Quantitative fMRI assessment of the differences in lateralization of language-related brain activation in patients with temporal lobe epilepsy.

Defining language lateralization is important to minimize morbidity in patients treated surgically for temporal lobe epilepsy (TLE). Functional magnetic resonance imaging (fMRI) offers a promising, noninvasive, alternative strategy to the Wada test. Here we have used fMRI to study healthy controls and patients with TLE in order to (i) define language-related activation patterns and their reproducibility; (ii) compare lateralization determined by fMRI with those from of the Wada test; and (iii) contrast different methods of assessing fMRI lateralization. Twelve healthy right-handed controls and 19 right-handed preoperative patients with TLE (12 left- and seven right-TLE) were studied at 3T using fMRI and a verbal fluency paradigm. A Wada test also was performed on each of the patients. Greater activation was found in several areas in the right hemisphere for the left-TLE group relative to controls or right-TLE patients. Relative hemispheric activations calculated based on either the extent or the mean signal change gave consistent results showing a more bihemispheric language representation in the left-TLE patients. There was good agreement between the Wada and fMRI results, although the latter were more sensitive to involvement of the nondominant right hemisphere. The reproducibility of the fMRI values was lowest for the more bihemispherically represented left-TLE patients. Overall, our results further demonstrate that noninvasive fMRI measures of language-related lateralization may provide a practical and reliable alternative to invasive testing for presurgical language lateralization in patients with TLE. The high proportion (33%) of left-TLE patients showing bilateral or right hemispheric language-related lateralization suggests that there is considerable plasticity of language representation in the brains of patients with intractable TLE.

Memory for objects presented early after intracarotid sodium amytal: a sensitive clinical neuropsychological indicator of temporal lobe pathology.

Results from a simple test of post-recovery recognition of objects presented immediately after intracarotid sodium amytal (ISA) injection were compared with those obtained using the 'Montreal' anterograde memory test procedure of post-recovery recognition of items presented later after injection in 16 patients with unilateral temporal lobe pathology undergoing routine bilateral ISA testing prior to epilepsy surgery. All 16 patients were given both memory tests following injection on both sides. Significantly fewer 'early objects' were recognized when injection was contralateral to pathology than when injection was ipsilateral to pathology (i.e. contralateral to an intact hemisphere), whereas there was no significant difference in the number of 'Montreal' anterograde items recognized regardless of side of pathology. Memory for objects presented early after ISA appears to be a sensitive measure although its potential as a valid indicator of temporal lobe pathology needs to be further refined.

The interpretation of sentence ambiguity in patients with unilateral focal brain surgery.

Interpretations of ambiguous sentences were studied in patients with unilateral anterior temporal lobectomy or selective amygdalo-hippocampectomy. The sentences represented lexical and syntactic ambiguities. In both left- and right-sided groups, regardless of type of surgery, total mean score on the test was below normal. Left-sided cases, regardless of type of surgery, provided significantly fewer alternative interpretations than right-sided cases. The results suggest greater left than right hemisphere specialization in both lexical and syntactic processing, but also suggest right hemisphere involvement in resolution of lexical ambiguity.

Awareness of and memory for arm weakness during intracarotid sodium amytal testing.

The traditional association between anosognosia for hemiplegia and the right hemisphere was investigated in 31 patients with unilateral temporal lobe pathology during intracarotid sodium amytal testing (ISA) before epilepsy surgery. Recall of arm weakness was examined by questioning at the end of the test, when memory for items presented during the hemiplegia was also examined. Significantly more patients were amnesic for left arm weakness than for right. Amnesia for right arm weakness (and speech arrest) was significantly associated with pathology in the temporal lobe on the non-injected side and with impaired recognition of the memory items. Amnesia for left arm weakness was independent of both. Examination of cases where injection was contralateral to a hemisphere without pathology, and which showed normal memory capacity under ISA conditions, revealed that 87% recalled right arm weakness, but only 22% recalled left arm weakness. Awareness of arm weakness during left hemiplegia was examined in nine patients. Five of them were not aware of the weakness. Three of the four others could not subsequently recall it. By inference from the generally unimpaired recall of right arm weakness, following left hemisphere inactivation by amytal, an intact right hemisphere is capable of both recognizing right arm weakness and mediating its subsequent recall. In contrast, the left hemisphere was aware of left arm weakness only in approximately 50% of cases and even when there had been awareness usually could not mediate its subsequent recall. The suggestion is made that the right hemisphere may have a specific mnestic function for arm weakness, and presumably for hemiplegia, additional to the gnostic function.

Sex-related asymmetries in the morphology of the left and right hippocampi? A follow-up study on epileptic patients.

Cell densities were determined in left and right surgically removed hippocampal tissue of epileptic patients. Pyramidal cells were studied in CA1, CA4, and the dentate gyrus. Lower densities of nucleolated cells were found for males in the right CA1 and CA4 than on the left while there was no significant left-right difference in females. Moreover, we found a probable sex difference in intercorrelations of nucleolated cells among the three subfields. In males, they were positive and significant on the left while they were low on the right. In females, positive significant intercorrelations were obtained between some subfields and not between other subfields, on either side. The present findings suggest greater hippocampal lateralization in males than in females with higher hippocampal neuronal connectivity on the left in males than on the right.

Changes in focal interictal epileptiform activity during and after the performance of verbal and visuospatial tasks in a patient with intractable partial seizures.

An 18-year-old male with intractable complex partial seizures is described in whom localised epileptiform discharges in the EEG were influenced in a specific manner by different cognitive tasks. The patient had impaired verbal skills but above average visuospatial ability, and seizures probably arising in the left temporal lobe. Comparison of verbal and visuospatial tasks showed that focal epileptiform activity was suppressed or enhanced depending on the nature of the immediate and preceding cognitive tasks. The finding of particular interest was the activity of a posterior temporal spike focus only during rest periods after verbal tasks, by contrast with an independent mid-to-anterior temporal focus that was suppressed during verbal tasks.

Regional differentiation of cell densities in the left and right hippocampi of epileptic patients.

Neuronal cell densities in surgically removed left or right hippocampal tissue of epileptic patients suffering from temporal lobe epilepsy were determined in CA1, CA4, and the dentate gyrus (DG). Mean densities showed no statistically significant left-right asymmetry in CA1 and the DG, consistent with findings by others. Mean densities did show previously unreported asymmetry in CA4; densities were significantly lower in the right CA4 than in the left. Another new finding is an asymmetry in regional intercorrelations: positive and significant correlations among the three subfields were obtained only in the left hippocampus. In addition, we confirmed previous findings of positive correlation between neuronal densities in CA1 and age of onset of habitual epilepsy, on either side. Taken together, the results suggest subtle left-right asymmetries in the vulnerability of the hippocampi to epilepsy-associated damage and/or higher neuronal connectivity or interdependence on the left than on the right.

Neurosurgery for epilepsy.

'Consideration of operative therapy should be given to more patients with refractory partial epilepsy...there can be little doubt that resources for the evaluation and surgical treatment of patients should be more widely available and more widely used in the UK.'

Hippocampal neuron loss in temporal lobe epilepsy: correlation with early childhood convulsions.

Hippocampal neuron densities in three areas (H1 zone, end folium, and dentate gyrus) were counted in each of 32 temporal lobectomy excision specimens using the technique of Mouritzen Dam. The association between severe neuronal loss in all three areas and early childhood convulsions that were prolonged and/or lateralized was highly significant. Lesser degrees of neuron loss in H1 and/or end folium were common and were not associated with early childhood convulsions, but were most often found in older patients with a particularly long history of epilepsy.

The radiologic investigation of temporal lobe epilepsy. Value of high resolution CT with temporal orientated sections.

The value of high resolution computed tomography of the temporal lobes using temporal lobe orientated sections and intrathecal contrast is described. The results of this technique are correlated with the pathologic findings in 13 patients subsequently proven to have temporal lobe gliomas. These patients all presented with drug resistant temporal lobe epilepsy and underwent temporal lobectomy. This technique was successful in detecting the tumours in 11 of 13 patients. The average size of the tumours was just over 2 cm. The importance of detecting these small tumours is emphasised because of the profound effect this has on management.

Recovery from unilateral visuo-spatial neglect?

Patients who had demonstrated unilateral visuo-spatial neglect on a simple drawing and copying task three to four weeks after a right hemisphere stroke were reassessed five months later. Although the incidence of neglect as defined had dropped markedly in that period, they remained impaired on tests of spatial analysis and visual perception relative to a group of right hemisphere patients without neglect. The measurement of neglect is discussed in the light of both these results and the stability of the neglect group's abnormal position preference on one of the tests administered.

A blind controlled trial of dextran 40 in the treatment of ischaemic stroke.

A blind controlled trial of dextran 40 in ischaemic stroke is reported. In the treated group mortality in the acute stage in patients with severe strokes was significantly reduced but survivors were severely disabled and six months later no significant benefit could be detected. In less severe strokes no effect of treatment was found. It is concluded that the action of dextran 40 in reducing acute mortality probably lay in preventing or reversing cerebral swelling but no evidence of the expected action in reducing the area of infarction following improved blood flow was found. The importance of extending assessment beyond the two weeks customary in therapeutic trials in stroke is emphasized.

Predicting the outcome of stroke: acute stage after cerebral infarction.

On admission to hospital during the acute phase of a stroke presumed due to ischaemic infarction in one cerebral hemisphere 93 patients were examined to determine the factors associated with a poor prognosis for immediate survival. The patients particularly at risk were those who were overtly unconscious and those with any combination of impaired consciousness, dense hemiplegia, and failure of conjugate ocular gaze towards the side of the limb weakness. Necropsy evidence suggested that these signs usually indicate infarction of the whole of one middle cerebral artery territory which is often secondary to internal carotid artery occlusion and commonly produces fatal cerebral oedema.

Prognostic factors in stroke.

Prognostic factors in 137 patients with acute ischaemic infarction of the cerebral hemisphere were examined in a prospective study with particular reference to acute mortality, delayed mortality and the ability to regain independent living. Adverse factors in the examination on admission to hospital with regard to all these aspects were found to be a reduction of the level of consciousness to any degree and paralysis of conjugate gaze. A severe hemiplegia and advancing age indicated a bad prognosis for delayed mortality and severe disability in survivors, but did not affect acute mortality. At three weeks after the onset, inability to walk unaided, a useless hand and or urinary incontinence was associated with an increased probability of death in the next few months and of failure to regain independence in the survivors. These adverse factors appeared to correlate with infarction extending beyond the middle cerebral artery territory, severe brain swelling and recent occlusion of the internal carotid artery.