Clinical History
The patient is on long-term treatment for depression and a 3-year history of insidious onset of involuntary movement, clumsy gait and slurring of speech, with progressive deterioration. Physical examination revealed choreoathetoid movement of upper and lower limbs and gait disturbance. Her mother died at 40 years with psychiatric illness.
Imaging Findings
Axial T2-weighted and coronal FLAIR MRI of the brain shows widened ventricular system, fissures and sulcal spaces suggestive of early involutional changes. There is atrophy of bilateral caudate nuclei with loss of protrusion on the frontal horns. The lentiform nuclei are also small. The thalami show preserved volumes.
Corresponding MRI images in an age- and gender-matched healthy control are provided for comparison.
Discussion
Huntington’s disease (HD) is a devastating neurodegenerative disorder with autosomal dominant inheritance. It is caused by an expansion (> 36) of the trinucleotide (CAG) repeat in the HD gene in Chromosome 4p, which encodes mutant huntingtin proteins that are thought to be ultimately responsible for the pathological changes in the central nervous system [1, 2].
HD usually manifests in mid-adult life and has a variable onset of presentation, but typically progresses to cognitive, psychiatric and motor deterioration. While a confident diagnosis can be made based on clinical grounds and key finding of positive family history, only genetic molecular testing can confirm HD. This patient was found to have an expanded allele with 48 CAG repeats, indicating full penetrance of the disease.
In the absence of genetic testing, neuroimaging may provide a clue to the diagnosis in the appropriate clinical context, while in diagnosed individuals it plays an important role in monitoring preclinical HD and predicting HD onset [3]. Structural imaging with MRI is preferred over CT, and shows gross atrophy with increased bicaudate ratio (Fig. 2), but also allows more objective regional and global volumetric measurements to be made. Striatal volumes are reduced long before symptoms manifest, and the degree of caudate atrophy has been found to correlate with changes in cognition and motor function [4]. Additional extrastriatal involvement of the pallidum, hippocampus, thalamus, brainstem, grey and white matter may also be present [5, 8]. Cerebral atrophy is a late finding.
More novel imaging techniques are geared towards early identification of abnormalities in tissue microstructure, physiology and function which are believed to occur prior to onset of structural changes [6]. In preclinical HD, striatal and/or extrastriatal regions have been shown to have increased apparent diffusion coefficient, fractional anisotropy and mean diffusion on Diffusion imaging, which are attributed to axonal degeneration [3, 5, 7], while on MR spectroscopy typically show elevated choline and decreased NAA, compatible with neuronal membrane breakdown [8]. Functional MRI depicts early alterations in neuronal activity, while Positron Emission Tomography demonstrates neurophysiological abnormalities [6]. Along with volumetric studies, these techniques play an important role in pharmacologic trials where they are being investigated as surrogate markers of disease response to neuroprotective therapy. However there remains no cure available for HD, and treatment remains symptomatic and supportive.
Differential Diagnosis List
Huntington's disease
Multiple System Atrophy
Early onset dementia
Previous generalised insult from trauma
