Cervical Spinal Cord Degeneration in Spinocerebellar Ataxia Type 7.

BACKGROUND AND PURPOSE: Spinocerebellar ataxia type 7 is an autosomal dominant neurodegenerative disease caused by a cytosine-adenine-guanine (CAG) repeat expansion. Clinically, spinocerebellar ataxia type 7 is characterized by progressive cerebellar ataxia, pyramidal signs, and macular degeneration. In vivo MR imaging studies have shown extensive gray matter degeneration in the cerebellum and, to a lesser extent, in a range of cortical cerebral areas. The purpose of this study was to evaluate the impact of the disease in the spinal cord and its relationship with the patient's impairment. MATERIALS AND METHODS: Using a semiautomated procedure applied to MR imaging data, we analyzed spinal cord area and eccentricity in a cohort of 48 patients with spinocerebellar ataxia type 7 and compared them with matched healthy controls. The motor impairment in the patient group was evaluated using the Scale for Assessment and Rating of Ataxia. RESULTS: Our analysis showed a significantly smaller cord area (t = 9.04, P < .001, d = 1.31) and greater eccentricity (t = -2.25, P =. 02, d = 0.32) in the patient group. Similarly, smaller cord area was significantly correlated with a greater Scale for Assessment and Rating of Ataxia score (r = -0.44, P = .001). A multiple regression model showed that the spinal cord area was strongly associated with longer CAG repetition expansions (P = .002) and greater disease duration (P = .020). CONCLUSIONS: Our findings indicate that cervical spinal cord changes are progressive and clinically relevant features of spinocerebellar ataxia type 7, and future investigation of these measures as candidate biomarkers is warranted.

Multimodal neurometabolic investigation of the effects of zolpidem on leukoencephalopathy-related apathy.

BACKGROUND AND PURPOSE: The symptomatic effect of zolpidem on apathy has been reported in neurological disorders such as strokes and post-anoxic brain injuries, but not in white-matter disease of the brain. METHODS: A 38-year-old patient presenting with severe apathy related to a genetic leukoencephalopathy but showing marked improvement of apathy after taking 10 mg of zolpidem was studied. To understand what may mediate such a clinical effect, a multimodal neurometabolic approach using 18 F fluorodeoxyglucose positron emission tomography (FDG-PET) and a dedicated magnetic resonance spectroscopy (MRS) sequence for gamma aminobutyric acid (GABA) and glutamine + glutamate metabolism was undertaken. RESULTS: Pre-zolpidem FDG-PET showed hypometabolism in the orbitofrontal cortex, dorsolateral cortex and basal ganglia compared to healthy controls. Post-zolpidem, FDG-PET displayed increased metabolism in the orbitofrontal cortex together with improvement in the emotional and auto-activation domains of apathy. There was no improvement in the cognitive domain of apathy, and no change in metabolism in the dorsolateral frontal cortex. Post-zolpidem, MRS showed increased GABA and glutamine + glutamate levels in the frontal cortex and pallidum. CONCLUSION: Our multimodal neurometabolic study suggests that the effects of zolpidem on apathy are related to increased metabolism in the orbitofrontal cortex and basal ganglia secondary to GABA modulation. Zolpidem may improve apathy in other white-matter disorders.