case files neurology
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case files neurology


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there is a physiologically incon-
gruent examination.
[3.3] A. Haloperidol is a potent blocker of dopamine D2 receptors and is a
common agent responsible for dystonic reactions in otherwise healthy
individuals.
CLINICAL PEARLS
\u2756 DYT-1 dystonia is an autosomal dominant disease, which can be
confirmed with genetic testing.
\u2756 DYT-1 and other primary dystonias usually have the abnormal
movements in association with action early in the course of the
disease.
\u2756 In mild cases of DYT-1 and other primary generalized dystonias,
systemic drugs, such as anticholinergics, benzodiazepines, and
baclofen may control symptoms, in severe cases, deep brain stim-
ulation of the globus pallidi may be required.
REFERENCES
Albanese A. The clinical expression of primary dystonia. J Neurol 2003;250:1145\u20131151.
Albanese A, Barnes MP, Bhatia KP, et al. A systematic review on the diagnosis and
treatment of primary (idiopathic) dystonia and dystonia plus syndromes: report
of an EFNS/MDS-ES Task Force. Eur J Neurol 2006;13(5):433\u2013444.
Geyer HL, Bressman SB. The diagnosis of dystonia. Lancet Neurol 2006;5:780\u2013790.
Krauss JK, Yianni J, Loher TJ, et al. Deep brain stimulation for dystonia. J Clin
Neurophysiol 2004;21(1):18\u201330.
Manji H, Howard RS, Miller DH, et al. Status dystonicus: the syndrome and its
management. Brain 1998;121:243\u2013252.
Tarsy D, Simon DK. Dystonia. N Engl J Med 2006;355:818\u2013829.
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\u2756 CASE 4
The patient is a 55-year-old man in good health until about 6 months ago. At
that time he noticed development of a tremor. He has no other complaints. On
examination, there is a tremor in the right arm at rest and while he walks, he
has a sustained tremor in both arms, and to some degree during finger-nose-
finger maneuver (fairly fine and without an obvious rhythm). He has a poker
face and a slow, deliberate gait. Tone is increased in the right arm and leg. The
physical examination is otherwise unremarkable. He and his wife deny his use
of alcohol or any other medications.
\u25c6 What is the most likely diagnosis?
\u25c6 What is the next diagnostic step?
\u25c6 What is the next step in therapy?
ANSWERS TO CASE 4: Parkinson Disease
Summary: This is a middle-aged man with asymmetric onset of tremor. In
addition he has mild poverty of movement (otherwise known as akinesia of the
face and body), tremor at rest, as well as increased tone.
\u25c6 Most likely diagnosis: Parkinson disease.
\u25c6 Next diagnostic step: Do an MRI of the brain to evaluate other
disorders in the differential diagnosis.
\u25c6 Next step in therapy: If the current symptoms are causing the patient
disability, initiate therapy with either dopamine agonist or monoamine
oxidase type B (MAO-B) inhibitor.
Analysis
Objectives
1. Understand the differential diagnosis of parkinsonism.
2. Know the clinical characteristics of Parkinson disease.
3. Describe the usefulness of different imaging modalities for evaluating
spinal cord injury and the importance of patient age.
4. Be aware of the different treatment options for Parkinson disease and
their role and liabilities.
Considerations
The patient described in the case above has tremor at rest, rigidity, and hypoki-
nesia, which are the three cardinal features of Parkinson disease\u2013and consti-
tute the syndrome of parkinsonism. The fourth of the cardinal features is
postural instability, which in idiopathic Parkinson disease typically has onset
several years later. The most common cause of parkinsonism is idiopathic
Parkinson disease. A careful search for secondary causes of parkinsonism should
be undertaken such as a history of medication use (antipsychotic agents),
metabolic or structural diseases of the brain (hydrocephalus), and infectious
etiologies. MRI of the brain is typically performed. Levodopa is a standard
agent used to treat the symptoms of Parkinson disease; unfortunately, no agent
has been shown to slow the progress of the disease.
APPROACH TO SUSPECTED PARKINSON DISEASE
Definitions
Substantia nigra\u2014(Latin for \u201cblack substance\u201d) or locus niger is a heteroge-
neous portion of the midbrain, and a major element of the basal ganglia sys-
tem. It consists of the pars compacta, pars reticulata, and the pars lateralis.
40 CASE FILES: NEUROLOGY
Lewy body\u2014an eosinophilic, round inclusion found in the cell cytoplasm
of substantia nigra, the nucleus basalis of Meynert, locus ceruleus, dor-
sal raphe, and the dorsal motor nucleus of cranial nerve X. They contain
alpha-synuclein, a presynaptic protein, the function of which is
unknown. Neurofilament proteins and ubiquitin are other important con-
stituents of Lewy bodies.
Clinical Approach
Parkinson disease is a disorder that gets its name from the Essay on the
Shaking Palsy by James Parkinson. Features of Parkinson disease can be
expressed in other ways including: difficulty arising from a chair, difficulty
turning in bed, micrographia, masked face, stooped, shuffling gait with
decreased arm swing; and sialorrhea. Although Parkinson disease is thought of
as a motor disorder, sensory systems are also affected. Loss of sense of smell
is almost universal. Pain is very common. Other system involvement can result
in autonomic disturbance, depression, a variety of speech disturbances includ-
ing dysarthria, palilalia, and stuttering. In Parkinson\u2019s monograph, he specifi-
cally stated \u201cthe senses and intellect are preserved.\u201d Research has shown that
isolated cognitive deficits are extremely common in Parkinson disease, espe-
cially executive dysfunction. In addition approximately 50% of patients
develop dementia.
The most obvious pathologic feature of Parkinson disease is loss of pig-
ment in the substantia nigra caused by loss of neurons in this region. The
remaining neurons may show an intra-cytoplasmic eosinophilic inclusion
called a Lewy body (Fig. 4\u20131). These neurons project rostrally in the brain to
innervate the striatum as well as the cerebral cortex. Parkinson disease is asso-
ciated with marked striatal dopamine (DA) depletion and is considered by
many to be a striatal dopamine deficiency syndrome. At death, DA loss is
greater than 90%, and approximately 70% DA loss results in symptom expres-
sion. Severity of DA loss best correlates with bradykinesia in Parkinson
disease\u2014the correlation with tremor is very poor. In recent years, we have
seen a much more comprehensive picture of the pathologic destruction by
Parkinson disease, which helps us to understand the wide variety of signs and
symptoms besides bradykinesia. Other morphologic and chemical deficits
have also been demonstrated in the brains of patients with Parkinson disease
in the cholinergic pedunculopontine nucleus, noradrenergic locus coeruleus,
serotonergic raphe nuclei, and glutamatergic centromedian/parafascicularis
complex of the thalamus. Still, there are many signs and symptoms that are
atypical for Parkinson disease and should raise our level of vigilance that
another disorder is present. These include:
\u2022 Early onset of, or rapidly progressing, dementia
\u2022 Rapidly progressive course
CLINICAL CASES 41
\u2022 Supranuclear gaze palsy
\u2022 Upper motor neuron signs
\u2022 Cerebellar signs\u2014dysmetria, ataxia
\u2022 Urinary incontinence
\u2022 Early symptomatic postural hypotension
\u2022 Early falls
The majority of cases of Parkinson disease are unknown. Familial Parkinson
disease, while rare, does occur, and is most commonly associated with a muta-
tion of the parkin gene, which is inherited in an autosomal recessive pattern.
This mutation is the most common cause of early onset Parkinson disease,
without Lewy bodies. Routine neuroimaging is usually normal in Parkinson
disease. Functional imaging designed to visualize the dopamine innervation of
the striatum, especially in combination with other imaging techniques may
provide a way to positively identify the disease, however these techniques