Cognitive functioning in sporadic amyotrophic lateral sclerosis: a six month longitudinal study.

OBJECTIVE: To observe changes in cognition over six months in subjects with recently diagnosed sporadic amyotrophic lateral sclerosis (ALS). METHODS: The study used a between-group and within-group longitudinal design. Nineteen ALS subjects and eight matched caregivers were recruited to participate in baseline neuropsychological assessments that were repeated six months later. Between group comparisons for these variables were undertaken at baseline and six months later. Within group/across time comparisons for these variables were carried out for both groups. Individual analyses for the neuropsychological variables using z scores were done for the ALS subjects using their baseline performance as the basis for comparison with their six month performance. RESULTS: The between-group and within-group comparisons did not show significant differences in cognitive function over time. In individual analyses, however, seven of 19 ALS subjects (36.84%) developed abnormal neuropsychological performance over six months. CONCLUSIONS: Early in the disease course, over one third of the ALS subjects developed cognitive deficits over six months. These findings support the hypothesis that cognitive deficits in ALS become more prominent over time.

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.

Dissociation of numbers and objects in corticobasal degeneration and semantic dementia.

BACKGROUND: Semantic memory is thought to consist of category-specific representations of knowledge that may be selectively compromised in patients with neurodegenerative diseases, but this has been difficult to demonstrate reliably across object categories. METHODS: The authors evaluated performance on several simple measures requiring number representations (including addition and magnitude judgments of single digits), and on a task that requires object representations (an object naming task) in patients with corticobasal degeneration (CBD; n = 13) and semantic dementia (SD; n = 15). They also examined regional cortical atrophy using voxel-based morphometric analyses of high resolution structural MRI in subgroups of five CBD patients and three SD patients. RESULTS: CBD patients were consistently more impaired on simple addition and magnitude judgment tasks requiring number representations compared to object representations. Impaired performance with numbers in CBD was associated with cortical atrophy in right parietal cortex. By comparison, SD patients demonstrated a greater impairment on a naming task requiring object representations relative to their performance on measures involving number representations. This was associated with left anterior temporal cortical atrophy. CONCLUSION: The cognitive and neuroanatomic dissociations between CBD and SD are consistent with the hypothesis that number and object representations constitute distinct domains in semantic memory, and these domains appear to be associated with distinct neural substrates.

Naming and recognizing famous faces in temporal lobe epilepsy.

OBJECTIVE: To assess naming and recognition of faces of familiar famous people in patients with epilepsy before and after anterior temporal lobectomy (ATL). METHODS: Color photographs of famous people were presented for naming and description to 63 patients with temporal lobe epilepsy (TLE) either before or after ATL and to 10 healthy age- and education-matched controls. RESULTS: Spontaneous naming of photographed famous people was impaired in all patient groups, but was most abnormal in patients who had undergone left ATL. When allowed to demonstrate knowledge of the famous faces through verbal descriptions, rather than naming, patients with left TLE, left ATL, and right TLE improved to normal levels, but patients with right ATL were still impaired, suggesting a new deficit in identifying famous faces. Naming of famous people was related to naming of other common objects, verbal memory, and perceptual discrimination of faces. Recognition of the identity of pictured famous people was more related to visuospatial perception and memory. CONCLUSIONS: Lesions in anterior regions of the right temporal lobe impair recognition of the identities of familiar faces, as well as the learning of new faces. Lesions in the left temporal lobe, especially in anterior regions, disrupt access to the names of known people, but do not affect recognition of the identities of famous faces. Results are consistent with the hypothesized role of lateralized anterior temporal lobe structures in facial recognition and naming of unique entities.

Brain metabolism in the cerebellum and visual cortex correlates with neuropsychological testing in patients with Alzheimer's disease.

This study was designed to measure glucose metabolic deficits in areas not typically recognized as abnormal on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scans in patients with Alzheimer's disease (AD), and to correlate such findings with subtle neuropsychological impairment. FDG-PET scans on 38 AD patients with no clinical evidence of visual, spatial or motor deficits were acquired on the PET HEAD scanner 40 min following the intravenous administration of 115 microCi.kg-1 of FDG. All FDG-PET scans were analysed blindly using a region of interest (ROI) template with regions for the primary visual cortex (PVC), secondary visual cortex (SVC) and cerebellum. Counts from the ROIs of these regions were normalized to whole brain activity and the results were compared with psychometric and neuropsychological measures. A number of significant correlations were found between these structures and various neuropsychological measures (P<0.05). Specifically, there were significant correlations between clock drawing and the cerebellum activity; memory and activity in the PVC, SVC and cerebellum; social score and activity in the PVC and left cerebellum; judgement and activity in the right SVC and right PVC; and the overall Mini-Mental State Examination and activity in the PVC, SVC and cerebellum. The results of this study suggest that metabolism in areas not typically recognized as abnormal on FDG-PET scans in AD, such as the PVC, SVC and cerebellum, is correlated with deficits in neuropsychological function. This may have important clinical and pathophysiological implications in the study of AD and other illnesses of dementia.

Clinical delineation and localization to chromosome 9p13.3-p12 of a unique dominant disorder in four families: hereditary inclusion body myopathy, Paget disease of bone, and frontotemporal dementia.

Autosomal dominant myopathy, Paget disease of bone, and dementia constitute a unique disorder (MIM 605382). Here we describe the clinical, biochemical, radiological, and pathological characteristics of 49 affected (23 male, 26 female) individuals from four unrelated United States families. Among these affected individuals 90% have myopathy, 43% have Paget disease of bone, and 37% have premature frontotemporal dementia. EMG shows myopathic changes and muscle biopsy reveals nonspecific myopathic changes or blue-rimmed vacuoles. After candidate loci were excluded, a genome-wide screen in the large Illinois family showed linkage to chromosome 9 (maximum LOD score 3.64 with marker D9S301). Linkage analysis with a high density of chromosome 9 markers generated a maximum two-point LOD score of 9.29 for D9S1791, with a maximum multipoint LOD score of 12.24 between D9S304 and D9S1788. Subsequent evaluation of three additional families demonstrating similar clinical characteristics confirmed this locus, refined the critical region, and further delineated clinical features of this unique disorder. Hence, autosomal dominant inclusion body myopathy (HIBM), Paget disease of bone (PDB), and frontotemporal dementia (FTD) localizes to a 1.08-6.46 cM critical interval on 9p13.3-12 in the region of autosomal recessive IBM2.

Neurobehavioral aspects of movement disorders.

Cognitive, behavioral, affective, and psychiatric symptoms occur in almost all movement disorders. Diagnosis and management of movement disorders depends critically on an understanding of these neurobehavioral symptoms. This article reviews the neurobehavioral aspects of two representative movement disorders; Parkinson's disease and Huntington's disease.

Age vs Alzheimer's: a computational model of changes in representation.

Previous research has demonstrated that the language of older adults leads to denser representations in a high dimensional model of memory than does the language of younger adults (Conley & Burgess, in press), and thus that density in the model (HAL or the hyperspace analogue to language) may constitute a useful metric in comparing memory for younger and older adults. This paper extends the previous research by examining the role of density in semantic representations that emerged from the language generated by adults with Alzheimer' s and comparing the results with age-matched normal controls. We found that, just as older adults have denser representations in semantic space than do younger adults, adults with Alzheimer's have still denser representations than normal older adults. These results support the hypothesis that greater density, normally associated in the model with good semantic depth, may in fact reach a "saturation point" and affect retrieval in older adults and especially adults with Alzheimer's.

Material-specific memory changes after anterior temporal lobectomy as predicted by the intracarotid amobarbital test.

PURPOSE: The intracarotid amobarbital test (IAT) has been shown to predict verbal memory changes after anterior temporal lobectomy (ATL). Seeking to extend these findings, we examined two questions: (a) What is the relationship between material-specific aspects of IAT memory and material-specific memory changes after ATL? and (b) Which IAT memory score(s) optimally predict memory changes after surgery, the memory score after injection ipsilateral to the seizure focus, the memory score after injection contralateral to the seizure focus, or the IAT asymmetry score, comprising the ipsilateral minus contralateral injection scores? METHODS: Seventy left hemisphere language-dominant patients undergoing ATL for treatment of medically refractory seizures were administered a verbal and visuospatial recognition memory test before surgery and 3 weeks after surgery. IAT memory recognition scores for words and designs were used to predict verbal and visuospatial memory changes after surgery. RESULTS: After surgery, left ATL patients declined in verbal memory, whereas right ATL patients declined in visuospatial memory. IAT total recognition memory scores (collapsed across all types of materials) and IAT word memory scores were associated with postoperative verbal memory decline. This relationship was significant for the IAT ipsilateral injection memory scores and the IAT hemispheric asymmetry scores. IAT memory performances were not related to visuospatial memory changes. CONCLUSIONS: Results indicate IAT memory measures to be related to postoperative verbal, but not visuospatial, memory change. A specific relationship was found between postoperative verbal memory change and IAT verbal memory after injection ipsilateral to the seizure focus, when relying primarily on the contralateral hemisphere. This finding is consistent with the functional reserve model of memory change in ATL.

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.

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.

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.

Robotic motion compensation for respiratory movement during radiosurgery.

Tumors in the chest and abdomen move during respiration. The ability of conventional radiation therapy systems to compensate for respiratory motion by moving the radiation source is inherently limited. Since safety margins currently used in radiation therapy increase the radiation dose by a very large amount, an accurate tracking method for following the motion of the tumor is of the utmost clinical relevance. We investigate methods to compensate for respiratory motion using robotic radiosurgery. Thus, the therapeutic beam is moved by a robotic arm, and follows the moving target tumor. To determine the precise position of the moving target, we combine infrared tracking with synchronized X-ray imaging. Infrared emitters are used to record the motion of the patient's skin surface. A stereo X-ray imaging system provides information about the location of internal markers. During an initialization phase (prior to treatment), the correlation between the motions observed by the two sensors (X-ray imaging and infrared tracking) is computed. This model is also continuously updated during treatment to compensate for other, non-respiratory motion. Experiments and clinical trials suggest that robot-based methods can substantially reduce the safety margins currently needed in radiation therapy.

Oral reading in dementia.

Reading has been thought to consist of three main processing components: the orthographic, phonological, and semantic lexicons. In traditional psycholinguistic models, these components have been treated independently such that the selective dysfunction of one does not necessarily imply the breakdown of another. Recently, it has been proposed that a word's semantic representation is essential to oral reading such that a disturbance within the semantic lexicon will disrupt processing within the orthographic and/or phonological lexicons. From this view, semantic deterioration should lead to fragmentation of the other systems contributing to reading, resulting in a specific pattern of errors during oral reading. This would include (1) a larger than normal advantage for reading words with regular spelling-to-sound correspondence over words with exception spelling, as well as the production of "regularization errors" when reading exception words; and (2) a smaller than normal difference between reading real words and pronounceable nonwords, or pseudowords (PW's). We found that patients with Semantic Dementia generally conformed to these hypothesized patterns of reading difficulty. Despite the presence of a semantic impairment, however, patients with Alzheimer's Disease, Frontotemporal Dementia, and Progressive Non-Fluent Aphasia did not demonstrate these patterns of reading difficulty. Our findings suggest that not all semantic impairments invariably lead to the disruption of the orthographic and phonological lexicons.

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.

Cortical reorganization in linear nevus sebaceous syndrome: a multimodality neuroimaging study.

The authors report the findings of multimodal structural, functional, and metabolic imaging in a patient with linear nevus sebaceous syndrome, intractable seizures, and right megalencephaly. Despite nearly continuous paroxysmal electrical activity from the megalencephalic region, imaging studies suggested nonfunctional tissue in this region with reorganization of cortical function to the unaffected ipsilateral hemisphere. Hemispherectomy has been successfully performed in previous patients; however, it could have led to marked left hemiparesis with significant functional morbidity in this patient because of ipsilateral reorganization of the primary motor cortex.

Psychiatric aspects of temporal lobe epilepsy before and after anterior temporal lobectomy.

OBJECTIVES: Psychopathology has been reported to be prevalent both before and after surgical treatment for medically intractable temporal lobe epilepsy. Individual patients were evaluated prospectively to assess the effect of anterior temporal lobectomy (ATL) on prevalence and severity of psychiatric disease. METHODS: Psychiatric status was assessed in a consecutive series of epilepsy patients before and 6 months after ATL using a structured psychiatric interview, psychiatric rating scales, and self report mood measures. RESULTS: A DSM-III-R axis I diagnosis was present in 65% of patients before and after surgery. The most common diagnoses were depression, anxiety, and organic mood/personality disorders. There was a trend for major psychiatric diagnoses to be more common in patients with right compared to left temporal lobe seizure focus, both before and after surgery. The apparent stability in the overall rate of psychiatric dysfunction concealed onset of new psychiatric problems in 31% of patients in the months shortly after surgery, and resolution of psychiatric diagnoses in 15% of patients. In the group as a whole, the severity of psychiatric symptoms was lower at 6 months postsurgery than before temporal lobectomy. CONCLUSIONS: The overall prevalence of psychiatric dysfunction was comparably high before and after ATL, but individual changes in psychiatric status and changes in severity of symptoms occurred in many patients in the 6 months after surgery.

Nonepileptic seizures after resective epilepsy surgery.

PURPOSE: To identify factors that are associated with the emergence of nonepileptic seizures (NES) after resective epilepsy surgery. METHODS: Twenty-two patients with medically refractory epilepsy in whom NESs were documented by EEG after resective surgery were compared with a larger series of epilepsy surgery patients on demographic, neurologic, and psychiatric variables. RESULTS: NES tended to become apparent in the first few months after surgery. Patients who developed NESs did not differ from other epilepsy surgery patients in terms of age, IQ, or preoperative psychiatric diagnoses. However, surgical NES patients' neurologic problems and seizures began later in life, the NES group included a larger proportion of female subjects and patients with right hemisphere surgery, and NES patients were more likely to develop non-NES psychiatric problems after surgery. CONCLUSIONS: The heterogeneous collection of behaviors subsumed under the label NESs are determined by multiple factors. Several variables were found to be specifically associated with the development of NES after resective epilepsy surgery: A disproportionate number of postsurgical NES patients are female, they have primary neurologic dysfunction in the right hemisphere, and their epileptic seizures often began after adolescence. We propose that at least one group of patients with somatoform tendencies develop NESs as part of the psychiatric instability that occurs often in the few months after resective surgery.

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.