We describe here three patients with the Alzheimer's Disease (AD) whose behavioral symptoms were improved remarkably as a result of the turmeric treatment, which is the traditional Indian medicine. Their cognitive decline and Behavioral and Psychological Symptoms of Dementia (BPSD) were very severe. All three patients exhibited irritability, agitation, anxiety, and apathy, two patients suffer from urinary incontinence and wonderings. They were prescribed turmeric powder capsules and started recovering from these symptoms without any adverse reaction in the clinical symptom and laboratory data. After 12 weeks of the treatment, total score of the Neuro-Psychiatric Inventory-brief questionnaire decreased significantly in both acuity of symptoms and burden of caregivers. In one case, the Mini-Mental State Examination (MMSE) score was up five points, from 12/30 to 17/30. In the other two cases, no significant change was seen in the MMSE; however, they came to recognize their family within 1 year treatment. All cases have been taking turmeric for more than 1 year, re-exacerbation of BPSD was not seen. The present cases suggest a significant improvement of the behavioral symptoms in the AD with the turmeric treatment, leading to probable benefit of the use of turmeric in individuals with the AD with BPSD.

We describe the case of a 61-year-old man presenting with subacute encephalopathy. The clinical manifestations included progressive dementia and pyramidal and extrapyramidal tract signs. Brain CT scan and MRI showed diffuse bilateral white matter changes in the cerebral hemispheres, basal ganglia, thalamus and brainstem. No contrast-enhanced lesion was observed. Peripheral blood studies, CSF analysis, and brain and muscle biopsies were nonspecific and failed to reveal diagnostic evidence of any specific disease. The patient was diagnosed with and treated for a cerebral demyelinating disorder. Post mortem examination showed diffuse infiltration of lymphoma cells without mass lesions in the extensive cerebral white and gray matter with minimal intravascular patterns, particularly in the perivascular and periventricular spaces. These findings were consistent with lymphomatosis cerebri (LC). In other visceral organs such as the lungs, liver, kidneys and adrenal glands, blood vessels were plugged by numerous neoplastic cells which were morphologically and immunohistochemically similar to those observed in the CNS, consistent with intravascular malignant lymphoma (IVL). To our knowledge, this is the first autopsy report showing the coexistence of LC and IVL. This case suggests a possible link between LC and IVL.

In this study, we describe the clinicopathologic findings in a 68‐year‐old man with panencephalopathic‐type CJD with a substitution from methionine to arginine at codon 232 (M232R) in the prion protein (PrP) gene and type 1 PrP. Initial symptoms of the patient were a rapidly progressive memory disturbance and disorientation. The patient showed myoclonus and periodic sharp‐wave complexes on electroencephalogram in the early stages of disease. Diffusion‐weighted MRI along with the presence of both neuron‐specific enolase and 14‐3‐3 protein in the CSF showed similarities to classic‐type sporadic CJD. The patient reached the akinetic mutism state 2 months following the onset of symptoms and died after 13 months. Neuropathologic examination revealed panencephalopathic‐type CJD pathology including widespread neuron loss with severe hypertrophic astrocytosis and status spongiosus in the cerebral gray matter, particularly in the neocortex. Cerebral white matter and the cerebellum also showed severe involvement. Immunohistochemical staining for PrP showed diffuse gray matter staining, indicating synaptic‐type PrP deposition without plaque‐type. Two different clinical phenotypes of M232R CJD were recognized despite the presence of the same PrP genotype, and the present case is speculated to correspond to the rapid‐type.

The relationship between the features of MRI in brainstem and pathological findings was investigated in eight autopsy cases with progressive supranuclear palsy (PSP). Features of T1-weighted images at midbrain level were atrophy of tegmentum and tectum, and dilatation of aqueduct. Histologically, these findings were consistent with atrophy of periaqueductal gray matter, quadrigeminal plate, and tegmentum. In these lesions, we detected neuronal loss, decrease in density of myelinated fibers, gliosis, rarefaction of tissues, and tau-positive structures such as neurofibrillary tangles (NFTs), glial fibrillary tangles (GFTs) and neuropil threads. At pons level, atrophy of tegmentum, atrophy of pontine base, and dilatation of prepontine cistern were found. Tau-positive structures were observed not only in tegmentum but also in pontine base. The density of the tau-positive structure was closely related to the severity of atrophy. Features of T2-weighted images were high intensity in the periaqueductal lesion and tegmentum in pons. In these lesions, severe histological findings were detected. The MRI features in brainstem were closely related to the histological findings as PSP.

We evaluated plasma noradrenaline (NA) levels at rest and during head-up tilt test in 20 patients with sporadic amyotrophic lateral sclerosis (ALS). Their fasting plasma NA levels ranged from 195 to 4227 pg/ml. The average plasma NA level was 483 pg/ml in five ambulatory patients, 341 in two wheelchair-bound patients, 1264 in 11 bedridden patients, and 208 in two respirator-dependent patients whose disability grading was the worst among the four groups. Arterial carbon dioxide (PCO2) was evaluated as a measure of respiratory function. The coefficient of correlation between PCO2 and plasma NA wasr=0.654 (p<0.01). Either respiratory failure or lower motor neuron dysfunction may relate to the elevation of plasma NA levels. In the two bedridden patients, plasma NA levels and heart rate at rest increased significantly as the disease progressed. Cardiovascular responses to head-up tilting were normal. These data suggest that the elevation of plasma NA levels may be related to progression of respiratory failure and lower motor neuron dysfunction. In conclusion, sympathetic hyperactivity in ALS is considered to be not primary, but secondary to somatic motor disabilities and respiratory failure.

脳卒中患者においてはその移動能力がADL全体を反映する可能性があり, また移動能力は家庭復帰の重要な条件でもある.こうしたことから我々は脳卒中患者の移動能力を評価するスケールを開発するため, 脳卒中リハビリテーション患者の移動能力獲得過程を10段階にレベル化し, 東名式移動能力レベル (TML) とした.TMLは「できるレベル」で評価し, 車椅子移乗介助レベルを4段階, 車椅子移乗自立・杖歩行介助レベルを4段階, 杖歩行自立レベルを2段階の計10段階に分類した.脳卒中患者20例のTMLを2名の医師が同時に評価したところ完全一致率は85%であった.さらに脳卒中患者104例にTMLとBarthel Indexを評価し, その相関を検討したところ, 両者は良く相関し, Spearmanの順位相関係数は0.936であった.このことからTMLは高い信頼性を有し, 脳卒中患者のADLを反映するスケールであると考えられた.

Amyotrophic lateral sclerosis (ALS) with dementia is characterized by rapidly progressive dementia and motor neuron involvement. The age at onset in 12 sporadic cases ranged from 43 years to 78 years. The initial symptoms are dementia, such as uninhibited behavior and personality change in most patients. Both dementia and motor neuron involvement appear within 1 or 2 years of the onset. The clinical picture of motor neuron disturbance was bulbar-type ALS. In ALS-dementia, lower motor neuron sign is predominant than upper motor neuron sign. The pattern of dementia indicated impaired frontal lobe function, confirmed by frontal sign such as perseveration, forced grasping and utilization behavior. These neurological signs are significant in association with the frontal lesion on CT, MRI and single photon emission computed tomography. The pathological findings show frontotemporal atrophy, mild non-specific neuronal loss of cortical superficial layer, fibrous gliosis of subcortical white matter, degeneration of substantia nigra and motor neuron involvement. The clinicopathological findings resembled those of dementia of frontal type and are distinct from those of Alzheimer's disease. We thus consider that the combination of motor neuron disease and dementia is a new clinicopathological entity, quite distinct from ALS or other dementias, as Yuasa and Mitsuyama proposed earlier.

The aim of this study is to clarify the clinicopathological characteristics of the multisystem degeneration seen in two male siblings with familial amyotrophic lateral sclerosis (FALS). A similar neurological disorder affected their elder sister and paternal uncle, but not their parents. The older brother (case 1) developed muscular weakness at 50 years of age and the younger brother (case 2), at 42 years of age. The duration of illness was 19 months in case 1 and 31 months in case 2. The clinical picture was the common (suspended) form in case 1 and the pseudopolyneuritic form in case 2. Pyramidal tract sign was obscure in both cases and cerebellar sign, sensory disturbance, sphincter disturbance and oculomotor palsy were not observed in either case. Neuropathological examination revealed similar findings in the two cases: 1) marked loss of lower motor neurons in the spinal anterior horn and motor nuclei of the lower brain stem in both cases, with neuronal loss of Onuf's nuclei in case 2; 2) very mild involvement in Clarke's nuclei, the dorsal and ventral spinocerebellar tracts and the middle root zone of the posterior column; 3) relatively well preserved Betz cells in the upper motor cortex with the appearance of a few macrophages, and mild changes in the pyramidal tract of the spinal cord; and 4) mild degenerative changes in the pallidoluysian system and the dentatorubral system. The most characteristic pathological findings common to both cases were the extremely mild involvement of the middle root zone of the posterior column, Clarke's nuclei and spinocerebellar tracts. The pattern of lower motor neuron system degeneration paralleled the development of clinical features. Genetic studies demonstrated no mutations in exons 1, 2 and 4 of Cu/Zn-binding superoxide dismutase gene. We emphasized the existence of mild involvement of middle root zone of posterior column, Clarke's nuclei and spinocerebellar tract in FALS with multisystemic degeneration.

右後大脳動脈領域梗塞に続発してそう状態をきたした56歳・男性を報告した.左不全片麻痺にて発症し, 2週間後よりそう状態を呈した.既往歴・家族歴に特記すべきことなく, 脳梗塞に続発したものと考えた.頭部CT・MRI所見では, 右大脳脚・視床・視床下部・後頭葉に梗塞巣が限局し, そう状態と限局性病変について検討した.責任病巣として, 右中脳腹側被蓋野 (A-10) ・中脳-前頭葉皮質ドーパミン系を想定し, 若干の考察を加え報告した.

64歳, 男性。右利き。左側頭葉後部白質および脳梁膨大部の梗塞により右同名半盲, 色彩呼称障害, 失読, および視覚失認を呈した。本例の視覚失語の特徴は絵カードの呼称が困難であるにも関わらず, 絵の異同弁別, 図形模写, 同一図形の matching などは可能であった点で, これは形態視が保たれていることを意味し, Lissauer の言う連合型視覚失認に一致すると思われた。また物品の指示, 絵カードのカテゴリー別分類, odd picture out test などが困難であったことから視覚失語とは鑑別された。従来連合型視覚失認の報告は両側性病変によるものが多いが, 本例は左側一側性病変と脳梁病変により連合型視覚失認を呈し, Lissauer の症例と責任病変が類似しているという点で興味深いと考えられた。

We examined the oculomotor and/or trochlear nuclei of 27 amytrophic lateral sclerosis (ALS) patients and 10 controls by histological and immunohistological methods. Their neurons were relatively well preserved. In 7 of 22 sporadic ALS patients (including 3/3 ALS with ophthalmoplegia) and in 4 of 5 ALS patients with dementia, some morphological changes similar to those in anterior horns (Bunina bodies, ubiquitin-positive skein-like inclusions, Lewy body-like inclusions, conglomerate inclusions and spheroids) were rarely, but clearly seen. These changes were not observed in controls. Our results suggest that the oculomotor and trochlear nuclei in ALS patients are slightly affected in a manner similar to that in the anterior horns, but the degree is less than that necessary for development of ophthalmoplegia in the majority of ALS patients.

To examine the clinical value of 28-kDa calbindin-D (CaBP) in cerebrospinal fluid (CSF) as a marker for the damage to Purkinje cells, we measured CSF CaBP levels using an enzyme immunoassay method in 107 patients with cerebellar and other neurological diseases, and 26 controls. The mean CaBP level was markedly elevated in patients with cerebellar diseases, and the elevation of CaBP level was more frequent in the diseases involving Purkinje cells, such as multiple system atrophy (MSA) and subacute cerebellar degeneration in association with lung cancer. Further, in MSA patients, the CaBP levels decreased with duration of illness. The mean levels of CaBP were also elevated in some of the other diseases. We conclude that the elevations of CaBP levels are not specific for cerebellar diseases, but CSF CaBP may be a useful marker for examining the Purkinje cell involvement in cerebellar diseases.

This report concerns the evaluation of the clinicopathological features of amyotrophic lateral sclerosis (ALS) in two male patients who survived ten years with the assistance of artificial respirators. The patients were 54 and 52 years old at disease onset and they were placed on respirators 32 and 27 months later, respectively. The patients did not show impairments in occulomotor, sensory and rectovesical functions nor develop bedsores, with the tetrad of ALS being negative. The main histopathological changes observed include neuron loss of the upper and lower motor systems and degeneration of the pyramidal tract. By contrast, other systems such as the posterior column, spinocerebellar tracts, Clarke's nucleus, oculomotor nucleus and Onuf's nucleus remained intact. These findings on our two patients suggests that there may be cases in which the selective features of ALS are maintained throughout prolonged respiratory management.

Ubiquitin-positive intraneuronal inclusions were found in the extramotor cortices of ten presenile dementia patients with motor neuron disease. There were inclusions in the hippocampal granular cells and in the small neurons of the superficial layers of the temporal and frontal cortices. Bunina bodies were present in the anterior horn cells in all cases. These results suggest that ubiquitin-related cytoskeletal abnormalities are common in cerebral non-motor small neurons in these patients.

We reported two respirator-aided 10-year-survival male patients with sporadic amyotrophic lateral sclerosis (ALS). Their ages at onset were 54 and 52, clinical features common in both cases, the durations to tracheotomy 32 months and 27 months respectively, and the durations for respiratory support over 8 years in both cases. There were normal external ocular movement, normal pelvic sphincter function, normal sensory system and no bed sores throughout 10 years of illness. The brain weighted 1,295 g in case 1 and 1,430 g in case 2, being normal macroscopically. The spinal cord was slightly wasted with atrophic anterior roots. The histopathological study demonstrated the typical pattern of ALS in spite of the prolonged survival with artificial respiration. Neuronal loss and gliosis of the motor nuclei in the spinal cord and brainstem were more striking than those of the natural course. Neither hypertrophic astrocyte, central chromatolysis nor neuronophagia was observed. This finding suggested inactive condition of the degeneration. The pattern of white matter degeneration in the cord indicated some pallor of anterior and lateral columns, severe pallor of pyramidal tracts and intact posterior column and spinocerebellar tracts. The giant pyramidal cells in the precentral gyrus were lost in both cases. Pyramidal degeneration was traceable up to the cerebral peduncles in the case 2 and undetectable in that portion in the case 1. On the other hand, the extraocular muscle nuclei, the Onuf's nuclei, the dorsal motor nucleus of the vagus nerve, intermediolateral and Clarke's nuclei were relatively preserved, though no cell count was done in Clarke's nuclei and Onuf's nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

Thirteen patients suffering from motor neuron disease with dementia were studied to analyze the clinicopathological spectrum. The diagnosis of the disease was made on the basis of a clinical history of progressive dementia and motor neuron involvement. The mean age at onset of 11 sporadic cases was 54.9 years (range, 43 to 69 years), with a mean duration of disease of 25 months (range, 11 to 47 months). The initial symptoms were dementia in 7 cases, motor neuron involvement in 2 cases, and both dementia and motor neuron involvement in 2 cases. The clinical picture of motor neuron disturbance in sporadic cases represented bulbar-type of amyotrophic lateral sclerosis (ALS). Bulbar palsy was the initial symptom in 7 sporadic cases and all 11 patients developed bulbar palsy with advancing course of illness. Muscular wasting and fasciculation were more predominant in the upper limbs, shoulder girdle and anterior chest. Fasciculation was more extensively and frequently observed in those portions than that of classical ALS. In contrast, muscle strength in the lower limbs was well preserved so that all patients could walk even when respiratory failure developed. Hyperreflexia including jaw jerk was found in all cases and positive Babinski sign in 7 cases. Parkinsonism appeared in the initial stage in one sporadic case and in two familial cases. The type of dementia with uninhibited behavior and personality change closely mimicked that of Pick's disease. The degree of dementia was mild or moderate in 8 cases and severe in 3 cases. Language disorder was characterized by progressive reduction of speech output, leading finally to mutism in 5 cases. Perseveration was observed in 10 cases. Visuospatial disorder was absent even in the advanced stage. Mild memory disturbance was noted in the early stage in 10 cases. Pathological examination was performed in 7 cases including one familial case, revealing frontal atrophy in 3 cases, frontotemporal atrophy in 2 cases and temporal atrophy in 2 cases. On microscopic examination there were mild neuronal loss, gliosis, mild spongy state of the cortical superficial layers and fibrous gliosis in the frontotemporal white matter. The scattered senile plaques in one case did not justify a diagnosis of Alzheimer's type dementia. Neither circumscribed atrophy nor Pick body was found in any case. The nucleus basalis of Meynert showed no neuronal loss. The substantia nigra showed a mild to severe loss of nerve cells without Lewy bodies in all cases.(ABSTRACT TRUNCATED AT 400 WORDS)