Neuroradiology Case of the Month

November 2002

Ramon de Guzman, MD and P-L Westesson, MD, PhD, DDS

Clinical Presentation: A 47-year-old man presented after an accident with injury to the head and face. He had ecchymosis, blurry vision and there was a question of injury to the skull or brain.

Radiological Findings: The CT scan of the head did not demonstrate traumatic injuries to the brain. There was, however, brain atrophy and specifically, the head of the caudates and the putamina were atrophic bilaterally (Fig.1).

Figure 1: Axial CT scan shows characteristic atrophy of the head of the caudate bilaterally with the “box-like” appearance of the frontal horns of the lateral ventricles.

Diagnosis: Huntington’s Disease.

Discussion:

Clinical Discussion
The patient had a known history of mental retardation and Huntington’s disease. Huntington’s disease is fairly common and affects approximately 4-5 persons per million [1]. The usual age of onset is in the 4th and 5th decades [1]. It is an inherited autosomal dominant disease with complete penetrance [1]. The marker linked to Huntington’s gene is localized to the short arm of chromosome 4 [2].

Clinically, Huntington’s disease manifests with choreoathetosis (typically), rigidity (less commonly), dementia and emotional disturbance. Once begun, the disease progresses relentlessly, and death occurs within 15 years after onset [1,3].

Neuroimaging Discussion
Neuroimaging as well as pathologic studies shows characteristic atrophy of the caudate and putamen (Fig.1). Caudal atrophy results in the loss of the bulge of the inferior lateral borders of the frontal horns. Volumetric studies of patients with Huntington’s disease should mark the reduction in the volume of striatal structures as well as some reduction in the thalamaus and mesial temporal lobes [4]. Putamen measurements when corrected for head volume have allowed investigators to distinguish effective and control subjects in 100% [5].

31P NMR studies have demonstrated significant elevation in the levels of phosphomonoesters and phosphodiesters in patients with Huntington’s disease compared to controls. This is thought to be secondary to molecular alterations with corresponding metabolic correlates and possibly reflecting a sub-cellular molecular neuropathology [6].

MR spectroscopy, N-acetyl aspartase (NAA) vs. choline has been shown to be reduced in both basal ganglia [7,8] as well as in the cortex of patients with symptomatic Huntington’s disease [9].

References:

1. Adams RD, Victor M. Principles of Neurology, 4th Edition. New York: McGraw Hill Information Service Co. Health Professions Division: 1989:35-77, 334-447, 488-500, 921-967.
2. Gusella JF, Wexler NS, Conneally PM. A polymorphic DNA marker genetically linked to Huntington’s disease. Nature 1983;306:234-238.
3. Kanazawa I. Clinical pathophysiology of basal ganglia disease. IN: Vinkin PJ, Bruyn GW, Klawans HL, Eds. Handbook of Clinical Neurology. Vol. 49, Amsterdam, Elsevier Science;1986, 65-86.
4. Jernigan TL, Salmon DP, Butters N et al. Cerebral structure on MRI. Part II. Specific Changes in Alzheimer’s and Huntington’s diseases. Biol Psychiatry 1991;29:68-81.
5. Harris GJ, Pearlson GD, Peyser CE et al. Putamen volume reduction on magnetic resonance imaging exceeds caudate changes in mild Huntington’s disease. Ann Neurol 1992;31:69-75.
6. Pettegrew JW, Koop SJ, Minshew NJ et al. 31P Nuclear Magnetic resonance studies of phosphoglyceride metabolism in developing and degenerating brain: preliminary observations. J Neuropathol Exp Neurol 1987;46:419-430.
7. Hoang TQ, Bluml S, Dubowitz DJ et al. Quantitative proton-decoupled 31P MRS and 1H MRS in the evaluation of Huntington’s and Parkinson’s diseases. Neurology 1998;50:1033-1040.
8. Jenkins BG, Koroshetz WJ, Beal MF et al. Evidence for impairment of energy metabolism in vivo in Huntington’s disease using localized 1H NMR spectroscopy. Neurology 1993;43:2689-2695.
9. Harms L, Meierkord H, Timm G et al. Decreased N-acetyl aspartate/choline ratio and increased lactate in the frontal lobe of patients with Huntington’s disease: a proton magnetic resonance spectroscopy study. J Neurol Neurosurg Psychiatry 1997;62:27-30.