Frontotemporal dementia with motor neuron disease (amyotrophic lateral sclerosis with dementia)

Frontotemporal dementia (FTD) with motor neuron disease means amyotrophic lateral sclerosis (ALS) with dementia. In the cerebrum of this condition, the medial cortex of the rostral temporal lobe is constantly and most remarkably involved. Another constant and quite characteristic lesion is neuronal loss localized to the CA1‐subiculum transitional area at the level of the pes hippocampi. The rostral portion of the parahippocampal gyrus, and the amygdaloid nucleus are also involved. Ubiquitinated intracytoplasmic inclusions are seen in the dentate granule cells and parahippocampal gyrus neurons. Some cases of ALS without dementia show the identical temporal lobe degeneration as well as the cortical ubiquitinated inclusions, thus raising the possibility of overlooked dementia or premature death of the patients. Similarly, recently proposed motor neuron disease‐inclusion dementia may be a forme fruste of ALS with dementia.     

TDP-43-immunoreactive neuronal and glial inclusions in the neostriatum in amyotrophic lateral sclerosis with and without dementia

TDP-43 is a major component of ubiquitin-positive, tau-negative inclusions in amyotrophic lateral sclerosis (ALS), and frontotemporal lobar degeneration. We immunohistochemically examined the neostriatum from 14 cases of classic ALS (cALS), six cases of ALS with dementia (ALS-D), and 20 control subjects. TDP-43-positive, crescent or circular inclusions were found in neostriatal small neurons in 19 of 20 cases of ALS, but not in controls. Two types of inclusions were found in the large neurons: ubiquitin-positive, TDP-43-negative rod-like inclusions, and ubiquitin- and TDP-43-positive pleomorphic inclusions. The latter were specific to ALS; they were found in seven cases of cALS and in all of ALS-D. TDP-43-positive glial inclusions were also found in 12 cases of cALS and in all of ALS-D. These TDP-43-positive neuronal and glial inclusions were more numerous in ALS-D than cALS. In ALS-D, neuronal loss in the substantia nigra was found in all the cases, whereas mild gliosis without obvious neuronal loss was noted in the neostriaum in only two cases. These findings suggest that the neostriatum is also involved in the disease process of ALS with and without dementia.     

“Forme fruste” of amyotrophic lateral sclerosis with dementia: A report of five autopsy cases without dementia and with ubiquitinated intraneuronal inclusions

We clinicopathologically investigated five autopsy cases of ALS without dementia and with ubiquitinated intraneuronal inclusions. The age at onset of symptoms ranged from 52 to 81 years and the duration of the disease was from 10 months to 3 years, 3 months. All five patients initially developed lower motor neuron signs, including bulbar signs, and upper motor neuron signs were found in the middle to late clinical stages, but dementia was not observed in all five cases. Thus, the clinical diagnoses of all five patients were ALS without dementia. Neuropathological examination of all five cases revealed not only obvious degeneration of upper motor neurons with neuronal loss of Betz cells, but also lower motor neuron involvement associated with Bunina bodies. In addition, ubiquitin‐immunoreactive intraneuronal inclusions in the hippocampal dentate granular cells and degeneration of the substantia nigra were observed in all five cases. Furthermore, neuronal loss with astrocytosis in the dorsomedial portion of the anterior first temporal gyrus was observed in all three cases in which this structure was examined. Neuronal loss with astrocytosis in the subiculum was found in four cases. Neuronal loss of the parahippocampal gyrus was observed in three of the five autopsy cases, and amygdala involvement was encountered in three of four cases in which this structure was investigated. Based on these clinicopathological findings and a review of the published literature, we concluded that our five cases were ALS without dementia, but with pathological hallmarks compatible with ALS with dementia. We also concluded that there is a “forme fruste” of ALS with dementia showing no overt dementia clinically.     

Sporadic amyotrophic lateral sclerosis with circumscribed temporal atrophy: A report of an autopsy case without dementia and with ubiquitinated intraneuronal inclusions

This report concerns an autopsy case of amyotrophic lateral sclerosis (ALS) with circumscribed temporal atrophy. The patient was a Japanese woman without hereditary burden who was 71‐year‐old at the time of death. She developed dysarthria and gait disturbance at age 69, followed by dysphagia. A neurological examination about 1 year 11 months after the onset of the disease revealed absence of character change and of dementia. Neuroradiological examination disclosed circumscribed atrophy of the anterior part of the right temporal lobe. The patient died of respiratory failure 2 years after the disease onset. No respirator administration was performed throughout the clinical course. Macroscopically, neuropathological examination showed circumscribed atrophy of the right first temporal gyrus. Histologically, there was neuronal loss in the cerebral cortex, including the first temporal gyrus, the parahippocampal gyrus, subiculum, amygdala, substantia nigra, brain stem motor nuclei, and anterior horns of the spinal cord, in addition to loss of Betz cells, obvious degeneration of the pyramidal tracts, and the presence of Bunina bodies. Ubiquitin‐immunoreactive intraneuronal inclusions were present in the hippocampal dentate granular cells, frontotemporal cortical layer II neurons, and motor neurons in the brain stem and spinal cord. Based on these clinicopathological findings and a review of the literature, we concluded that our case was atypical ALS without dementia, showing temporal lobe atrophy macroscopically, in addition to pathological hallmarks compatible with ALS with dementia. We also note the possibility that there is a forme fruste of ALS with dementia showing no overt dementia clinically.     

Atypical amyotrophic lateral sclerosis with dementia mimicking frontal Pick's disease: a report of an autopsy case with a clinical course of 15 years

This report concerns an autopsy case of atypical amyotrophic lateral sclerosis (ALS) with dementia mimicking frontal Pick's disease. The patient was a Japanese woman without hereditary burden who was 45 years old at the time of death. She developed abnormal behavior and amnesia at age 30, followed by disinhibition, aspontaneity, urinary incontinence, abulia, and rectal incontinence. Neurological signs compatible with ALS developed about 14 years after the disease onset. No respirator was used throughout the clinical course. Macroscopically, neuropathological examination showed atrophy of the frontotemporal lobes with accentuation in the convexities of the frontal lobes. Histologically, there was neuronal loss in the cerebral cortex, parahippocampal gyrus, amygdala, caudate nucleus, substantia nigra, brain stem motor nuclei, and anterior horns of the spinal cord, in addition to marked degeneration of the pyramidal tracts. Ubiquitin-immunoreactive neuronal inclusions were present in the frontotemporal cortical layer II neurons and motor neurons in the brain stem and spinal cord. In the hippocampal dentate granular cells, many ubiquitin-immunoreactive neurites were present without ubiquitin-immunoreactive intraneuronal inclusions. Based on these clinicopathological findings and a review of the literature, we concluded that our case was atypical ALS with dementia of long disease duration. We also note the possibility that motor neuron disease-inclusion dementia with a long clinical course may develop into ALS in the final stage of the illness.     

Memory deficits in amyotrophic lateral sclerosis patients with dementia and degeneration of the perforant pathway A clinicopathological study

Degeneration of the perforant pathway, not extensively surveyed so far in amyotrophic lateral sclerosis (ALS) with dementia, was found in eight out of twelve autopsied patients with clinically detectable dementia. Because the severity of degeneration of the entorhinal cortex and that of spongiosis of the outer half of the molecular layer of the dentate gyrus were correlated in these eight patients, it is suspected that the degeneration of the perforant pathway may explain these concomitant lesions. This was further corroborated by occasional involvement of the parahippocampal white matter and subiculum, other components of this pathway. Moreover, six of them manifested clinically detectable memory deficits and three of them exhibited amnesia or episodic memory impairments similar to Alzheimer's disease (AD). Abnormal intensity restricted the dentate gyrus on brain magnetic resonance imaging in a severe case looks like the degeneration of the molecular layer. This involvement of the perforant pathway in ALS patients and its correlation to memory deficits should be taken in account for evaluation of dementia.     

Frontotemporal and motor neurone degeneration with neurofilament inclusion bodies: additional evidence for overlap between FTD and ALS

We present the case of a patient who had clinical frontal lobe dementia without apparent motor neurone disease (MND), with pathologic findings not typical of any single currently classified frontotemporal degeneration (FTD). At autopsy, the brain had frontal and temporal atrophy with neuronal loss, gliosis, and superficial spongiosis, typical of all FTDs. There were at least three different morphologic types of intracytoplasmic neuronal inclusions in a variety of brain and brainstem regions, including the hippocampal dentate gyrus and pyramidal neurones, the neocortex (in particular, the motor cortex), basal ganglia, thalamus, subthalamic nucleus, basis pontis, and inferior olivary nuclei. Inclusions had the morphologies of Pick-like bodies, pleomorphic inclusions, and hyaline conglomerate (HC)-like inclusions. None of these were positive with tau immunostains. Pick-like bodies in the dentate gyrus were labelled with ubiquitin. The pleomorphic inclusions in the neocortex and dentate gyrus and the HC-like inclusions in the motor and parietal cortex were strongly positive with immunostains for neurofilament. We discuss the differential diagnosis and compare this case with those disorders to which it is most similar. In particular, we compare the unique neurofilament-positive inclusions to the inclusions of FTD-MND, to Pick bodies, and to the basophilic and HC inclusions that are occasionally seen in amytrophic lateral sclerosis (ALS). Although FTD-MND may be found in ALS, the findings in this case may have additional implications for a link between FTD and ALS.     

Ubiquitinated neuronal inclusions in the neostriatum in patients with amyotrophic lateral sclerosis with and without dementia--a study of 60 patients 31 to 87 years of age

OBJECTIVE AND METHODS: Neuronal degeneration in amyotrophic lateral sclerosis (ALS) is associated with ubiquitinated cytoskeletal alterations in the motor neuron system. Ubiquitin-positive inclusions are also seen in the limbic system in ALS with dementia (ALS-D). Recently, similar inclusions were reported to occur in the neostriatum in a case of ALS-D. We, therefore, immunohistochemically examined the neostriatum from 60 patients with ALS and 60 control subjects. RESULTS: Two forms of ubiquitin-positive inclusions were found in the ALS neostriatum: rod-like inclusions in the large neurons and crescent-shaped inclusions in the small neurons. The former were found in 14 ALS and 18 control subjects, whereas the latter were specific to ALS; the crescent-shaped inclusions in small neurons were found in 27 ALS patients, and the immunohistochemical and ultrastructural features were identical to those of the extra-motor inclusions of ALS. Moreover, characteristic temporal lesions consistent with those seen in ALS-D were found in 8 patients, of whom 2 had shown dementia. CONCLUSION: The present findings strongly suggest that neostriatal small neurons are also involved in the disease process in ALS.     

Differing patterns of temporal atrophy in Alzheimer's disease and semantic dementia

OBJECTIVE: To characterize and quantify the patterns of temporal lobe atrophy in AD vs semantic dementia and to relate the findings to the cognitive profiles. Medial temporal lobe atrophy is well described in AD. In temporal variant frontotemporal dementia (semantic dementia), clinical studies suggest polar and inferolateral temporal atrophy with hippocampal sparing, but quantification is largely lacking. METHODS: A volumetric method for quantifying multiple temporal structures was applied to 26 patients with probable AD, 18 patients with semantic dementia, and 21 matched control subjects. RESULTS: The authors confirmed the expected bilateral hippocampal atrophy in AD relative to controls, with involvement of the amygdala bilaterally and the right parahippocampal gyrus. Contrary to expectations, patients with semantic dementia had asymmetric hippocampal atrophy, more extensive than AD on the left. As predicted, the semantic dementia group showed more severe involvement of the temporal pole bilaterally and the left amygdala, parahippocampal gyrus (including the entorhinal cortex), fusiform gyrus, and the inferior and middle temporal gyri. Performance on semantic association tasks correlated with the size of the left fusiform gyrus, whereas naming appeared to depend upon a wider left temporal network. Episodic memory measures, with the exception of recognition memory for faces, did not correlate with temporal measures. CONCLUSIONS: Hippocampal atrophy is not specific for AD but is also seen in semantic dementia. Distinguishing the patients with semantic dementia was the severe global but asymmetric (left > right) atrophy of the amygdala, temporal pole, and fusiform and inferolateral temporal gyri. These findings have implications for diagnosis and understanding of the cognitive deficits in AD and semantic dementia.     

Amyotrophic lateral sclerosis with dementia: The clinicopathological spectrum

Amyotrophic lateral sclerosis with dementia (ALS‐D) is a non‐Alzheimer‐type dementia characterized by both frontotemporal degeneration and motor neuron disease and marked by ubiquitin‐positive, tau‐ and α‐synuclein‐negative intraneuronal inclusions and dystrophic neurites. New neuropathological diagnostic criteria for ALS‐D are proposed on the basis of the present investigation of 28 autopsy cases. Clinical features included those of typical ALS‐D, primary lateral sclerosis, atypical ALS with frontotemporal atrophy and atypical Pick's disease without Pick's bodies. Macroscopically anterior frontotemporal atrophy was observed involving or not involving the precentral gyrus. Microscopically non‐specific neuronal loss and gliosis with spongiosis were seen, particularly in superficial layers II and III of the frontotemporal cortices. Diffuse fibrous gliosis was seen in the frontotemporal white matter. The substantia nigra and amygdala showed neuronal loss and gliosis. In all 28 cases, degeneration of both the lower and upper motor neuron systems, consistent with classic sporadic ALS, was present. The distribution and degree of degenerative frontotemporal lesions and motor neuron disturbance were of various patterns. Ubiquitin‐positive and tau‐ and α‐synuclein negative intraneuronal inclusions and dystrophic neurites in extramotor cortices were observed in all cases. Furthermore, ubiquitin‐positive inclusions in lower motor neurons were found in all cases. The distribution pattern and density differed between neuronal inclusions and dystrophic neurites and correlated with clinicopathological phenotypes. Therefore, the ALS‐D spectrum may be broader than that previously recognized, extending to primary lateral sclerosis, atypical ALS and to atypical Pick's disease without Pick bodies. Further investigation is needed to determine the characteristics of the ubiquitinated component in ALS‐D.     

Coexistence of amyotrophic lateral sclerosis and argyrophilic grain disease: A non‐demented autopsy case showing circumscribed temporal atrophy and involvement of the amygdala

We report a case of a 68‐year‐old right‐handed man with sporadic amyotrophic lateral sclerosis (ALS) and argyrophilic grain disease (AGD) having a 22‐month duration. His initial symptoms were dysarthria and swallowing difficulty at the age of 67. Subsequently bulbar palsy and pyramidal signs developed. His cognitive functions including face recognition, personality, and behavior were not changed compared with that of before the disease onset. However, magnetic resonance imaging disclosed severe right side‐predominant temporal atrophy. The neurological diagnosis was bulbar type ALS. Pathological examination disclosed histological evidence of ALS, including loss of Betz cells and lower motor neurons, corticospinal tract degeneration, and Bunina bodies. In addition, severe neuronal loss in the bilateral temporal cortex with an anterior gradient was found. Ubiquitin‐positive inclusions were encountered in the spinal anterior horn cells and hippocampal dentate gyrus, while few ubiquitin‐positive inclusions were noted in the affected temporal cortex. The amygdala, especially the basolateral nuclear group, was severely affected by neuronal loss with tissue rarefaction. Moderate neuronal loss was encountered in the parahippocampal gyrus, and to a lesser degree, in the ambient gyrus. Unexpectedly, many argyrophilic grains, coiled bodies, tau‐positive bush‐like astrocytes, pretangles, and ballooned neurons were found in the limbic system and temporal cortex. In the hippocampus, selective tau accumulation with minor neurofibrillary changes was observed in CA2 neurons. The present case suggests that (i) ALS and AGD do rarely coexist, and (ii) when ALS patients have severe temporal atrophy, not only ALS with dementia but also concurrent AGD should be considered in the differential diagnosis.     

Dynamic alterations of spontaneous neural activity in patients with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a multi-system disease featured by movement disorder. Studies on ALS using static neuroimaging indexes demonstrated inconsistent results. However, recent work indicated that the intrinsic brain activity was time-varying, and the abnormal temporal dynamics of brain activity in ALS remains unknown. Resting-state functional magnetic resonance imaging data were first obtained from 54 patients with ALS and 54 healthy controls (HCs). Then the dynamic regional homogeneity (d-ReHo) was calculated and compared between the two groups. Correlation analyses between altered d-ReHo and clinical scores were further performed. Compared with HCs, ALS patients showed higher d-ReHo in the left lingual gyrus while lower d-ReHo in the left rectus gyrus and left parahippocampal gyrus. Moreover, the d-ReHo in the left lingual gyrus exhibited correlation with disease progression rate in ALS at a trend level. Our findings suggested that altered dynamics in intrinsic brain activity might be a potential biomarker for diagnosing of ALS.

     

Microglial activation and TDP-43 pathology correlate with executive dysfunction in amyotrophic lateral sclerosis

While cognitive deficits are increasingly recognized as common symptoms in amyotrophic lateral sclerosis (ALS), the underlying histopathologic basis for this is not known, nor has the relevance of neuroinflammatory mechanisms and microglial activation to cognitive impairment (CI) in ALS been systematically analyzed. Staining for neurodegenerative disease pathology, TDP-43, and microglial activation markers (CD68, Iba1) was performed in 102 autopsy cases of ALS, and neuropathology data were related to clinical and neuropsychological measures. ALS with dementia (ALS-D) and ALS with impaired executive function (ALS-Ex) patients showed significant microglial activation in middle frontal and superior or middle temporal (SMT) gyrus regions, as well as significant neuronal loss and TDP-43 pathology in these regions. Microglial activation and TDP-43 pathology in middle frontal and superior or middle temporal regions were highly correlated with measures of executive impairment, but not with the MMSE. In contrast, only one ALS-D patient showed moderate Alzheimer’s disease (AD) pathology. Tau and Aβ pathology increased with age. A lower MMSE score correlated with tau pathology in hippocampus and SMT gyrus, and with Aβ pathology in limbic and most cortical regions. Tau and Aβ pathology did not correlate with executive measures. We conclude that microglial activation and TDP-43 pathology in frontotemporal areas are determinants of FTLD spectrum dementia in ALS and correlate with neuropsychological measures of executive dysfunction. In contrast, AD pathology in ALS is primarily related to increasing age and associated with a poorer performance on the MMSE.     

~(18)F-FDG PET显像观察特发性快眼动睡眠期行为障碍患者脑葡萄糖代谢特点的研究

目的探讨~(18)F-FDG PET显像观察特发性快眼动睡眠期行为障碍(iRBD)患者脑葡萄糖代谢改变和iRBD脑葡萄糖代谢改变与病程间的相关性。方法纳入多导睡眠监测(PSG)确诊的iRBD患者20例(iRBD组)和年龄、性别匹配的健康对照者19例(对照组)。两组均行~(18)F-FDG PET脑显像。基于自动解剖标记模板将大脑划分为90个左右对称的脑区,计算各脑区葡萄糖代谢半定量值。对iRBD组和对照组各脑区葡萄糖代谢半定量值进行独立样本t检验;并对iRBD组脑葡萄糖代谢改变与病程行Pearson相关分析。结果 (1)与对照组比较,iRBD组的双侧背外侧额上回、双侧眶部额上回、双侧眶部额中回、双侧海马、双侧海马旁回、双侧杏仁核、左侧眶部额下回、左侧岛叶、左侧内侧与旁扣带脑回、左侧中央旁小叶、左侧苍白球的葡萄糖代谢半定量值均增高(P0.05);双侧距状裂周围皮质、双侧楔叶、双侧舌回、双侧枕上回、双侧枕中回、双侧枕下回、双侧角回、双侧颞上回、双侧颞中回、右侧颞横回的葡萄糖代谢半定量值均降低(P0.05)。Pearson相关分析结果,iRBD组双侧杏仁核、双侧颞上回、右侧楔叶、右侧枕上回、右侧颞横回、左侧海马、左侧颞中回的葡萄糖代谢半定量值与病程呈正相关(P0.05);而双侧眶部额上回、双侧眶部额中回、左侧中央旁小叶、左侧眶部额下回、左侧内侧和旁扣带回、右侧背外侧额上回、右侧海马旁回的葡萄糖代谢半定量值与病程呈负相关(P0.05)。结论 iRBD患者脑内存在疾病相关的葡萄糖代谢水平改变,有助于客观评估iRBD病情的变化。     

Facial Emotion Processing in Schizophrenia: A Meta-analysis of Functional Neuroimaging Data

Background: People with schizophrenia have difficulty with emotion perception. Functional imaging studies indicate regional brain activation abnormalities in patients with schizophrenia when processing facial emotion. However, findings have not been entirely consistent across different studies. Methods: Activation likelihood estimation (ALE) meta-analyses were conducted to examine brain activation during facial emotion processing in patients with schizophrenia, controls, and patients compared with controls. Secondary meta-analyses were performed to assess the contribution of task design and illness chronicity to the results reported. Results: When processing facial expressions of emotions, both patients with schizophrenia and healthy controls activated the bilateral amygdala and right fusiform gyri. However, the extent of activation in these regions was generally much more limited in the schizophrenia samples. When directly compared with controls, the extent of activation in bilateral amygdala, parahippocampal gyrus and fusiform gyrus, right superior frontal gyrus, and lentiform nucleus was significantly less in patients. Patients with schizophrenia, but not controls, activated the left insula. A relative failure to recruit the amygdala in patients occurred regardless of whether the task design was explicit or implicit, while differences in fusiform activation were evident in explicit, not implicit, tasks. Restricting the analysis to patients with chronic illness did not substantially change the results. Conclusions: A marked underrecruitment of the amygdala, accompanied by a substantial limitation in activation throughout a ventral temporal-basal ganglia-prefrontal cortex “social brain” system may be central to the difficulties patients experience when processing facial emotion.     

Morphological differences of intraneuronal ubiquitin‐positive inclusions in the dentate gyrus and parahippocampal gyrus of motor neuron disease with dementia

Semiquantitative morphological analysis of cerebral intraneuronal ubiquitin‐positive tau‐negative inclusions, a pathologic marker for motor neuron disease with dementia (MND‐D), was performed in the dentate gyrus and parahippocampal gyrus of 20 clinicopathologically confirmed patients with MND‐D. The forms of the inclusions were tentatively classified into three types: (i) C‐type, consisting of relatively large and intensely stained crescent or circular structures; (ii) L‐type, showing fine linear structures around the nuclei; and (iii) G‐type, showing faintly stained granular structures. The frequencies of the C‐type, L‐type and G‐type was 0.5–9.3%, 0.2–6.5% and 0–6.6% of dentate granule cells, respectively. In contrast to the dentate gyrus, almost all inclusions showed either the C‐type or L‐type form in the parahippocampal gyrus. A positive correlation was noted only between incidences of C‐type inclusion of the dentate gyrus and that of the parahippocampal gyrus (r = 0.69, P < 0.05). The morphological differences of the inclusions probably reflect different stages of their formation.     

Parkinsonism, dementia and vertical gaze palsy in a Guamanian with atypical neuroglial degeneration

A 58-year-old Chamorro female patient, who died in 1993, was examined clinicopathologically. At the age of 51, she suffered from hemiparkinsonism, then bradykinesia, rigidity without tremor, and dementia. Extrapyramidal symptoms developed, and at the age of 57, vertical gaze palsy was noted. The clinical diagnosis was parkinsonism-dementia complex (PDC) with vertical gaze palsy. The brain showed atrophy in the frontal and temporal lobes, and the atrophy was accentuated in the dentate gyrus, Ammon’s horn and parahippocampal gyrus. The basal ganglia, thalamus and midbrain were moderately atrophic. The substantia nigra and locus ceruleus were completely depigmented. Numerous neurofibrillary tangles (NFTs) were seen in the subiculum and amygdaloid nucleus. Many NFTs were evident in the parahippocampal gyrus, lateral occipitotemporal gyrus, insula, Sommer sector, basal nucleus of Meynert, lateral nucleus of the thalamus, subthalamic nucleus and brain stem, and several were observed in the globus pallidus and hypothalamus. The Sommer sector, substantia nigra, locus ceruleus and basal nucleus of Meynert showed severe loss of neurons, and a moderate loss of neurons was exhibited by the globus pallidus. These findings were apparently consistent with those associated with PDC. However, in this patient, severe neuronal loss was seen in the subthalamic nucleus and lateral nucleus of the thalamus, and grumose degeneration, which has not previously been reported in PDC, was seen in the dentate nucleus. In addition, many tufted astrocytes, which have been reported to occur in progressive supranuclear palsy (PSP) and postencephalitic parkinsonism, but scarcely observed in PDC, were present. Furthermore, astrocytic plaques, which have been considered as a specific finding of corticobasal degeneration (CBD), were observed in the cerebral cortex. On the other hand, granular hazy astrocytic inclusions, previously reported to occur in PDC, were not seen. Chromatolytic neurons were not observed. The question thus arises as to whether it is appropriate to consider this patient as having suffered from a combination of PDC, PSP and CBD. From the view points of absence of granular hazy astrocytic inclusions and chromatolytic neurons, and of tufted astrocytes in the neostriatum, it is conceivable that this patient is a case of a new disease entity. Received: 11 January 1999 / Revised, accepted: 6 April 1999     

An autopsy case of senile dementia with numerous neocortical senile plaques and preserved subcortical nuclei

An 80-year-old retired teacher developed impairment of memory and suffered from delusions of theft. Four years later, she became disoriented as to person, time and situation, restless, began mutter to herself, and displayed night delirium and insomnia. She was subsequently diagnosed as having senile dementia of the Alzheimer type (SDAT). She died of bronchopneumonia and multiple metastases from breast cancer at the age of 85 years. Family history was non-contributory. The brain weighed 1,020 g and showed diffuse atrophy. Histologically, there was moderate loss of neurons in the cerebral cortex, which was accentuated in the frontal and temporal lobes. In addition, numerous senile plaques were observed in the neocortex and hippocampus. Several senile plaques were also found in the amygdala, innominate substance, neostriatum, claustrum, thalamus, hypothalamus and tegmentum of the mesencephalon. Neurofibrillary tangles (NFTs) were mostly restricted to the hippocampus and parahippocampal gyrus, their number being compatible with the patient's age. No obvious neuronal loss was noted in the nucleus basalis of Meynert, neostriatum, substantia nigra or locus ceruleus, which are well known to be involved in Alzheimer's disease and SDAT. Recently, Terry et al proposed a new disease concept, "SDAT without neocortical NFTs". The histopathology of the cerebral cortex in our patient was very similar, if not identical, to those observed in their patients. However, the above authors did not mention any subcortical changes, leaving the detailed neuropathological picture unclear. Tentatively, we classified the present case as senile dementia with numerous neocortical senile plaques and preserved subcortical nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)     

Temporal lobe gray matter in schizophrenia spectrum: a volumetric MRI study of the fusiform gyrus, parahippocampal gyrus, and middle and inferior temporal gyri

Although several brain morphologic studies have suggested abnormalities in the temporal regions to be a common indicator of vulnerability for the schizophrenia spectrum, less attention has been paid to temporal lobe structures other than the superior temporal gyrus or the medial temporal region. In this study, we investigated the volume of gray matter in the fusiform gyrus, the parahippocampal gyrus, the middle temporal gyrus, and the inferior temporal gyrus using magnetic resonance imaging in 39 schizotypal disorder patients, 65 schizophrenia patients, and 72 age and gender matched healthy control subjects. The anterior fusiform gyrus was significantly smaller in the schizophrenia patients than the control subjects but not in the schizotypal disorder patients, while the volume reduction of the posterior fusiform gyrus was common to both disorders. Volumes for the middle and inferior temporal gyri or the parahippocampal gyrus did not differ between groups. These findings suggest that abnormalities in the posterior region of the fusiform gyrus are, as have been suggested for the superior temporal gyrus or the amygdala/hippocampus, prominent among the temporal lobe structures as a common morphologic substrate for the schizophrenia spectrum, whereas more widespread alterations involving the anterior region might be associated with the development of full-blown schizophrenia.     

Association between absence of the adhesio interthalamica and amygdala volume in schizophrenia

Abnormal neurodevelopment in midline structures such as the adhesio interthalamica (AI) has been reported in schizophrenia, but not consistently replicated. We investigated the prevalence and anterior-posterior length of the AI in 62 schizophrenia patients (32 males, 30 females) and 63 healthy controls (35 males, 28 females) using magnetic resonance imaging. We also explored the relation between the AI and volumetric measurements for the third ventricle, medial temporal structures (amygdala, hippocampus, and parahippocampal gyrus), superior temporal sub-regions, and frontal lobe regions (prefrontal area and anterior cingulate gyrus). The AI was absent in 24.2% (15/62) of the schizophrenia patients and in 9.5% (6/63) of the controls, showing a significant group difference. For the length of the AI, schizophrenia patients had a shorter AI than controls, and males had a shorter AI than females. The subjects without an AI had a significantly larger third ventricle and smaller parahippocampal gyrus than the subjects with an AI for both groups. We found a significant diagnosis-by-AI interaction for the amygdala. The schizophrenia patients without an AI had a smaller bilateral amygdala than those with an AI, whereas the AI was not associated with the volume of the amygdala in the control subjects. These findings suggest that the absence of AI in schizophrenia could be a marker of developmental abnormalities in the neural network including the thalamus and connected amygdaloid regions, which may play an important role in the pathogenesis of schizophrenia.