PARKINSONS & MOVEMENT
DISORDERS CENTER OF MARYLAND
Affiliated with the
American Parkinsons Disease Association through Johns Hopkins University
Stephen Grill, MD, PhD &
Susanne Goldstein, MD
10770 Hickory Ridge Road,
Columbia, MD 21044
410-884-7001, Fax:
410-884-7002
pdmdcenter.com
Parkinson’s Disease
A progressive degenerative disease resulting from
loss of dopaminergic neurons in the substantia nigra. Cardinal symptoms:
Tremor, rigidity, bradykinesia. Also may develop postural instability,
dementia, and many other symptoms.
Symptoms responsive to dopaminergic therapy: tremor, rigidity,
bradykinesia.
Usual medications:
Carbidopa/Levodopa (Sinemet) 25/100, 25/250: mainstay medication; all
patients respond. Theoretically may hasten disease progression although no
clinical evidence for this. May hasten onset of dyskinesias although data not
entirely clear. Dosed initially qam & noon, 5pm but as disease progresses
more frequent dosing.
Carbidopa/Levodopa CR (Sinemet CR) 25/100, 50/200: long acting formulation;
studies controversial over whether there is true prolongation of duration of
action.
Pergolide (Permax): 0.05, 0.25, 1.0 mg: Ergot dopamine agonist;
stimulates D1 & D2 receptors.
Effective (although not indicated) as monotherapy in early disease. Indicated as adjunctive therapy to reduce
motor fluctuations. Poorer side effect profile compared to Carbidopa/Levodopa.
Slow titration to effective dose (usually
1 – 1 ˝ mg qam, noon, 5pm).
Ropinirole (Requip): 0.25, 0.5, 1.0, 2.0, 5.0 mg: Non ergot dopamine agonist;
stimulates D1 receptors. Effective and
indicated as monotherapy in early disease and adjunctive therapy to reduce
motor fluctuations. Poorer side effect profile compared to Carbidopa/Levodopa.
Slow titration to effective dose
(usually 3 – 7 mg qam, noon, 5pm).
Pramapexole (Mirapex) 0.25, 0.5, 1.0 mg: Non ergot dopamine agonist;
stimulates D1 receptors. Effective and
indicated as monotherapy in early disease and adjunctive therapy to reduce
motor fluctuations. Poorer side effect profile compared to Carbidopa/Levodopa.
Slow titration to effective dose
(usually 1 – 1 ˝ mg qam, noon, 5pm).
Amantadine 100 mg.: Antiviral agent with dopaminergic
properties. Weak action as monotherapy in early disease. May be effective as
adjunctive therapy too and is used to reduce dyskinesias. Usual dose is 100 mg
tid-qid.
Artane (Trihexphenidyl), 2 mg , 5 mg: Anticholinergic. Weak
effects, particularly used in treating tremor in early disease. Side effect
profile poor (dry mouth, dry eyes, confusion, hallucinations, urinary
retention)
Selegiline (Edlepryl, Deprenyl) 5 mg: MAOb inhibitor.
Theoretically would be thought to have neuroprotective benefit. Initial studies
demonstrating neuroprotective effect were flawed. If given qam & noon,
should not have interactions with tricyclics or SSRI’s because it is
specifically an MAOb inhibitor.
Entacapone (Comtan) 200 mg: COMT inhibitor. Prolongs
the duration of action of l-dopa. Should be dosed with each dose of
carbidopa/levodopa.
Symptoms unresponsive to
dopaminergic therapy: Postural instability, freezing, speech abnormalities,
depression, dementia, sleep disturbances, constipation, sexual dysfunction,
bladder dysfunction, sweating, sensory phenomenon, others.
Motor fluctuations: With advancing disease, motor fluctuations
with “wearing off”, dyskinesias and others develop. Many of these patients show
improvement after stereotactic brain surgeries to implant deep brain
stimulators in the Vim of the thalamus, globus pallidus, or subthalamic
nuclei.
The stimulator device consists of a battery with
electronics and electrodes as shown here:
Essential Tremor An hereditary, autosomal
dominant disease characterized by postural and kinetic tremors of the arms,
neck, voice, and/or legs. In contrast to the resting tremors of Parkinson’s
disease, these are often more disabling. Most are improved with small amounts
of ETOH.
Mainstay medications:
Primidone (mysoline): 50 mg, 250 mg. Effective in most patients.
Slow titration schedule beginning at 25 mg tid. Maximum effective dose is 250
mg tid. Rarely, may develop vertigo after 1st or 2nd
dose. May develop fatigue at high doses especially in elderly.
Propranolol (Inderal). Effective in most patients.
Side effect profile worse (Depression, impotence, reduced exercise tolerance;
relatively contraindicated in asthma, diabetics on Insulin). May be used prn
prior to stressful event.
In medically refractory patients, deep brain
stimulation in the Vim of the thalamus often of great benefit.
Dystonia
Involuntary
sustained muscle contractions producing twisting and repetitive movements and
abnormal postures. May be idiopathic or symptomatic. May be focal (single area
involved), segmental, (two or more contiguous areas), Multifocal, or
generalized. Focal dystonias include Bkeopharospasm, spasmodic dysphonia
(voice), cervical dystonia, and limb dystonia
Cervical dystonia: Note hypertrophied Hand dystonia
Foot Dystonia
Sternocleidomastoid muscle
For generalized dystonia medical treatments include anticholinergic medications and benzodiazepines. For focal dystonias, botulinum toxins injected into the overactive muscles may reduce the dystonic contractions. There are two toxins available: Botulinum toxin A (Botox) and Botulinum toxin B (Myobloc). This can also treat selected muscles in persons with generalized dystonia.
Cerebellar Ataxia
Clinical features include wide-based unsteady gait,
dysarthria, disturbances of extraocular movements, kinetic (intentional)
tremor, and dysmetira. May result from
strokes of the cerebellum and its pathways. Also may be present on a genetic
basis. There are several forms of autosomal dominant spinocerebellar ataxia. No
medications found to be clearly helpful. Attention to use of assitive devices
and preventing falls is important.
Myoclonus: brief muscle jerks caused
by neuronal discharge. May be spontaneous or triggered by external stimuli. May
be focal, segmental, generalized or multifocal. Klonopin, Keppra, Depakote
often helpful.
Other Movement Disorders: Chorea, Restless Legs Syndrome,
Stiff-person syndrome, Tic disorders (Tourettes),