Widespread cortical and subcortical brain atrophy in Parkinson's disease with excessive daytime sleepiness.

Our aim was to determine regional brain atrophy in Parkinson's disease (PD) patients with excessive daytime sleepiness (EDS) using voxel-based morphometry (VBM). From 71 consecutive probable PD patients, nine non-demented and non-hallucinating patients with an Epworth Sleepiness Scale (ESS) ≥ 10 and 13 PD patients with an ESS ≤ 3 were selected as having EDS and as not having EDS, respectively. We also enrolled 22 healthy age- and sex-matched controls. Regional brain atrophy was assessed using VBM with 3-T magnetic resonance imaging. There was no difference in the dosage of dopaminergic drugs between PD patients with EDS and PD patients without EDS. PD patients with EDS showed marked atrophy in the gray matter of the frontal lobe, temporal lobe, occipital lobe, limbic lobe including the nucleus basalis of Meynert compared to controls (false discovery rate corrected p < 0.05). In contrast, PD patients without EDS did not show any significant difference in gray matter atrophy compared to controls (false discovery rate corrected p < 0.05). PD patients with EDS showed significant atrophy of the frontal lobe, temporal lobe, occipital lobe, limbic lobe including the nucleus basalis of Meynert compared to PD patients without EDS (uncorrected p < 0.001). PD patients with EDS, even without dementia and hallucination, showed significant gray matter atrophy compared to PD patients without EDS and controls.

B-type natriuretic peptide and cardiovalvulopathy in Parkinson disease with dopamine agonist.

OBJECTIVE: To elucidate the usefulness of plasma B-type natriuretic peptide (BNP) values for evaluating adverse effects of pergolide or cabergoline on cardiovalvulopathy in patients with Parkinson disease. METHODS: Twenty-five patients treated with pergolide or cabergoline (ergot group) and 25 patients never treated with ergot derivatives (non-ergot group) were enrolled. Plasma BNP values and detailed echocardiography were evaluated. Thirty age- and gender-matched controls were similarly evaluated. RESULTS: Patients with regurgitation more than grade 3 were more frequent in the ergot group than in the non-ergot group as well as control groups (24%, 0%, 3%, p = 0.001). Both composite regurgitation scores and plasma BNP values were significantly higher in the ergot group than in controls. In the ergot group, the cumulative dose correlated to both tenting area (r = 0.57, p = 0.004) and tenting distance (r = 0.62, p = 0.001). Furthermore, plasma BNP values were higher in patients with severe or multiple regurgitation groups (p < 0.001), and were correlated with composite regurgitation score (r = 0.70, p < 0.001). Multiple regression analyses revealed that BNP values were independently correlated with both composite regurgitation and left ventricular ejection fraction. CONCLUSION: The combination of comprehensive echocardiography and plasma B-type natriuretic peptide levels elucidates the presence of cardiac damage in patients with Parkinson disease using ergot derivative dopamine agonists.

Cognitive impairment in spinocerebellar ataxia type 6.

OBJECTIVE: The aim of this study was to evaluate cognitive impairment in patients with spinocerebellar ataxia type 6 (SCA6) and to verify the role of cerebellar involvement in intellectual abilities. METHODS: Cognitive function was examined in 18 patients with genetically confirmed SCA6 and in 21 age and education matched controls using a test battery for attention, verbal and visuospatial memory, as well as executive function. RESULTS: Verbal fluency and immediate visual memory task were markedly impaired in SCA6 compared with the control group (p = 0.007, 0.004 and 0.014, respectively). The results of the Rule Shift Cards Test was reduced in patients with SCA6, but the reduction was not significant. These cognitive dysfunctions did not correlated with CAG repeat length, age at onset, ataxic motor dysfunctional scale or depression. CONCLUSIONS: Our results demonstrate that specific cognitive deficits occur in patients with SCA6, independent of ataxic motor dysfunction. These deficits may reflect disruption of cortico-cerebellar circuits.

Primary lateral sclerosis presenting parkinsonian symptoms without nigrostriatal involvement.

We encountered three patients with primary lateral sclerosis (PLS) showing bradykinesia, frozen gait, and severe postural instability, as well as slowly progressive spinobulbar spasticity. Cranial magnetic resonance (MR) imaging showed precentral gyrus atrophy. Central motor conduction was markedly prolonged or failed to evoke a response. Positron emission tomography (PET) showed significant reduction of [18F]fluoro-2-deoxy-D-glucose uptake in the area of the precentral gyrus extending to the prefrontal, medial frontal, and cingulate areas. No abnormalities were seen in the nigrostriatal system with PET using [18F]fluorodopa or [11C]raclopride or with proton MR spectroscopy. Thus, widespread prefrontal, medial, and cingulate frontal lobe involvement can be associated with the parkinsonian symptoms in PLS.

Diversity of V gamma gene segments rearranged to the J gamma 4 gene in mice.

Because there are limited numbers of V gamma gene segments and most V gamma rearrangements occur within clusters of the J gamma-C gamma genes in mice, gamma-chains display limited diversity compared with other TCR chains. In this study, we examined the nucleotide sequences of the V gamma-J gamma genes expressed in the gamma delta T cells appearing at the inflamed sites after Salmonella infection in DBA/2 mice. Most of the productive gamma gene rearrangements were V gamma 1-J gamma 4, whereas V gamma 2 and a unique V gamma, the 5' region of which was identical with sequences of the V gamma 2 gene, and the 3' region of which was identical with that of the V gamma 1 gene, were found to be rearranged to J gamma 4 gene, albeit at low frequency. Analysis of the ontogenic appearance of the rearrangements in the J gamma 4-C gamma 4 locus revealed that V gamma 2-J gamma 4 gene rearrangement was frequent in fetal thymocytes at the early stage of gestation. Most of the early fetal V gamma 2-J gamma 4 rearrangements exhibited the identical junction, a nonfunctional canonical sequence. The sequence analysis of the coding joint and the reciprocal recombination signal joint suggests that short homology-mediated direct recombination and chromosomal inversion mechanism are involved in fetal V gamma 2-J gamma 4 gene rearrangement. Taken together, our data suggest that the recombination of multiple V gamma segments with J gamma 4 can diversify the V gamma repertoire.