Combinations of the presence or absence of cerebral microbleeds and advanced white matter hyperintensity as predictors of subsequent stroke types.

BACKGROUND AND PURPOSE: Previous studies have shown microbleeds to be a risk factor for intracerebral hemorrhage and white matter hyperintensity (WMH) to be a risk factor for ischemic stroke. This study was performed to determine whether combinations of the presence or absence of microbleeds and advanced WMH are risk factors for subsequent recurrent stroke types. METHODS: In 266 patients with stroke, microbleeds on T2*-weighted MR images were counted, and WMH on T2-weighted images was graded. Patients were divided into 4 groups by the combinations of the presence or absence of microbleeds and advanced WMH and were followed up for stroke recurrence. RESULTS: During a mean follow-up period of 564.8 +/- 220.5 days, 26 patients developed recurrent strokes, including 10 intracerebral hemorrhages and 16 ischemic strokes. Patients with microbleeds without advanced WMH (n = 42) developed only intracerebral hemorrhages (n = 8), and the recurrence rate of intracerebral hemorrhage in those patients estimated by the Kaplan-Meier method was the highest in the 4 groups (14.3% in 1 year and 21.2% in 2 years). In contrast, patients with advanced WMH without microbleeds (n = 39) developed only ischemic strokes (n = 6), and the estimated recurrent rate of ischemic stroke in those patients was the highest in the 4 groups (10.5% in 1 year and 17.4% in 2 years). Cox proportional hazards regression analysis revealed that microbleeds were associated with intracerebral hemorrhage (hazard ratio [HR], 85.626; 95% confidence interval [CI], 6.344-1155.649) and that advanced WMH was negatively associated with intracerebral hemorrhage (HR, 0.016; 95% CI, 0.001-0.258). Advanced WMH was associated with ischemic stroke (HR, 10.659; 95% CI, 2.601-43.678). CONCLUSION: It appears that patients at high risk of subsequent intracerebral hemorrhage or ischemic stroke can be identified by combinations of the presence or absence of microbleeds and advanced WMH.

Radial mass analysis of the flagellar filament of Salmonella: implications for the subunit folding.

X-ray fiber diffraction patterns of the R-type straight flagellar filament of Salmonella typhimurium SJW1655 strain showed layer-lines with an axial spacing of 1/437 A-1, which could be resolved only due to very small disorientation angles (< 2 degrees) of the filaments in oriented sol specimens. Although the equatorial layer-line was situated between the relatively strong first layer-lines right above and below it, these small disorientation angles and a new method of two-dimensional angular deconvolution allowed us to determine the equatorial layer-line intensities quite accurately. The equatorial data were phased by using the amplitude difference between the native flagellar filament and its heavy atom derivatives. One of the heavy-atom derivatives was prepared by introducing a cysteine residue by site-directed mutagenesis and applying a mercury compound. From the equatorial structure factors, the radial density distribution of the filament was calculated at 11 A resolution. A prominent feature was two pairs of high density peaks at radii of around 25 and 45 A and a deep density trough between them, which corresponds to the concentric double tubular structure in the core region that has been found in the density map recently deduced by helical image reconstruction from electron micrographs of frozen hydrated filaments. The molecular masses were estimated for four radial segments that correspond to the morphological domains identified in the map of helical image reconstruction. Then the domains were assigned to sequence positions by correlating the estimated masses with those of proteolytic fragments of flagellin. The assignment is consistent with the distributions of secondary structures and in particular alpha-helical coiled-coils that were predicted from the sequence. It also helps to understand how the polymerization behaviour is affected by truncation of the disordered terminal regions of flagellin and why mutations in a specific region are responsible for changes in the polymorphic shape of the filament.

The structure of the R-type straight flagellar filament of Salmonella at 9 A resolution by electron cryomicroscopy.

The supercoiled forms of the flagellar filaments are thought to be constructed from a mixture of two distinct subunit conformations arranged in a regular manner. We analyzed the structure of one of the two straight flagellar filaments, each of which is built up with all its subunits in one of the two conformations. The filament we studied was isolated from the strain SJW1655 of Salmonella typhimurium and had a right-handed helical symmetry. With recent advancements in electron cryomicroscopy, such as a liquid helium temperature stage for frozen hydrated specimens and a stable field emission source, and also by averaging high resolution data with a proper correction of the contrast transfer function, the density distribution map of this straight flagellar filament was generated in far more detail than before by including data up to 9 A resolution. The structure shows a densely packed core region from about 15 to 55 A in radius, where a pair of concentric tubular features of high density is present without well-defined subunit boundaries, and an outer part from 55 to 115 A, where the subunits are mostly well separated from each other. The outer tube in the core region, from 35 to 55 A in radius, contains many rod-like features with near-axial orientation and closest lateral distances of around 10 A, which are most likely to represent the alpha-helical bundles that were predicted in our previous report. In the inner tube, from 15 to 30 A in radius, the rod-like features are less clear. Between the inner and outer tubes are the short spoke-like densities, which are radially tilted and are connecting the two tubes. The outer part, from 55 to 115 A, contains an axially elongated column density and a slewed projection with a narrow neck region. When compared with the other straight filament having left-handed helical symmetry, this outer part does not show any significant changes in orientation, suggesting that the switch in the subunit conformation and packing involved in the polymorphic transitions is quite subtle and only occurs within the core region. Reassignment of each structural domain to the amino acid sequence is suggested, based on the volume of each domain, which was determined rather precisely by a proper correction of the contrast transfer function for both amplitudes and phases.

Characteristic magnetic resonance imaging findings in spinocerebellar ataxia 6.

OBJECTIVE: To clarify the characteristic magnetic resonance imaging (MRI) findings in patients with spinocerebellar ataxia 6 (SCA6) diagnosed by genetic analysis. PATIENTS AND METHODS: Using MRI, we examined 10 patients genetically diagnosed as having SCA6 and 40 control subjects. RESULTS: The mean (+/-SD) CAG repeat length in 10 patients with SCA6 was 22.9 +/- 1.3. There was a significant inverse correlation between the CAG repeat size and age at onset in the SCA6 group (r = -0.86, P = .003). In patients with SCA6, the areas of the cerebellar vermis and hemispheres in sagittal MRI were significantly smaller than those in the control subjects. In transaxial MRI, the anteroposterior diameter of the pons and the diameter of the middle cerebellar peduncle were mildly decreased and the red nucleus was slightly atrophied in patients with SCA6. There was no significant difference in the diameter of the midbrain, medulla oblongata, fourth ventricle, superior cerebellar peduncles, dentate nucleus, or globus pallidus between the SCA6 and control groups. A high-signal intensity in the transverse pontine fibers was not observed in any of the patients with SCA6 on T2-weighted and/or proton-weighted axial MRI. CONCLUSIONS: The cerebellum and its afferent and efferent systems were affected in patients with SCA6. These results seem to distinguish the MRI findings of SCA6 from those of other forms of spinocerebellar ataxia.

Prevalence and risks of dementia in the Japanese population: RERF's adult health study Hiroshima subjects. Radiation Effects Research Foundation.

OBJECTIVES: To study the prevalence rate of dementia and its subtypes in Japan and to investigate the relationship of risk factors, such as demographic features and disease history, to the prevalence of Alzheimer's disease or vascular dementia. DESIGN: A prevalence study within a longitudinal cohort study. SETTING: The original Adult Health Study (AHS) cohort consisted of atomic-bomb survivors and their controls selected from residents in Hiroshima and Nagasaki using the 1950 national census supplementary schedules and the Atomic Bomb Survivors Survey. Since 1958, the AHS subjects have been followed through biennial medical examinations. PARTICIPANTS: Subjects were 637 men and 1585 women aged 60 years or older in the AHS cohort. Forty-eight subjects resided in hospitals and institutions. MEASUREMENTS: In addition to the biennial medical examinations ongoing since 1958, a screening test for cognitive impairment (CASI) was conducted by trained nurses between September 1992 and September 1996. The prevalence of dementia and its subtypes was assessed in 343 subjects suspected to have dementia and in 272 subjects with high CASI scores who were selected randomly. RESULTS: The prevalence of dementia based on DSM III/R criteria, using neurological examination, the IQCODE, and CDR > or = 1, was 7.2%. The prevalence of Alzheimer's disease was 2.0% in men and 3.8% in women, and the prevalence of vascular dementia was 2.0% in men and 1.8% in women. The relationship of risk factors to Alzheimer's disease or vascular dementia was investigated by the multivariate logistic linear regression analysis. Odds ratios of Alzheimer's disease for age (in 10-year increments), attained education (in 3-year increments), history of head trauma, and history of cancer are 6.3, 0.6, 7.4, and 0.3, respectively. Odds ratios of vascular dementia for age, history of stroke, and history of hypertension are 2.0, 35.7, and 4.0, respectively. Neither type of dementia showed any significant effect of sex or radiation exposure. CONCLUSION: This study is the first study of Japanese dementia rates carried out with a protocol similar enough to that of a US study to allow meaningful comparisons. The prevalence rates demonstrated are more similar to US rates than were found in many previous reports in Japan.

Standardization of the clinical diagnosis of the dementia syndrome and its subtypes in a cross-national study: the Ni-Hon-Sea experience.

BACKGROUND: Clinical investigators from Seattle, Honolulu, Tokyo, and Hiroshima participated in two standardization exercises in which data were collected on independent assessments. Exercises were conducted to evaluate the interobserver agreement on clinical diagnoses of dementia and dementia subtypes in a cross-national study of dementia prevalence and incidence rates in the United States and Japan. METHOD: Fifteen clinicians from four participating sites assessed the diagnosis of 85 patients based on standardized summaries of clinical and diagnostic test data on each patient. Diagnostic guidelines and conventions were adopted on the basis of group consensus during standardization exercises. RESULTS: Using DSM-III-R criteria, generally good levels of agreement for all dementia diagnostic categories occurred in both years. For most measures of diagnostic agreement, improvements were observed between the 1995 and 1996 standardization sessions. Interrater agreement was highest for discrimination between dementia and nondementia (1996 overall kappa, K = .90). The kappa values for dementia subtypes in 1996 ranged from .5 to .85, and for all sites combined the value was .67. For dementia subtypes, percent agreement was highest for vascular dementia and Alzheimer's disease, but was less reliable for other types of dementia. CONCLUSIONS: Clinicians from different cultures and medical traditions can reliably use the DSM-III-R criteria to classify dementia cases in cross-national research. The interrater agreement on dementia and its subtypes improved after clear-cut guidelines for interpretation of diagnostic criteria were developed and followed.

Abnormalities of acetylcholinesterase in Alzheimer's disease with special reference to effect of acetylcholinesterase inhibitor.

In brains from Alzheimer's disease patients, a high activity of acetylcholinesterase (AChE) was detected in the senile plaque-rich fraction and its isozyme pattern was mainly type A, containing a collagen-like tail. AChE inhibitors, including physostigmine, E-2020, amiridin, tetrahydroaminoacridine (THA) and Nicergoline had a poor effect on AChE present in the senile plaque-rich fraction isolated from Alzheimer brain than that either in the soluble fraction of Alzheimer brain or in the control brain. However, AChE purified from rat skeletal muscle (type A) was significantly more susceptible to AChE inhibitors than that purified from rat brain (G4 form) or from human erythrocytes (G2 form). E-2020 inhibited all 3 types of isozymes more effectively than physostigmine, amiridine, Nicergoline or THA. The inhibitory effect of AChE inhibitors on AChE solubilized from senile plaque was also small as compared with AChE in normal human brain, rat brain, human erythrocytes or rat skeletal muscle. These results suggest that the characteristics of AChE present in senile plaques are abnormal or different from that in normal brain or skeletal muscle. As AChE in the Alzheimer brain seems to contain a higher degree of glycosylation, the hydrophobic property of anomalous AChE may serve a seed of amyloid fibril in senile plaques.

Objective evaluation of fatigue by event-related potentials.

The purpose of this study was to assess the relationship between mental fatigue and event-related potentials (ERPs). Six healthy men (mean age: 22 years old) performed a simple calculation for 6 h. Auditory ERPs were recorded before and after the calculating task. The scores of subjective fatigue symptoms were significantly increased, and P300 latency of auditory ERPs was significantly prolonged by the calculating task (P<0.05). We suggest that the recording of ERPs may be useful for the objective evaluation of mental fatigue.

The relationship between photosensitive temporal lobe epilepsy and eye closure activity.

We describe a 16-year-old female patient affected by photo-induced temporal lobe epilepsy. During intermittent photic stimulation she showed a photoparoxysmal response in the EEG. This case was diagnosed from clinical symptoms, single photon emission computer tomography, and EEG data. The clinical symptoms were relieved by the administration of carbamazepine. As these photoparoxysmal responses were observed not only during photic stimulation, but also when patient was closing her eyes during an eye-opening test in complete darkness, we propose the existence of an alternative pathway such as from the extraocular muscles or orbicularis oculi, or activation of cortical activity due to the change of consciousness by closing eyes in inducing photosensitive epilepsy. We describe an additional case and discuss a novel aspect of photo-induced temporal lobe epilepsy.

Creutzfeldt-Jakob disease associated with autonomic nervous system dysfunction in the early stage.

A 54-year-old man presented with tremor and unusual behavior. He was admitted two months later because of dementia and myoclonus. Periodic synchronous discharges were observed on the electroencephalogram. Based on these findings, we diagnosed the case as Creutzfeldt-Jakob disease. About two weeks after admission, decubitus, bowel dysfunction and hypohidrosis occurred. We observed various autonomic nervous system dysfunctions such as abnormal pupillary response to autonomic drugs, reduced coefficient of variation of R-R interval, and abnormal diurnal blood pressure variation.

Folic acid-responsive neurological diseases in Japan.

Folic acid (folate) levels were measured in the serum of patients with various neurological diseases in Japan. Thirty-six patients showed decreased serum folate levels among 343 consecutive neurological patients (10.5%). Folate administration (15 mg/d) to folate-deficient patients improved neurological symptoms in 24 of 36 cases (67%). Serum folate levels were significantly lower in female than in male folate-deficient patients. Folate-deficient patients showed predominantly axonal neuropathy, which responded to folate supplementation more markedly. Male patients more frequently exhibited neuropathy, especially demyelinating and motor-dominant neuropathy, than females. Anemia was correlated with male sex and low serum folate levels. Male patients were more responsive than females to folate treatment. More male patients had taken excess alcohol or received gastrectomies than females. Neurological symptoms were more frequently improved by folate supplementation in patients with neuropathy than exclusive encephalopathy. Serum folate levels were lower in patients with encephalopathy, especially those with dementia, while folate therapy was more effective in neurological patients without dementia. Dysgeusia and anemia improved in all patients after folate administration. Neurological patients with malabsorption or treated with continuous drip infusion were resistant to folate therapy. Since folate-responsive neuroencepahlopathies are not rare among patients with neurological diseases in Japan, the serum folate level would serve as a valuable indicator for folate supplement therapy.

Ratios of nerve conduction parameters in proximal to distal limbs remain constant through the second to the eighth decades.

We investigated the effect of age on nerve conduction parameters to establish a diagnostic validity in demyelinating neuropathies of the aged. We evaluated 257 subjects (age 10-76 years old) with no history or signs of peripheral neuropathies. The CMAP amplitude ratio (proximal CMAP/distal CMAP), duration ratio, and area ratio were almost the same throughout the second to eighth decades. The respective lower limits of the normal CMAP amplitude ratio (mean-3 SD) were 0.79 (median nerve), 0.75 (ulnar nerve), 0.57 (peroneal nerve), and 0.45 (tibial nerve). The upper limits of the normal CMAP duration ratio (mean +3 SD) were 1.21 (median nerve), 1.22 (ulnar nerve), 1.37 (peroneal nerve), and 1.35 (tibial nerve). The lower limits of the normal CMAP area ratio (mean-3 SD) were 0.81 (median nerve), 0.78 (ulnar nerve), 0.60 (peroneal nerve), and 0.57 (tibial nerve). No age-related changes were observed in the amplitude ratio or duration ratio SNAP, although the standard deviation increased with age. Since the amplitude, duration and area ratios are easily calculated and age-independent, they can provide useful and reliable information on aged patients with demyelinating neuropathies by conventional nerve conduction studies.

Sarcoidosis: correlation of HRCT findings with results of pulmonary function tests and serum angiotensin-converting enzyme assay.

We examined correlations between findings on chest high resolution computed tomography (HRCT), pulmonary function and values of serum angiotensin converting enzyme (ACE) in 25 patients with sarcoidosis. The most frequent CT features were small nodular opacities. The small nodules, representing the confluence of epithelioid granulomas, are strongly correlated with peribronchovascular, perilobular, and centrilobular lesions, where there is an abundance of lymphatic plexus. This strongly suggests the importance of the lymph vessels in the pathogenesis of sarcoidosis. The pulmonary functions tests showed obstructive defects in 6 and mixed-type defects in 2 of the 25 patients. Furthermore, an elevation of V50/V25 ratio suggesting small-airway disease was detected in many patients who showed normal values of FEV1.0% and %VC. This fact indicates that small-airway disease was manifested earlier in sarcoidosis patients. Statistically significant negative correlations were found between visual score and %VC, %FVC, FEV1.0%, %TLC, and %DLco, but there was no significant correlation between visual score and serum ACE. ACE is derived from granuloma-forming epithelioid cells, and the activity of ACE decreased rapidly in mature granulomas. Epithelioid cells in the mature granulomas which can be recognized on HRCT scan have stopped or are about to stop the release of ACE. In this study, serum ACE activity was found to be elevated and correlated with %V25 and V50/V25 at an early stage of the disease. The results of this study provide meaningful insights into the process of sarcoidosis in lung.

[Resistance against oral antibiotics to Streptococcus pneumoniae isolated from adult respiratory tract infections].

The resistance against oral antibiotics to Streptococcus pneumoniae (S. pneumoniae) isolated from adult patients with respiratory tract infections in the Kurume area in 1998 was studied. The frequency of resistant strains, which were isolated penicillin-intermediate S. pneumoniae and resistant S. pneumoniae (PISP, PRSP) were both 41.2%. We examined the minimal inhibitory concentrations (MIC) of oral antibiotics and the susceptibility ratio of the strains for the drugs based on the breakpoint MIC. The breakpoint MIC of pneumonia against oral beta-lactam antibiotics to PISP, PRSP, which were determined by Japan Society of Chemotherapy, were high in the order of FRPM > CDTR, CFPN > CFTM > CFDN, CPDX. In the case of the new oral quinolones, DU6859a > SPFX > LVFX > CPFX showed good results, in this order, DU6859a showed the most significant inhibitory effect to PISP, PRSP (MIC90 0.06 microgram/ml). By serotyping the percentage of 19, 6, 23 was 42.9%, 21.4% and 14.3%.

[Vasomotor impairment in patients with diabetic neuropathy--evaluation by laser Doppler flowmetry].

Using laser Doppler flowmetry, we evaluated cutaneous microcirculation in 28 patients with diabetic neuropathy and 18 control subjects. Skin blood flow in the hand was significantly reduced in the patients compared with that in age-matched controls. Skin blood flow in the hand of the patients correlated significantly with the amplitude of sensory nerve action potential of the median nerve. Significant correlation was shown in the patients between skin blood flow in the hand and changes in systolic blood pressure on standing from a supine position. However, there was no correlation between skin blood flow in the hand and variation in the R-R interval. These results suggest that the skin blood flow may decrease with the progression of diabetic neuropathy, particularly sympathetic autonomic neuropathy, and that neural control may be an important factor in the regulation of skin blood flow. Cold water immersion test revealed that there was no significant difference in vasoconstrictive response during the cold challenge, while recovery time of vasodilatory response after withdrawal of the thermal challenge was significantly prolonged in the patients as compared with that in the controls. In addition, it is suggested that the patients with a small increase or normal in skin blood flow of the hand may possess abnormalities predominantly in vasoconstrictive tone, whereas the patients with a decrease in skin blood flow of the hand in vasodilatory tone. Consequently, microcirculation in skin of extremities changes under the balance of vasoconstrictive and vasodilatory tones in patients with diabetic neuropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of vitamin B12 deficiency with broad neurologic disorders and canities].

The patient was a 48-year-old woman with gait disturbance as her initial symptom. Two years after the onset of the gait disturbance, she developed motor weakness and a sensory disturbance in her limbs, and dementia. On admission to our hospital, the patient's serum vitamin B12 and folic acid levels were low, and she was found to have normochromic anemia. She also had widespread coarse hair and canities was diagnosed. The patient's paresthesia resolved in response to injection of 500 micrograms mecobalamin every other day, and the Hasegawa dementia scale score and the patient's hand grip strength improved. Her gait also improved, and she became able to walk on tiptoe. Her hair returned to normal. Supplementation with high-dose methyl B12 appeared to be effective to some extent in treating a broad range of neurologic disorders besides subacute combined degeneration of the spinal cord. In addition, the hair abnormality may be a marker of vitamin B12 deficiency.

[Relationship between impaired blood pressure control and multiple system involvement in chronic alcoholics].

Chronic ethyl alcohol (ethanol) abuse is associated with different types of neurological involvement. Impaired blood pressure control such as in hypertension and/or orthostatic hypotension is a known autonomic dysfunction in chronic alcoholics. Although abstinence appears to improve blood pressure, the precise mechanisms underlying the effects of alcohol remain unknown. We suspected that abnormal blood pressure might influence the outcome of alcohol-related neurological symptoms. We therefore reviewed the alcohol history of 28 male patients admitted to our hospital with multiple system involvement. No family history of spinocerebellar degeneration was found. All of the patients had a history of chronic alcohol abuse. The duration of alcohol abuse in 28 patients was 28.8 + 11.2 yrs. Daily ethanol consumption was less than 83 ml in 6 patients between 83 ml and 138 ml in 11 and more than 138 ml in 11. We assessed the relationship between impaired blood pressure control, clinical characteristics, and outcome after abstinence for a period ranging from 30 days to 6 years in 22 chronic alcoholics who had drunk more than 83 ml/day. All of the patients had various types of autonomic dysfunction, and a high incidence of impaired blood pressure control and decreased CVR-R were noted. The symptoms improved or even completely resolved after cessation of alcohol consumption, however, 8 of the 22 patients in our study reached a plateau and have permanent symptoms. Patients with no improvement as a result of abstinence had a long history of excessive drinking. Brain CT/MRI, SPECT and P300 studies were conducted. SPECT and P300 were performed in both the supine and standing position in 5 and 7 patients, respectively. Five patients who had severe orthostatic hypotension with syncope were found to have cerebrovascular lesions on MRI. Changes in P300 amplitude and/or distribution and latency were noted after a fall in blood pressure. Although the etiology of impaired blood pressure control in alcoholics remains unknown, we believe that abnormal blood pressure affects the outcome of alcohol-related neurological symptoms.

[An autopsy case of catastrophic antiphospholipid syndrome presenting with recurrent multiple cerebral infarction associated with lung cancer].

We reported an autopsy case of cerebral infarction with primary lung cancer. The patient was a 50-year-old man. Despite having been treated with warfarin potassium and ticlopidine hydrochloride, he relapsed cerebral infarction. His laboratory data on admission showed that lupus anticoagulant was positive, together with a high value of beta-thromboglobulin, thrombin-antithrombin III complex, markers of platelet and coagulation activation, CEA and CA 19-9. The autopsy finding revealed a primary papillary adenocarcinoma in the right lower lung, multiple cerebral infarction, renal infarction, pulmonary infarction and splenic infarction. The atherosclerotic changes were mild in the whole tissues and findings of vasculitis were not observed. Recurrence of cerebral infarction was effectively suppressed with the addition of steroid therapy to antithrombotic therapy. This case was considered as catastrophic antiphospholipid syndrome. It is necessary to differentiate antiphospholipid syndrome in case of the abnormal coagulation and fibrinolytic factors with recurrent cerebral infarction. Moreover, systemic examinations are important, because malignant tumor may exist on the background of the case.

[Cognitive dysfunction among the elderly evaluated by the cognitive abilities screening instrument (CASI)].

The Cognitive Abilities Screening Instrument (CASI) was developed by Japanese and American researchers, including the authors, to examine cognitive functions, based on previous neuropsychological tests, such as Hasegawa's Dementia Scale and the MMSE. From the Adult Health Study (AHS) population of the Radiation Effects Research Foundation, 2052 men and women aged 60 or over and living in Hiroshima were evaluated for their cognitive functions using the CASI. Dementia was diagnosed in 93 and 1,959 were considered not to suffer from dementia based on the DSM-III-R criteria using neurological examination and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) completed by caregivers. Multivariate regression analysis not only indicated that total score was higher with lower age and higher education but that the slope of its decrease is steeper with higher age and fewer years of education. The slope of score decrease with increase of age was steeper for women than for men. Furthermore, CASI items were categorized by domains of cognitive function. Multivariate regression analysis for each cognitive domain showed clear effects of age and level of education. The effect of age for the nondementia subjects was large in cognitive domains dealing with temporal orientation, short-term memory, and list-generating fluency. The most useful cognitive domains for diagnosing dementia were temporal orientation, short-term memory, and list-generating fluency, as was indicated by high sensitivity and specificity.

[An elderly case of juvenile muscular atrophy in the unilateral upper extremity with tremor in both hands].

A 75-year-old man had noticed muscle atrophy and weakness of his right hand and forearm at the age of 25. The symptoms slowly progressed and then stopped. Right hand tremor appeared at about age 40. There was no symptom in his left upper extremity, and his gait was normal. He now shows severe muscle atrophy in his right hand and forearm. There was distally dominant weakness of the right upper extremity and his hand grip was 0 kg on the right and 25 kg on the left. On admission there was no weakness in the bilateral lower extremities. He had postural tremor in both hands and fingers. The tendon reflexes were hypoactive in the upper extremities and normal in the lower extremities. Abnormalities in the superficial sensation were unremarkable, whereas vibration sensation in both the upper and lower extremities was mildly disturbed. Electromyography revealed chronic denervation, especially in the right upper extremity. The sensory nerve conduction study results and somatosensory evoked potentials in the upper extremities were normal. Cervical MRI demonstrated spondylotic changes, canal stenosis from the C5 to C7 levels, and compression of the spinal cord. His hand tremor was dominant on the right with a peak frequency of about 7 Hz. Tremor frequency and power were decreased by mechanical load. Hirayama's disease (juvenile muscular atrophy of unilateral upper extremity) was the most probable diagnosis, although aging might have produced various additional abnormalities. The tremor seen in this patient showed characteristics of enhanced physiological tremor.