No abstract

We showed that humanin (HN), an endogenous peptide against Alzheimer disease-related insults, was expressed in muscles of patients with chronic progressive external ophthalmoplegia (CPEO), a major mitochondrial disease. Because HN was recently found to block proapoptotic Bax function and exert its versatile cytoprotective effects in association with an increase in ATP levels, HN expression may thus reflect a physiological response against degenerative changes in the muscles of patients with CPEO. We found HN expression in all four patients examined, each of whom had different mitochondrial DNA mutations including two different single DNA deletions, multiple deletions, and no major mutations detected. We also found that HN expression was not linked to focal cytochrome c deficiency, strongly associated with the subtype of CPEO with single deletions. These results suggest that HN expression is more closely related to degenerative changes in all types of CPEO. Notably, HN was also expressed in non-degenerative muscle fibers of patients with CPEO or Leigh syndrome, who had the 8993T>G mutation in the mitochondrial ATPase 6 gene known to be associated with impaired ATP synthesis. Collectively, our findings suggest that HN may be specifically expressed in response to defects in energy production in muscles with mitochondrial abnormalities.

Background: The relation between atherosclerosis and brain atrophy remains unclear in patients with risk factors for cardiovascular diseases. Objective: This study was performed to clarify the relation between brain atrophy and carotid atherosclerosis. Methods: A total of 142 patients (78 women and 64 men, mean age 74 years) with no neurologic disturbances were studied. Brain atrophy was evaluated on the basis of the brain atrophy index (BAI, BAI = brain parenchyma/intracranial space A 100%), calculated by means of digitized computed tomographic scans obtained at the level of the basal ganglia. Carotid atherosclerosis was evaluated on the basis of the plaque score (PS), defined as the sum of all plaque heights in both carotid arteries, intima-media thickness (IMT), and vessel diameter (VD) of the common carotid artery as assessed by ultrasonography. Results: Age negatively correlated with BAI in both men (r = –0.587, p < 0.001) and women (r = –0.724, p < 0.001). PS of the carotid artery also negatively correlated with BAI in men (r = –0.502, p < 0.001) as well as women (r = –0.480, p < 0.001). VD and IMT of the right carotid artery negatively correlated with BAI in women (VD; –0.256, p < 0.05, IMT; –0.216, p < 0.05) but not in men. Other characteristics were unrelated to BAI. Multiple regression analysis showed that age and PS were independent predictors of brain atrophy in both sexes. The percentage of variance of BAI values explained by this model in women (51.9%) was much greater than that in men (35.5%). Conclusion: Carotid atherosclerosis may be a useful morphological index of brain atrophy.

Purpose: To quantify impairment of the basal ganglia (globus pallidus and thalamus) in adult-onset dentatorubral-pallidoluysian atrophy (DRPLA).Methods: Five patients with genetically deˆnite adult-onset DRPLA (aged 51 to 65 years, mean 55.6 years) and 5 age-and sex-matched healthy controls underwent conventional magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) of the brain in the voxels predominantly containing the globus pallidus or the thalamus.Results: Conventional MRI studies showed apparently normal intensities in the globus pallidus and thalamus. MRS showed that the choline (Cho) W creatine (Cr) ratio for the patients' globus pallidus, the region preferentially aŠected in DRPLA, was signiˆcantly higher than that in the controls (pº0.05). The N-acetylaspartate (NAA) W Cr ratio for the globus pallidus and the Cho W Cr and NAA W Cr ratios for the thalamus, the region relatively spared in this disease, did not diŠer signiˆcantly between the patients and controls.Conclusions: MRS may sensitively and speciˆcally detect biochemical alterations in susceptible regions of patients with adult-onset DRPLA.

Brainstem encephalitis is not a classic paraneoplastic syndrome and usually involves monophasic neurological deterioration and has negative magnetic resonance imaging (MRI) findings. We describe a patient with brainstem encephalitis who had elevated anti-Ri antibody levels and double-step neurological deterioration associated with different abnormal lesions on MRI. Immunosuppression with steroids and intravenous immune globulin combined with aggressive treatment of the tumor successfully led to the resolution of brainstem symptoms and MRI lesions. In patients with unusual signs and symptoms of paraneoplastic encephalitis mimicking multiple sclerosis, onconeural antibody studies are recommended.