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Reorganization of language-specific cortex in patients with lesions or mesial temporal epilepsy.

OBJECTIVE: To examine brain activation profiles for receptive language function, using magnetoencephalography (MEG), in patients with left hemisphere space-occupying lesions and patients with left temporal lobe epilepsy due to mesial temporal sclerosis (MTS) and to evaluate whether cross- and intrahemispheric plasticity for language varied as a function of lesion type or location. METHODS: Twenty-one patients with MTS and 23 lesional patients underwent preoperative language mapping while performing a word recognition task. The anatomic location of late activity sources was determined by co-registering MEG coordinates onto structural MRI scans. A language laterality index was calculated based on the number of activity sources in each hemisphere. The location of language-specific activity was examined in relation to its proximity or overlap with Wernicke's area. RESULTS: A higher incidence of atypical language lateralization was noted among patients with MTS than lesional patients (43 vs 13%). The majority of MTS patients with early seizure onset (before age 5) showed atypical language lateralization. In contrast, the precise location of receptive language-specific cortex within the dominant hemisphere was found to be atypical (outside of Wernicke's area) in 30% of lesional patients and only 14% of MTS patients. CONCLUSIONS: There is an increased probability of a partial or total displacement of key components of the brain mechanism responsible for receptive language function to the nondominant hemisphere in mesial temporal sclerosis patients. Early onset of seizures is strongly associated with atypical language lateralization. Lesions in the dominant hemisphere tend to result in an intrahemispheric reorganization of linguistic function.

Adolescent↗

Organization of receptive language-specific cortex before and after left temporal lobectomy.

OBJECTIVE: To examine brain activation associated with receptive language in patients with left temporal lobe epilepsy (TLE) before and after an anterior temporal lobectomy using magnetoencephalography (MEG), and to evaluate which patients were most likely to show a change in the lateralization and localization of the mechanisms supporting receptive language and if such changes were associated with neuropsychological function. METHODS: Twelve patients with left TLE underwent preoperative Wada testing, and pre- and postoperative neuropsychological testing and MEG language mapping. The anatomic location of receptive language-related activity sources observed with MEG was determined by coregistering MEG data with structural MRI scans. Language laterality indices were calculated based on the number of reproducible activity sources in each hemisphere. The proximity of language-specific activity sources to Wernicke's area was also examined. RESULTS: Although the small sample size precluded formal statistical analyses, patients with atypical (bilateral) hemispheric dominance preoperatively were more likely than patients with typical (left-hemisphere) dominance to show evidence of increased right hemisphere participation in language functions after surgery. Patients with left hemispheric dominance preoperatively were more likely to show intrahemispheric changes involving a slight inferior shift of the putative location of Wernicke's area. Patients with bilateral representation tended to perform worse on neuropsychological test measures obtained both pre- and postoperatively. CONCLUSION: Interhemispheric functional reorganization of language-specific areas may occur in patients undergoing left anterior temporal lobectomy. Intrahemispheric reorganization may take place even when the resection does not directly impinge upon Wernicke's area.

Amobarbital↗

Reading impairment in the neuronal migration disorder of periventricular nodular heterotopia.

OBJECTIVE: To define the behavioral profile of periventricular nodular heterotopia (PNH), a malformation of cortical development that is associated with seizures but reportedly normal intelligence, and to correlate the results with anatomic and clinical features of this disorder. METHODS: Ten consecutive subjects with PNH, all with epilepsy and at least two periventricular nodules, were studied with structural MRI and neuropsychological testing. Behavioral results were statistically analyzed for correlation with other features of PNH. RESULTS: Eight of 10 subjects had deficits in reading skills despite normal intelligence. Processing speed and executive function were also impaired in some subjects. More marked reading difficulties were seen in subjects with more widely distributed heterotopia. There was no correlation between reading skills and epilepsy severity or antiepileptic medication use. CONCLUSION: The neuronal migration disorder of periventricular nodular heterotopia is associated with an impairment in reading skills despite the presence of normal intelligence.

Adolescent↗

DWI predicts future progression to Alzheimer disease in amnestic mild cognitive impairment.

The authors assessed whether measures of hippocampal water diffusivity at baseline can predict future progression to Alzheimer disease (AD) in amnestic mild cognitive impairment (aMCI). Higher baseline hippocampal diffusivity was associated with a greater risk of progression to AD in aMCI (p = 0.002). Magnetic resonance diffusion-weighted imaging may help identify patients with aMCI who will progress to AD as well as or better than structural MRI measures of hippocampal atrophy.

Age Factors↗

Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD.

OBJECTIVE: To use fMRI to investigate whether hippocampal and entorhinal activation during learning is altered in the earliest phase of mild cognitive impairment (MCI). METHODS: Three groups of older individuals were studied: 10 cognitively intact controls, 9 individuals at the mild end of the spectrum of MCI, and 10 patients with probable Alzheimer disease (AD). Subjects performed a face-name associative encoding task during fMRI scanning, and were tested for recognition of stimuli afterward. Data were analyzed using a functional-anatomic method in which medial temporal lobe (MTL) regions of interest were identified from each individual's structural MRI, and fMRI activation was quantified within each region. RESULTS: Significantly greater hippocampal activation was present in the MCI group compared to controls; there were no differences between these two groups in hippocampal or entorhinal volumes. In contrast, the AD group showed hippocampal and entorhinal hypoactivation and atrophy in comparison to controls. The subjects with MCI performed similarly to controls on the fMRI recognition memory task; patients with AD exhibited poorer performance. Across all 29 subjects, greater mean entorhinal activation was found in the subgroup of 13 carriers of the APOE epsilon4 allele than in the 16 noncarriers. CONCLUSIONS: The authors hypothesize that there is a phase of increased medial temporal lobe activation early in the course of prodromal Alzheimer disease followed by a subsequent decrease as the disease progresses.

Aged↗

MR spectroscopy of brain white matter in the prediction of dementia.

BACKGROUND: Previous 1H-MR spectroscopy (MRS) studies compared biochemical spectra of persons with dementia with those of healthy control subjects. Given the long prodromal period of Alzheimer disease (AD), the authors sought to investigate whether biochemical changes can be observed also in the preclinical period. METHODS: The authors prospectively followed 509 elderly persons (ages 60 to 90), who were free of clinical dementia at baseline, for on average 5.9 years. At baseline, 1H-MRS of the brain (1.5 T) was performed in a plane above the lateral ventricles that comprised mainly white matter voxels. Standard ratios of N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr) were calculated. Structural MRI was administered to assess white matter lesions and hippocampal atrophy. All persons were followed for incident dementia through repeated neuropsychological testing and linkage with medical records. RESULTS: During follow-up, 37 persons developed dementia, of whom 27 fulfilled criteria for AD. Overall, biochemical ratios on 1H-MRS at baseline were not associated with the risk of incident dementia. However, people with higher Cho/Cr ratios had a higher risk to develop dementia or AD within 4 years (hazard ratio for dementia per SD increase 1.55 [95% CI 1.05 to 2.28]). This association attenuated and became nonsignificant after adjustment for white matter lesions on MRI. CONCLUSION: These data suggest that there are biochemical changes on 1H-MR spectroscopy of brains of persons with presymptomatic dementia.

Aged↗

Neocortical neuronal, synaptic, and glial loss in multiple sclerosis.

BACKGROUND: Recent pathologic investigations have shown that neocortical lesions are frequent in multiple sclerosis (MS). Structural MRI has shown that neocortical atrophy occurs early and can be substantial, but the specific substrate for this atrophy has not been defined quantitatively. OBJECTIVE: To investigate cortical thickness as well as neuronal, glial, and synaptic densities in MS. METHODS: We studied brain samples from 22 patients with MS and 17 control subjects. Neocortical lesions and cortical thickness were assessed on sections stained for myelin basic protein. Neuronal, glial, and synaptic densities were measured in type I leukocortical lesions, nonlesional neocortex, and non-MS control cortex. Immunoautoradiography was used to quantify synaptic densities. RESULTS: Neocortical lesions were common in patients with MS. Subpial type III (44%) and leukocortical type I (38%) lesions were more abundant than intracortical type II (18%) lesions. An overall relative neocortical thinning of 10% (p = 0.016) was estimated for the patients. Within the type I lesions, we found evidence for substantial cell (glial, 36%, p = 0.001; neuronal, 10%, p = 0.032) and synaptic (47% decrease in synaptophysin, p = 0.001) loss. Nonlesional neocortex did not show significant relative changes in neuronal, glial, or synaptic density. CONCLUSIONS: Neocortical neuronal and glial degeneration is significant in multiple sclerosis. Synaptic loss was particularly striking in the neocortical lesions, which should make a major independent contribution to the expression of pathology. New therapies should be directed toward limiting this damage.

Adult↗

fMRI study of episodic memory in relapsing-remitting MS: correlation with T2 lesion volume.

OBJECTIVE: To determine whether memory loss in patients with multiple sclerosis (MS) results from faulty encoding or retrieval, we correlated extent of T2-weighted lesion involvement with brain activation patterns on fMRI scans obtained while patients performed a verbal episodic memory task. METHODS: We performed a neurologic examination, neuropsychological testing, and an event-related fMRI scan on 36 patients with relapsing-remitting MS. In addition, we obtained T2-weighted structural MRI scans to measure lesion volume. We performed a regression analysis to examine the association between lesion volume and regional brain activation. RESULTS: Increasing lesion volume correlated with increasing magnitude of brain activation, primarily in the left frontal and parietal association cortices. Significant correlations of function with lesion volume were primarily observed during the memory retrieval phase of the task. CONCLUSIONS: These results extend previous fMRI studies in multiple sclerosis (MS) by demonstrating an association between greater disease burden and increased neural recruitment during episodic memory. In addition, the stronger correlations observed between lesion volume and brain activation during retrieval than encoding would suggest that retrieval processes are more affected by MS-related cerebral pathology.

Adult↗

A positron emission tomography study of primary orthostatic tremor.

Primary orthostatic tremor (OT), a clinical syndrome in which a rapid (14 to 16 Hz), regular lower limb tremor causes unsteadiness on standing, may be associated with a postural upper limb tremor of similar frequency. We used H2 15O PET to analyze the abnormal pattern of cerebral activation associated with the postural upper limb tremor in four patients with primary OT. Patients had regional cerebral bloodflow (rCBF) measured during involuntary tremor while maintaining a posture with their outstretched right upper limb and again at rest. Tremor was associated with abnormal bilateral cerebellar and contralateral lentiform and thalamic activation. These findings were evident on group analysis of pooled PET data after transformation into standard stereotactic space and in single subjects when PET images were coregistered with structural MRI of the brain. At rest, cerebellar blood flow was significantly increased bilaterally in OT when compared with age- and sex-matched controls. We have previously demonstrated similar abnormal bilateral cerebellar activation in essential and writing tremors and conclude that abnormal bilateral overactivity of cerebellar connections is a common feature of tremulous disorders.

Aged↗

Autosomal dominant progressive syndrome of motor-speech loss without dementia.

This patient report describes a 68-year-old man with progressive dissolution in motor-speech without concomitant language or cognitive decline, with presumed autosomal dominant inheritance. Motor-speech impairments included marked difficulty in articulating words and in coordinating articulation, phonation, and respiration. Brain imaging results revealed severe focal atrophy of the posterior frontal region extending to the anterior parietal and superior temporal regions bilaterally on structural (MRI) and functional (single photon emission computed tomography) brain imaging studies. The involved neural substrate represented the primary motor cortex, premotor cortex (supplementary motor area), and the postcentral gyrus. Familial history included similar difficulties in his mother, her sister, and his own sister. The isolated involvement of the motor-speech processes alone indicated that this syndrome was distinguishable from progressive aphasia associated with prominent loss of language and from Alzheimer's disease.

Aged↗

Frontotemporal dementia (Pick's disease): clinical features and assessment.

The clinical presentation in frontotemporal dementia (FTD) reflects the distribution of the pathologic changes rather than the exact histologic subtype of the disease. Three major clinical syndromes can be identified: 1) frontal variant FTD (dementia of frontal type) in which changes in social behavior and personality predominate, reflecting the orbitobasal frontal lobe focus of the pathology. Traditional cognitive tests are insensitive, but more specific measures are under development; 2) semantic dementia (progressive fluent aphasia) in which there is a breakdown in the conceptual database which underlies language production and comprehension, although deficits in nonverbal semantic knowledge can also be shown on neuropsychologic testing. Patients with semantic dementia have asymmetric anterolateral temporal atrophy with relative sparing of the hippocampal formation, which is typically worse on the left side. A variant of this syndrome affecting the right temporal lobe presents with progressive prosopagnosia; 3) progressive nonfluent aphasia in which the phonologic and syntactic components of language are affected in association with left peri-Sylvian atrophy. The assessment of patients with potential FTD involves a multidisciplinary approach. The development of comprehensive caregiver-based neuropsychiatric instruments, neuropsychologic tasks sensitive to semantic memory and other key cognitive impairments, and functional (hexamethyly-propyleneamine-SPECT) and structural (MRI) brain imaging represent significant advances in the field.

Aphasia, Primary Progressive↗

Early detection and longitudinal changes in amyotrophic lateral sclerosis by (1)H MRSI.

OBJECTIVE: To determine 1) the reproducibility of metabolite measurements by (1)H MRS in the motor cortex; 2) the extent to which (1)H MRS imaging (MRSI) detects abnormal concentrations of N-acetylaspartate (NAA)-, choline (Cho)-, and creatine (Cre)-containing compounds in early stages of ALS; and 3) the metabolite changes over time in ALS. METHODS: Sixteen patients with definite or probable ALS, 12 with possible or suspected ALS, and 12 healthy controls underwent structural MRI and multislice (1)H MRSI. (1)H MRSI data were coregistered with tissue-segmented MRI data to obtain concentrations of NAA, Cre, and Cho in the left and right motor cortex and in gray matter and white matter of nonmotor regions in the brain. RESULTS: The interclass correlation coefficient of NAA was 0.53 in the motor cortex tissue and 0.83 in nonmotor cortex tissue. When cross-sectional data for patients were compared with those for controls, the NAA/(Cre + Cho) ratio in the motor cortex region was significantly reduced, primarily due to increases in Cre and Cho and a decrease in NAA concentrations. A similar, although not significant, trend of increased Cho and Cre and reduced NAA levels was also observed for patients with possible or suspected ALS. Furthermore, in longitudinal studies, decreases in NAA, Cre, and Cho concentrations were detected in motor cortex but not in nonmotor regions in ALS. CONCLUSION: Metabolite changes measured by (1)H MRSI may provide a surrogate marker of ALS that can aid detection of early disease and monitor progression and treatment response.

Amyotrophic Lateral Sclerosis↗

Structural and functional neuroimaging in Alzheimer's disease: an update.

The field of neuroimaging has made several recent advances understanding Alzheimer's disease, a debilitating disease which affects approximately 4 million people in the United States [1]. Despite recent therapeutic advances, available treatments at present are aimed primarily at slowing progression of the disease rather than halting it completely or reversing its progression. Early detection of the disease has, therefore, been a major focus of a variety of neuroimaging techniques, including Positron Emission Tomography (PET), functional Magnetic Resonance Imaging (fMRI), and structural MRI. Recently, these techniques have also been found to be useful in monitoring cognitive and pathological progression of the disease, as well as monitoring response to clinical intervention treatment. A methodology review will be included here as well as a critical evaluation of the advantages and disadvantages of the various techniques.

Alzheimer Disease↗

Cortical areas differentially involved in multiplication and subtraction: a functional magnetic resonance imaging study and correlation with a case of selective acalculia.

A patient with an intracranial hemorrhage showed differential impairment among arithmetic types (impaired in multiplication but not in subtraction). A functional magnetic resonance imaging (fMRI) experiment using normal volunteers also revealed a differential activation between the two arithmetic types. The fMRI result could account for the selective acalculia of the patient in that the lesion shown by structural MRI included the region with multiplication-higher activation and spared subtraction-higher regions. These findings suggest that the cognitive mechanism and neural substrates differ among the simple arithmetic operations.

Adult↗

Pilomotor seizures and status in non-paraneoplastic limbic encephalitis.

BACKGROUND AND AIMS: To describe an unusual clinical presentation of a patient with voltage-gated potassium channel Ab- positive, non-paraneoplastic limbic encephalitis. METHODS: We performed video-EEG monitoring, structural MRI, (18)F-FDG-PET, (1)H-MRS, neuropsychological testing and antibody serology. RESULTS: A 42-year-old male patient presented in an acute phase of non-paraneoplastic limbic encephalitis confirmed by MRI, with antibodies to voltage-gated potassium channels. His pilomotor status was pharmacoresistant to antiepileptic drugs, but responded to corticosteroid and azathioprine treatment. The MRI findings improved. The pilomotor seizures recurred when the immunosuppressive therapy was discontinued after 18 months. MRI at that time was consistent with hippocampal sclerosis. Complete seizure control was achieved after reintroduction of steroids. CONCLUSION: Pilomotor seizures were the predominant seizure type in this case of non-paraneoplastic limbic encephalitis. Immunosuppressive therapy may provide recovery including seizure control. However, long-term immunosuppression may be necessary to prevent relapse. Hippocampal sclerosis and chronic epilepsy might evolve as sequelae of limbic encephalitis.

Adult↗

Magnetization transfer imaging in chronic schizophrenia.

BACKGROUND: It has recently been suggested that new imaging methods such as magnetization transfer imaging (MTI) may play an important role in detecting subtle gray- and white-matter abnormalities in schizophrenia. The aim of the study was to investigate whether MTI, analyzed on a voxel-by-voxel basis, could identify areas of abnormal magnetization transfer ratio (MTR) in patients with schizophrenia. MATERIAL/METHODS: Twenty schizophrenic patients and 23 healthy controls matched for handedness and demographic variables underwent MTI and T1-weighted structural MRI in a 3-tesla scanner. Post-processing was performed with SPM99 and included co-registration of the MT-weighted and non-MT-weighted images, calculation of the MTR maps, spatial normalization, and smoothing. Differences in the MTR maps between groups were assessed using two-sample t-tests. Significant changes in MTR were detected at an individual voxel threshold of p < 0.05. RESULTS: Group comparisons revealed no significant MTR changes, although there was a trend towards MTR reduction in the left superior temporal gyrus, in the right occipital cortex, and left periventricular white matter in patients compared with controls prior to correction for multiple comparisons (p < 0.001, uncorrected). CONCLUSIONS: MTI and voxel-by-voxel statistical analysis used in the study failed to identify regions of significant MTR reductions in schizophrenic patients. Our results disagree with findings of widespread MTR abnormalities reported in recent literature.

Adult↗

Correlation of neuroradiological, electroencephalographic and clinical findings in cortical dysplasias in children.

INTRODUCTION: Cortical dysplasias (CD) are defined as malformations of cortical development. They result from impairment of neuronal proliferation, migration and differentiation. CD are common pathological substrates in patients with early-onset childhood epilepsy and/or developmental delay as well as neurological signs. Recognition of the importance of cortical dysplasias has been shown in many studies when introducing structural MRI. The following study was performed in order to correlate the neuroimaging findings with the electroencephalographic and clinical picture of children with cortical dysplasias. MATERIALS AND METHODS: 46 patients with the presence of CD features in MRI were identified. There were 18 female and 28 male patients. The age ranged from 3 months to 12 years (mean age = 6.2, median age = 3.1). The objectives of the study were explained to the parents or legal representatives of children when possible and also informed consent was obtained. Multiple EEG recordings as well as detailed clinical analysis of all patients were performed. Statistical analysis was conducted in order to correlate the type of CD with clinical outcome and electrophysiological findings. RESULTS: There were 31 patients with focal dysplasias, 6 with schizencephaly, 4 with heterotopias, 3 lissencephaly and 2 with band heterotopia. 80% presented epilepsy (60% of them drug-resistant). Additionally, we tried to elucidate the clinical characteristics of epilepsy. In 75% of epilepsy patients the electroencephalographic changes correlated with anatomical localization of CD. 74% of patients were mentally retarded and 30% had focal neurological deficits. CONCLUSIONS: There were no correlations between the type of CD and the severity of the clinical picture, especially the level of mental retardation and presence of drug-resistant epilepsy. Different age at epilepsy onset and various responsiveness to antiepileptic drugs in the majority of patients may reflect different dynamics in epileptogenicity of the underlying CD.

Cerebral Cortex↗

Neck pain.

Six conditions cause most of the neck pain complaints seen by primary care physicians: cervical muscle strain or sprain, torticollis, acceleration injury, myofascial pain dysfunction syndrome, and cervical osteoarthritis or rheumatoid arthritis. Most of them can be diagnosed and treated by the primary care physician. Of the more unusual causes, one should not miss a clinical fracture; a herniated cervical disc, spinal cord compression from a disc, or epidural tumor; infection of the disc or the vertebral body; subluxation of the vertebral bodies; or pain referred from the chest or mediastinal structures. MRI offers new opportunity for early diagnosis of myelopathy owing to OA or RA, vertebral osteomyelitis, and metastatic involvement of cervical vertebrae.

Humans↗