Neuropathology in juvenile Huntington disease

Juvenile onset Huntington disease (HD) often has variant clinical and neuropathological features: Case 1 (CAG repeat length 140): Onset age 3 with so‐called cerebral palsy. By age 5 marked dysarthria, bradykinesia and extensor plantar responses. At age 7 generalized seizures and myoclonic jerks. He died at age 8. Grossly there was Vonsattel grade 3 neostriatal atrophy and a small cerebellum. Microscopically there was typical grade 3 neostriatal neuron loss, mild neuron loss in external globus pallidus and thalamus, and severe Purkinje cell loss. Case 2 (family history positive): Onset with behavioral problems at age 10, spasticity and decreased reflexes at age 12, transient mild chorea during rapid alternating movements at 13 (gone at 16), by age 19 obsessive‐compulsive disorder, falls, dysarthria, rigidity, bradykinesia and dystonic posturing which became severe. He died at 21. Grossly there was cortical and brainstem atrophy with grade 3 to 4 neostriatal atrophy. Microscopically there were typical changes of adult HD, plus atrophy and neuron loss in pre‐ and postcentral and especially occipital cortices, and mild Bergmann gliosis in the cerebellum with neuronal atrophy in the dentate nucleus. These findings show that chorea is not necessarily the main manifestation of neuronal dysfunction and death in HD, and that cerebral and cerebellar cortices may show pathologic changes. Supported by NIH.