Disease duration: the key to accurate CSF tap test in iNPH.

OBJECTIVES: The cerebrospinal fluid tap test for idiopathic normal pressure hydrocephalus (iNPH) is one of the good predictors of the shunt treatment, although this test has a low sensitivity. We aimed to identify key parameters that could be used to improve this sensitivity. MATERIALS & METHODS: During 2010-2011, we recruited and then followed 93 patients with possible iNPH for 12 months after shunt. Among them, 82 patients were finally enrolled in this study. The modified Rankin Scale, iNPH grading scale, and several quantitative measurements were evaluated at entry, after the tap test, before and after shunt. Area under the receiver-operating characteristic curves (AUCs), sensitivities, and specificities of the tap test for predicting shunt effectiveness were calculated for each measurement. They were additionally assessed after stratification by disease duration since the initial presentation of iNPH symptoms. RESULTS: The gait disturbance on the iNPH grading scale had the highest accurate scale at the tap test for predicting effectiveness 12 months after shunt: AUC 0.74, sensitivity 56.5%, specificity 91.7%. This AUC increased to 0.76, 0.91 and 0.94 in the subgroup of disease duration <24, <12, and <6 months, respectively. The sensitivity and specificity of the gait disturbance on the iNPH grading scale in the subgroup of <12 months' duration were 92.3% and 90.0%. CONCLUSIONS: The shorter period of clinical symptoms, for example, <12 months, made the tap test sufficiently accurate examination for predicting improvement 12 months after shunt surgery. The findings imply that the tap test should be applied to patients being considered for shunt surgery as soon as possible.

Actions anchored by concepts: defective action comprehension in semantic dementia.

OBJECTIVE: To study the ability of patients with semantic dementia to understand actions, in order to examine the contribution of semantic memory to action comprehension. METHODS: The ability to comprehend symbolic and instrumental actions was assessed in 6 patients with semantic dementia and 10 healthy controls. The patients were also given the imitation test of meaningful and meaningless actions. RESULTS: In all patients with semantic dementia, comprehension of both symbolic and instrumental actions was defective. The comprehension of symbolic actions was more impaired than that of instrumental actions. Their ability to imitate other's actions was well preserved. CONCLUSION: This study showed that comprehension of action was impaired in semantic dementia, suggesting that semantic memory has an important role in comprehension of human action.

Impact of white matter changes on clinical manifestation of Alzheimer's disease: A quantitative study.

BACKGROUND AND PURPOSE: There have been conflicting results involving the clinical significance of white matter changes in patients with Alzheimer's disease (AD). We studied the association between the volume of white matter hyperintensities (WMHs) on T2-weighted images and cognitive, neurological, and neuropsychiatric symptoms. METHODS: The subjects were 76 AD patients who had WMHs but no obvious cerebrovascular diseases. We quantified the volume of WMHs by using fast-fluid-attenuated inversion recovery images and whole brain atrophy by using 3D spoiled gradient-echo images. Effects of WMHs and brain atrophy on dementia severity, cognitive function, neuropsychiatric disturbances, and neurological findings were examined. RESULTS: Whole brain atrophy was significantly associated with dementia severity and cognitive disturbances, as well as with grasp reflex and some kinds of neuropsychiatric disturbances. After we controlled for the effects of brain atrophy, duration of symptoms, and demographic factors, we found that WMH volume was not associated with global cognitive disturbances or dementia severity but was significantly associated with urinary incontinence, grasp reflex, and aberrant motor behaviors. Brain atrophy and WMH volume were not significantly correlated either before or after controlling for age, sex, education, and duration of symptoms. WMH volume was associated with hypertension, but brain atrophy was not positively correlated with any vascular risk factors. CONCLUSIONS: Our results support the hypothesis that WMHs in AD patients are superimposed phenomena of vascular origin. WMHs contribute to specific neurological and neuropsychiatric manifestations but not to global cognitive impairment, which is more closely associated with brain atrophy.

Visuoperceptual impairment in dementia with Lewy bodies.

BACKGROUND: In dementia with Lewy bodies (DLB), vision-related cognitive and behavioral symptoms are common, and involvement of the occipital visual cortices has been demonstrated in functional neuroimaging studies. OBJECTIVES: To delineate visuoperceptual disturbance in patients with DLB in comparison with that in patients with Alzheimer disease and to explore the relationship between visuoperceptual disturbance and the vision-related cognitive and behavioral symptoms. DESIGN: Case-control study. SETTING: Research-oriented hospital. PATIENTS: Twenty-four patients with probable DLB (based on criteria of the Consortium on DLB International Workshop) and 48 patients with probable Alzheimer disease (based on criteria of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association) who were matched to those with DLB 2:1 by age, sex, education, and Mini-Mental State Examination score. MAIN OUTCOME MEASURES: Four test items to examine visuoperceptual functions, including the object size discrimination, form discrimination, overlapping figure identification, and visual counting tasks. RESULTS: Compared with patients with probable Alzheimer disease, patients with probable DLB scored significantly lower on all the visuoperceptive tasks (P<.04 to P<.001). In the DLB group, patients with visual hallucinations (n = 18) scored significantly lower on the overlapping figure identification (P = .01) than those without them (n = 6), and patients with television misidentifications (n = 5) scored significantly lower on the size discrimination (P<.001), form discrimination (P = .01), and visual counting (P = .007) than those without them (n = 19). CONCLUSIONS: Visual perception is defective in probable DLB. The defective visual perception plays a role in development of visual hallucinations, delusional misidentifications, visual agnosias, and visuoconstructive disability charcteristic of DLB.

Cognitive loss in dementia with Lewy bodies and Alzheimer disease.

BACKGROUND: Dementia with Lewy bodies (DLB) is emerging as a common cause of degenerative dementia. Some preliminary evidence exists that the pattern of cognitive impairment in DLB is different from that in Alzheimer disease (AD). OBJECTIVE: To delineate features of cognitive impairment of DLB on standardized neuropsychological tests. METHODS: We performed neuropsychological assessments of 26 patients with probable DLB (based on criteria of the consortium on DLB international workshop) and of 52 patients with probable AD (based on criteria of the National Institute of Neurological and Communicative Disorders and Stroke [now the National Institute of Neurological Disorders and Stroke])-Alzheimer's Disease and Related Disorders Association) who were matched to the patients with DLB 2:1 by age, sex, education, and Mini-Mental State Examination score. RESULTS: Compared with the group with probable AD, the group with probable DLB scored significantly lower on the picture arrangement, block design, object assembly, and digit symbol substitution subtests of the Wechsler Adult Intelligence Scale-Revised and on the Raven Colored Progressive Matrices test and significantly higher on the Mini-Mental State Examination locational orientation subtest and the Alzheimer's Disease Assessment Scale word recall subtest. A discriminant analysis revealed that the word recall score on the Alzheimer's Disease Assessment Scale and the block design score on the Wechsler Adult Intelligence Scale-Revised were the best discriminant factors. CONCLUSIONS: The disproportionately severe visuoperceptual, visuoconstructive, and visuospatial dysfunction and the disproportionately mild memory impairment in DLB compared with AD, which likely reflect the distribution of the pathologic changes in DLB, can help to differentiate DLB from AD.

Apolipoprotein E epsilon 4 and the pattern of regional brain atrophy in Alzheimer's disease.

BACKGROUND: Although the APOE epsilon 4 allele increases the risk of developing AD, the effects of the epsilon 4 allele on brain atrophy in clinical AD patients are controversial. OBJECTIVE: To investigate a possible relationship between the genetic variants of APOE and brain atrophy in patients with AD. METHODS: Using MRI-based volumetry techniques, the authors compared the volumes of the hippocampal formation, amygdaloid complex, and whole brain in probable AD patients (based on criteria of the National Institute for Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association) with different APOE alleles. One group (n = 46) had the epsilon 3/3 allele, one group (n = 46) had the epsilon 3/4 allele, and one group (n = 46) had the epsilon 4/4 allele. The three groups were matched for age, sex, disease duration, education level, and severity of dementia represented by their score of the Mini-Mental State Examination. A possible difference in pattern of cognitive deficits with dose of the APOE epsilon 4 allele was also examined. RESULTS: The normalized hippocampal volume was correlated with the number of APOE epsilon 4 alleles (r = -0.285, p = 0.0007). The amygdalar volume was also correlated with the number of APOE epsilon 4 alleles (r = -0.178, p = 0.037). The number of APOE epsilon 4 alleles was positively correlated with the whole-brain volume (r = 0.185, p = 0.030). It was also correlated with Wechsler Adult Intelligence Scale-Revised performance IQ (r = 0.203, p = 0.017) and with Wechsler Memory Scale-Revised attention/concentration score (r = 0.191, p = 0.025). CONCLUSIONS: Different patterns of regional brain atrophy were found among patients of different APOE genotypes. The effect of APOE epsilon 4 allele on the brains of AD patients may have regional specificity.

The effect of APOE epsilon4 allele on cerebral glucose metabolism in AD is a function of age at onset.

BACKGROUND: Although the APOE epsilon4 allele is a well-known risk factor for developing AD, the impact of the epsilon4 allele on clinical manifestations in patients with AD is still controversial. One possible reason for this controversy is that previous studies did not consider the effect of patient age at symptom onset. OBJECTIVE: To investigate the possible impact of patient age at onset of AD on the effect of APOE genotype on regional cerebral glucose metabolism (rCMRglc). METHODS: The authors compared rCMRglc between probable AD patients (based on criteria of the National Institute of Neurologic Disease and Stroke/AD and Related Disorders Association) with APOE epsilon4/4 and APOE epsilon3/3 alleles in early-onset (< or =65 years old) and late-onset (>65 years old) groups. In each group, the patients with APOE epsilon4/4 and APOE epsilon3/3 alleles were comparable for age at onset, age at examination, sex, disease duration, education level, and severity of dementia. RESULTS: In the early-onset group, the patients with the APOE epsilon4/4 genotype showed a significant decrease of rCMRglc in the medial temporal lobe and a significant increase of rCMRglc in the inferior parietal and posterior temporal cortices as compared with those patients with the APOE epsilon3/3 genotype. In the late-onset group, there were no significant differences in the rCMRglc pattern between the patients with APOE epsilon4/4 and APOE epsilon3/3 alleles. CONCLUSIONS: The current findings indicate that the impact of the APOE epsilon4 genotype on cerebral glucose metabolism of patients with AD may be a function of age at symptom onset.

Medial temporal and whole-brain atrophy in dementia with Lewy bodies: a volumetric MRI study.

OBJECTIVE: Dementia with Lewy bodies (DLB) is emerging as a common cause of degenerative dementia. A recent pathologic study has indicated that the medial temporal lobe in patients with DLB was less atrophic than that in patients with AD. The purpose of this study was to examine whether medial temporal MRI volumetry was useful to differentiate DLB from AD clinically. METHODS: We compared the volumes of the hippocampal formation, amygdaloid complex, and whole brain in 27 patients with probable DLB (based on the criteria of the Consortium on DLB International Workshop), 27 patients with probable AD (based on criteria of the National Institute of Neurological Disease and Stroke/Alzheimer's Disease and Related Disorders Association), and 27 normal elderly subjects using an MRI-based volumetric technique. The three groups were matched for age and sex. Severity of cognitive disturbances represented by their Mini-Mental State Examination score was comparable between the DLB and AD groups. RESULTS: Hippocampal volume (normalized to intracranial volume) in the DLB group was significantly larger than that in the AD group, but significantly smaller than that in the normal control group. There were no significant differences in the amygdala and whole-brain volume between the DLB group and the AD group, but the atrophies of the amygdala and whole brain were more severe in the DLB group than those in the control group. CONCLUSIONS: These findings indicate the usefulness of MRI hippocampal volumetry in clinically discriminating patients with DLB from patients with AD.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes with acanthocytosis: a clinicopathological study of a unique case.

A case of a unique combination of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like syndrome (MELAS) with acanthocytosis is reported. Neuropathological examination revealed pellagra-like change in Betz cells, brain-stem neurons and anterior horn cells as well as findings compatible with mitochondrial encephalomyopathies. Abnormal function of nicotinic acid-related enzymes could be the cause of the complicated clinicopathologic findings in this case. This is the first report of MELAS with acanthocytosis.

Regional cerebral glucose metabolism in dementia with Lewy bodies and Alzheimer's disease: a comparative study using positron emission tomography.

Regional cerebral metabolic rate of glucose (rCMRglc) was studied in 19 patients with a clinical diagnosis of dementia with Lewy bodies (DLB) and 19 patients with a clinical diagnosis of Alzheimer's disease (AD), using [18F]fluorodeoxyglucose ([18F]FDG) and positron emission tomography (PET). The two groups were matched with age, gender, disease duration and severity of cognitive disturbances. In 'dementia with Lewy bodies' (DLB) patients, when compared with AD patients, significant rCMRglc decreases were distributed in the temporo-parieto-occipital association cortices and the cerebellar hemispheres. In contrast, the medial temporal and cingulate rCMRglc were significantly lower in AD patients than those in DLB patients. These different regional emphases of glucose hypometabolism are consistent with the pathological and neurochemical differences between DLB and AD and explain the different clinical features of the two diseases.

Regional differences in cerebral blood flow during recitation of the multiplication table and actual calculation: a positron emission tomography study.

UNLABELLED: Regional cerebral differences in activation by two types of calculation, quantitative number processing and use of rote verbal arithmetic memory, were investigated. METHODS: The two types of processing were induced by serial number subtraction (the Subtra-task) and recitation of the multiplication table (the Multi-task), respectively. Regional cerebral blood flow (rCBF) under the two tasks was measured in ten healthy right-handed Japanese men using (15)O-labeled water and positron emission tomography (PET). Statistical parametric mapping (SPM) was used for estimating rCBF differences during these tasks. RESULTS: The activated areas during the Subtra-task were consistent with those reported to be involved in quantitative number processing. Although most of the regions activated during the Multi-task were in common with the regions activated during the Subtra-task, the spatial extent of the activation during the Multi-task was smaller. Moreover, the left lenticular nucleus was activated during the Multi-task, but not in the Subtra-task, while the prefrontal cortex was activated in the Subtra-task but not in the Multi-task. CONCLUSION: The difference in the regions activated by the two tasks, and the difference in the spatial extent of each region by the two tasks indicated that the anatomical networks of the two processes were segregated.

Memory and cerebral blood flow in cases of transient global amnesia during and after the attack.

We administered various memory tests and neuroimaging examinations to four pure cases who met Hodges' clinical criteria for transient global amnesia (TGA), during and after the attack. The purpose of the present study was to determine whether procedural learning is acquired during TGA and whether priming effects are preserved during TGA, and to investigate the anatomical basis of various memory subcomponents through these cases. Episodic memory was severely disturbed only during TGA, consistent with previous studies. Procedural learning during TGA examined by a drawing skill test and a reading skill test developed by us, and the Tower of Toronto, was preserved during TGA, consistent with one earlier report dealing with procedural memory during TGA. Priming effects during TGA have never been assessed. A word completion priming task with Kanji letters developed by us demonstrated that priming effects were preserved during TGA. Neuroradiologically, single photon emission computed tomograph hippocampal images clearly revealed a hypoperfusion confined to the medial portion of the bilateral temporal lobe only during the attack. These findings indicate that the medial portion of the temporal lobe is important for episodic memory as described in previous reports, but did not play an important role in procedural memory and priming effects.

Completion phenomenon in transcortical sensory aphasia.

We investigated completion phenomenon for proverbs in cases demonstrating transcortical sensory aphasia due to a variety of diseases. Lack of this completion was exclusively observed in patients with focal atrophy. These patients showed a selective and consistent impairment in word comprehension without phonemic cue effects in naming. The completion phenomenon was present in patients demonstrating transcortical sensory aphasia due to other cerebral diseases. In these patients, comprehension deficits were not selective for words, or words not comprehended were inconsistent and some phonemic cue effects were observed. In a previous study, we reported that completion phenomena for multiplication tables, serial numbers and names of days were frequently noted in patients with focal atrophy. Together with the present findings, these results suggest that lack of proverb completion may be attributed to a selective, systematic and complete loss of the meaning representations for language units such as words and proverbs. In addition, pathological processes of focal atrophy with temporal predominance might selectively affect the semantic memory for language as a unit.

Campylobacter fetus infection of abdominal aortic aneurysm.

A 61-year-old man with Campylobacter fetus infection of an abdominal aortic aneurysm treated surgically is presented herein, the fifth survival case reported in the literature. Fever and back pain preceded the enlargement of atherosclerotic abdominal aortic aneurysm. The patient tolerated satisfactorily total excision of the aneurysm followed by axillo-femoral prosthetic bypass. Antibiotic therapy consisted of intravenous infusion of fosfomycin and gentamicin and oral administration of minocycline. The organism cultured from the aneurysmal wall and intraluminal thrombi was identified as Campylobacter fetus from its typical characteristics. It is concluded that this organism should be considered in all cases of infected aneurysm in elderly or debilitated patients.

[A case of predominantly right-temporal lobe atrophy with disturbance of identifying familiar faces].

A right-handed 72-year-old man (I.K.) who complained of difficulty identifying familiar faces was investigated on a series of tests of face perception (face matching, recognition of age and sex, and meaning of facial expressions), facial identity (faces of families and famous persons as retrograde ones and his doctor's faces as anterograde ones) and other neuropsychological abilities. His scores of face perception tests were normal or mildly disturbed. His memory performances measured with WMS-R and Rey-Osterrieth figure were normal. But he could identify none of anterograde and retrograde faces and failed to experience any familiarity with those faces. In addition, he could not recognize none of voices of family members and a doctor, despite of being able to recognize about the age and sex of voice. On the other hand, he could describe personalities of his family members and doctors, but knew none of famous people. Memory for personal events in the recent and remote past was well preserved, while that for social events was severely disturbed in both past. In addition to impairment of identification of familiar faces, he had severe problems with identifying famous common buildings and animals. He also presented Gogi (word meaning) aphasia and impairment of semantic memory for some common objects. Tyrrell et al. reported a similar case and McNeil et al. examined the patient on covert recognition of face in detail. On their task, he showed no covert effects and they attributed the result to impairment of face recognition units themselves. Their way of thinking seems to give an explanation of I.K.'s disturbance of anterograde and retrograde memory for faces.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of lobar atrophy with stereotypic unusual laughing].

We report a case of a Pick's disease (frontal predominant type) with unusual laughing. The patient was a 54-year-old, right handed, female. The patient began to show low activity and inappropriate laughing at about 51 years. She did not speak at all and showed weird laughing with a voice "hi hi hi hi hi hi" frequently at first presentation. When asked some questions, she sometimes answered with a nod. Almost all of her laughing did not match with the situation and seemed to lack a relationship between affective change and observed expressions. The laughing could be elicited by non specific and varied stimuli. She often interrupt laughing voluntarily unlike pathological laughing. Neurological examination revealed visual rooting reflex and forced grasping reflex but there was no signs of pseudobulbar palsy often observed in patients with pathological laughing. Her electromyogram of facial expression during the laughing showed that electric discharge of M. corrugator supercilii was over 4 times as much as that in normal laughing. And it showed also that the duration of her laughing was several seconds as normal laughing. CT and MRI scans demonstrated atrophy in the fronto-temporo-parietal lobe bilaterally (L > R), most prominent in the frontal lobe. SPECT scan showed a significant diminution of blood flow in the atrophic region. An EEG was normal. We consider that the laughing of the present case is not due to an emotional disturbance but rather a disorder of affective expression as pathological laughing.

[Assessment for intelligence on patients with Pick's disease].

In contrast to Alzheimer's disease, it is unclear whether the MMS (Mini-Mental State) or the RCPM (Raven's Coloured Progressive Matrices) is clinically useful as a mental test battery in patients with Pick's disease, and it has not been fully evaluated whether intelligence of these patients really deteriorate along with the staging of dementia. The present study aimed to make these problems clear. We administered the MMS and the RCPM to 17 cases of Pick's disease, including 7 cases with predominantly frontal lobe atrophy and 10 cases with predominantly temporal lobe atrophy, which were all classified into 3 groups according to the staging of dementia by using the NM scale (New Clinical Scale for Rating of Mental States). We also investigated whether these patients had "Denkfaulheit" (laziness of thinking) and/or "gogi" aphasia (word meaning aphasia), which may affect performances on the mental test batteries. Two cases with predominantly frontal lobe atrophy and 5 cases with predominantly temporal lobe atrophy were assessed by the same examinations several years later. In cases with predominantly frontal lobe atrophy, all the patients presented with "Denkfaulheit". However, the mean RCPM score was normal in the mildly damaged patients, suggesting that their intelligence were relatively preserved. In the moderately and severely damaged groups, their intelligence could not be assessed owing to their severe "Denkfaulheit". In cases with predominantly temporal lobe atrophy, all the patients had "gogi" aphasia and 3 cases of the severely damaged groups presented with "Denkfaulheit".(ABSTRACT TRUNCATED AT 250 WORDS)

[Neuropsychological findings of functional cortical mapping in patients with brain tumors].

In 3 patients with brain tumors involving language areas, we investigated functional cortical regions and epileptogenic foci using subdural electrode stimulation before operation. These stimulation studies were useful in preserving postoperatively their language function. The following neuropsychological findings were obtained; (1) Stimulation of Broca area (Brodmann 44 and 45) did not produce anarthria (phonetic disintegration), but semantic and phonemic parahasias and word finding difficulties. (2) Stimulation of lower motor cortex elicited anarthria. (3) Buccofacial apraxia was not produced only by stimulation of frontal operculum. (4) When anarthria was elicited by stimulation, difficulty in retrieving both Kana and Kanji letter-forms and paragraphia in Kana letters were sometimes observed. (5) Stimulation at Exner's writing centre did not produce writing deficits, but elicited word finding difficulties and paraphasias.

[Comparison between anomia with word comprehension difficulty and Gogi aphasia due to lobar atrophy].

We used naming and pointing tests and a proverb completion task to compare two cases of aphasia that exhibited a selective disturbance of word processing. One patient had anomia with word comprehension difficulty due to partial ablation of the left temporal lobe and the other patient had Gogi aphasia due to lobar atrophy with left temporal predominance. We presented 90 pictures of common objects divided into 9 categories in the naming and pointing tests, and used 10 well-known Japanese proverbs as stimuli in the proverb completion task. Performance of the naming and pointing tests was severely impaired in both patients. In the patient with anomia, words the patient could not name or point to varied from session to session and phonemic cue effects were frequently observed. The proverb completion phenomenon was positive. These findings indicate that the patient had an obstruction of the access route to the intact word store or a partial rarefaction of the word store itself. In the patient with Gogi aphasia, the words the patient could not name or point to were consistent from one occasion to another, and no phonemic cue effects or signs of familiarity were observed at all. The proverb completion phenomenon was totally negative. These findings indicate that the patient has lost the word store itself. MR images in the case of anomia revealed a lesion extending from the anterior to the central portion of the inferior part of the left temporal lobe. In the case of Gogi aphasia, the MR images displayed knife-edged focal atrophy in the anterior aspect of both temporal lobes, more prominently on the left.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effects of aging and hyperlipidemia on plasma osteopontin level].

In order to elucidate a possible mechanism for accelerated atherogenesis as well as enhanced vascular calcification observed during the normal aging process, we measured plasma osteopontin (OPN) levels and examined their relation to aging and certain disease parameters. In all cases examined, no significant relation was found between the plasma OPN level and age, body mass index, blood pressure, plasma levels of glucose and insulin, serum levels of creatinine, triglyceride, and high density lipoprotein cholesterol. On the other hand, a significant negative correlation was found between the plasma OPN level and serum total cholesterol concentration (n = 78, r = -0.355, p = 0.0014). The serum level of low density lipoprotein (LDL) cholesterol, calculated by the formula of Friedewald, also showed a significant negative correlation to the plasma OPN level (n = 78, r = -0.301, p = 0.0075). In cases without diabetes mellitus and hypertension, a significant positive correlation was found between the plasma OPN level and age (n = 22, r = 0.445, p = 0.0378). It is postulated that OPN plays a negative regulatory role in the development of vascular calcification. Therefore, the observed negative relationship between the plasma OPN level and the serum levels of total cholesterol and LDL cholesterol, suggests a possibility that hypercholesterolemia facilitates vascular calcification by suppressing OPN synthesis. On the other hand, in non-diabetic and normotensive cases, the positive relationship between the plasma OPN level and age may reflect a defense mechanism against age-related increase of vascular calcification.