Autopsied centenarian case of Alzheimer's disease combined with hippocampal sclerosis, TDP-43, and α-synuclein pathologies.

A Japanese woman showed slowly progressive memory disturbance starting at the age of 84 years, and disorientation gradually appeared. Head computed tomography revealed severe hippocampal atrophy, whereas the atrophy of the frontal lobe was considerably mild for her age. Behavioral and psychological symptoms of dementia were relatively inconspicuous during the disease course. Apolipoprotein E gene analysis showed ε3/ε4 heterozygosity. She died at the age of 100 years and she was clinically diagnosed as having Alzheimer's disease (AD). Autopsy revealed numerous neurofibrillary tangles, particularly in the hippocampal region, and extensively distributed senile plaques in the brain. Although the findings were compatible with the pathological criteria for AD, combined pathologies of hippocampal sclerosis, trans-activation response DNA-binding protein 43 kDa, and α-synuclein were also revealed. We believe that the clinicopathological findings of the present case are of significance for the diagnosis of elderly dementia and pathogenesis of AD.

Pathological diagnosis of combined Alzheimer's disease and argyrophilic grain dementia in a very elderly man who presented with advanced behavioural and psychological symptoms.

This case report describes a Japanese man who presented with slowly progressive memory disturbances that began at the age of 79 years. The man also displayed conspicuous behaviour and psychological symptoms in the early stage of dementia. Computed tomography revealed atrophy of the amygdala and severe hippocampal deterioration, particularly in the anterior portion. Lateral ventricular dilatation, mainly affecting the anterior and inferior horns, was also observed. Interestingly, cerebral neocortical atrophy in the frontal and temporal lobes was considerably mild for the patient's age. Apolipoprotein E gene analysis showed epsilon 3 homozygosity. The patient died at the age of 96 years, and his clinical diagnosis was Alzheimer's disease with severe behavioural and psychological symptoms of dementia. In addition to indicating considerable hippocampal atrophy, an autopsy revealed numerous neurofibrillary tangles and argyrophilic grains in the brain, as well as extensive senile plaques. Cerebral amyloid angiopathy was also recognized. The pathological findings were suggestive of both Alzheimer's disease and argyrophilic grain dementia; other neurodegenerative disorders were not apparent. The clinicopathologic findings of the present case suggest significant consideration should be made when determining the clinical diagnosis and pathogenesis of senile dementia.

An autopsy case of a centenarian with the pathology of senile dementia of the neurofibrillary tangle type.

A Japanese woman showed slowly progressive memory disturbance since the age of 85 years. Later, disorientation gradually appeared. Head computed tomography revealed severe hippocampal atrophy, particularly in the posterior portion, and lateral ventricular dilatation, particularly in the inferior horn at the age of 99 years. The amygdala was relatively preserved from atrophy, and atrophy of the frontal lobe was relatively mild for her age. Apolipoprotein E gene analysis showed the ε3 homozygous phenotype. The woman died at the age of 101 years, and her clinical diagnosis was mild Alzheimer's disease. No apparent behavioural and psychological symptoms of dementia were observed during the disease course. Autopsy revealed severe hippocampal atrophy with numerous neurofibrillary tangles and ghost tangles, particularly in the hippocampal region, but senile plaques were rarely observed in the brain. The pathological findings were compatible with senile dementia of the neurofibrillary tangle type, whereas other neurodegenerative disorders were not recognized. The clinicopathologic findings of the present case are considered significant for the clinical diagnosis and pathogenesis of senile dementia of the neurofibrillary tangle type.

[An autopsied case of argyrophilic grain dementia with parkinsonism due to multiple lacunar infarctions].

A 77-year-old Japanese woman developed parkinsonism and showed tremor in the upper extremities, bradykinesia, and gait disturbance. She was diagnosed with Parkinson's disease. Treatment with L-3,4-dihydroxyphenylalanine (L-DOPA) was ineffective. Two years later, dementia symptoms such as memory disturbance and disorientation gradually manifested and abnormal behaviors including egocentric behavior were observed. No apparent pyramidal tract signs, focal cerebral signs, or cerebellar dysfunction was observed. The patient died at the age of 90 years, and the clinical diagnosis was Parkinson's disease with dementia. The brain weight was 1,110 g. Multiple infarctions were observed in the basal ganglia and thalamus with état criblé. Argyrophilic grains corresponding to Saito's stage III were observed mainly in the limbic system. Neuronal loss with gliosis and tissue rarefaction was detected in the subiculum, parahippocampal gyrus, and amygdala. Oligodendroglial coiled bodies and argyrophilic threads were also observed in the areas in which the grains were abundant. Neurofibrillary tangles and senile plaques corresponding to Braak stage III and Consortium to Establish a Registry for Alzheimer's Disease (CERAD) stage B, respectively, were detected. The number of neurons of the substantia nigra and locus coeruleus was found to be unchanged. Pathological features of Parkinson's disease, including Lewy bodies and α-synuclein-positive abnormal structures, were not observed. On the basis of the pathological features, we made a diagnosis of argyrophilic grain dementia (AGD) with multiple infarctions. The patient's dementia was thought to be due to AGD, and parkinsonism was suspected to be due to multiple infarctions of the basal ganglia. The clinical findings of the patient described in this case study include important findings that will help in clinically discriminating between different dementias such as Alzheimer's disease and AGD.

Technical communication: anatomy and clinical implications of ultrasound-guided selective femoral nerve block.

In this study we evaluated the anatomic basis and clinical findings of ultrasound-guided femoral nerve block performed close to the distal apex of the femoral triangle. Cadaver studies were conducted in 9 thighs of fresh bodies within 24 hours postmortem. In all cases, during injection of 10 mL of blue dye, the skin proximal to the injection site was compressed to prevent the proximal flow. In the first thigh, from the area just distal to the inguinal ligament, an epidural catheter was advanced distally beneath the fascia iliaca over the femoral nerve. In the remaining cases, 10 mL of blue dye was injected into the femoral nerve at the level of the proximal adductor canal and dye spread was evaluated after local dissection. The clinical study was conducted in 20 patients with severe varus deformities. Ten milliliters of 0.75% ropivacaine was injected as in the cadaveric series. The femoral nerve was successfully dyed in all cases of the cadaver study, whereas the muscular branch to the sartorius muscle and quadriceps muscle, with the exception of the vastus medialis muscle, evaded dyeing. All 20 patients with varus knee deformities reported analgesia; none of them experienced motor block. We conclude that local anesthetic injection at the site where the superficial femoral artery has passed beneath the medial border of the sartorius muscle (8 to 12 cm distal to the inguinal crease), combined with efforts taken to prevent proximal flow may anesthetize the sensation of the anterior-to medial aspect of the knee and motor branch of the vastus medialis muscle, without blocking the sartorius or quadriceps muscles.

[An autopsied case of senile onset frontotemporal lobar degeneration].

A Japanese male with no family history of neurological disease or dementia showed behavioral abnormalities including egocentric and antisocial behavior at the age of 80. Over the next few years, other psychiatric symptoms such as allotriophagy and stereotypical behavior were also observed and his abnormal behavior became a social problem. Neurological examination revealed no apparent motor abnormalities, pyramidal and extrapyramidal signs, or ataxia. Aphasia, including semantic dementia was not apparent. The severity of memory disturbance was relatively milder than his psychiatric symptoms. Daily living activities and conversational ability were relatively maintained until shortly before his death at the age of 86. The clinical diagnosis was Alzheimer disease. Autopsy revealed that the brain weighed 950 g; frontotemporal atrophy with lateral ventricular dilatation was apparent. Neuron loss, gliosis, and tissue rarefaction were recognized in the frontotemporal cortex, subiculum, transentorhinal cortex, amygdala, and insular cortex and were particularly noticeable in the superficial layer of the cortex. Many ubiquitin-positive/TDP-43 positive but tau-negative dystrophic neurites with a few neuronal cytoplasmic inclusions were widely observed. Neuronal cytoplasmic inclusions were also observed in the dentate gyrus of the hippocampus. Although the spinal cord was not investigated, there was no apparent involvement of the motor neuron system. Small numbers of neurofibrillary tangles and senile plaques were observed, corresponding to Braak stage II and CERAD stage B, respectively. Argyrophilic grains, Lewy bodies and Pick bodies were not observed. The patient was pathologically diagnosed with frontotemporal lobar degeneration with ubiquitin-positive/TDP-43-positive inclusions (FTLD-TDP) and without motor neuron disease. No mutation was found in the TDP-43 gene. We considered the psychiatric symptoms and head CT findings of the present patient to be important observations for helping to discriminate between Alzheimer disease or other neurodegenerative diseases with dementia, and FTLD-TDP.

[An autopsy case of senile dementia suspected to be influenced by cerebral amyloid angiopathy with multiple cortical microinfarcts].

A Japanese male showed gradually progressing dementia with psychiatric symptoms including abnormal behavior, night and day reversal, nocturnal delirium, loud shouting, agitation, resistance to care, and loud soliloquy. The patient had a history of right cerebral embolism due to atrial fibrillation 1 month before the onset of dementia. Head CT revealed widespread cerebral infarction in the right cerebral hemisphere with bilateral lateral ventricular dilatation. The patient died at the age of 83, 10 months after the onset of cerebral embolism. The clinical diagnosis was mixed-type dementia. On autopsy the brain weighed 1,160 g. Widespread cerebral amyloid angiopathy (CAA) was observed, with distribution most severe in the cerebral cortical vessels and slightly milder in the leptomeningial and subarachnoid vessels. The artery, arteriole, and capillary walls were thickened by the deposition of amorphous, eosinophilic and beta-protein immunopositive amyloid. Abeta-deposition was more severe in capillaries and CAA tended to be more severe in the occipital regions. Multiple cortical microinfarcts were found, particularly in the crests of the cerebral gyri of watershed zones. Cerebral white matter, basal ganglia, thalamus, brainstem and spinal cord were relatively preserved from CAA. Infarction was not apparent, except for an embolic lesion in the right cerebral hemisphere and the cortical microinfarcts. We did not observe fibrinoid necrosis, granulomatous angiitis or giant cell reaction associated with CAA-vasculopathies. Rare instances were observed of neurofibrillary tangles and senile plaques corresponding to Braak stages II and A, respectively. We thought the multiple cortical microinfarcts occurred due to chronic hypoperfusion associated with CAA-associated vasculopathies of capillaries in the cerebral cortex. We suspected that the dementia was influenced by the CAA with multiple cortical microinfarcts. Pathologic findings of the patient suggest that CAA without AD-related Abeta-deposition might exist and that capillary Abeta-deposition might be an important factor of hemodynamic perturbation.

An autopsy case of diffuse neurofibrillary tangles with calcification: early stage pathologic findings.

A 66-year-old man with no medically remarkable past or family history gradually showed personality changes, memory disturbance, sleeplessness and abnormal behavior. Neurologic examination showed no focal signs and neither parkinsonism nor cerebellar ataxia was recognized. He died 4 years after the onset of dementia due to chronic renal failure. Neuropathologic examination revealed neuronal loss and gliosis in the temporal cortex, particularly in the subiculum, parahippocampal gyrus and entorhinal cortex, and insular cortex. NFTs were observed to be widespread in the cerebral cortex, especially the temporal cortex and brainstem, while senile plaques were not observed. Gallyas-Braak silver staining revealed the presence of numerous NFTs, glial inclusions and neuropil threads throughout the cerebral neocortex, limbic system, hippocampus and brainstem. The subiculum showed the most severe involvement; severe atrophy, severe neuron loss, and numerous ghost tangles (extracellular NFTs) were apparent. Although NFTs contained both monoclonal anti-3repeat-tau antibody (RD3) and RD4 immunoreactivity, this differed between the intracellular NFTs and ghost tangles. RD3 immunoreactivity was mainly observed in ghost tangles and neuropil threads, whereas RD4 immunoreactivity was mainly observed in intracellular NFTs and glial inclusions. Calcification was also found to be widespread in the cerebral cortex and white matter, basal ganglia, thalamus, cerebellar cortex, white matter and dentate nucleus. These characteristic neuropathologic findings lead to the pathologic diagnosis of diffuse neurofibrillary tangles with calcification (DNTC). It is argued that this patient showed early stage pathologic signs of DNTC due to a short disease duration, which may provide clues regarding the progression of this rare disease.

[Comparison of activities of daily living for a convalescent rehabilitation ward and general ward for stroke patients].

We investigated changes in the Activities of Daily Living (ADL) of stroke patients in a convalescent rehabilitation ward and a general ward using a Functional Independent Measure (FIM). The subjects were 109 patients hospitalized for rehabilitation purposes at the Oyamada Memorial Spa Hospital. The change in FIM at the time of hospitalization and that at 1 week later was investigated in 81 patients in the convalescent rehabilitation group (CRG) and 28 patients in the control group (CG). In addition, the CRG was investigated again after one month. Intensive rehabilitation service based on ADL and worksheets was introduced in the CRG. On the other hand, these were not introduced in the CG. The total score of FIM increased significantly (p<0.01) in the first week after hospitalization in both groups. The FIM-gain after one week in the CRG was high. With regard to each item, a significant improvement was observed in patients' motor skills while eating, grooming, bathing, dressing the upper body, dressing the lower body, toilet, bladder management, transfer bed/chair, toilet and tub, and walking/wheelchair (11/13). Multiple regressions were used to assess the relationships between FIM-gain (one week, one month), age, rehabilitation intensity and other predictive variables. Better rehabilitation outcomes were observed in patients with lower level of dementia and high rehabilitation intensity. It was thought that planned rehabilitation based on ADL was effective in the CRG, and it was suggested that the CRG's system is effective in the rehabilitation of stroke patients.