Neuropsychological and perfusion MR imaging correlates of revascularization in a case of moyamoya syndrome.

Serial neurocognitive and perfusion MR imaging findings are described in the perioperative course of a 48-year-old woman with a superficial temporal artery to middle cerebral artery bypass for right hemispheric ischemia due to moyamoya syndrome. Neurocognitive testing reflected both global and focal cerebrovascular dysfunction, which suggests that perfusion augmentation following surgical revascularization may engender cognitive and neurologic improvement beyond focal regions of established ischemia.

Memory decline in the aged: treatment with lecithin and physostigmine.

Normal aged subjects were given lecithin and placebo for 5 weeks each in a double-blind crossover study. Supraspan tests of memory and learning failed to show any significant changes as a result of these treatments. Addition of a single IV infusion of physostigmine did not improve performance. These findings neither support nor weaken the "cholinergic hypothesis" of cognitive impairment in aging and dementia, but they imply that simple cholinergic hypofunction is unlikely.

Predictors of outcome after anterior temporal lobectomy: the intracarotid amobarbital test.

The intracarotid amobarbital test (IAT) examines hemispheric memory and language. We set out to determine whether memory performance on the IAT correlated with seizure relief after anterior temporal lobectomy in 117 patients with refractory epilepsy. The IAT assessed recognition memory performance for nine items with correction for false-positive recognitions. We then compared performance of one hemisphere with that of the other, defining a correctly lateralized memory deficit as worse performance when using the hemisphere containing the operated temporal lobe than when using the other hemisphere. The analysis included concurrent factors that might also affect outcome, such as age at first risk for epilepsy, presence or absence of tumor, and Full Scale IQ. A discriminant function analysis demonstrated that patients with a correctly lateralized memory deficit on the IAT had an increased probability of being seizure-free following surgery after controlling for other predictors. The performance of the nonoperated temporal lobe related to outcome, although less strongly. The magnitude of the difference in performance between the two hemispheres and the performance of the operated hemisphere did not relate to outcome. Patients who became seizure-free had an earlier age at first risk than did those with persistent seizures, and tumor presence weakly correlated with postoperative outcome. IQ did not correlate with outcome. We conclude that the IAT predicts seizure relief after anterior temporal lobectomy independent of other known risk factors we examined.

Hemispheric asymmetries in arousal affect outcome of the intracarotid amobarbital test.

OBJECTIVE: To evaluate changes in arousal and their impact on memory performance during the intracarotid amobarbital test (IAT). METHODS: Along with memory measures, level of arousal was evaluated through clinical ratings and nonverbal self-ratings in epilepsy patients undergoing IAT before anterior temporal lobectomy. RESULTS: Irrespective of seizure focus, left-sided amobarbital injection resulted in decreased objective and subjective arousal more often than right-side injection. Impaired objective arousal was greater when the left hemisphere was injected second, because of the presumed additive effects of systemic amobarbital residual from the first injection. Decreased objective arousal was related to poorer performance on memory testing following left-hemisphere injection. CONCLUSIONS: The IAT, as practiced in most centers, is biased, so patients with right temporal lobe seizure focus are more likely to "pass" the test, whereas patients with left seizure focus are more likely to "fail" the test. The significant impact of changes in arousal on memory testing needs to be considered when using IAT results to select patients for temporal lobectomy.

Functional MRI lateralization of memory in temporal lobe epilepsy.

OBJECTIVE: To determine the feasibility of using functional magnetic resonance imaging (fMRI) to detect asymmetries in the lateralization of memory activation in patients with temporal lobe epilepsy (TLE). BACKGROUND: Assessment of mesial temporal lobe function is a critical aspect of the preoperative evaluation for epilepsy surgery, both for predicting postoperative memory deficits and for seizure lateralization. fMRI offers several potential advantages over the current gold standard, intracarotid amobarbital testing (IAT). fMRI has already been successfully applied to language lateralization in TLE. METHODS: fMRI was carried out in eight normal subjects and 10 consecutively recruited patients with TLE undergoing preoperative evaluation for epilepsy surgery. A complex visual scene encoding task known to activate mesial temporal structures was used during fMRI. Asymmetry ratios for mesial temporal activation were calculated, using regions of interest defined in normals. Patient findings were compared with the results of IAT performed as part of routine clinical evaluation. RESULTS: Task activation was nearly symmetric in normal subjects, whereas in patients with TLE, significant asymmetries were observed. In all nine patients in whom the IAT result was interpretable, memory asymmetry by fMRI concurred with the findings of IAT including two patients with paradoxical IAT memory lateralization ipsilateral to seizure focus. CONCLUSIONS: fMRI can be used to detect asymmetries in memory activation in patients with TLE. Because fMRI studies are noninvasive and provide excellent spatial resolution for functional activation, these preliminary results suggest a promising role for fMRI in improving the preoperative evaluation for epilepsy surgery.

Alpha-synuclein cortical Lewy bodies correlate with dementia in Parkinson's disease.

BACKGROUND: Dementia is a frequent complication of idiopathic parkinsonism or PD, usually occurring later in the protracted course of the illness. The primary site of neuropathologic change in PD is the substantia nigra, but the neuropathologic and molecular basis of dementia in PD is less clear. Although Alzheimer's pathology has been a frequent finding, recent advances in immunostaining of alpha-synuclein have suggested the possible importance of cortical Lewy bodies (CLBs) in the brains of demented patients with PD. METHODS: The brains of 22 demented and 20 nondemented patients with a clinical and neuropathologic diagnosis of PD were evaluated with standard neuropathologic techniques. In addition, CLBs and dystrophic neurites were identified immunohistochemically with antibodies specific for alpha-synuclein and ubiquitin; plaques and tangles were identified by staining with thioflavine S. Associations between dementia status and pathologic markers were tested with logistic regression. RESULTS: CLBs positive for alpha-synuclein are highly sensitive (91%) and specific (90%) neuropathologic markers of dementia in PD and slightly more sensitive than ubiquitin-positive CLBs. They are better indicators of dementia than neurofibrillary tangles, amyloid plaques, or dystrophic neurites. CONCLUSION: CLBs detected by alpha-synuclein antibodies in patients with PD are a more sensitive and specific correlate of dementia than the presence of Alzheimer's pathology, which was present in a minority of the cases in this series.

A category-specific naming impairment after temporal lobectomy.

Unilateral temporal lobectomy patients and normal control subjects were tested in a speeded naming task with pictures of living and nonliving things that were equated for name frequency, familiarity, and visual complexity. Although right temporal lobectomy patients and normal subjects performed equally well with the living relative to nonliving things, left temporal lobectomy patients were disproportionately impaired at naming nonliving things. This result has several implications: First, it supports the existence of category-specific naming impairments. In particular, it undermines the proposal that living-nonliving dissociations are artifactual, resulting from the greater difficulty of living things. Second, it demonstrates an asymmetry in the neural representation of nonliving things, in favor of the left hemisphere. Third, it casts doubt on the hypothesis that the anterior temporal cortices are convergence zones that are particularly necessary for the naming of living things.

Impaired face and word recognition without object agnosia.

A leading account of high-level visual recognition proposes that the recognition of faces, objects, and words is mediated by two processing capacities. Words are assumed to require the capacity to represent numerous parts, whereas faces are processed wholistically. and hence require the representation of complex units. Object recognition requires the capacity to represent both numerous and complex parts. As object recognition depends upon the same processing capacities underlying face and word recognition, this account predicts that patients with severe alexia and prosopagnosia should be deficient in tests of object recognition. We report a patient who is unable to recognize words or faces, yet performs relatively well on tests of object recognition. The two-capacity theory cannot accommodate this pattern of performance without additional assumptions.

Impaired spelling in Alzheimer's disease: a linguistic deficit?

Different kinds of real words and pronounceable pseudowords (PWs) were presented for writing to dictation to patients with the diagnosis of probable Alzheimer's disease (AD) and to age- and education-matched healthy controls. Though spelling less accurately on all tasks, AD patients responded in a manner generally qualitatively similar to controls. Except for a slightly enhanced effect of spelling regularity in real word writing accuracy, AD patients showed the same sensitivity to various lexical, orthographic and phonological variables as controls. Both groups showed no difference in spelling accuracy for words and PWs with regular vs ambiguous spelling patterns, and groups also showed similar orthographic preferences when spelling PWs having several different acceptable pronunciations. Finally, AD patients and controls produced similar types of errors when spelling real words. Dementia severity was related to the overall accuracy, but not to the pattern, of spelling responses. It is suggested that the decline in response accuracy in cognitively demanding writing tasks in patients with more advanced dementia is most likely due to semantic impairment and impairments of nonlinguistic functions of attention, executive control and praxis, rather than to a disturbance within language specific processes.

Neuropsychological function in adults after high dose fractionated radiation therapy of skull base tumors.

PURPOSE: To evaluate the long term effects of high dose fractionated radiation therapy on brain functioning prospectively in adults without primary brain tumors. METHODS AND MATERIALS: Seventeen patients with histologically confirmed chordomas and low grade chondrosarcomas of the skull base were evaluated with neuropsychological measures of intelligence, language, memory, attention, motor function and mood following surgical resection/biopsy of the tumor prior to irradiation, and then at about 6 months, 2 years and 4 years following completion of treatment. None received chemotherapy. RESULTS: In the patients without tumor recurrence or radiation necrosis, there were no indications of adverse effects on cognitive functioning in the post-acute through the late stages after brain irradiation. Even in patients who received doses of radiation up to 66 Cobalt Gy equivalent through nondiseased (temporal lobe) brain tissue, memory and cognitive functioning remained stable for up to 5 years after treatment. A mild decline in psychomotor speed was seen in more than half of the patients, and motor slowing was related to higher radiation doses in midline and temporal lobe brain structures. CONCLUSION: Results suggest that in adults, tolerance for focused radiation is relatively high in cortical brain structures.

Physicians' and families' perspectives on the medical management of dementia.

The role of physicians in the long-term management of patients with the primary diagnosis of progressive dementia was investigated by surveying the opinions of 57 physicians and 47 family members. Respondents were asked to evaluate the difficulty and helpfulness of various activities physicians perform in the diagnosis, treatment, and management of patients with dementia. Both physicians and families rated the diagnostic services provided by physicians very highly. Although families found physicians' explanations of the diagnosis and prognosis extremely helpful, physicians reported this as an area of difficulty. Physicians and families expressed considerable frustration with the limited medical treatments and interventions for the relief of symptoms associated with dementia. Despite the acknowledged sensitivity of physicians to the social-psychological consequences of dementia, physicians were found to be least helpful in addressing these issues, either directly or through referral to allied health and social services. This study outlines areas of physician education that need improvement and calls for development of an interdisciplinary network of services for the biopsychosocial management of dementia.

Cross-cultural cognitive examination: validation of a dementia screening instrument for neuroepidemiological research.

OBJECTIVE: Validation of a new instrument for screening dementia, the Cross Cultural Cognitive Examination (CCCE), is described. DESIGN: Criterion and concurrent validation and cross-cultural comparison of a new instrument. PARTICIPANTS: All individuals over the age of 40 in a village in southern Guam participated in a door-to-door survey. Alzheimer's and Parkinson's Disease patients and healthy controls aged 40-90 participated in the US mainland study. MEASUREMENTS: The CCCE was administered to all subjects. Effects of age, language, education, and gender on test performances and social-cultural differences were assessed. Concurrent validation of the test with respect to other well accepted screening instruments was determined. RESULTS: High specificity (> 94%) and sensitivity (> 99%) for detecting dementia were found in Guam and US mainland samples, and these were not biased by differences in gender, linguistic preference, education, or cultural background. Sensitivity and specificity of the CCCE matched or exceeded that of already accepted dementia screening instruments. CONCLUSIONS: These validation studies support the usefulness of the CCCE for identifying patients with generalized dementia, rather than focal types of cognitive impairment, quickly and reliably in cross-cultural neuroepidemiological research.

A comparison of memory for verbal and non-verbal material in schizophrenia.

Verbal memory impairment has been well explored in schizophrenia, but it is unclear whether findings relate to the type of material to be learned or the component process required by the memory task. Also, sparse data on non-verbal memory also open the question of how well schizophrenia patients encode this material. We tested whether episodic memory performance in schizophrenia varies as a function of stimulus material (verbal/non-verbal) and determined the integrity of various component memory processes. Memory tests that differ in stimulus material (words, California Verbal Learning Test, CVLT; designs, Biber Figure Learning Test-Extended, BFLT-E) yet produce similar memory component measures were used. Subjects were 28 neuroleptic-medicated inpatients with a diagnosis of chronic schizophrenia. Results showed that both verbal and non-verbal memory performance was impaired relative to age-matched controls. Learning and recall measures were most severely impaired, with memory storage problems and impairment in recognition memory evident. On the verbal task, the relative sparing of recognition memory suggested retrieval processes, in addition to encoding processes, were disrupted. On the non-verbal task, the deficits appeared more limited to encoding. Therefore, while the operational integrity of components such as encoding were compromised regardless of material, retrieval processes showed material-specific effects. To the degree verbal and non-verbal memory functions can be lateralized in the brain, these data support the possibility of deficits in both right and left hemisphere declarative memory systems in schizophrenia.

Differences between nouns and verbs after anterior temporal lobectomy.

To test the claim that lesions of left anterior and middle temporal cortical structures specifically impair processing of nouns but not verbs, 56 left-hemisphere-language-dominant patients who had undergone anterior temporal lobectomy (ATL) completed tasks assessing confrontation naming of pictured objects and actions, generation of synonyms for nouns and verbs, and semantic lexical judgments about nouns and verbs. Compared with right ATL patients, left ATL patients were impaired across different tasks that assessed naming and comprehension of high-imageability as well as low-imageability nouns. These groups did not differ, however, in verb naming or comprehension on most tasks. Results are consistent with the hypothesized specialization of left temporal lobe structures for processing nouns and suggest that naming problems commonly seen after left ATL extend beyond difficulties with retrieving object names and may be related to subtle disturbances in comprehension of the meanings underlying nominal word forms.

Comparison of reading and spelling in patients with probable Alzheimer's disease.

Patients with probable Alzheimer's disease (AD) are reported to show mild, but reliable, difficulties reading aloud and spelling to dictation exception words, which have unusual or unpredictable correspondence between their spelling and pronunciation (e.g., touch). To understand the cognitive dysfunction responsible for these impairments, 21 patients and 27 age-and education-matched controls completed specially designed tests of single-word oral reading and spelling to dictation. AD patients performed slightly below controls on all tasks and showed mildly exaggerated regularity effects (i.e., the difference in response accuracy between words with regular spellings minus exception words) in reading and spelling. Qualitative analyses, however, did not demonstrate response patterns consistent with impairment in central lexical orthographic processing. The authors conclude that the mild alexia and agraphia in AD reflect semantic deficits and nonlinguistic impairments rather than a specific disturbance in lexical orthographic processing.

Lexical semantic and associative priming in Alzheimer's disease.

Semantic memory impairment was investigated in patients with probable Alzheimer's disease (AD) using a threshold oral word reading task to assess priming of different lexical relationships. Healthy elderly controls showed significant priming for associatively related nouns (tempest-teapot) and also for nouns semantically related either because both designate basic-level exemplars of a common superordinate category (cousin-nephew) or because the target names the superordinate category of the prime (daughter-relative). AD patients, in contrast, showed preserved priming of lexical associates but impaired priming of certain semantic relationships. They showed no priming between words designating coordinate exemplars within a category, despite preserved priming of the superordinate category label. Findings are consistent with the view that at least part of the semantic deficit in AD is due to disruption of semantic knowledge that affects relationships among basic-level concepts, more than the relationships between these concepts and their corresponding superordinate category of membership.

Dementia resulting from dural arteriovenous fistulas: the pathologic findings of venous hypertensive encephalopathy.

PURPOSE: Dural arteriovenous fistulas (DAVFs) are acquired arteriovenous shunts located within the dura. The highly variable natural history and symptomatology of DAVFs range from subjective bruit to intracranial hemorrhage and are related to the lesion's pattern of venous drainage and its effect on the drainage of adjacent brain. We examined the prevalence and features of DAVFs in patients with progressive dementia or encephalopathy. METHODS: The records and radiologic studies of 40 consecutive patients with DAVFs treated at our institution were reviewed. RESULTS: Five (12.5%) of 40 consecutive patients with DAVFs had encephalopathy or dementia. In each patient, high flow through the arteriovenous shunt combined with venous outflow obstruction caused impairment of cerebral venous drainage. Hemodynamically, the result was widespread venous hypertension causing diffuse ischemia and progressive dysfunction of brain parenchyma. Results of CT or MR imaging revealed abnormalities in each patient, reflecting the impaired parenchymal venous drainage. Pathologic findings in one patient confirmed the mechanism of cerebral dysfunction as venous hypertension. The hemodynamic mechanism and resulting abnormality appeared identical to that seen in progressive chronic myelopathy resulting from a spinal DAVF (Foix-Alajouanine syndrome). Remission of cognitive symptoms occurred in each patient after embolization. CONCLUSION: Venous hypertensive encephalopathy resulting from a DAVF should be considered a potentially reversible cause of vascular dementia in patients with progressive cognitive deficits.

Dopamine supports sentence comprehension in Parkinson's Disease.

OBJECTIVE: To determine the role of dopamine in the executive resource component of sentence comprehension. METHODS: We studied sentence-picture matching in 20 right-handed, non-demented, native English speakers with mild Parkinson's disease (PD) when 'on' and 'off' their levodopa, taking into account disease duration to control for endogenous dopamine metabolism. We also administered a verbal working memory measure that does not involve specific grammatical manipulations. RESULTS: PD patients 'off' levodopa demonstrated a significant discrepancy in their comprehension of grammatically complex sentences compared to grammatically simpler sentences that was not evident when PD patients were 'on' levodopa. An error analysis demonstrated that impaired comprehension of grammatically complex sentences when 'off' levodopa was associated with poorer performance on foils requiring working memory resources. Performance on an independent measure of verbal working memory correlated only with comprehension of grammatically complex sentences during levodopa supplementation, but working memory according to this measure did not differ during 'on' and 'off' states. CONCLUSION: Dopamine supports the executive resources contributing to sentence comprehension in PD.

The continuum of deep/phonological alexia.

Two patients exhibited all the characteristics of deep alexia shortly following brain injury. Both subsequently recovered some reading abilities and evolved to show a pattern of oral reading consistent with phonological alexia. These findings suggest that deep alexia and phonological alexia share common underlying deficits that are mediated by common neurological systems. A two-deficit psycholinguistic model is presented to account for the apparent continuity between deep alexia and phonological alexia.

Repetition of single words and nonwords in Alzheimer's disease.

Repetition of single words and pronounceable nonwords (pseudowords) was assessed in Alzheimer's Disease (AD) patients to evaluate how lexical phonological processing might be accomplished when semantic and conceptual knowledge is impaired. AD patients performed significantly worse than healthy elderly controls on all repetition tasks. However, repetition abilities and dementia severity were not correlated, and AD patients produced the same distribution of error types as controls. Furthermore, despite their semantic problems, AD patients, like controls, showed a significant advantage for repeating real words compared to pseudowords, even when repeating low frequency phonologically complex words whose meaning is not likely to have been retained. The results support the postulated existence of a lexical phonological system that is used to repeat both known and novel words and that processes linguistic information independent of its meaning.