Nobuyuki Murakami

Ubiquitin-positive intraneuronal inclusions in the extramotor cortices of presenile dementia patients with motor neuron disease

SummaryUbiquitin-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.

Effects of turmeric on Alzheimer's disease with behavioral and psychological symptoms of dementia

We describe here three patients with the Alzheimers 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.

Ubiquitin-positive inclusion in anterior horn cells in subgroups of motor neuron diseases: A comparative study of adult-onset amyotrophic lateral sclerosis, juvenile amyotrophic lateral sclerosis and werdnig-hoffmann disease

This report concerns the expression of ubiquitin in anterior horn cells of various subgroups of adult and infantile motor neuron disease (MNDs); immunohistochemical techniques were employed. Ubiquitin-positive skein-like inclusions (SLIs) were found in all cases of adult-onset amyotrophic lateral sclerosis (ALS), including 16 cases with sporadic ALS, two cases of familial ALS with posterior column degeneration and Lewy body-like hyaline inclusions (LBHIs), two sporadic ALS cases with LBHIs, and three cases of sporadic ALS with dementia. SLIs were not found in anterior horn cells of 5 cases with Werdnig-Hoffmann disease (WHD). However, granular ubiquitin-positive deposits were seen in ballooned neurons of WHD patients. No ubiquitinated materials were found in the perikarya of two sporadic juvenile ALS patients with basophilic inclusions (BIs), but granular ubiquitin-immunoreactive deposits were occasionally observed in the BIs. These results suggest that ubiquitin-positive SLIs are characteristic features of various forms of adult-onset ALS and that aggregated ubiquitinated granules are characteristic of ballooned neurons of WHD. Ubiquitinated structures and their distribution patterns may reflect degenerative processes of anterior horn cells, and may be useful for classifying subgroups of motor neuron diseases.

Parkinsonism-dementia complex on Guam — Overview of clinical aspects

Parkinsonism-dementia complex (PDC) is the second most common neurodegenerative disorder in Guam, after amyotrophic lateral sclerosis (ALS). PDC was first described by Hirano 1961. A familial appearance is seen among some PDC cases, which may also include ALS, and vice versa, but subsequent research including pedigree analysis, prospective case control registries, and the search for specific gene markers has failed to yield a satisfactory genetic explanation. Important diagnostic indicators of the illness include rigido-akinetic type Parkinsonism and severe dementia.In PDC, rigidity is so marked that postural deformities such as a generally flexed posture become rather prominent. Gait disturbances are a common initial symptom. Hyperreflexia and spinal muscular atrophy, developing mainly in the distal extremities, are frequently observed. These mixedsyndrome patients can be seen as clear support for the view that Guam ALS and PDC constitute a single mixed disease entity with a spectrum of clinical expression.The present paper offers an overview and description of the clinical features of PDC.

An autopsy case of lymphomatosis cerebri showing pathological changes of intravascular large B-cell lymphoma in visceral organs

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.

An autopsied case of panencephalopathic-type Creutzfeldt-Jakob disease with mutation in the prion protein gene at codon 232 and type 1 prion protein.

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.

Cerebrospinal fluid 28-kDa calbindin-D as a possible marker for Purkinje cell damage

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.

Clinicopathological Study of Two Respirator‐assisted Long Survival Cases of Amyotrophic Lateral Sclerosis

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, Clarkes nucleus, oculomotor nucleus and Onufs 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.