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Washington University Experience | NEURODEGENERATION | Huntington Disease | 11A0 Case 11 History
Case 11 History The patient was a 42yo male with known Huntington's disease of early onset who died at a nursing facility where he lived at age 42. His illness started at age 34 when he noted the gradual onset of resting tremor in both upper limbs that spread to his lower limbs within one year. One year later, he developed difficulty with walking, freezing, and balance. He became stiffer and slower requiring maximal assistance to walk. Speech became softer and more difficult to understand, and he developed occasional dysphagia. His father, paternal uncle, and paternal grandmother had similar symptoms with akinesia and rigidity beginning after the age of 40. None of the "affected" family members had genetic testing before they died and none of the asymptomatic relatives agreed to examination. The phenotype of his mother's grandfather was unknown except that he died of a "neurological problem." At initial evaluation here in the neurology clinic three or four years after onset of his disease, neurological examination showed that he was awake, alert, oriented to person, place, and time but was mildly inattentive. He could register three of three objects but recalled none of three at 5 minutes. Speech was severely dysarthric and hypophonic but language was normal. He had marked facial masking. He had difficulty opening his mouth on command and could barely protrude his tongue. He had normal strength but severe rigidity and bradykinesia in all four limbs. Reflexes were symmetrically brisk in his upper and lower limbs with sustained clonus at the knees and ankles. Plantar reflexes were extensor bilaterally. He had a 3 Hz large amplitude flexion-extension rest tremor in both upper limbs that persisted with action. He had excessive flexion of the upper limbs while standing and circumducted both legs while walking. He had severe postural instability and would fall spontaneously when not assisted. Brain MRI demonstrated marked caudate and putamen atrophy as well as mild diffuse cortical atrophy. Genetic testing for Huntington's disease showed heterozygosity of the 3 CAG repeat region on 4p16.3 with a normal allele of 17 trinucleotide repeats and an abnormal allele of 49 repeats. Genetic testing for the Machado-Joseph spinocerebellar ataxia 3 gene disclosed normal allele lengths (20 and 21 CAG repeats). Levodopa/carbidopa (200 mg/50 mg) provided symptomatic improvement with a 17 point reduction on the unified Parkinson's disease rating scale (LIPDRS) and motor subscale including improvement in tremor, finger and hand dexterity, postural stability, and rising from a chair. While taking levodopa he could rise from a chair independently and walk to the bathroom without assistance for the first time in 2 years. He could feed himself but still required assistance for dressing and bathing. Clinical improvement continued to increase with doses of levodopa up to 800 mg a day but there was no additional benefit at higher doses. He maintained benefit for at least one year and then his clinical status slowly declined with worsening Parkinsonism that was less responsive to levodopa. He also developed significant spasticity requiring baclofen in early 1998. He died at age 42 at his nursing facility. ---- At autopsy the weight of the whole unfixed brain was 1240g.
