Cerebral atrophy and its relation to cognitive impairment in Parkinson disease.

OBJECTIVE: Voxel-based morphometry was used to compare the amounts of gray matter in the brains of patients with Parkinson disease (PD) and normal control subjects (NCs) and to identify the specific regions responsible for cognitive dysfunction in PD. METHODS: Patients were classified into nondemented (ND) and demented (D) groups according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders (4th ed.), and a group comparison was performed. In the ND patients, a correlation was also performed between local gray matter density and the score on Raven Colored Progressive Matrices (RCPM), a test of executive and visuospatial function. RESULTS: In patients with advanced ND-PD vs NCs, atrophic changes were observed in the limbic/paralimbic areas and the prefrontal cortex. In D vs ND patients, atrophic change was observed widely in the limbic/paralimbic system, including the anterior cingulate gyrus and hippocampus as well as the temporal lobe, dorsolateral prefrontal cortex, thalamus, and caudate nucleus. The RCPM score was positively correlated with the gray matter density in the dorsolateral prefrontal cortex and the parahippocampal gyrus. CONCLUSIONS: In patients with Parkinson disease (PD), atrophic changes occur mainly in the limbic/paralimbic and prefrontal areas. These atrophic changes may be related to the development of dementia in PD.

Occipital hypoperfusion in Parkinson's disease without dementia: correlation to impaired cortical visual processing.

OBJECTIVE: The purpose of this study was to analyse changes in regional cerebral blood flow (rCBF) in Parkinson's disease (PD) without dementia. METHODS: Twenty eight non-demented patients with PD and 17 age matched normal subjects underwent single photon emission computed tomography with N-isopropyl-p-[(123)I]iodoamphetamine to measure rCBF. The statistical parametric mapping 96 programme was used for statistical analysis. RESULTS: The PD patients showed significantly reduced rCBF in the bilateral occipital and posterior parietal cortices (p<0.01, corrected for multiple comparison p<0.05), when compared with the control subjects. There was a strong positive correlation between the score of Raven's coloured progressive matrices (RCPM) and the rCBF in the right visual association area (p<0.01, corrected for multiple comparison p<0.05) among the PD patients. CONCLUSIONS: This study showed occipital and posterior parietal hypoperfusion in PD patients without dementia. Furthermore, it was demonstrated that occipital hypoperfusion is likely to underlie impairment of visual cognition according to the RCPM test, which is not related to motor impairment.

Age-related changes in brain neuromagnetic responses to face perception in humans.

In order to investigate the effects of ageing on face perception, we studied the magnetic responses to face images in 15 young (19-38 years) and 10 elderly (51-81 years) subjects. Face-specific responses (160mF), which originate in the inferior occipitotemporal cortices, and face non-specific responses (100m), which originate in the primary visual cortices, were evoked in all subjects. Averaged peak latency of the 160mF in the elderly group (174.0+/-9.1 ms) was significantly longer (P<0.0005) than that in the young group (161.5+/-5.1 ms), while no inter-group difference was found in the 100m latency. There was a significant correlation between age and 160mF latency (+0.35 ms/year, R=0.747) suggesting age-related decline of face perception.

Effects of pinealectomy and sham-surgery on the area postrema in rats: a quantitative histological study with special reference to capillaries and neuronal cell nuclei.

This study aimed to clarify the effects of pinealectomy and sham-surgery on the area postrema (AP) by quantitative histological methods. Male, Wistar rats of normal (NO), sham-operated (SX), and pinealectomized (PX) groups were used in the late dark phase at 7 weeks of age. Consecutive frontal sections including the AP were stained with hematoxylin and eosin, and immunostained using PGP 9.5 for neurons, or GFAP or vimentin for glial cells. Consecutive sections of the AP were separated into five portions starting from the point of the central canal opening to the fourth ventricle in the caudal direction, and used for measurements. Mean cross-sectional areas of capillaries showed a lower value in the SX group than in the other two groups (vs NO, P<0.005; vs PX, P<0.03). In addition, the frequency distributions of the nuclear diameters of nerve cells showed different patterns among the three experimental groups (P<0.01), the frequency of large nuclei being higher in the SX group than in the other two groups. Possible mechanisms of the effects of sham-pinealectomy and pinealectomy and significance of the pineal-AP relation are discussed. The results of this study indicate that stuctural changes in the AP can be induced by intracranial surgery, suggesting certain pineal involvement in these changes.

[Medical treatment of dystonia].

The treatment of dystonia is exclusively difficult. Recently botulinum toxin has been introduced into the market, but its indication is still limited. Oral administration of high dosage of anticholinergic drugs is firstly recommended for the treatment of dystonia. Effective cases usually do not show obvious side effects. Likely, diazepam is another choice, and the drug usually does not bring any adverse effect in cases with good results. Effects of other drugs such as l-dopa and antidopaminergic agents are still under discussion. In cases with myoclonus and/or tremor clonazepam can be useful for improvement of the phasic symptoms. As the prognosis of dystonia especially that of focal dystonia is not hopeless, the patients with dystonia should be informed of the facts.

Extrastriatal mean regional uptake of fluorine-18-FDOPA in the normal aged brain--an approach using MRI-aided spatial normalization.

The aim of this study was to define the mean regional 6-[(18)F]fluoro-l-dopa (FDOPA) uptake rate constant (K(i)) values in the striatal and extrastriatal regions of the brain of normal subjects using magnetic resonance imaging (MRI)-aided spatial normalization of the FDOPA K(i) image and using automatic region of interest (ROI) analysis. Dynamic three-dimensional FDOPA positron emission tomography (PET) and three-dimensional magnetic resonance (MR) images were acquired in 13 aged normal subjects. The FDOPA add image and the K(i) image of each subject were transformed into standard stereotactic space with the aid of individual coregistered MR image. The mean regional K(i) values of the striatal and extrastriatal regions before normalization were compared with the respective values after normalization. Then automatic ROI analysis was performed on the MRI-aided spatially normalized K(i) images of the 13 normal subjects. The K(i) values on original images and those on spatially normalized images were in good agreement, indicating that the spatial normalization technique did not change the regional K(i) values appreciably. Automatic ROI analysis of the spatially normalized FDOPA K(i) images of the normal subjects, showed high K(i) values in ventral and dorsal regions of the midbrain, amygdala, hippocampus, and medial prefrontal cortex, in addition to caudate nucleus and putamen, which correspond to the dopaminergic projections in the brain. Spatial normalization technique helped to establish a database of FDOPA K(i) images of normal subjects and high K(i) values were observed widely besides striatal regions corresponding to the dopaminergic projections in the brain.

Effect of swallowing training on swallowing disorders in Parkinson's disease.

The purpose of the present study was to determine whether swallowing training improves swallowing function in patients with Parkinson's disease. Ten patients (5 males, 5 females) who had symptoms of dysphagia and 12 healthy volunteers were studied. The initiation time of the swallowing reflex, the "premotor time" (PMT), was calculated from an electromyogram of the submental muscles before and after swallowing training. Patients with Parkinson's disease had a significantly longer PMT (p = 0.0014) than did healthy controls. There was no correlation between PMT and the duration of the disease (r = -0.146; p = 0.6867) or the patient's age (r = 0.602; p = 0.0653). After swallowing training, the patients' PMTs decreased significantly (p = 0.0051).

[Diagnostic utility of positron emission tomography for parkinsonism after chronic manganese exposure].

Positron emission tomography (PET) with [18F] 6-fluoro-L-dopa (18F-FDOPA) was performed in three South Korean patients with parkinsonism who developed after chronic manganese exposure. A 51-year-old man (patient 1) suffered from masked face, marked postural tremor of hands, dystonia in the neck and the upper extremities, severe retropulsion and lateropulsion which were typical for chronic manganese intoxication. 18F-FDOPA scan was normal. Other two patients, a 46-year-old man (patient 2) and a 47-year-old man (patient 3), showed tremor at rest and rigidity predominantly on the right side, bradykinesia, stooped posture and postural instability; all of these were typical for Parkinson's disease (PD). There was reduced uptake of 18F-FDOPA in the striatum, particularly in the posterior putamen predominant on the left side, in both patient 2 and 3. From these results, patient 1 was diagnosed as pure manganism, while patient 2 and 3 were primarily as PD, because loss of nigrostriatal fibers was obvious with asymmetry of affection in the putamen. PET with 18F-FDOPA provides valuable information for differentiation between PD and manganism, although it is not clear whether development of parkinsonian symptoms in patient 2 and 3 was modified by excessive manganese exposure.

[Quality of life in elderly patients with cerebral vascular disease and Parkinson's disease].

We developed a questionnaire for the study of background factors and quality of life (QOL) in elderly patients with cerebral vascular disease (CVD) and Parkinson's disease (PD). The questionnaire covered the background factors and four sections such as physical, functional, psychological and social health sections. Each section had 15 questions and disease-specific questions for CVD or PD were included in the physical health section. We analyzed 107 patients with CVD (76 elderly patients, aged 65 or more, 31 non-elderly patients under 65) and 136 patients with PD (91 elderly, 45 non-elderly). In the background section, of a total of 243 patients with CVD and PD, the elderly patients needed the assistance of their spouse and their sons wives more frequently than non-elderly patients. With regard to rehabilitation, non-elderly CVD patients had rehabilitation more frequently than the elderly CVD patients, while a higher percentage of elderly patients with PD had rehabilitation training more frequently than the non-elderly PD patients. In the QOL section, there was no difference between elderly and non-elderly CVD patients, while elderly PD patients were statistically more significantly disabled physically and weak-minded psychologically. The physical disabilities of the elderly PD patients in this statistical investigation included slow motion, stooped posture, frozen gait, difficulty in turning and standing up, constipation and dysuria. The psychological problems of elder PD patients included forgetfulness and a feeling of aging. These patients had significantly fewer consultations by family and relatives than the non-elderly PD patients. The overall tendency of QOL in patients with CVD and PD was similar to that of PD patients.

CAG repeat number correlates with the rate of brainstem and cerebellar atrophy in Machado-Joseph disease.

We compared the CAG repeat length and the severity of the brainstem and cerebellar atrophy visualized by MRI in 30 patients with Machado-Joseph disease. We found a strong correlation between the CAG repeat number and the quotient of the degree of atrophy divided by age at examination. These results suggest that the rate of disease progression is dependent on the CAG repeat size and disease progression may commence at birth.

Somatosensory homunculus as drawn by MEG.

We studied a detailed somatosensory representation map of the human primary somatosensory cortex using magnetoencephalography. Somatosensory-evoked magnetic fields following tactile stimulation of multiple points in the right hemibody (including the tongue, lips, fingers, arm, trunk, leg, and foot) were analyzed in five normal subjects. We were able to estimate equivalent current dipoles (ECDs) following stimulation of the tongue, lips, fingers, palm, forearm, elbow, upper arm, and toes in most subjects and those following the stimulation of the chest, ankle, and thigh in one subject. The ECDs were located in the postcentral gyrus and generally arranged in order along the central sulcus, which is compatible with the somatosensory "homunculus." Linear distances, averaged in five subjects, from the receptive area of the thumb to that of the tongue, little finger, forearm, upper arm, and toes were estimated to be 2.42 +/- 0.28, 1.25 +/- 0.28, 2.21 +/- 0.72, 2.75 +/- 0.63, and 5.29 +/- 0.48 cm, respectively. The moment of each ECD, which suggested the size of the cortical areas responsive to the stimulation, was also compatible with the bizarre proportion of the homunculus with a large tongue, lips, and fingers. According to these results, we were able to reproduce a large part of the somatosensory homunculus quantitatively on an individual brain MRI.

Auditory and visual event-related potentials and flash visual evoked potentials in Alzheimer's disease: correlations with Mini-Mental State Examination and Raven's Coloured Progressive Matrices.

We investigated possible correlations among neurophysiological examinations [auditory and visual event-related potentials (A-ERPs, V-ERPs), and flash visual evoked potentials (F-VEPs)] and neuropsychological tests [Mini-Mental State Examination (MMSE) and Raven's Coloured Progressive Matrices (RCPM)] in 15 subjects with probable or possible Alzheimer's disease (AD) according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria. The P300 latency of A-ERPs was correlated with the scores of MMSE but not with those of RCPM. The P300 latency of V-ERPs was more significantly correlated with the scores of RCPM than with those of MMSE. The P2 latency of F-VEPs was more significantly correlated with the scores of RCPM than with those of MMSE. The P2 latency of F-VEPs was not correlated with the P300 latency of A-ERPs but was correlated with the P300 latency of V-ERPs. The close relationship among V-ERPs, F-VEPs and RCPM suggests that these examinations at least partly reflect the functions of visual association areas in AD. Furthermore, discrepancy between P300 latency by A-ERPs and V-ERPs suggests that the mechanism responsible for P300 generation is not identical between these two stimulus modalities.

Videofluorographic study of swallowing in Parkinson's disease.

We studied 16 patients with Parkinson's disease (PD) with dysphagia and 8 young and 7 elderly normal controls videofluorographically to evaluate the nature of swallowing disorders in PD patients. In 13 patients, abnormal findings in the oral phase were residue on the tongue or residue in the anterior and lateral sulci, repeated pumping tongue motion, uncontrolled bolus or premature loss of liquid, and piecemeal deglutition. Thirteen patients showed abnormal findings in the pharyngeal phase, including vallecular residue after swallow, residue in pyriform sinuses, and delayed onset of laryngeal elevation. Ten of these patients also showed abnormal findings in both the oral and pharyngeal phases. Aspiration was seen in 9 patients. The oral transit duration was significantly longer in the patients with and without aspiration than in the control subjects. The stage transition duration, pharyngeal transit duration, duration of the upper esophageal sphincter (UES) opening, and total swallow duration were significantly longer in the patients with and without aspiration than in the young controls, but were not longer than in the elderly controls. These durational changes in the pharyngeal phase of swallowing were similar to those in the elderly controls. The findings suggest that the disturbed motility in the oral phase of swallowing may be due to bradykinesia. Although PD patients with dysphagia evince a variety of swallowing abnormalities, the duration of pharyngeal swallowing may remain within the age-related range until the symptoms worsen.

Sensory conduction study of cisplatin neuropathy: preservation of small myelinated fibers.

We report a patient with peripheral neuropathy caused by cisplatin for the treatment of testicular tumor. Routine studies of nerve conduction and somatosensory evoked potentials demonstrated large myelinated fiber neuropathy suggesting ganglioneuronopathy. We also performed a CO2 laser evoked potential study, and found that small myelinated fibers, which are related to pain sensation, were well preserved in this patient.

Pain-related and electrically stimulated somatosensory evoked potentials in patients with Machado-Joseph disease and multiple system atrophy.

We investigated the ascending somatosensory pathway for pain in 8 patients with Machado-Joseph disease (MJD) and multiple system atrophy (MSA). Pain-related somatosensory evoked potentials (pain SEPs) by CO2 laser stimulation were examined together with conventional electrically stimulated somatosensory evoked potentials (electric SEPs). The sporadic cerebellar ataxia of patients with MSA showed a normal pattern of pain SEPs as well as electric SEPs. However, pain and electric SEPs were abnormal for the central and/or peripheral ascending pathway in MJD. These abnormalities of pain and electric SEPs in MJD were not related to the clinical severity of sensory impairment, but they indicate that MJD presents a subclinical abnormality for the ascending somatosensory pathways not only for vibratory sense but also for pain sense.

Pineal effects on adrenal medulla, area postrema and brain water content in relation to intracranial surgery.

We aimed to explore whether and how the pineal influences the adrenal medulla, the area postrema and the brain water content; and is influenced by sham pinealectomy (SPX) in its structures and melatonin secretion. Quantitative morphological methods were mainly used in rats and golden hamsters. Experimental results showed: (1) Pineal effects on the A cell system of the adrenal medulla were inhibitory to the synthesis and secretion of epinephrine into the perivascular space and stimulatory to the opioid synthesis, and augmented by SPX. Time-of-day changes were also influenced by SPX and PX. (2) The sizes of a part of the nuclei of nerve and glia cells in the area postrema and the brain water content increased by SPX depending on the presence of the pineal, suggesting the pineal's stimulatory effects on these following SPX. (3) SPX caused morphological changes suggesting an increased activity of pinealocytes. However, corresponding consistent increases in plasma melatonin levels were not seen following SPX. Possible interpretations of these observations were discussed.

Pain-related somatosensory evoked potentials in dementia.

Pain-related somatosensory evoked potentials (pain SEPs) were examined in 25 demented and non-demented patients to investigate the cognitive function for pain in the progression of dementia. Pain SEPs by CO2 laser stimulation were recorded together with auditory event-related potentials (auditory ERPs). P340 in pain SEPs and P300 in auditory ERPs were analysed. The latency of P300 evoked in mildly demented patients was inversely correlated with the Mini-Mental state examination score, and the latency of P340 was also inversely correlated to that score but to a lesser extent. Pain SEPs were not recorded in 4 of 7 severely demented patients. These results indicate that the P340 component of pain SEPs is apparently different from the P300 component of auditory ERPs and suggest that the pain perception in severely demented patients may be abnormal.

Similarities and differences in supporting and chromaffin cells in the mammalian adrenal medullae: an immunohistochemical study.

BACKGROUND: The adrenal medulla is a typical paraganglion, having the same origin as the sympathetic ganglia, and contains at least two types of parenchymal cells: chromaffin cells and supporting cells. We previously reported that the extent of cellular association of chromaffin cells with supporting cells was remarkably higher in noradrenaline (NA)-than in adrenaline (A)-cell regions in the adrenal medullae of the rat and pig. METHODS: Cryostat sections of adrenal medullae of nine mammalian species fixed with Zamboni fluid for 24 h were immunostained by ABC methods using antisera to S-100 protein and PNMT. RESULTS: The distribution patterns of A and NA cells in the adrenal medullae were classified into four types. In the chipmunk and rabbit, adrenomedullary chromaffin cells consisted of A cells. S-100-immunoreactive cells were present more frequently in NA- than in A-cell regions in seven species (rat, golden hamster, cat, dog, pig, ox, and horse). These cells sent out cytoplasmic processes and formed a network by immunoreactive elements among NA cells. The cell-association patterns of S-100-positive cells with NA cell were classified into three types. In A-cell regions, only a few S-100-positive cells were seen in most of the species, although the frequency of S-100-labeled cells were exceptionally high in the horse. CONCLUSIONS: The close association of supporting cells with NA cells was commonly found in the adrenal medulla in many mammalian species, irrespective of the proportions and distribution patterns of A cells and NA cells. On the other hand, species differences existed in details of the cellular association between supporting cells and NA cells.

Rapid growth of hepatocellular carcinoma after or during interferon treatment of chronic hepatitis C: report of three cases.

We report herein the cases of three patients in whom marked rapid growth of hepatocellular carcinoma (HCC) became evident after or during interferon (IFN) treatment for chronic hepatitis C. The HCC tumors were 10, 4.7, and 3.1 cm in size, and were found 7 months, 10 weeks, and 10 weeks after the initiation of IFN, respectively, in cases 1, 2, and 3. The clinical courses of these three patients suggest that the progression of HCC was more rapid during the IFN treatment period. Thus, we propose that abdominal ultrasonic (US) examination should be performed monthly in patients with chronic hepatitis who undergo IFN treatment.