Cortical functional abnormality assessed by auditory-evoked magnetic fields and therapeutic approach in patients with chronic dizziness

A long-lasting dizzy sensation is a common complaint in elderly subjects. The pathogenesis and effective treatment of such chronic dizziness (CD), however, have not yet been fully elucidated because of lack of methods for evaluating this sensation. On the basis of assumption that CD may be attributable partly to cortical functional abnormality, we attempted to estimate the function of auditory cortex by measurements of auditory-evoked magnetic fields (AEFs). Magnetic field signals in the parieto-temporal cortex were evoked by 1000-Hz tone-burst with 90-dB normal hearing level sounds, and the highest-amplitude magnetic waveforms at approximately 100-ms (N100m) were analyzed as electrical current arrows in normal subjects (n=11), patients with CD (n=27) and patients with cerebral infarction but no dizzy sensation (n=9). In the normal subjects, the current arrows pointed to a nearly straight line with small directional distortion as indicated by a rotation-degree parameter, dI(rot) of 1.59+/-0.46. In 17 of 27 CD patients, the directions of current arrows were markedly distorted showing abnormally high dI(rot) values greater than 2.50 (the mean plus two standard deviations of normal values) and disclosed a clockwise or counter-clockwise rotation in either side or both sides of parieto-temporal cortex. In all the patients with cerebral infarction, the current arrows exhibited the similar pattern as the normal subjects. None of them exhibited abnormally high dI(rot) values. We hypothesized that the rotational abnormality may be caused by abnormal neuronal excitation, since non-evoked magnetic fields in temporal lobe epilepsy demonstrated the similar current rotational abnormality as reported previously. Seven CD patients were treated with anticonvulsants, and four showed remarkable amelioration of dizzy sensation. In all the four patients with symptomatic amelioration, the disappearance of rotational abnormality in AEFs or the tendency towards disappearance was observed following symptomatic amelioration. The results of the present study suggest that the auditory center may contribute to the maintenance of equilibrium, and its dysfunction may lead to the development of CD. AEFs measurements may make it possible to evaluate the functional abnormality of auditory center and may be useful for studying the pathophysiology and treatment of CD.     

Voxel-based comparison of regional cerebral glucose metabolism between PSP and corticobasal degeneration

OBJECTIVES: Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are neurodegenerative disorders that may be accompanied by dementia and parkinsonism as clinical symptoms. The purpose of this study was to elucidate cerebral metabolic differences of these two diseases with cognitive impairments by [18F] fluorodeoxyglucose (FDG) and positron emission tomography (PET). METHODS: A total of 12 patients with PSP (age: 62.8+/-6.0 years old, m: 7, f: 5, Mini-Mental State Examination (MMSE): 23.4+/-2.6), 12 patients with CBD (age: 64.8+/-6.3 years old, m: 6, f: 6, MMSE: 22.9+/-4.5), and age-matched healthy subjects (normal control (NC)) (age: 63.8+/-7.7 years old, m: 7, f: 5) were subjected to FDG-PET to obtain glucose metabolic images. We compared regional cerebral metabolic images by a voxel-by-voxel analysis with statistical parametric mapping (SPM) among PSP, CBD, and NC subjects, and evaluated differences of hypometabolic regions. RESULTS: The patients with PSP showed reduced cerebral glucose metabolism in the medial and lateral frontal gyri, basal ganglia, and midbrain compared with NC, whereas the patients with CBD showed significant reduction in the parietal lobes (p<0.001). SPM also revealed parietal hypometabolism in CBD patients compared with PSP patients (p<0.001). CONCLUSIONS: The predominant parietal glucose metabolic reduction in CBD patients was different from previously reported findings. This finding would be the characteristic substance of patients with CBD accompanying cognitive impairments. Our findings suggest that measurement of glucose metabolism by PET and a voxel-based analysis is useful to understand the pathophysiology of these two diseases with cognitive impairments.     

Clinicopathological features of chronic hypersensitivity pneumonitis

OBJECTIVE: Only limited information exists concerning the clinical and pathological features of chronic hypersensitivity pneumonitis (HP) in Japan and elsewhere. We present data on clinicopathological features of chronic HP obtained through a Japanese nationwide survey. METHODOLOGY: We studied the clinical and pathological findings in 10 patients with chronic HP who underwent surgical lung biopsy or postmortem examination. RESULTS: There were three types of clinical course: six of the 10 patients had persistent symptoms followed by repeated acute episodes; two showed a subacute onset with persistent symptoms; and two exhibited an insidious onset. Five patients made no attempt to avoid antigen exposure and they all had progressive disease. Pathological findings indicated that lesions were mainly centrilobular with or without epithelioid cell granulomas in specimens obtained during the acute or subacute stage. In contrast, most patients in the chronic stage predominantly showed interstitial fibrosis with a usual interstitial pneumonia pattern. CONCLUSIONS: The pathological findings of chronic HP depend on the stage of the disease at tissue sampling.     

Increased synthesis of calcitonin gene-related peptide stimulates keratinocyte proliferation in murine UVB-irradiated skin

Repeated ultraviolet (UV) irradiations have been shown to induce keratinocyte proliferation with acanthosis, stimulate the cutaneous nerve proliferation, and increase the synthesis of calcitonin gene-related peptide (CGRP). In the current study, we examined the role of CGRP in the UVB-induced proliferation of murine keratinocytes. UVB irradiation increased the number of bromodeoxyuridine (BrdU)-labeled basal keratinocytes and caused acanthosis. In addition, CGRP expression was up-regulated in the peripheral nerves of the upper dermis and lower epidermis. Repeated intradermal injections of CGRP increased the number of BrdU-labeled basal cells and caused acanthosis. Intradermal injections of capsaicin prior to UVB-irradiation inhibited the UVB-induced CGRP expression, BrdU labeling in basal keratinocytes and epidermal thickening. Intradermal injections of anti-CGRP antibody inhibited the UVB-induced BrdU labeling in basal keratinocytes, but epidermal thickening was not significantly inhibited. These results indicate that CGRP is one of the stimulators to UVB-induced keratinocyte proliferation. On the other hand, expression of substance P, another neuropeptide in the peripheral nerve, was not up-regulated by UVB irradiation.     

Combined Analysis of CSF Tau Levels and [(123)I]Iodoamphetamine SPECT in Mild Cognitive Impairment: Implications for a Novel Predictor of Alzheimer's Disease

OBJECTIVE: The aim of this study was to establish an objective and reliable index to predict the development of Alzheimer's disease in a large pool of elderly patients with mild cognitive impairment. METHOD: Twenty-three patients with probable Alzheimer's disease, 22 patients with mild cognitive impairment who eventually developed Alzheimer's disease, eight patients with mild cognitive impairment who did not develop dementia, and 19 cognitively normal subjects were included in the study. The authors constructed a new diagnostic index, the CSF-CBF index, based on CSF tau levels divided by regional cerebral blood flow (CBF) in the posterior cingulate cortex. RESULTS: Receiver operating characteristic analysis showed that applying a cutoff value for the CSF-CBF index of 296.0 achieved a sensitivity of 88.5% and a specificity of 90.0% in discriminating mild cognitive impairment that progressed to Alzheimer's disease from mild cognitive impairment that did not progress to Alzheimer's disease. CONCLUSIONS: The CSF-CBF index is useful in predicting Alzheimer's disease in subjects with mild cognitive impairment.     

2,3,7,8-Tetrachlorodibenzo-p-dioxin treatment induces c-Fos expression in the forebrain of the Long-Evans rat

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most toxic environmental pollutants. In the present study, we examined c-Fos expression in the central nervous system (CNS) after administration of a lethal dose of TCDD to the adult Long-Evans rat to clarify if the CNS participates in TCDD-induced intoxication. A single dose of TCDD (dissolved in olive oil, 50 microg/kg) or olive oil alone was administered to the rats by gavage. Animals were allowed to survive for 1 day to 5 weeks. Three days after the administration, a significantly large number of Fos-immunopositive cells were found in the hypothalamus (i.e. dorsomedial hypothalamic nucleus, paraventricular hypothalamic nucleus, medial preoptic nucleus), central amygdaloid nucleus and bed nucleus of the stria terminalis. These results suggest that some TCDD toxicity may be induced by its direct action on the CNS.     

Evaluation of distal extracranial internal carotid artery by transoral carotid ultrasonography in patients with severe carotid stenosis

BACKGROUND AND PURPOSE: Conventional ultrasonography techniques do not allow visualization of the distal cervical segment of the internal carotid artery (ICA). In a study of patients with severe ICA stenosis, we performed transoral carotid ultrasonography (TOCU) to assess its ability to image this segment of the artery. METHODS: The study participants consisted of 20 consecutive patients who had severe carotid stenosis and who underwent carotid endarterectomy between 1999 and 2000. TOCU, conventional carotid ultrasonography, and cerebral angiography were prospectively performed before and after carotid endarterectomy. RESULTS: In all patients, the distal portion of the ICA could be clearly detected by B mode using TOCU and no plaque was observed. The diameter of the distal portion of the ICA significantly increased after carotid endarterectomy (3.9 +/- 0.5 mm [mean +/- SD]), compared with before (3.5 +/- 0.8 mm), when it was estimated by TOCU (P <.01). In seven patients, the postoperative diameter of the distal ICA increased >10%. The mean increase in the postoperative diameter was estimated to be 15.0 +/- 23.0% by TOCU, which significantly correlated with the findings (23.9 +/- 33.7%) based on cerebral angiography (P <.01). The diameter increased >10% postoperatively in 71% of the patients with the degree of cross-sectional stenosis >95% as shown by carotid ultrasonography and in 86% of the patients whose preoperative diameter was <3.0 mm. CONCLUSION: TOCU provides additional information regarding the characteristics of the distal ICA that can be obtained neither by conventional carotid ultrasonography nor by angiography.     

Alteration of the horizontal mandibular condyle size associated with temporomandibular joint internal derangement in adult females

OBJECTIVES: The purpose of this retrospective study was to analyse the relationship between horizontal size of the mandibular condyle and internal derangement (ID) of the temporomandibular joint (TMJ). METHODS: One hundred and thirty-nine joints in 88 women aged over 18 years were included in this study. The horizontal condylar size was measured in the antero-posterior and medio-lateral (ML) dimensions using axial magnetic resonance (MR) images. Radiological findings of ID were also assessed from MR imaging. RESULTS: The condyles in the joints with permanent disk displacement were smaller than those in joints without displacement in both dimensions (Fisher's protected least significant difference, P<0.05). There were statistically significant correlations between horizontal condylar size in the ML dimension and both disk morphology and radiological stage of ID (Spearman's correlation coefficient by rank, P<0.05). CONCLUSIONS: The results of this study suggest a possible relationship between horizontal condylar size and disk displacement. It is also suggested that the condyle becomes smaller in the ML dimension with advancement of ID.