case files neurology
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case files neurology

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with tardive dyskinesia. As Huntington disease
progresses, bradykinesia is a problem and is exacerbated by neuroleptics.
It is not uncommon for these agents to be discontinued as the disease
2. Depression is very common as is irritability and anxiety and usually
treated with selective serotonin reuptake inhibitors (SSRIs).
3. Problems with swallowing and aspiration are apparent late in the
course. Discussion in consideration of percutaneous gastric (PEG) tube
is advised especially early in the course of the disease to provide ade-
quate nutrition and decrease aspiration.
4. Genetic counseling of the patient\u2019s relatives is extremely important.
5. Care should be extended to help to prevent falling and injury.
Table 2\u20131
Neuroleptics (tardive) *
Antiparkinsonian medications
Anticonvulsants *
Amphetamines *
* Those entities that merit consideration in this case.
Comprehension Questions
[2.1] A 24-year-old man is noted to have dance like movements of his arms and
head. The best test to confirm the diagnosis of Huntington disease is:
A. Cerebral positron emission tomography (PET) scanning
B. Genetic testing
C. MRI scan
D. Rectal biopsy
[2.2] The same patient noted in question 2.1 is noted to have disabling
chorea. Which of the following is most likely to be helpful for the chor-
eiform movements?
A. Haloperidol 1 mg 1 to 3 times per day.
B. Carbidopa/levodopa 3 times per day
C. Deep brain stimulation of the subthalamus
D. Fluoxetine 10 mg daily
[2.3] Which of the following clinical features are associated with juvenile or
childhood Huntington disease?
A. Seizures
B. Myoclonus
C. Rigidity
D. Dystonia
E. All of the above
[2.1] B. Greater than 40 CAG repeats in the huntingtin gene confirms the
diagnosis of Huntington disease.
[2.2] A. Judicious use of dopamine-blocking agents are effective in many
patients with chorea. These need to monitored for side effects, particu-
larly parkinsonism and tardive dyskinesia. Levodopa can worsen chorea,
although in Huntington disease patients with significant bradykinesia,
this can be helpful.
[2.3] E. Onset of Huntington disease in childhood (~5% of patients) is more
severe and can be of the Westphal variant, which looks more like
parkinsonism with bradykinesia and rigidity. Dystonia, myoclonus,
and seizures are additional clinical features that may occur.
\u2756 Huntington disease is a classical autosomal dominantly inherited
disease, yet the family history can be negative. However, the
diagnosis can be ruled in with genetic testing.
\u2756 Medications are rarely a complete answer to treatment of
Huntington disease.
\u2756 Abnormal triplet repeat nucleotides such as the three nucleotides
cytosine, adenine, and guanine (CAG) in the huntingtin gene
located on chromosome 4p 16.3 is associated with HD.
\u2756 In huntington\u2019s disease the CAG sequence is repeated between 40
and 100 times and as the repetition grows, the disease becomes
more severe (anticipation).
\u2756 Paternal inheritance (from the father) is more strongly associated
with earlier onset (anticipation) and worse disease.
Anderson KE, Marshall FJ. Behavioral symptoms associated with Huntington\u2019s
disease. Adv Neurol 2005;96:197\u2013208.
Bates GP. History of genetic disease: the molecular genetics of Huntington
disease\u2014a history. Nat Rev Genet 2005;6:766\u2013773.
Handley OJ, Naji JJ, Dunnett SB, et al. Pharmaceutical, cellular and genetic thera-
pies for Huntington\u2019s disease. Clin Sci (Lond) 2006;110:73\u201388.
Semaka A, Creighton S, Warby S, et al. Predictive testing for Huntington
disease: interpretation and significance of intermediate alleles. Clin Genet
\u2756 CASE 3
A 21-year-old man is referred for evaluation and treatment of abnormal
movements. He was doing well until the age of 8 when he developed problems
with supination of the left arm. He later developed tremor of the left hand, abnor-
mal sustained movements of the left leg; in particular, inversion of the left foot,
and back spasms such that he could not walk. His ability to walk improved
somewhat, and he was able to ambulate after age 15. Currently he is attending
college and doing well. He writes and operates a computer keyboard exclusively
with his right hand because of the rhythmic spasms on the left. His voice has
been involved for the past 4 years. He has been tried on trihexyphenidyl, car-
bidopa/levodopa, carbamazepine, and diazepam with very modest improvement.
His examination was remarkable for abnormal involuntary movements of his
upper extremities, left more than right, consisting of a rhythmic, tremor with arm
sustention, associated with wrist flexion/extension as well as a pinching motion
of the thumb and index finger. In addition, there are rhythmic, rostral trunk
movements associated with his movements, and his voice is affected by signifi-
cant tremor. The patient also has rapid, nonstereotyped movements of distal and
proximal muscles that suggest multifocal myoclonus in combination with sus-
tained, stereotypic muscle contractions of the left wrist, arm extensors, and fin-
ger flexors. His head assumes opisthotonic postures with walking but is
extended to the right during much of the examination. His mental status exam,
sensation, tendon reflexes, muscle bulk, and strength is normal. Gait is impaired
because of the involuntary movements described above. There is no postural sta-
bility, and Romberg test is negative. There is also scoliosis to the left.
\u25c6 What is the most likely diagnosis?
\u25c6 What is the next diagnostic step?
\u25c6 What is the next step in therapy?
Summary: This is a 21-year-old man with a history of progressive dystonia
beginning in his left upper extremity and spreading to back and left lower
extremity. His abnormal movements are complex, involving dystonia,
myoclonus, and tremor that limit his posture, gait, and extremity use.
\u25c6 Most likely diagnosis: Primary generalized dystonia\u2013DYT-1
\u25c6 Next diagnostic step: MRI of brain
\u25c6 Next step in therapy: Deep brain stimulation of the globus pallidus,
pars interna
1. Describe the classification of dystonia.
2. Understand the differential diagnosis of dystonia.
3. Describe the diagnostic modalities that are useful in the evaluation of
patients with dystonia.
4. Be aware of the therapeutic modalities that are useful in the treatment
of patients with dystonia.
This is a case of childhood onset of generalized torsion dystonia. Dystonia is
a syndrome characterized by sustained muscle contraction, which provokes
twisting and repetitive movements or abnormal postures. A key differentia-
tion is to identify primary versus secondary dystonia. Secondary dystonia has
an underlying etiology such as drug effect, and can be amenable to therapy,
whereas primary dystonia has no discernible cause. After searching for sec-
ondary causes including laboratory testing and brain imaging, primary dys-
tonia is concluded. In this case, with the early onset, two types (of the 15
types of primary dystonia) would be considered: DYT-1, early-onset torsion
dystonia, caused by mutation in the torsin A gene at chromosome 9q34; and
DYT-5, dopa-responsive dystonia. See Table 3\u20131 for differential diagnosis of
Dystonia\u2014Sustained muscle contractions cause twisting and repetitive
movements or abnormal postures.
Myoclonus\u2014Sudden, involuntary jerking of a muscle or group of muscles.
Opisthotonos\u2014Great rigid spasm of the body with the back fully arched
and the heels and head bent back.
Clinical Approach