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We intended to clarify the phenotypic and molecular diversities of spinocerebellar ataxia type 2 (SCA2) in Japan. DNA was extracted from the peripheral blood of 436 patients, including 126 patients with chronic neuropathy, 108 with amyotrophic lateral sclerosis, and 202 with cerebellar ataxia. We then PCR-amplified and sequenced the ATXN2 gene. The biopsied sural nerves of mutation-positive patients were subjected to light-microscopic and electron-microscopic analyses. Transfection analyses were performed using a Schwann cell line, IMS32. We found PCR-amplified products potentially corresponding to expanded CAG repeats in four patients. Two patients in the chronic neuropathy group had a full repeat expansion or an intermediate expansion (39 or 32 repeats), without limb ataxia. The sural nerve biopsy findings of the two patients included axonal neuropathy and mixed neuropathy (axonal changes with demyelination). Schwann cells harbored either cytoplasmic or nuclear inclusions on electron microscopic examination. Both patients recently exhibited pyramidal signs. In the third patient in the cerebellar ataxia group, we identified a novel 21-base duplication mutation near 22 CAG repeats (c.432_452dup). The transfection study revealed that the 21-base-duplication mutant Ataxin-2 proteins aggregated in IMS32 and rendered cells susceptible to oxidative stress, similar to a CAG-expanded mutant. The fourth patient, with 41 repeats, had ataxia and spasticity. The two patients with cerebellar ataxia also had peripheral neuropathy. Patients with expanded CAG repeats can exhibit a neuropathy-dominant phenotype not described previously. The novel 21-base-duplication mutant seems to share the aggregation properties of polyglutamine-expanded mutants.

Looking back at the cases of brain cutting conducted in Sumitomo Hospital over the past 32 years, cases where clinical brain imaging could be compared with pathological findings other than degenerative diseases are examined and carefully selected, and instructive examples of them are presented. Although there are some limitations, the comparison between clinical brain imaging and pathological finding is significant to the final diagnosis and understanding of the pathogenesis of brain lesions.

Background The coexistence of distinct neurodegenerative diseases in single cases has recently attracted greater attention. The phenotypic co-occurrence of progressive supranuclear palsy (PSP) and amyotrophic lateral sclerosis (ALS) has been documented in several cases. That said, the clinicopathological comorbidity of these two diseases has not been demonstrated. Case presentation A 77-year-old man presented with gait disturbance for 2 years, consistent with PSP with progressive gait freezing. At 79 years old, he developed muscle weakness compatible with ALS. The disease duration was 5 years after the onset of PSP and 5 months after the onset of ALS. Neuropathological findings demonstrated the coexistence of PSP and ALS. Immunohistochemical examination confirmed 4-repeat tauopathy, including globose-type neurofibrillary tangles, tufted astrocytes, and oligodendroglial coiled bodies as well as TAR DNA-binding protein 43 kDa pathology in association with upper and lower motor neuron degeneration. Immunoblotting showed hyperphosphorylated full-length 4-repeat tau bands (64 and 68 kDa) and C-terminal fragments (33 kDa), supporting the diagnosis of PSP and excluding other parkinsonian disorders, such as corticobasal degeneration. Genetic studies showed no abnormalities in genes currently known to be related to ALS or PSP. Conclusions Our case demonstrates the clinicopathological comorbidity of PSP and ALS in a sporadic patient. The possibility of multiple proteinopathies should be considered when distinct symptoms develop during the disease course. Electronic supplementary material The online version of this article (10.1186/s12883-019-1402-7) contains supplementary material, which is available to authorized users.

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A 62-year-old woman experienced uncomfortable genial sensation in 2010. Her uncomfortable sensation was exacerbated during rest at night and improved by walking. She exhibited short-stepped gait with postural disturbance and was diagnosed as suffering from Parkinson's disease (PD) in 2013. Administration of clonazepam and pramipexisole improved her uncomfortable genial sensation. In persistent genital arousal disorder (PGAD)/restless genial syndrome (RGS), abnormal genital sensation occurred without sexual desire, which was relieved by clonazepam administration. PGAD/RGS often coexists with restless legs syndrome (RLS). PGAD/RGS and RLS share common characteristics. This is the first case report of PD following PGAD/RGS, suggesting similar underlying mechanisms between PGAD/RGS and RLS associated with PD.

This report presents the case of an 83-year-old female with a tumor in the right temporal lobe. She experienced various epileptic visual auras including visual perseveration. Visual perseveration is classified into polyopia and palinopsia. Epileptic visual perseveration is a rare phenomenon, and the mechanism has not been fully explained. MRI revealed a tumor in the right temporal lobe with edema in the occipital white matter. To reveal mechanisms of epileptic polyopia and palinopsia, we recorded EEG and (123)I-IMP-SPECT when she experienced epileptic attacks. EEG showed epileptic discharges beginning at the occipital area, which spread to the temporal and parietal areas. During the EEG recording, the main symptom was an unformed hallucination. SPECT showed that blood flow increased in the right medial temporal and parietal lobes and, to a slightly lesser extent, in the right occipito-temporal area when the polyopia and palinopsia frequently appeared. Involvement of the multiple foci may have caused the different kinds of visual symptoms. The medial temporal and parietal areas were likely responsible for polyopia and palinopsia at least for this patient.

Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant disease caused by mutations in the gene encoding protein kinase C gamma (PKC gamma). We report an SCA14 family with a novel deletion of a termination-codon-containing region, resulting in a missense change and a C-terminal 13-amino-acid extension with increased kinase activity. Notably, one patient with a severe phenotype is the first homozygote for the mutation causing SCA14. We show the novel molecular consequences of increased kinase activities of mutants: aprataxin (APTX), a DNA repair protein causative for autosomal recessive ataxia, was found to be a preferential substrate of mutant PKC gamma, and phosphorylation inhibited its nuclear entry. The phosphorylated residue was Thr111, located adjacent to the nuclear localization signal, and disturbed interactions with importin alpha, a nuclear import adaptor. Decreased nuclear APTX increased oxidative stress-induced DNA damage and cell death. Phosphorylation-resistant APTX, kinase inhibitors, and antioxidants may be therapeutic options for SCA14.

Objective : Auditory P300 has been reported to be abnormal in demented patients with Parkinson's disease. However, it is still controversial which factors in Parkinson's disease influence P300 parameters. Methods : Forty patients with Parkinson's disease were included. Patients were divided into two groups: patients with dementia (PDD) and without dementia (PDND). An ‘odd-ball’ paradigm was used for auditory event-related potentials. Results : P300 latency was markedly delayed in PDD patients. Age and DRS1 (attention) were the most important factors influencing P300 latency. Conclusions : Although there have been reports of P300 in the past, its abnormalities reflect the deficit of attention in Parkinson's disease.

Objective We compared brain perfusion image using 3D-SSP analysis of 123I-IMP SPECT between Parkinson's disease patients with auditory verbal hallucination and those without auditory hallucination. Methods Eighty-three cases with Parkinson's disease were studied. In 6 of these patients, auditory hallucination was noted. Among them, four cases had verbal hallucination and two other cases had elementary hallucination. Auditory hallucination was not found in the other 77 cases. Results Right thalamic perfusion was significantly increased in the verbal hallucination group compared to the group that lacked auditory hallucination. Conclusion In Parkinson's disease, the right thalamic hyperactive state may be related to verbal hallucination.

The pathophysiology of depression and anxiety in Parkinson’s disease remains obscure. We aimed to compare the fractional anisotropy (FA) values of Parkinson’s disease (PD) patients with and without depression to investigate the nature of depression in PD. Twenty-eight patients were divided into two groups: those with depression and those without. Diagnosis of depression was made using the DSM-IV criteria. Patients in the two groups were matched for Hoehn Yahr stage. There were significant reductions in FA values in the bilateral frontal ROIs possibly representing anterior cingulate bundles. The anterior cingulate bundles play an important role in depression in PD, and some aspects of depression in PD have pathological processes in common with de novo depression.

Background Few imaging studies investigated frontal dysfunctions in Parkinson's disease. Objectives We investigated relationships between Wisconsin Card Sorting Test (WCST) and brain perfusion in patients with non-demented Parkinson's disease. Methods Patients were divided into two groups according to WCST score: (1) CA (number of category achieved)≤2 or (2) CA≥3. We performed three-dimensional stereotactic surface projection and volume of interest analysis using 123I-IMP scintigraphy. Results Hypoperfusions of the bilateral posterior cingulate, rostrodorsal prefrontal, and left frontopolar cortices were shown in CA≤2 group, with the left cingulate and right rostrodorsal prefrontal cortices showing prominent hypoperfusion. CA and PE (perseverative errors) scores significantly correlated with perfusion of the left posterior cingulate cortex. PE score also correlated with perfusion of the right rostrodorsal prefrontal cortex. Conclusion Data indicated participations of various regions in task achievement. Careful interpretation of WCST scores is required.

Background Although excessive daytime sleepiness (EDS) in Parkinson's disease (PD) has received a great deal of attention, the underlying pathological mechanism of its development and the relative contributions of brain function to this process are poorly understood. Objective To compare the fractional anisotropy (FA) values of PD patients with EDS and those without EDS, and to investigate the mechanism of EDS in this disease. Methods Eleven patients with PD with EDS, 26 patients with PD without EDS and 10 controls participated in this study. Patients with an ESS (Epworth Sleepiness Scale) score ≥10 were defined as having EDS. The FA values of 5 regions of interest (ROI) including the fornix were compared between the three groups. Results There were significant reductions in FA values of the fornix fiber in patients with EDS. ESS scores had significant correlation with FA values of the fornix. Conclusions Our study is the first to find the fornix fiber degeneration in PD patients with EDS. These results indicate that fornix dysfunction may have some correlations with EDS in PD.

Pathophysiology of hallucinations in Parkinson’s disease is poorly understood. This study investigated relationships between visual hallucinations and visual acuity. Twenty-six consecutive patients with Parkinson’s disease participated in this study. Patients were divided into two groups: patients with visual hallucinations (VH group) and those without visual hallucinations (no-VH group). Unaided and corrected eyesight was evaluated in all patients, and if frequent use of prescription glasses or contact lenses was involved, eyesight using these lenses was also measured as the patient’s own best eyesight. If a patient did not use prescription glasses or contact lenses, the patient’s own best eyesight was defined as the unaided eyesight. Multivariate regression analysis demonstrated that agonist use and best eyesight were different after the backward elimination method. Visual hallucinations were closely related not to uncorrected eyesight or unaided eyesight but to the patient’s best eyesight. It is suggested that impaired visual acuity is a risk factor for visual hallucinations.

Objective – To compare brain perfusion image using three-dimensional stereotactic surface projection (3D-SSP) analysis of N-isopropyl-p-123I iodoamphetamine (123I-IMP) single photon emission computed tomography (SPECT) between patients with Parkinson's disease with orthostatic hypotension and those without orthostatic hypotension. Materials and methods – Fifteen patients with Parkinson's disease and orthostatic hypotension and 13 patients with Parkinson's disease without orthostatic hypotension were studied. We compared brain perfusion image between the two groups by 3D-SSP. Results – Bilateral anterior cingulate gyrus perfusion of the patients with orthostatic hypotension was significantly decreased compared to that of the patients without orthostatic hypotension. Conclusions – The disorder of anterior cingulate gyrus may participate in the autonomic failure in Parkinson's disease.

Background: Decreased cardiac metaiodobenzylguanidine (MIBG) uptake was reported in Parkinson’s disease and this contributes to the differential diagnosis between Parkinson’s disease and other forms of parkinsonism such as multiple system atrophy. However, decreased MIBG uptake of the thyroid has not been demonstrated. Objective: To compare MIBG uptake of the thyroid among Parkinson’s disease, multiple system atrophy and controls. Methods: Twenty-six patients with Parkinson’s disease, 11 patients with multiple system atrophy and 14 controls were examined in this study. Planar images were taken 15 minutes (early images) and 3 hours (late images) after intravenous injection of 111 MBq 123 I-MIBG. Results: MIBG uptake of the thyroid on early images decreased significantly in Parkinson’s disease compared to controls (p < 0.0001) and multiple system atrophy (p = 0.018). MIBG uptake of the thyroid on early images decreased significantly also in multiple system atrophy compared to controls (p = 0.027). On late images, thyroid uptake differed significantly only between Parkinson’s disease and controls (p = 0.010). Conclusions: Our study is the first to demonstrate decreased MIBG uptake of the thyroid in Parkinson’s disease. Sympathetic nervous denervation of Parkinson’s disease occurred not only in the heart but also in the thyroid.

Objective: The pathophysiology of hallucinations in Parkinson disease is poorly understood. This study investigated the relation between visual hallucination and visual evoked potentials (VEPs) in Parkinson disease. Methods: Nineteen patients with Parkinson disease were studied. The authors divided patients into 2 groups: patients with visual hallucinations (VH group) and those without visual hallucinations (no-VH group). VEPs using a checkerboard stimulus were recorded under a drug-free state. Results: On multivariate regression analysis, only the average P100 latency was selected and remained significant after the backward elimination method. Conclusion: The authors demonstrated a close association between visual hallucinations and elongated VEP latency in Parkinson disease. VEPs may become one of the predictors for visual hallucination.

Background: No method for the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease (sCJD) has been established except for pathologic examination. Objective: To identify a reliable marker for the clinical diagnosis of MM2-type sCJD. Methods: CSF, EEG, and neuroimaging studies were performed in eight patients with MM2-type sCJD confirmed by neuropathologic, genetic, and western blot analyses. Results: The eight cases were pathologically classified into the cortical (n = 2), thalamic (n = 5), and combined (corticothalamic) (n = 1) forms. The cortical form was characterized by late-onset, slowly progressive dementia, cortical hyperintensity signals on diffusion-weighted imaging (DWI) of brain, and elevated levels of CSF 14-3-3 protein. The thalamic form showed various neurologic manifestations including dementia, ataxia, and pyramidal and extrapyramidal signs with onset at various ages and relatively long disease duration. Characteristic EEG and MRI abnormalities were almost absent. However, all four patients examined with cerebral blood flow (CBF) study using SPECT showed reduction of the CBF in the thalamus as well as the cerebral cortex. The combined form had features of both the cortical and the thalamic forms, showing cortical hyperintensity signals on DWI and hypometabolism of the thalamus on [18F]2-fluoro-2-deoxy-d-glucose PET. Conclusion: For the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease, cortical hyperintensity signals on diffusion-weighted MRI are useful for the cortical form and thalamic hypoperfusion or hypometabolism on cerebral blood flow SPECT or [18F]2-fluoro-2-deoxy-d-glucose PET for the thalamic form.

Background Intellectual deterioration occurs in 10-40% of patients with Parkinson’s disease. However, there are many conflicting studies on its relation with brain perfusion and the nature of this dementing process remains controversial.Objective To compare cortical perfusion by SPECT using 123I-IMP between Parkinson’s disease patients with dementia and those without dementia and to investigate the correlation between dementia in Parkinson’s disease and brain perfusion in various areas.Methods Fifty-two cases of Parkinson’s disease and 10 control cases were studied. The Parkinson’s disease with dementia group included 30 cases and the Parkinson’s disease without dementia group included 22 cases.,Results By multiple logistic regression method, we demonstrated significant hypoperfusion in the occipital cortex in Parkinson’s disease with dementia.Conclusions The cause of dementia in Parkinson’s disease may vary. We demonstrated that occipital hypoperfusion was closely correlated to dementia in Parkinson’s disease compared to frontal, parietal and temporal perfusion.

The authors report 2 cases of primary spinal intramedullary lymphoma and review all previously reported magnetic resonance imaging findings on this disease. The most common finding was a solid and homogeneously enhanced mass that was hyperintense on T2-weighted images, without associated syringomyelia. In a few cases, swelling of the spinal cord was minimal.

Objective -- To report a case of idiopathic spinal epidural lipomatosis (SEDL) presented with unique radicular pain most likely caused by enlarged veins surrounding nerve roots. Patient A 26-year-old male presented with radicular pain of the right T6-T7 area. He also showed Becker's nevus in the corresponding area. CT myelography and magnetic resonance imaging revealed epidural lipomatosis posterior to T4 -T8 of the spinal cord. Surgical removal of adipose tissue and a hemilaminectomy of T4 T7 were performed and resulted in relief of the radicular pain. Conclusions Lipomatosis was histologically confirmed and surrounded by enlarged veins. These abnormally enlarged veins compressed the nerve roots and were thought to cause radicular pain. Also, Becker's nevus of this case seems to have some relationship with SEDL.

A 30-year-old woman presented with ataxic gait and progressive mental deterioration, and 3 years later developed myoclonus in the limbs. Subsequently, she lapsed into an akinetic state and died more than 6 years after the onset of disease. The brain weighed 670 g, and preferential degeneration was found in the medial thalamus and the inferior olivary nucleus. In the cerebrum and cerebellum, gliosis and neuronal depletion were only mild and disintegration of the parenchymal structures was inconspicuous, despite pronounced atrophy. The patient had methionine homozygosity at codon 129 of the PrP gene and protease-resistant PrP type 2 in the brain. On PrP immunostaining, plaque-like deposits were detected in the cerebral and cerebellar cortices. Severe brain atrophy such as in the present case has never been described in the thalamic variant of sporadic CJD.

A 61-year-old man with recurrent ischemic attacks was examined by diffusion-weighted MRI (DWI). He had reversible right hemiparesis and dysarthria five times during admission. DWI was obtained on the first two attacks, the last attack and four days after the last attack. The first two attacks were clinically diagnosed as transient ischemic attack (TIA), and the last attack was cerebral infarction with symptoms persistent for one week with Babinski's sign. In the first and last images the apparent diffusion coefficient (ADC) declined to approximately 80% of the corresponding area. We conclude that different images showed TIA with ADC declining, TIA without ADC declining, the hyperacute phase of cerebral infarction before ADC declining, and cerebral infarction after ADC declining. Consecutive DWIs were helpful to understand the character of recurrent ischemic attacks.

Objective Silent or asymptomatic cerebrovascular disease is believed to be an important risk factor for symptomatic stroke and vascular dementia. Although non-specific complaints such as mild to moderate headache and/or dizziness may also be caused by silent stroke, which remains a topic of controversy. Methods To investigate the relationship between silent brain infarcts and non-specific complaints, we assessed findings on magnetic resonance images using a common protocol in the following three groups of subjects; Group 1: 78 subjects with non-specific complaints, Group 2:47 subjects with vascular risk factors, and Group 3: 75 normal subjects without any subjective complaints or vascular risk factors. In addition to silent stroke, deep white matter lesions on MRI were also evaluated. All subjects were recruited from 12 institutes of the study group located at various parts of Japan. Results Silent brain infarcts were demonstrated in 44 %, 43%, and 20% of subjects in Groups 1, 2, and 3, respectively. In Group 1, the average number of infarcts per individual who had silent brain infarction was 1.8, which was significantly fewer than 3.8 in Group 2 or 3.5 in Group 3 (p

This study evaluated efficacy and safety of donepezil hydrochloride (donepezil) at 5 mg/day in patients with mild to moderately severe Alzheimer’s disease for 24 weeks in a double-blind, placebo-controlled comparative trial. In this study, 268 patients were enrolled and 39 of these (15%) were withdrawn. In the evaluable population of efficacy, Protocol-Compatible (PC) analyzed patients (n = 228), better effects than that of placebo were confirmed using two primary efficacy measures: a cognitive performance test, the Japanese version of the Alzheimer’s Disease Assessment Scale – cognitive subscale (ADAS-J cog, p = 0.003) and a clinical global assessment, the Japanese version of the Clinical Global Impression of Change (J-CGIC, p = 0.000). The superiority of donepezil was also shown by secondary measures: the Sum of the Boxes of the Clinical Dementia Rating (CDR-SB), the Mental Function Impairment Scale (MENFIS) and the caregiver-rated modified Crichton scale (CMCS). The same results were obtained in the intention-to-treat (ITT) analysis (n = 263). The incidence of drug-related adverse events was 10% (14/136) in the donepezil and 8% (10/131) in the placebo group; no significant difference was seen between the two groups. The main adverse events were gastrointestinal symptoms, and these were almost all mild, and they all disappeared with continued administration or temporary discontinuation of donepezil. These results indicate that the donepezil appears to be effective and well tolerated in patients with mild to moderately severe Alzheimer’s disease.

With the increment of the aged, primary and secondary prevention of cerebrovascular disease in the Japanese diabetics are crucial problems. Early detection of asymptomatic infarction, not rare in diabetics, is important in the view of cost benefits. Little is known about the development and progression of asymptomatic infarction. We investigated the number of lacuna during a period of 5 years in 51 non-insulin-dependent diabetes mellitus (NIDDM). At the initiation of this study, 22 patients were free from lacuna and another 29 patients had asymptomatic multiple lacunae. In the former patients, no risk factors were different between the 13 patients with still no lacuna and the nine patients with lacuna-developed after 5 years. In the latter patients, the 17 patients with worsening lacunar state had significantly higher systolic blood pressure, and a higher prevalence of macroalbuminuria than the 12 patients with no increment of lacuna. Multiple logistic regression analysis showed that macroalbuminuria after 5 years was the only contributing factor to the increased lacuna. Therefore, in the NIDDM, macroalbuminuria induced an increase of lacuna in magnetic resonance imaging, although numbers of cases were relatively small. Prevention of the development of macroalbuminuria are essential to avoid the progression of asymptomatic lacuna.

Spinocerebellar ataxia 6 (SCA6) is an autosomal dominant spinocerebellar degeneration caused by the expansion of the polymorphic CAG repeat in the human alpha1A voltage-dependent calcium channel subunit gene (CACNL1A4 gene). We have analyzed 60 SCA6 individuals from 39 independent SCA6 Japanese families and found that the CAG repeat length is inversely correlated with the age of onset (n = 58, r = -0.51, P < 0.0001). SCA6 chromosomes contained 21-30 repeat units, whereas normal chromosomes displayed 6-17 repeats. There was no overlap between the normal and affected CAG repeat number. The anticipation of the disease was observed clinically in all eight parent-child pairs that we examined; the mean age of onset was significantly lower (P = 0.0042) in children than in parents. However, a parent-child analysis showed the increase in the expansion of CAG repeats only in one pair and no diminution in any affected cases. This result suggests that factors other than CAG repeats may produce the clinical anticipation. A homozygotic case could not demonstrate an unequivocal gene dosage effect on the age of onset.

A 27-year-old woman was admitted to our hospital with tetraparesis, dysesthesia and hypoesthesia of all regions below the breasts, urinary disturbance, and difficulty in breathing. Since age 21 idiopathic thrombocytopenic purpura (ITP) was diagnosed and steroid therapy was continued. At age 26, she had splenectomy for her ITP. On admission, steroid pulse therapy was administered with a tentative diagnosis of transverse myelitis. Symptoms gradually ameliorated. At age 29, she gradually lost her left vision, and multiple sclerosis was diagnosed and steroid therapy was administered, and her left vision gradually ameliorated. There are several reports describing other autoimmune disorders that arise after splenectomy. Since the spleen acts as a major pool of type 2 helper T cells, it is plausible that peripheral type 1 helper T cell activity may increase after splenectomy, promoting the development of autoimmune disorders. We considered there would be a close relation between splenectomy for ITP and multiple sclerosis in this case.

Hereditary spinocerebellar ataxias (SCAs) are classified as autosomal dominant, autosomal recessive, X-linked, or mitochondrial. Mutations in SYNE1 are responsible for a group of recessively inherited cerebellar ataxias in French-Canadian families, known as spinocerebellar ataxia, autosomal recessive 8 (SCAR8).1 Patients with SCAR8 were reported to show late-onset ataxia with slow progression and significant dysarthria as well as cerebellar atrophy.1,2 Here, we report 4 novel homozygous SYNE1 mutations in 3 Japanese patients with cerebellar ataxia and their unique clinical and genetic characteristics. Acknowledgment: The authors thank Drs. Tamotsu Kubori and Masaya Oda (Sumitomo Hospital) for performing the neurophysiologic examinations of patient 1.

Non-fatal or small infarction, especially with multiple occurrence, is a feature of cerebrovascular disease complicating diabetes mellitus. The atherosclerosis of the cervical and cerebral arteries, especially in the posterior circulation, in diabetes is more severe than that in non-diabetics. We reviewed the incidence of vascular lesions, and clinical history in 25 male and 26 female diabetic autopsy subjects. In addition, the long-term effects of blood pressure and glucose values were evaluated in 267 stroke patients without cerebral embolism, 99 of whom had diabetes mellitus. Asymptomatic cerebral infarction is not rare in diabetic subjects, and can now be accurately pathologically and clinically evaluated using MRI. The results of our study indicate that high blood pressure and poor blood glucose control are associated with the higher incidence of cerebral infarction in the diabetic patients.

We studied risk factors and the relationship of lacunes to diabetes mellitus, age, hypertension, hyperlipidemia, atherosclerosis and also to intellectual impairment, comparing brain MRI (magnetic resonance imaging) findings to the multiple risk factors and the results of a cube-handdrawing test. Brain MRI was performed using a Shimazu SMT-150, 1.5 Tesla, in 118 asymptomatic NIDDM and 39 asymptomatic nondiabetic patients. In diabetics, 65 had lacunes and the incidence of lacunes was significantly higher in diabetics with coronary insufficiency by ECG and hypertension, but not significantly different in those with or without the other risk factors. Cube hand-drawing is a good indication of space cognition ability supported by the wide association areas of the brain. Drawing was tested in 41 diabetics and 39 nondiabetics. Correlation of lacunes to deformity in drawing and age was high in both diabetics and nondiabetics. Multiple lacunes were closely related to intellectual impairment.(Internal Medicine 33: 317-320, 1994)

Recently, the age of patients receiving chronic hemodialysis has markedly increased and diabetic nephropathy in aged subjects is often induced by dialysis. Consequently, many aspects of the patterns and features of cerebrovascular diseases complicated by dialysis are changing.1. Cerebral hemorrhage in chronic dialysis patients are more frequent and more severer than in non-dialysis subjects or the general population. Subcortical hemorrhage, is more frequently seen in dialytics, the cause of which is unknown. However, in aged persons, amyloid degeneration of the cerebral arteries is common, so cerebral hemorrhage due to amyloid angiopathy must be cautiously checked, although we have no clinical method of detecting amyloid angiopathy in daily practices.The incidence of cerebral hemorrhage in dialytics has decreased in recent years, perhaps due to effective control of hypertension and improvement of dialysis techniques, but the frequency of cerebral infarction may increase again. Pathogenesis of cerebral hemorrhage in dialytics is discussed.2. In a cranial MRI study on 71 dialysis patients without cerebrovascular signs and symptoms, ischemic changes were classified into cerebral white matter lesions, lacunes and brain stem infarctions.a) Ischemic brain changes on MRI were found in 38 subjects (53.5%), but cerebral hemorrhage was found in only 1 patient (1.4%). In the remaining 32 (45.1%), there were no abnormal images. Ischemic lesions on MRI were found more than half of the dialysis subjects and increased with advancing age; above 70 years of age, practically all patients showed ischemic changes on MRI imaging. The frequency of brainstem lesions showed no age-difference. Lacunes were reduced after middle-age, while cerebral white matter lesions increased linearly with advancing age. Although asymptomatic cerebral lesions were found in many of dialysis patients, whether they were really “asymptomatic” or not, is an important issue. Psychiatric evaluations are needed in dialysis patients, because depression or other psychiatric manifestations are not rare in these subjects.3. Six dialysis patients with cerebral hemorrhage or cerebral infarction verified on MRI and/or at autopsy are presented. A 47-year-old male patient with autosomal dominant polycystic kidney disease (PKD) showed a massive cerebral hemorrhage in the putaminal region. Intracranial aneurysms were not found in this patient. Genetic relationship in autosomal dominant PKD is discussed, especially in relation to collagen genes.4. Incidental cerebral aneurysms were found in 88 subjects aged sixty years or more among 1, 200 non-selected routine autopsies. Rupture occurred in 17% of all aneurysms, while fatal ruptures were found in 78% of aneurysms more than 6mm in diameter. MRI imaging is necessary in cases of dialysis to find silent cerebral aneurysms, the rupture of which may often be fatal.5. Subdural hematoma (SDH) are not rare in dialysis patients. We must remain alert to this disorder, because SDH is apt to be misinterpreted in dialysis patients.6. We propose that a liason of therapists including internal medicine, neurology, neurosurgery or orthopedics should be organized for prevention and management of cerebrovascular lesions in chronic dialysis.

Lymphocytic hypophysitis (LYH) is a rare neuroendocrine disorder characterized by autoimmune inflammation of the pituitary gland. Visual disturbance is one of the most common and serious symptoms of LYH. Most of the visual symptoms in LYH are secondary to compression of the optic chiasm and some reports have described direct inflammatory involvement of the optic pathways. We describe a 30-year-old man with a 9-day history of bilateral blurred vision. Ophthalmic examination demonstrated severely impaired vision without temporal hemianopsia. Hypothyroidism, hypocortisolism, and hypogonadism were detected in laboratory tests. Central diabetes insipidus was diagnosed by a hypertonic saline infusion test. MRI revealed thickening of the pituitary stalk and enlargement of the hypophysis, which was enhanced with gadolinium. High intensity of the posterior lobe was not recognized on T1-weighted images. These findings established a clinical diagnosis of lymphocytic panhypophysitis. Methylprednisolone pulse therapy was introduced and his visual acuity gradually recovered. The anterior pituitary function improved, but desmopressin was still required. Pattern-reversal visual evoked potentials (VEP) have been widely used to detect optic nerve lesions caused by multiple sclerosis and brain tumors. However, there have been no previous reports of their usefulness for LYH. The P100 latency in our case was slightly prolonged and the amplitude was markedly reduced. These findings are similar to ischemic optic neuropathy and other conditions in which axonal damage is prominent. The prolonged latency and low amplitude on VEP examination in this case showed rapid improvement in parallel with the recovery of visual acuity. Taken together, our case implies the usefulness of pattern-reversal VEP for the diagnosis of optic neuritis in LYH, especially for the evaluation of its pathogenic mechanisms.

Dinucleotide repeat polymorphism has been observed in the promoter of the alpha-synuclein (alpha-SYN)/NAC precursor protein (NACP) gene. Alpha-SYN/NACP allele 3 (described by Xia et al. (Ann. Neurol., 40 (1996) 207), equivalent to allele 1 described by Krüger et al. (Ann. Neurol. 45 (1999) 611) is reported to be significantly more frequent among patients with sporadic Parkinson's disease (sPD) than controls. In this study, we genotyped the same alpha-SYN/NACP polymorphism in Japanese sPD patients and healthy controls, but found that any aliele showed no significant difference between the two groups.

Brain and spinal magnetic resonance imaging (MRI) play an important role in the diagnosis of multiple sclerosis (MS). McDonald criteria allow MRI evidence for dissemination in space and dissemination in time to be used to diagnose MS in patients who present with clinically isolated syndromes. Long spinal cord lesion on spinal MRI is a diagnostic finding of opticospinal MS with autoantibodies to the aquaporin-4 water channel. Magnetic resonance spectroscopy, diffusion tensor imaging and magnetization transfer ratio map may reveal chemical pathology and tract change in normal appearing white matter of MS.

Objectives Sleep attacks (SAs) in Parkinson's disease (PD) are rare, but clinically important because they significantly impair the daily lives of patients. Causes of SAs include long-term activation of dopaminergic (especially D3) receptors. Recent studies suggest that SAs in PD may be related to impairment of hypothalamic orexin neurons, similar to narcolepsy. Whether orexin is associated with long-term activation of dopaminergic receptors remains uncertain. Patients and methods We measured levels of orexin in samples of spinal cerebrospinal fluid (CSF) from 25 patients with PD, including 9 with excessive daytime sleepiness and 4 with SAs. Furthermore, in the four patients with SAs, the selective dopamine D1/D2 agonist pergolide was substituted for the causative drugs with D3 stimulatory activity, and CSF-orexin levels were measured before and after switching treatment. Results In the 25 patients with PD, including the 4 patients with SAs, lower CSF-orexin levels were associated with a longer disease duration, which has been linked to a higher incidence of SAs. Switching treatment to pergolide significantly increased CSF-orexin levels and completely resolved SAs in the four patients with PD. Conclusion Despite the small number of patients studied, our results suggest that orexin transmission is most likely involved in SAs in PD and that abrogation of D3 receptor stimulation may increase orexin and thereby inhibit SAs.

Objective – Dementia occurs frequently in patients with Parkinson’s disease (PD). However, the nature of the dementing process remains controversial. We evaluated various cognitive functions in patients with PD, compared fractional anisotropy (FA) values between PD patients with and without dementia. Methods – Thirty-seven consecutive patients with Hoehn-Yahr stage III or IV PD participated in this study. Patients were divided into two groups: (i) PD with dementia group (PDD) and (ii) PD without dementia group (PDND). There were 11 PDD and 26 PDND cases. Ten controls were also studied. Results – The PDD group showed significant FA reduction in the bilateral posterior cingulate bundles compared with PDND. FA values in the left posterior cingulate bundle showed significant correlations with many cognitive parameters. Interpretation – Our results showed that the posterior cingulate areas play some important roles in the dementing process in PDD. However, as the pathological processes responsible for dementia in PD patients may be multifaceted, further studies are necessary.

Introduction – It is generally assumed that executive dysfunctions in Parkinson's disease (PD) are caused by degeneration of the basal ganglia or frontal cortex or both. However, there have been few studies investigating the relationship between executive dysfunctions and cerebral pathological change. The objective of this study was to evaluate various cognitive functions in non-demented patients with PD, and to compare the fractional anisotropy (FA) values of PD patients with and without executive dysfunction. Materials and Methods – Twenty-one consecutive non-demented patients with PD were enrolled in this study. Patients were divided into two groups on the basis of their Wisconsin Card Sorting Test score. Results – There was significant FA reduction in the left parietal white matter in the group in which the number of categories achieved was ≤2 relative to the group that achieved >2. Conclusion – Accumulating evidence suggests that conventional ‘frontal’ tasks correlate with both frontal lobe and parietal lobe function, and we suggest that pathological changes in the left parietal lobe may cause, in part, disturbances in executive tasks in PD.

Thrombosis involving a brain infarction frequently occurs in patients with a malignant tumor. Although nearly all types of tumor have been reported in association with a hypercoagulable state, pleural mesothelioma-associated Trousseau syndrome is extremely rare.A 69-year-old female was admitted to our hospital with cough, sputum, and breathing difficulties. She was diagnosed as having a mesothelioma from a percutaneous pleural biopsy. Although there were no risk factors for atherosclerosis, brain infarctions showed frequent relapses, even under anticoagulant therapy, and there was a marked hypercoagulable state.Attention should be paid to this syndrome when unexplained brain infarctions occur in patients with pleural mesothelioma.