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.

Five cases of brain injury following amniocentesis in mid-term pregnancy.

This paper describes the neuroimaging and neuropathological findings in five cases of severe brain damage after traumatic mid-trimester amniocentesis, all performed between 1986 and 1994. Although fetal injury after amniocentesis has been reported, reports of brain injury are infrequent. Continuous ultrasound monitoring may reduce the risk of fetal injury but follow-up ultrasound scans can be falsely reassuring. Withdrawal of blood-stained fluid, particularly if it contains tissue fragments, should alert the operator to the possibility of fetal damage. Histological examination of such tissue fragments may confirm the nature of the fetal damage. The consequences of fetal brain injury are severe, all five of our cases showed evidence of disruption of brain development compatible with mid-term injury. Obstetricians and their patients should be aware of the small but significant risk of brain damage after mid-term amniocentesis.

Temporal lobe epilepsy with and without psychosis: exploration of hippocampal pathology including that in subpopulations of neurons defined by their content of immunoreactive calcium-binding proteins.

We have investigated relationships between hippocampal/temporal lobe neuropathology and psychosis in subjects with temporal lobe epilepsy, paying particular attention to possible differences in density of hippocampal neurons immunoreactive for calcium-binding proteins. There was a trend for a greater prevalence of left handedness in the psychotic (n = 6) than the non-psychotic (n = 26) cases (P = 0.0504). Psychotic cases also differed from non-psychotic ones in having: (1) more focal lesions outside the hippocampus (P = 0.006); (2) less severe CAI neuron loss (P = 0.015); and (3) a trend, after Bonferroni correction, for a higher density of calbindin-immunoreactive neurons in the CA4 (P = 0.022). An additional finding was that dentate granule cell dispersion was significantly associated with the presence of a reduced density of calretinin-immunoreactive neurons in CA4 (P = 0.002) and with a more severe loss of CA4 neurons visible with Nissl stain (P = 0.003). Thus, cases of temporal lobe epilepsy with psychosis were distinguishable on the basis of a higher density of calbindin-reactive neurons in CA4 as well as on more general aspects of their pathology.

Somatosensory extinction for meaningful objects in a patient with right hemispheric stroke.

Implicit, high level processing of extinguished objects has often been described in the visual modality. In the tactile domain, however, research on this topic is meagre and it is still uncertain whether processing of tactually presented stimuli can be affected by the same attentional disorders as visual stimuli. In this paper we describe a patient, ENM, with visual neglect and light touch extinction who, in a naming task of objects presented in the tactile modality, simultaneously to both hands, showed extinction for left hand objects. He was, nevertheless, able to make above chance Same/Different judgements on the two stimuli. We also tested two neurologically intact subjects who performed the test wearing a ski-glove on the left hand to impair the recognition of left hand objects. In these subjects, Same/Different judgements were at chance level when recognition rate was as low as that found in patient ENM. This happened when either the objects, although sharing the same name were different in shape (conditions Same-Different) or when the two objects were different with respect to the category name but were actually physically similar (conditions Different-Similar). However, when the objects were either identical or completely different, i.e., in a condition where judgement could be based simply on the physical analysis of the object shape (condition Same Identical and Different Dissimilar), their Same/Different judgements were above chance, despite the tactual deficit. Our conclusion was that patient ENM showed implicit recognition of left hand objects, at least in the Same Different and in the Different-Similar conditions, whereas, in the same conditions, normal subjects with an artificial sensory impairment did not. Our results also show that Same/Different judgements may be, in some conditions, less demanding than naming tasks, as suggested by Farah et al. Furthermore, patient ENM performed the test both with uncrossed and crossed hands. We found that extinction always affected the hand contralateral to the brain damage, although there was a tendency for a decrement of the ipsilesional hand performance in the crossed condition. We discuss these findings with reference to the most recent theories on the existence of a body centered spatial frame of reference.

Hemifield-specific visual recognition memory impairments in patients with unilateral temporal lobe removals.

Recent evidence on visual neglect suggests that each hemisphere maintains a retinotopically organized representation of the visual world contralateral to the current fixation point and that this representation is based not only on analysis of the current retinal input but, equally importantly, on information retrieved from memory. This idea predicts that unilateral damage to memory systems should produce a lateralized impairment of memory for the retinotopically contralateral visual world. To test this prediction we examined visual recognition memory performance in the left and right visual hemifields of patients who had undergone partial unilateral temporal lobe removals for the relief of epilepsy, either in the left hemisphere (n = 5) or the right (n = 5). The patients were given complex artificial scenes to remember, constructed of independent left and right halves, and were then tested for recognition of the left and the right halves separately. Stimuli were exposed tachistoscopically throughout and fixation was maintained on a central position. Patients made significantly more errors with half-scenes in the hemifield contralateral to their removal than in the ipsilateral hemifield, an increase of 50% in the error rate on average. The effect was seen equally in patients with left and right removals. This finding supports the idea that visual memory retrieval is retinotopically organized.

Severe amnesia: an usual late complication after temporal lobectomy.

A patient developed the severe amnesic syndrome 8 years after temporal lobe surgery for epilepsy. He underwent left temporal lobectomy (6 cm, 43.5 g; hippocampal sclerosis) aged 19, and remained seizure free for 8 years until a convulsion followed a head injury. He became severely amnesic after a fourth convulsion 16 months later. He was right-handed, pre-operative IQ was average, verbal memory poor and non-verbal memory normal. Post-operatively, these were unchanged. After the first post-operative seizure he began professional training. After onset of amnesia IQ was unchanged, anterograde memory severely impaired and retrograde amnesia dense for at least 16 months. He died 2 years later. Magnetic resonance imaging before amnesia showed absence of anterior left temporal lobe, atrophy of left fornix and mamillary body, and normal right temporal lobe. Four months after onset of amnesia, right hippocampal volume had reduced by 36%. Autopsy showed: previous left temporal lobectomy with absence of left amygdala and hippocampus, atrophy of fornix and mamillary body; neuronal loss in the right hippocampus, severe in CA1 and CA4; intact right amygdala and parahippocampal gyrus; recent diffuse damage associated with cause of death. A convulsion can cause severe hippocampal damage in adult life. Hippocampal zones CA1 and/or CA4 are critical for maintaining memory and the amygdala and parahippocampal gyrus cortex alone cannot support acquisition of new memories.

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 role of light scatter in the residual visual sensitivity of patients with complete cerebral hemispherectomy.

Various residual visual capacities have been reported for the phenomenally blind field of hemispherectomized patients, providing evidence for the relative roles of cortical and subcortical pathways in vision. We attempted to characterize these functions by examining the ability of five patients to detect, localize, and discriminate high-contrast flashed, flickering and moving targets. Dependent measures were verbal, manual, and oculomotor responses. As a control for light scatter, intensity thresholds for monocular detection of targets in the hemianopic field were compared with thresholds obtained when using an additional half eyepatch to occlude the blind hemiretina of the tested eye. One unilaterally destriate patient was tested on the same tasks. In photopic conditions, none of the hemispherectomized patients could respond to visual cues in their impaired fields, whereas the destriate patient could detect, discriminate, and point to targets, and appreciate the apparent motion of stimuli across his midline. Under reduced lighting, the threshold luminance required by hemispherectomized patients to detect stimuli presented monocularly was similar to that required for their detection when all visual information was occluded in the blind field, and only available to the visual system indirectly via light scatter. In contrast, the destriate patient's monocular threshold in his blind field was substantially lower than that for stimuli directly occluded in the blind field. As we found no range of stimuli which the hemispherectomized patients could detect or discriminate that was not also associated with discriminable scattered light, we conclude that the subcortical pathways which survive hemispherectomy cannot mediate voluntary behavioural responses to visual information in the hemianopic field.

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.

Selective amygdalohippocampectomy for hippocampal sclerosis: postoperative MR appearance.

PURPOSE: To analyze the anatomic consequences of selective amygdalohippocampectomy (AH) in patients with hippocampal sclerosis and to correlate the clinical outcome with the MR appearance. METHODS: Seventeen patients were examined with clinical and neuropsychologic examination and cranial MR after AH (7 transcortical AH, 10 trans-Sylvian AH). The clinical and neuropsychologic outcomes after AH were compared with those of anterior lobectomy (ATL). RESULTS: There was no significant difference in seizure cure between transcortical or trans-Sylvian AH and ATL. However, patients with left AH fared significantly better in terms of verbal IQ and nonverbal memory when compared with those with left ATL. Verbal memory and cognition were not significantly different in the two AH groups. Variable amounts of hippocampal and amygdala remnants were found in both AH groups and did not correlate with seizure cure. White matter change consistent with gliosis probably secondary to wallerian degeneration was demonstrated in the anterior temporal lobe to a mean distance of 4.5 cm after transcortical AH and to a lesser degree as a consequence of trans-Sylvian AH. Nine patients (53%) (4 transcortical All, 5 trans-Sylvian AH) demonstrated wallerian degeneration in the optic radiations after surgery. All had incomplete contralateral quadrantanopia. CONCLUSIONS: There is more secondary damage to the temporal lobe after AH than was previously recognized. The extent of hippocampal and amygdala resection in AH do not seem to be directly related to seizure cure. Visual field defects are common in AH because of the anterior but variable course of the optic radiations

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.

Levels of processing for visual stimuli in an "extinguished" field.

Volpe et al. (Nature 282, 722, 1979 [19]) described an experimental study of four patients with parietal tumours who were able to judge whether two simultaneous stimuli were identical or different, even when they were unable to name the stimulus contralateral to their brain injury. We report the case of another patient, E.M., in whom we have investigated this phenomenon further. E.M. had undergone a right temporal lobectomy to prevent recurrent seizures. She could correctly name photographs of objects presented in isolation to either the left or right visual field, at 150 msec exposure (although she was impaired for single objects on the left at 10 msec exposures). She was able to judge correctly whether two simultaneous objects on the left and right had the same or different names, even though she was often unable to name the object on the left. These judgements remained above chance when same-name pairs of stimuli showed the same object but seen from two different viewpoints, or even when they showed visually dissimilar exemplars of the same name category. This implies that the patient based her same-different judgements on categorical information about the pair of objects, even though she was often unable to name the contralateral object.

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.