Long-term cognitive outcome of hemiconvulsion–hemiplegia–epilepsy syndrome affecting the left cerebral hemisphere

Long-term cognitive outcome following hemiconvulsion–hemiplegia–epilepsy (HHE) syndrome has been poorly studied, with little attention to the implications of side of involvement in HHE. This retrospective study describes language lateralization and cognitive performance in five patients with HHE syndrome affecting the left cerebral hemisphere. All of the patients had to have intracarotid sodium amytal testing (IAT) to be included in this study. The mean age of the patients was 30.2 years (range: 13–50). All patients had their hemiconvulsive seizures before age 1½ years (range: 6–13 months). All patients had right-sided hemiatrophy of the body, left mesial temporal sclerosis, and seizures originating from the left temporal lobe. The habitual seizures began at a mean age of 4.5 years (range: 1.5–12 years). Performance on tests of intelligence, verbal memory, and visual memory was examined. Language was represented in the right cerebral hemisphere in three patients, the left hemisphere in one patient, and both hemispheres with predominance on the right side in the fifth patient. Intellectual functioning was in the borderline to extremely low range among the patients with right hemispheric or bilateral representation for language. These patients were variably impaired on measures of verbal and visual memory. The patient with left hemispheric representation for language performed in the average range on tests of intellectual functioning and verbal memory, whereas scores on visual memory were variable. This study demonstrated that reorganization of language to the right cerebral hemisphere or its bilateral representation is common in patients with HHE syndrome affecting the left cerebral hemisphere, and is associated with poor cognitive outcome.     

Hemiconvulsion-hemiplegia-epilepsy evolving to contralateral hemi-Lennox-Gastaut-like phenotype

Background

Hemiconvulsion-hemiplegia-epilepsy (HHE) involves infantile-onset acute hemiconvulsive febrile status epilepticus with subsequent unilateral cerebral atrophy and hemiparesis. Chronic epilepsy later develops, typically involving refractory focal seizures; however, the underlying pathophysiology of this epilepsy is not well understood.

Clinical relevance of memory performance during Wada is stimulus type dependent

OBJECTIVES: This study aimed to investigate whether different types of memory stimulus provide different information during the Wada or intracarotid amytal procedure (IAP) in patients with refractory medial temporal lobe epilepsy (MTLE). METHODS: Eighty nine surgical candidates with documented MTLE and selected for left hemispheric language dominance underwent memory assessment with verbal and dually encodable stimuli during a presurgical IAP. RESULTS: The overall IAP memory performance with the left hemisphere is significantly better than with the right hemisphere regardless of lesion side. This can be explained by the left hemispheric advantage of encoding all stimuli, whereas the right hemisphere has only limited resources to encode verbal stimuli. More importantly, it appeared that dually encodable items remain more readily recognised following injection ipsilateral to the lesion, whereas verbal items are always better recognised following right hemisphere injection regardless of lesion side. CONCLUSIONS: Verbal IAP stimuli show left hemispheric sensitivity in left language dominant MTLE patients. The dually encodable items of the IAP appear lesion sensitive.     

Seizures During Cognitive Testing in Patients with Temporal Lobe Epilepsy: Possibility of Seizure Induction by Cognitive Activation

In 18 of 185 patients under consideration for epilepsy surgery, 20 seizures were observed during neuropsychological evaluation. We wished to determine whether the task at seizure onset corresponded neuropsychologically to lateralization of the epileptic focus. The patients' characteristics and the circumstances of the seizures were as follows: Fourteen patients had right temporal lobe epilepsy (RTE) and four had left temporal lobe epilepsy (LTE). Although a wide range of cognitive functions had been tested, all but one seizure occurred during assessment of memory performance. In the RTE patients, 12 of 16 seizures occurred during visual memory testing. Two seizures were observed during a verbal memory task, and one seizure was observed during mental rotation. In two LTE patients, seizures were elicited during verbal memory testing. Two LTE patients with seizures during visual memory testing had speech dominance of the right hemisphere. This high correspondence between the eliciting performance and the focus localization suggests that cognitive performances ipsilateral to the epileptic focus may affect seizure threshold in focal epilepsies.     

Memory performance during the intracarotid amobarbital procedure and neuropsychological assessment in medial temporal lobe epilepsy: the limits of material specificity

We investigated the relationship between material-specific memory performance elicited during the Wada test, or intracarotid amobarbital procedure (IAP), and classic neuropsychological assessment in 89 surgical candidates with refractory medial temporal lobe epilepsy (MTLE). The neuropsychological battery included measures of simple and complex verbal and visual memory, whereas the IAP material consisted of verbal and dually encodable stimuli. Neuropsychological testing revealed that reduced verbal memory performance was associated with left-sided MTLE, whereas visual memory tasks revealed no differences between patients with left-sided and right-sided MTLE. During IAP, memory performance was worse with the ipsilesional hemisphere, regardless of lesion side. Most importantly, performance on verbal memory tests was significantly, but moderately, correlated with left hemispheric IAP performance, indicating that memory tasks using verbal material are a valid marker of left hemispheric integrity in left language-dominant MTLE patients and significantly predict left hemispheric memory performance during IAP. In contrast, performance on classic visual memory tests is unrelated to right hemispheric IAP performance, suggesting that the currently used visual memory stimuli do not reflect right hemispheric sensitivity.     

不同半球脑梗死记忆障碍的研究

目的本文通过对不同半球脑梗死所致记忆障碍进行研究,明确记忆障碍与脑损害部位是否有必然联系,探索不同的记忆障碍在脑部相应区域的定位。方法将《临床记忆量表》[13]与《WMSCR》[6]两种量表结合起来并加用Rey复杂图形以检测视空间记忆能力,脑梗死组与对照组各40例用上述记忆量表测验,对不同脑损害的记忆功能进行较为全面的评价。结果脑梗死组记忆成绩无论临床记忆量表、韦氏记忆量表测验均明显低于对照组(P<0.05),其中部分分测验(言语记忆)的差别非常显著(P<0.01)。脑梗死组记忆成绩明显低于对照组(P<0.01),脑梗死组左半球与右半球病变不同的记忆内容比较也有显著性差异。结论不同的记忆功能在大脑的分工是有区别的,左半球主要对语文记忆起作用,右半球对非语文记忆起作用。在图形、空间记忆方面右半球起主导地位,而在短时记忆中左半球占优势。     

Hemiconvulsion-hemiplegia-epilepsy syndrome. Magnetic resonance findings in a 3-year-old boy

The term ‘hemiconvulsion-hemiplegia-epilepsy syndrome’ (HHE) was first used by Gastaut et al. to describe the sequential combination of unilateral or predominandy unilateral clonic seizures (hemiconvulsion), occurring during the first 2 years of life, immediately followed by an ipsilateral flaccid hemiplegia lasting 7 or more days. In the following phase partial epileptic seizures occur.We report a case of HHE syndrome in a 3-year-old boy with partial seizures (hemiconvulsion lasting 15–30 minutes) followed by left hemiplegia and hyporeflexia. Magnetic resonance imaging showed diffuse and high signal hyperintensity of the whole right cerebral hemisphere. Diffusion-weighted images showed a reduction of the apparent diffusion coefficient in the subcortical region. Magnetic resonance arteriography showed a narrow flow signal in the distal territory of the right middle cerebral artery. The authors emphasize the importance of neuroradiological findings in early diagnosis and in the follow-up of HHE syndrome.     

Creative innovation with temporal lobe epilepsy and lobectomy

ObjectivesSome patients with left temporal degeneration develop visual artistic abilities. These new artistic abilities may be due to disinhibition of the visuo-spatially dominant right hemisphere. Many famous artists have had epilepsy and it is possible that some may have had left temporal seizures (LTS) and this left temporal dysfunction disinhibited their right hemisphere. Alternatively, unilateral epilepsy may alter intrahemispheric connectivity and right anterior temporal lobe seizures (RTS) may have increased these artists' right hemisphere mediated visual artistic creativity.MethodsTo test the disinhibition versus enhanced connectivity hypotheses we studied 9 participants with RTS and 9 with left anterior temporal seizures (LTS) who underwent unilateral lobectomy for the treatment of medically refractory epilepsy. Creativity was tested using the Torrance Test of Creative Thinking (TTCT).Results and conclusionsThere were no between group differences in either the verbal or figural scores of the TTCT, suggesting that unilateral anterior temporal ablation did not enhance visual artistic ability; however, for the RTS participants' figural creativity scores were significantly higher than verbal scores. Whereas these results fail to support the left temporal lobe disinhibition postulate of enhanced figural creativity, the finding that the patients with RTS had better figural than verbal creativity suggests that their recurrent right hemispheric seizures lead to changes in their right hemispheric networks that facilitated visual creativity. To obtain converging evidence, studies on RTS participants who have not undergone lobectomy will need to be performed.     

Body side of motor symptom onset in Parkinson's disease is associated with memory performance.

The relation of body side of motor symptom onset in Parkinson's disease (PD) to memory measures associated with hemispheric dominance was examined. Fourteen patients with right body side motor symptom onset (RPD, inferred left hemisphere dysfunction) and 16 patients with left side onset (LPD, right hemisphere dysfunction) were administered measures of verbal (Hopkins Verbal Learning Test-Revised) and visual memory (Brief Visual Memory Test-Revised), that require similar task demands and are associated with left or right hemisphere dominance, respectively. The LPD group demonstrated poorer visual than verbal memory, both within group and in comparison to the RPD group. By contrast, the RPD group showed poorer verbal than visual memory within group. These findings suggest that side of motor symptom onset is associated with asymmetrical memory dysfunction.     

Functional MRI evidence for language plasticity in adult epileptic patients: Preliminary results

The present fMRI study explores the cerebral reorganisation of language in patients with temporal lobe epilepsy, according to the age of seizures onset (early or late) and the hippocampal sclerosis (associated or not). Seven right-handed control volunteers and seven preoperative adult epileptic patients performed a rhyme decision (language condition) and a visual detection (control condition) tasks in visually presented words and unreadable characters, respectively. All patients were left hemisphere dominant for language. Appropriate statistical analyses provided the following preliminary results: (1) patients compared with healthy subjects showed lower degree of hemispheric lateralization with supplementary involvement of the right hemisphere; (2) the degree of hemispheric specialization depends on the considered region; (3) patients with early seizures show signs of temporal and parietal reorganization more frequently than patients with late onset of seizures; (4) patients with early seizures show a tendency for intra-hemispheric frontal reorganisation; (5) associated hippocampal sclerosis facilitates the inter-hemispheric shift of temporal activation. Although our patients were left hemisphere predominant for language, the statistical analyses indicated that the degree of lateralization was significantly lower than in healthy subjects. This result has been considered as the indication of atypical lateralization of language.     

Exceptional verbal intelligence after hemispherotomy in a child with Rasmussen encephalitis

We report a longitudinal case study of a left-handed girl who underwent left hemispherotomy at 7 years for Rasmussen encephalitis (RE). Presurgical evaluation showed mild hemiparesis, no visual defect, and light neuropsychological impairment with short-term memory weakness. Language fMRI showed a right hemispheric dominance. Postoperatively, the patient exhibited right hemiplegia and hemianopsia but preserved intellectual capacities. She became seizure-free, and antiepileptic medication was discontinued. Long-term follow-up showed very high verbal intelligence at 11 years of age (VCI of 155) and improvement in working memory as well as language and reading abilities. Furthermore, a significant visuoverbal discrepancy became increasingly pronounced. Thus, early surgical treatment of epilepsy avoided the global cognitive deterioration usually associated with RE. Finally, such a high level of verbal functioning combined with low spatial reasoning with a single hemisphere provides additional information on the neurocognitive profile of children with RE after hemispherotomy.     

Language Lateralization in Children with Benign Partial Epilepsy

To investigate the relationship between epilepsy and hemispheric asymmetries for language, a dual-task procedure was used to assess language lateralization in children with benign rolandic childhood epilepsy. In the sample selection, care was taken to include factors believed to influence both the mental capabilities of epileptic patients and the individual functional cerebral organization. Results suggest that the interhemispheric prevalence pattern is related to the focus site. Controls as well as epileptic patients with a right hemispheric focus showed the expected left language lateralization; conversely, children with a left unilateral focus showed a different pattern of functional representation, suggesting an involvement of the right hemisphere in language mechanisms. It is emphasized that this atypical cerebral organization is found in subjects with no structural lesion and no therapy. It seems likely that the presence of a focal epileptic activity itself can alter the cerebral mechanisms underlying cognitive functions. A relationship between this modified hemispheric specialization and subtle neuropsychological dysfunctions observed in the children with focal epilepsy is suggested.     

Crossed aphasia in a patient with complex partial seizures: Evidence from intracarotid amobarbital testing,functional cortical mapping,and neuropsychological assessment

Abstract

We report a right-handed patient who became transiently aphasic following a right temporal lobectomy for control of intractable complex partial seizures. Pre-operative intracarotid amobarbital testing revealed right-hemisphere language dominance, although bilateral language representation was present. Memory testing during unilateral electrical hippocampal simulation with depth electrodes indicated reliance on left-hemisphere mesial temporal lobe structures for verbal memory. Functional mapping for language during surgery established several right perisylvian regions that, when stimulated, produced speech arrest and/or paraphasic substitution. One-year follow-up neuropsychological assessment demonstrated an increase in verbal learning and decrease in visual memory, a pattern associated with patients who have undergone right temporal lobectomy. These data demonstrate that (1) right cerebral language dominance can be observed when ipsilateral seizure onset is present (2) verbal memory and language dominance are not necessarily linked, and (3) some reported cases of crossed aphasia may in fact have bilateral language representation.     

Crossed aphasia in a patient with complex partial seizures: evidence from intracarotid amobarbital testing, functional cortical mapping, and neuropsychological assessment.

We report a right-handed patient who became transiently aphasic following a right temporal lobectomy for control of intractable complex partial seizures. Preoperative intracarotid amobarbital testing revealed right-hemisphere language dominance, although bilateral language representation was present. Memory testing during unilateral electrical hippocampal simulation with depth electrodes indicated reliance on left-hemisphere mesial temporal lobe structures for verbal memory. Functional mapping for language during surgery established several right perisylvian regions that, when stimulated, produced speech arrest and/or paraphasic substitution. One-year follow-up neuropsychological assessment demonstrated an increase in verbal learning and decrease in visual memory, a pattern associated with patients who have undergone right temporal lobectomy. These data demonstrate that (1) right cerebral language dominance can be observed when ipsilateral seizure onset is present (2) verbal memory and language dominance are not necessarily linked, and (3) some reported cases of crossed aphasia may in fact have bilateral language representation.     

Language lateralization correlates with verbal memory performance in children with focal epilepsy

Purpose: Assessment of language dominance with functional magnetic resonance imaging (fMRI) and neuropsychological evaluation is often used prior to epilepsy surgery. This study explores whether language lateralization and cognitive performance are systematically related in young patients with focal epilepsy. Methods: Language fMRI and neuropsychological data (language, visuospatial functions, and memory) of 40 patients (7–18 years of age) with unilateral, refractory focal epilepsy in temporal and/or frontal areas of the left (n = 23) or right hemisphere (n = 17) were analyzed. fMRI data of 18 healthy controls (7–18 years) served as a normative sample. A laterality index was computed to determine the lateralization of activation in three regions of interest (frontal, parietal, and temporal). Results: Atypical language lateralization was demonstrated in 12 (30%) of 40 patients. A correlation between language lateralization and verbal memory performance occurred in patients with left‐sided epilepsy over all three regions of interest, with bilateral or right‐sided language lateralization being correlated with better verbal memory performance (Word Pairs Recall: frontal r = ?0.4, p = 0.016; parietal r = ?0.4, p = 0.043; temporal r = ?0.4, p = 0.041). Verbal memory performance made the largest contribution to language lateralization, whereas handedness and side of seizures did not contribute to the variance in language lateralization. Discussion: This finding reflects the association between neocortical language and hippocampal memory regions in patients with left‐sided epilepsy. Atypical language lateralization is advantageous for verbal memory performance, presumably a result of transfer of verbal memory function. In children with focal epilepsy, verbal memory performance provides a better idea of language lateralization than handedness and side of epilepsy and lesion.     

Decompressive hemicraniectomy in a space-occupying presentation of hemiconvulsion-hemiplegia-epilepsy syndrome

A case of an acute life-threatening presentation of hemiconvulsion–hemiplegia–epilepsy (HHE) syndrome requiring an urgent decompressive hemicraniectomy is described. A 9 month-old baby had a status epilepticus following a sustained fever, leading to a comatose state and a right pupillary dilatation associated with a left hemiplegia. The MRI showed a swelling right hemisphere with marked temporal herniation. The baby underwent a decompressive right hemicraniectomy with temporal cortical biopsies. The post-operative course was favourable. The histological findings were unspecific, showing a gliotic spongiosis with disseminated granular cells. The post-operative MRI depicted a right hemisphere atrophy. To our knowledge, a space-occupying presentation of HHE syndrome requiring surgical decompression has never been described before while only a few reports dealt with the neuropathological aspects of this syndrome.     

Determination of cortical language dominance using functional transcranial Doppler sonography in left-handers.

OBJECTIVE: Verbal analytical functions are primarily related to the left hemisphere in right-handers, but there is yet no agreement about cortical language dominance in left-handers. Also, there are some contradictory reports about sex differences in cortical language lateralization. The aim of this study is to investigate cortical language dominance in left-handers and to explore gender influence on cortical language representation. METHODS: We performed functional transcranial Doppler sonography (previous validated for determination of cerebral language lateralization) during a word generation task, measuring changes in mean cerebral blood flow velocity (BFVmean) in both middle cerebral arteries (MCA) in 150 healthy subjects (75 left-handers and 75 right-handers). In left-handers we observed significant increase BFVmean in right MCA in 58 (77.3%) subjects. Bilateral increase was observed in 11 (14.7%) subjects and increase in left MCA in 6 (8%) subjects. In right-handed group 93.3% subjects showed left cortical dominance, while 6.7% showed bilateral language representation. RESULTS: Current results showed significant (P<0.0001) right hemispheric language dominance in healthy left-handed subjects. CONCLUSIONS: Our results showed significant difference in hemispheric dominance for verbal function between righthanders and lefthanders. Also there is statistically insignificant female gender tendency for bilateral hemispheric language representation in both handedness.     

Language after hemispherectomy in childhood: contributions from memory and intelligence

After hemispherectomy (removal or disconnection of an entire cerebral hemisphere) in childhood for treatment of intractable epilepsy, gross speech and language functions are often rescued. Whether more complex functions, such as syntactic processing, are selectively impaired, remains controversial. Here we present a cross-sectional study of expressive and receptive language functions in 30 patients who have undergone hemispherectomy (17 left, 13 right). The patients had developed epilepsy-induced pathology either during the pre/perinatal period (19 cases), or after a period of normal development (11 cases; onset range=20 months to 10 years). The patients were assessed at least 1 year post surgery on tests of receptive vocabulary, expressive and receptive grammar, instruction comprehension, and semantic association. Measures of verbal and nonverbal intelligence, short-term verbal memory, and working memory were also obtained. Principal component analysis revealed that two core components could be extracted from the five language measures, one reflecting receptive vocabulary abilities, and the other a composite of the other four measures. Regression analyses revealed that the best predictor of the composite language score was the short-term verbal memory score with some contribution from verbal intelligence, while the only predictor of receptive vocabulary was verbal intelligence. The results suggest that during childhood the lone left and right hemispheres have a similar potential for developing an adequate level of receptive vocabulary. However, congenital pathology affecting either hemisphere, and postnatal damage to the left hemisphere result in substantial language deficits that are reflected also in limitations in short-term verbal memory, and, to a lesser extent, in verbal intelligence.     

Asymmetry of neuronal activity during extracellular microelectrode recording from left and right human temporal lobe neocortex during rhyming and line-matching

Recordings of neuronal activity in humans have identified few correlates of the known hemispheric asymmetries of functional lateralization. Here, we examine single-unit activity recorded from both hemispheres during two delayed match-to-sample tasks that show strong hemispheric lateralization based on lesion effects; a line-matching (LM) task related to the right hemisphere, and a rhyming (RHY) task related to the left. Nineteen neuronal populations were recorded with extracellular microelectrodes from the left temporal neocortex of 11 awake patients, and 18 from the right in 9 patients during anterior temporal lobectomy for complex partial seizures under local anesthesia. All subjects were left hemisphere dominant for language. Twelve (32%) populations exhibited statistically significant changes in activity at p <.05. Although changes in firing frequency were recorded from both hemispheres during both tasks, the RHY task elicited changes in activity several hundred milliseconds earlier on the left side than on the right. The LM task, on the other hand, induced changes earlier on the right side than on the left. Both hemispheres contained units active during verbal responses regardless of which behavior elicited the response. Our results indicate that cerebral dominance is reflected in earlier neuronal activity in the anterior temporal lobe during tasks lateralized to that hemisphere.     

A study of functional plasticity of the brain in childhood. I. Critical period dislodging lateralization of language in the brain]

To investigate the functional plasticity of the brain in childhood, the intelligence and language tests, brain CT and dichotic listening test were performed on 34 patients with hemiplegia. All 13 patients with left hemiplegia, 8 to 37 years old, showed a right ear dominance suggesting the lateralization of language in the left hemisphere. Among 21 patients with right hemiplegia, 7 to 22 years old, 16 patients who had suffered from the left hemispheric damage before 6 years and 1 month of age, showed the left ear dominance suggesting the lateralization of language in right hemisphere except 2 patients. On the contrary, 3 patients with right hemiplegia who had suffered from the left hemispheric damage after 6 years and 6 months of age showed a right ear dominance. It was concluded that the critical period for the dislodging of language lateralization in the brain from the damaged left hemisphere to the intact right hemisphere is the first half of 6 years after birth. Five patients out of 8 patients with right hemiplegia showed significantly lower scores in performance than in verbal WISC IQ. The compensation of language function rather than performance function was considered to be characteristic for the left-hemispheric damage in childhood.