Download UNIVERSITY OF SANTO TOMAS FACULTY OF MEDICINE AND

UNIVERSITY OF SANTO TOMAS
FACULTY OF MEDICINE AND SURGERY
DEPARTMENT OF NEUROLOGY
WRITTEN REPORT ON MOVEMENT DISORDER
(CASE 9)
SUBMITTED BY:
Ong, Yumi Czarina
Ongoco, Renncee
Ordoveza, Michelle Eloise
Pacquing, Paul Christian
Paderna, Nikki Eleanor
Padolina, Dianna Jean
Pagkalinawan, Leah
3C
March 5, 2010
CASE 9: MOVEMENT DISORDERS
65 year-old, housewife
Chief complaint: Tremors
History of Present Illness
Three years prior to admission:
 She noticed her left arm had a tendency to curl up toward her body when she
wasn’t using it.
 Her left 4th and 5th fingers trembled; she started having difficulty in finding the
right keys on her computer keyboard.
 Her left leg felt stiff and dragged somewhat when she walked.
 She gradually had rigidity in her left arm and progressed to her shoulder and neck
causing a lot of pain and stiffness.
 Referred to an orthopedist and another doctor
o Given some cortisone shot in the shoulder but there was no relief of
symptoms
o Cranial CT scan was done and was unremarkable
Months later, she consulted a neurologist for 2nd opinion. At this time,
 Her axial position is flexed (Forward flexed posture) and gait slow and shuffling
(Festinating gait)
 Her left arm did not swing when compared to the right
 When she greeted the examiner with a soft voice, she gave a little smile, but most
of the time her face was expressionless (Mask-like fascies).
 During their interview, her left hand showed rest tremors although strength and
coordination of her extremities were intact.
 She was slow in performing repetitive movements (Bradykinesia).
 Her limbs were rigid especially the left extremities.
I. SALIENT FEATURES
PERTINENT POSITIVES
o 65 year old, Female
o persistence of hand tremors and
limb rigidity
o (+) unilateral resting tremors (L)
o Forward flexed posture
o (+) Festinating/ shuffling gait
o (+) Mask-like fascies
o (+) Bradykinesia
o (+) rigidity of the left extremities
o soft speech
o decrease left arm swing
PERTINENT NEGATIVES
o Intact strength and coordination of
extremities
o No relief of symptoms after
cortisone shot
II. CLINICAL IMPRESSION
Based on the salient features of the patient, the most likely diagnosis is
Parkinson’s disease, a slow progressive movement disorder that is caused by the
degeneration of dopamine producing cells in the substancia nigra thereby
decreasing dopamine production. The patient manifested with all the cardinal
features of Parkinson’s disease namely bradykinesia, rigidity and rest tremor.
III. DIFFERENTIALS
A. PARKINSON-PLUS SYNDROMES
Several primary neurodegenerative disorders have parkinsonian features, such as
bradykinesia, rigidity, tremor, and gait disturbances, in common. These neurologic
conditions are associated with complex clinical presentations that reflect degeneration in
various neuronal systems. However, because of the common parkinsonian features, the
disorders have been collectively named Parkinson-plus syndromes. Although separate
clinical syndromes have been identified, modern immunocytochemical techniques and
genetic findings suggest many underlying similarities broadly grouped into 2 types:
synucleinopathies and tauopathies.
Patients with Parkinson-plus syndromes typically have a worse prognosis than those
with Parkinson disease (PD), and Parkinson-plus syndrome responds poorly to the
standard anti-Parkinson treatments. An adequate response to treatment in a patient with
parkinsonian symptoms may indicate that a Parkinson-plus syndrome is developing, and
searching for the signs and symptoms of degeneration in other neuronal systems is
important.
Clinical clues suggestive of Parkinson-plus syndromes include the following:
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Lack of response to levodopa/carbidopa (Sinemet) or dopamine agonists in the
early stages of the disease
Early onset of dementia
Early onset of postural instability
Early onset of hallucinations or psychosis with low doses of levodopa/carbidopa
or dopamine agonists
Ocular signs, such as impaired vertical gaze, blinking on saccade, square-wave
jerks, nystagmus, blepharospasm, and apraxia of eyelid opening or closure
Pyramidal tract signs not explained by previous stroke or spinal cord lesions
Autonomic symptoms such as postural hypotension and incontinence early in the
course of the disease
Prominent motor apraxia
Alien-limb phenomenon
Marked symmetry of signs in early stages of the disease
Truncal symptoms more prominent than appendicular symptoms
Absence of structural etiology such as a normal-pressure hydrocephalus (NPH)
Patient
Drug induced
Parkinsonism
Essential
Tremor
Wilson’s
Disease
Huntington’s Parkinson
plus
syndrome
History
PE
findings
IV. DIAGNOSIS: Idiopathic Parkinson’s Disease
Parkinson’s disease is the second most prevalent neurodegenerative disease. It
occurs worldwide, in all ethnic groups with a higher incidence in whites than in
Africans and Asians. It has a prevalence of 1-2/1000 of the general population and
about 2/100 among those older than 65 since its prevalence typically increase with
age. The onset of the disease ranges from 35-85 years of age with its peak in the
early 60s. The course of the illness usually takes about 10 to 25 years.
Most cases of Parkinson’s disease are idiopathic (typical). Others maybe
secondary to any or a combination of any of the following possible etiologies for
dopaminergic cell death in Parkinson’s: genetic mutation, oxidative stress,
proteasomal dysfunction, abnormal kinase activity, and environmental factors.
Genetic Mutations leading to dopaminergic cell death includes abnormal folding
of the α-synuclein protein in the PARK1 locus of the SNCA gene (autosomal
dominant) and mutation at the locus PARK2 of the PRKN gene; P1N1 (PARK6)
and PARK7 gene (autosomal recessive) - early onset Parkinson’s disease.
Environmental causes include MPTP and rotenone as they cause nigral
degeneration. Aside from these, atypical forms such as multiple systems atrophy,
progressive supranuclear palsy, and corticobasal degeneration may also lead to
Parkinson’s.
Pathophysiology
Parkinson’s disease is caused by the disruption of dopaminergic
neurotransmission in the basal ganglia, where there is progressive death of
dopaminergic neurons while cytoplasmic inclusions or Lewy bodies are present in
the remaining neurons. The dopamine of the substancia nigra inhibits the firing of
the striatal cells. In its absence, the cell fire action potential more rapidly thereby
producing disordered striatal output. This significantly affects the modulation
between the direct and indirect pathways whose net effect is a decrease in the
thalamocortical neuronal activity.
Clinical Features
1. Rest tremors or Parkinsonian tremors - occurs when the limb is in an
attitude of repose and is suppressed or diminished by willed movement, at
least momentarily, only to reassert itself once the limb assumes a new
position. It usually starts as unilateral
2. Rigidity – increase resistance to passive movements through direct effect
on alpha motor neuron; usually affect the limbs
3. Bradykinesia- Akinesia – slowness or absence of movement not
attributable to weakness; can be reflected by infrequency of swallowing,
slowness of chewing, a limited capacity to make postural adjustments of
the body and limbs in response to displacement, absence of arm swing in
walking, etc.
4. Postural instability- he most potentially dangerous, because it can lead to
falls with resulting fractures. It is also one of the manifestations that
responds less well to levodopa therapy.
5. Masked-like fascies – secondary to reduction in movements of the small
facial muscles
6. Festinating Gait – shuffling start
7. “Stoop” appearance – flexed posture
8. Hypovolemic speech – soft voice
9. Autonomic dysfunction
10. Dementia - in advance stages
Risk Factors
 Increased risk is associated with advancing age, male gender, family
history of having the disease, head injury, exposure to pesticides,
drinking well water, and rural living.
 On the other hand, reduced risk is associated with use of nonsteroidal
anti-inflammatory drugs, estrogen replacement in postmenopausal
women and coffee drinking.
Diagnostic Procedures
 Diagnosis is mainly clinical.
o It must satisfy 2 out of the three cardinal features of
parkinsonism  Tremor, Rigidity and Bradykinesia
o Similarly, two of the following  marked response to
levodopa, asymmetry of signs and asymmetry of onset
 NO definitive tests
 Imaging studies may be used to rule out etiology of secondary
Parkinson’s disease
o PET scan – can be used to visualize dopamine uptake in
substancia nigra and basal ganglia
o SPECT (Single photon emission computed tomography)
o EMG – to differentiate it from essential tremor in terms of
frequency
V. TREATMENT:
Pharmacologic Approach
The patient’s symptoms, comorbidities and the progressive course of the disease
should be considered in choosing the drug of choice. Dopaminergic therapy at a
relatively early stage may be most effective in alleviating symptoms of parkinsonism
and may also favorably affect the mortality rate due to the disease.
DRUG OF CHOICE:
Levodopa
L-dihydroxyphenylalanine (L-dopa) is the most effective agent for the treatment of
Parkinson disease. Dopa is the amino acid precursor of dopamine and norepinephrine,
Levodopa being the levorotatory stereoisomer of dopa.
Theoretical basis: striatal dopamine is depleted in patients with Parkinson disease but
the remaining diseased nigral cells are sill capable of producing some dopamine by
taking up its precursor L-dopa. The number of neurons in the striatum is not diminished,
and they remain receptive to ingested dopamine acting through the residual nigral
neurons.
Side effects: nausea, vomiting, anorexia, mild orthostatic hypotension, end-of-dose
reduction in efficacy, involuntary dyskinetic movements: restlessness, head wagging,
grimacing, lingual-labial dyskinesia, choreoathetosis, dystonia of limbs, neck, trunk,
psychiatric symptoms: depression, delusion, hallucination, insomnia, anxiety and other
changes in mood and personality. On-off phenomenon are fluctuations in clinical state
and unrelated to the timing of doses, off-periods of marked akinesia alternate over the
course of a few hours with on-periods of improved mobility but often marked dyskinesia.
Contraindications: psychotic patients because it may exacerbate the mental
disturbance, patients with angle-closure glaucoma, cardiac disease, active peptic ulcer
disease, patients with history of melanoma or with suspicious undiagnosed skin lesions.
Drug Interactions: Pyridoxine or Vitamine B6 enhance the extracerebral metabolism
of Levodopa and prevent its therapeutic effect. Patients taking Monoamine oxidase A
inhibitors should not be given Levodopa even within 2 weeks of discontinuance, because
such combination can lead to hypertensive crises.
Adjuncts:
Decarboxylase inhibitor (Carbidopa, Benserizide)- unable to penetrate CNS,
decarboxylation of L-dopa to dopamine is greatly diminished in peripheral tissues
allowing greater proportion of L-dopa to reach nigral neurons at the same time
reducing peripheral side effects of L-dopa and dopamine such as nausea,
hypotension.
Long-acting preparation of Levodopa-Carbidopa (Sinemet-CR) – reduce
dyskinesias in patients with advanced disease.
Catechol-O-methyltransferase (COMT) inhibitors (Entacapone) – extends
plasma half-life and duration of L-dopa effect by preventing its breakdown.
Other drugs:
Dopamine Agonists – has direct dopaminergic effect on striatal neurons, while partially
bypassing the depleted nigral neurons. It can be used in the early phase of the disease and
modifying effects of L-dopa later in the illness. It has fewer dyskinetic motor
complications and putative neuroprotective effect that is alleged to slow the progress of
disease.
Less potent than L-dopa in managing the main features of Parkinson disease and
produces similar side effects.
Ergot derivatives: Bromocriptine, Pergolide, Lisuride – direct stimulating
effect on dopamine (D2) receptors located on striate neurons.
Non-ergot derivatives: Ropinirole, Pramipexole – has similar type and duration
of effectiveness.
Side effects: anorexia, nausea, vomiting, constipation, dyspepsia, reflux esophagitis,
postural hypotension, arrhythmia, dyskinesia, mental disturbances: confusion,
hallucination, delusions, headache, nasal congestion, increased arousal, pulmonary
infiltrates, pleural and retroperitoneal fibrosis, erythromelalgia
Contraindications: psychotic illness, recent myocardial infarction, active peptic
ulceration, peripheral vascular disease
Anti-cholinergic Agents – very satisfactory when the predominant manifestation is
tremor with patients in the early phase of the disease.
Little effect on the postural, hypokinetic and other disease manifestations.
Side effects: mental slowing, confusional states, hallucinations, impairment of memory,
dryness of mouth leading to acute suppurative parotitis
Antiviral agent (Amantadine) – mild or moderate benefit for tremor, hypokinesia and
postural symptoms. It reduces L-dopa – induced dyskinesias.
MOA: antagonism of N-methyl-D-aspartate (NMDA), potentiate dopaminergic function
by influencing synthesis, release or reuptake of dopamine.
Side effects: leg swelling, worsen congestive heart failure, exaggerating cognitive
changes in patients with glaucoma, acute toxic psychosis, livedo reticularis
Caution: patients with history of seizures and heart failure
Neuroprotective Effects
– drugs that slow the progression of the disease
Monoamine oxidase inhibitor (Selegiline) – inhibits the intracerebral metabolic
degradation of dopamine and slows the progression of the disease in its early stages. Its
neuroprotective effect may relate to its metabolite, desmethylselegiline, which involves
antiapoptotic mechanism.
MOA: selective irreversible inhibitor of monoamine oxidase B at normal doses retards the
breakdown of dopamine, therefore enhances and prolongs the antiparkinsonism effect of
Levodopa and may reduce mild on-off or wearing-off phenomena.
Drug Interactions: Meperidine, Tricyclic antidepressants, serotonin reuptake inhibitors
* Anticholinergic agents or L-dopa should not be discontinued abruptly in
advanced Parkinson disease because the patient may become totally immobilized by a
sudden and severe increase of tremor and rigidity leading to neuroleptic syndrome and
can be fatal. Reducing the medication dose is adequate.
VI. PROGNOSIS
Parkinsons Disease is chronic and progressive. Symptoms and progression
may vary from one individual to another. Some people become severely disabled
while others experience only minor motor disruptions.
Reference:
Fauci AS., Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson LJ, Loscalzo J. 2008.
Harrison’s Principles of Internal Medicine, 17th edition. Mc-Graw-Hill, USA. p25492553
Haines, D. 2006. Fundamental Neurosciences for Basic and Clinical Applications.
MayoClinic. http://www.mayoclinic.com/health/parkinsons-disease/DS00295
Ropper, AH, Brown, RH. 2005. Adams and Victor’s Principles of Neurology, 8th edition. McGraw Hill, USA.
Thomas B, Flint Beal M. 2007. Parkinson’s disease. Human Molecular Genetics. Vol 16
Review Issue 2. R183-R194.
Westmoreland, B., Bennaroch, E., Daube, J., Reagan, T., and Sandok, B. 1994. Medical
Neurosciences: An approach to anatomy, pathology, and physiology by systems and
levels.
Zigmond,
M
and
Burke
R.
Pathophysiology
of
Parkinson’s
Neuropsychopharmacology: The Fifth Generation of progress: 1789-1792.
Disease.