A sixty-one-year-old Caucasian female initially presented with 2 years of progressive generalised chorea, anxiety and memory difficulties.  These symptoms steadily progressed over the next 5 years as she developed dementia and progressive gait disturbance with pyramidal weakness. In the terminal stages of her illness, at sixty-six-years-old, she had recurrent hospital admissions for pyrexia of unknown origin and finally refractory seizures and death.

Her serum investigations were non-diagnostic; she was negative for both CADASIL and Huntington Disease mutations.  Her MRI demonstrated diffuse confluent white matter changes involving the corpus callosum and the vermis.  She also had an abnormal electroencephalogram late in the course of her disease, with lateralised periodic discharges recorded during episodes of non-convulsive status epilepticus.

Her autopsy revealed pathognomonic histologic features of Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP).  Since the most commonly implicated mutated gene, CSF1R, did not reveal significant abnormalities, post-mortem whole exome sequencing was undertaken and is near completion.

Our case demonstrates the possibility of establishing an accurate diagnosis with imaging, histopathology and genetic testing in cases of early-onset dementia with white matter changes.  Recently elucidated entities offer diagnostic closure to patients, families and clinicians and can inform prognosis and genetic counselling.  Furthermore, potential therapeutic options for leukodystrophies appear to be on the horizon.  Our case report is the first, to our knowledge, in the literature to present with generalised chorea and to exhibit vermian hyperintensity on T2-weighted MRI.