Case of the Week
Section Editors: Matylda Machnowska1 and Anvita Pauranik2
1University of Toronto, Toronto, Ontario, Canada
2BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
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March 4, 2021
Huntington Disease
- Background:
- Inherited neurodegenerative disorder caused by an expanded trinucleotide CAG sequence in huntingtin gene (HTT) on chromosome 4
- Intranuclear inclusions of mutated huntingtin interact and impair the function of a number of transcription factors, leading to the loss of GABAergic neurons in the striatum and cortical areas.
- Clinical Presentation:
- Patients present with a movement disorder in the form of choreoathetosis, rigidity (Westphal variant), dementia, and emotional disturbances.
- Key Diagnostic Features:
- Generalized age-inappropriate cortical volume loss
- Atrophy of the corpus striatum involving the caudate and putamen
- The atrophy of the caudate nucleus (CN) results in a loss of the normal bulge of these nuclei on the frontal horns with resultant focal dilatation of the frontal horns, often giving them a "boxlike” configuration.
- Signal changes in the form of either a hyperintensity (due to neuronal loss and gliosis) or hypointensity (iron accumulation) may be seen in the striatum on T2-weighted images.
- MRS: Reduced NAA and creatine in the basal ganglia of 60% of symptomatic and 30% of presymptomatic patients; elevation of lactate in the occipital cortex and basal ganglia which correlates with the duration of symptoms; decrease in NAA/creatine ratio in keeping with neuronal loss in the basal ganglia
- fMRI: Reduced task activation in several subcortical and cortical regions
- 18F-FDG PET: Significant decrease in glucose uptake in the cortex (frontal and temporal lobes) and striatum in both premanifest HD gene carriers and HD patients
- Differential Diagnoses:
- Leigh syndrome: Onset <2 years; T2 hyperintensities in CN and tegmentum; no atrophy of CN or putamen
- Neurodegeneration with brain iron accumulation (NBIA):
- Pantothenate kinase-associated neurodegeneration (PKAN): Iron deposition in the globus pallidus and, to a lesser extent, later in the substantia nigra with classic “eye-of-the-tiger” appearance
- Neuroferritinopathy: Early T2 hyperintensity in basal ganglia; followed by iron deposition and low T2 signal in putamen, globus pallidus, and dentate nucleus; the caudate and thalamus may be involved
- Aceruloplasminemia: Widespread iron deposition, most commonly in CN, putamen, globus pallidus, thalamus, red nucleus, and dentate nucleus; cerebellar atrophy may be present
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Extrapontine myelinolysis: Commonly present with central pontine myelinolysis; involves bilateral ventrolateral thalami, basal ganglia, CN, and internal and external capsules
- Treatment:
- No cure is available.
- Pharmacologic therapy is based on symptom management: dopamine-depleting agents, antidepressants, antipsychotics, and benzodiazepines.
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