Dopaminergic function in spinocerebellar ataxia type 6 patients with and without parkinsonism.

BACKGROUND: Although pure cerebellar ataxia is usually emphasized as the characteristic clinical feature of spinocerebellar ataxia type 6 (SCA6), parkinsonism has been repeatedly described in patients with genetically confirmed SCA6. METHODS: We conducted a positron emission tomography study using a combination of [18F]fluoro-L-dopa for dopamine synthesis and [11C]raclopride for dopamine D2 receptor function on six genetically confirmed SCA6 patients, both with and without parkinsonism. To the best of our knowledge, this is the first dopamine receptor imaging study of patients with SCA6. RESULTS: Most patients had somewhat decreased dopaminergic function, and this decrease was significant in the caudate nucleus. In addition, one SCA6 patient with parkinsonism had whole striatal dysfunction of both dopamine synthesis and dopamine D2 receptor function. CONCLUSIONS: The pathology of SCA6 may not be restricted to the cerebellum, but may also be distributed across various regions, including in both presynaptic and postsynaptic dopaminergic neurons to some degree. Patients with SCA6 may show apparent parkinsonism after the progression of neurodegeneration.

Posterior reversible encephalopathy syndrome in Parkinson disease probably caused by prominent supine hypertension and blood pressure fluctuation.

We present the case of a 77-year-old man with a 10-year history of Parkinson disease (PD), who developed posterior reversible encephalopathy syndrome (PRES). We diagnosed the case as PRES based on clinical features and MRI findings. He experienced orthostatic hypotension and supine hypertension, including nocturnal hypertension. PRES may result from marked supine/nocturnal hypertension and fluctuation in blood pressure. In addition, exacerbated factors could be representative of neuroleptic malignant syndrome. The hypertensive effect of istradefylline should also not be excluded. We believe this is the first case report of a patient with PD developing PRES without vasopressor use.

Cortical and subcortical brain atrophy in Parkinson's disease with visual hallucination.

BACKGROUND: The aim of this study was to investigate the cortical and subcortical brain structures in Parkinson's disease (PD) with visual hallucination (VH), and to elucidate the association between the proposed hypothesis of VH in PD and regional brain volume changes. METHODS: We used 3T magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) to investigate the brain structures of PD patients with VH (PD-VH; n = 13) and PD patients without VH (PD-C; n = 13). RESULTS: The PD-VH patients showed significant cortical atrophy compared to the PD-C patients in the bilateral dorsolateral prefrontal cortex, left rostral region of the prefrontal cortex, left ventral section of the cingulate cortex, bilateral primary visual cortex, and secondary visual cortex including the left inferior occipital gyrus, right lingual cortex, right supramarginal gyrus, and left fusiform gyrus. Significant subcortical atrophic changes were observed in the white matter of the right parahippocampal gyrus, the bilateral posterior part of the cingulate gyrus, the left lingual gyrus, and the right middle occipital gyrus. CONCLUSIONS: VH in PD can occur due to distinctive neuroanatomical involvement.

Impaired pain processing in Parkinson's disease and its relative association with the sense of smell.

BACKGROUND AND PURPOSE: Many non-motor symptoms are associated with Parkinson's disease (PD). Of these, pain and olfactory disturbance tend to be common premotor symptoms. PD has been shown to exhibit abnormal central pain processing, although underlying mechanisms are not yet fully understood. In order to investigate this further, we assessed PD patients by specific Aδ stimulation with intra-epidermal needle electrode and determined olfactory function. METHODS: Forty-two patients (18 males and 24 females) with PD and 17 healthy control subjects (8 males and 9 females) were studied. A thin needle electrode was used to stimulate epidermal Aδ fibers, and somatosensory evoked potentials (SEPs) recorded at the vertex. Olfactory function was evaluated using the Odor Stick Identification Test for Japanese (OSIT-J) and its relationship with pain-related SEPs was investigated. RESULTS: There were no significant differences in N1 latencies or P1 latencies although N1/P1 peak-to-peak amplitudes were significantly lower (p < 0.01) in PD patients than in control subjects. In PD patients, there were significant correlations between N1/P1 amplitudes and disease duration (r = -0.35, p < 0.05), Hoehn-Yahr stage (r = -0.38, p < 0.05) and UPDRS part III (r = -0.42, p < 0.01). Furthermore, the OSIT-J scores correlated with SEP amplitude (r = 0.41, p < 0.01). CONCLUSION: Pain processing in PD patients was impaired under specific nociceptive stimulation of Aδ fibers and significant correlation with smell dysfunction was detected. We suggest that this mechanism may involve the limbic system during PD pathology.

[Development of a telephone survey system for patients with amyotrophic lateral sclerosis using the ALSFRS-R (Japanese version) and application of this system in a longitudinal multicenter study].

To investigate the various clinical courses of patients with amyotrophic lateral sclerosis (ALS), we developed a telephone survey system for determining the activities of daily living (ADL) status of patients with ALS. In this system, every 3 months, clinical research coordinators (CRCs) conducted a telephone survey using the flow charts of the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R; Japanese version). To confirm the reliability of the results of the telephone survey, we compared the scores of 37 ALS patients obtained in the telephone surveys (telephone scores) to the scores obtained during clinical examinations by neurologists (neurologists' scores). The mean (SD) age of the included patients was 62.6 (11.8) years. Eighteen patients answered the surveys themselves, whereas the primary caregivers of 19 patients answered the surveys for the patients. Before the study, we informed the CRCs of the study plan, general knowledge of ALS, procedures of the telephone survey, ethical issues relevant to the study, and requisite considerations for ALS patients and caregivers. The intraclass correlation coefficient (ICC) between the telephone scores and the neurologists' scores in the 37 ALS patients was 0.97 (95% confidence interval [CI], 0.94-0.98). The kappa statistics of 12 questions of the ALSFRS-R between the telephone scores and the neurologists' scores ranged from 0.58 to 0.85. The ICC of the scores of the 18 cases in which the patients answered the telephone questions themselves was 0.96 (95% CI, 0.89-0.98). The ICC of the scores of the 19 cases in which the caregivers answered the telephone questions was 0.97 (95% CI, 0.92-0.99). These results showed a good reliability of the telephone survey, regardless of whether the patients themselves or the caregivers answered telephone questions. In 2006, a longitudinal multicenter study of Japanese ALS patients was initiated called the Japanese Consortium for Amyotrophic Lateral Sclerosis research (JaCALS). In the JaCALS, prospective clinical information was obtained using this telephone survey system. Of the 284 ALS patients who were registered at JaCALS over a year ago, 93% were followed up and provided ALSFRS-R scores and information relevant to prognosis. We have established an efficient and reliable telephone survey system for studying the longitudinal clinical courses of patients with ALS.

Progressive and widespread brain damage in ALS: MRI voxel-based morphometry and diffusion tensor imaging study.

We investigated 17 patients with sporadic amyotrophic lateral sclerosis (ALS) using voxel-based morphometry (VBM) and voxel-based analysis of diffusion tensor images (DTI) at baseline and after a six-month follow-up. Compared with 17 healthy controls, ALS patients at baseline showed only minimal white matter volume decreases in the inferior frontal gyrus but marked decreases in the gray matter of several regions, especially in the bilateral paracentral lobule of the premotor cortex. DTI revealed reduced fractional anisotropy in the bilateral corticospinal tracts, insula, ventrolateral premotor cortex, and parietal cortex. Increased mean diffusivity was noted bilaterally in the motor cortex, ventrolateral premotor cortex, insula, hippocampal formation, and temporal gyrus. At the six-month follow-up, ALS patients showed widespread volume decreases in gray matter, and DTI abnormalities extended mainly into the bilateral frontal lobes, while volume changes in the white matter remained minimal but more distinct. Our combined VBM and DTI techniques revealed extra-corticospinal tract neuronal degeneration mainly in the frontotemporal lobe of ALS patients. In particular, follow-up examinations in these patients showed that whole-brain DTI changes occurred predominantly in the regions of brain atrophy. These objective analyses can be used to assess the disease condition of the ALS brain.

Idiopathic hypertrophic pachymeningitis.

Idiopathic hypertrophic pachymeningitis is a rare disorder of unknown origin. It is a fibrosing inflammatory process that involves the dura mater. Herein are described 14 patients with idiopathic hypertrophic pachymeningitis; their clinical, laboratory and radiological findings, as well as their treatment, are analyzed. Neuropathological findings of six cases including two autopsied cases are also presented. The main clinical features were headache and cranial nerve palsies. Many patients had mild to moderate elevation of C-reactive protein, and three patients had perinuclear antineutrophil cytoplasmic antibody. The CSF in most cases showed inflammatory changes. Neuroimaging studies revealed diffuse or localized thickening of the dura, and MRI findings were key to diagnosis of this disorder. The clinical course was chronic. All patients were treated with corticosteroid and improved intially, but half of them experienced relapses. Two patients received surgical intervention. Pathological examination in two autopsied cases revealed diffuse thickening of the dura, especially in the posterior part of the falx cerebri and the tentorium cerebelli. Microscopic examination of the dura showed dense fibrosis with inflammatory cell infiltration composed mainly of lymphocytes. The cell infiltration was marked at the surface of the dura mater. One case had necrotizing vasculitis of the small arteries located in the dura and the cerebral surface. There were no giant cells, caseation necrosis, or epitheloid granuloma. Four patients underwent biopsy of the dura, and the pathological study showed non-specific inflammatory changes. The relationship of idiopathic hypertrophic pachymeningitis with connective tissue disease or vasculitis syndrome is discussed.