapone) Prescribing
Information. Roche Laboratories, Inc. 1998.
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Surgical Options

• Surgical Treatments
• Pallidotomy
• Deep brain stimulation

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Deep Brain Stimulation
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Other Areas

• Constipation
• Urinary Symptoms
• Orthostatic Hypotension
• Male Impotence
• Depression

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Treatment

• Other
• Diet
• Hydration
• Exercise
• Stress Management
• Counseling
• Education

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Research

• Neuroprotective Studies
• Symptomatic Relief
• Alternative Therapy
• Exercise
• Dietary Supplement
• Spiritual/Prayer
• Surgical Studies
• Stem cells
• RPE

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Research (cont.)

• New Drugs on the Horizon
• Ropinerole CR

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Websites

• Movement Disorders
• www.WEMOVE.org
• American Parkinsons Disease Association
• www.apdaparkinson.com
• National Parkinsons Foundation
• www.parkinson.org
• Michael J. Fox website
• MichaelJFox.com
• For community resources
• www.healingwell.com