Object. The authors sought to determine the impact of early temporal lobectomy (in patients younger than age 17 years) on intellectual functioning. The efficacy of temporal lobectomy for treating seizures is well established and the procedure is becoming more acceptable as a treatment for children whose seizures are intractable. However, cognitive outcomes of temporal lobectomy in children and adolescents are largely unreported. The present study takes advantage of a unique multicenter collaboration to examine retrospectively intellectual functioning in a large sample of children who underwent temporal lobectomy.Methods. Intellectual functioning was assessed before and after temporal lobectomy for treatment of medication-resistant seizures in 82 patients at eight centers of epilepsy surgery. All children underwent standard presurgical examinations, including electroencephalography—video monitoring, magnetic resonance (MR) imaging, and neuropsychological testing, at their respective centers.Forty-three children underwent left temporal lobectomy and 39 underwent right temporal lobectomy. For the entire sample, there were no significant declines in intelligence quotient (IQ) following surgery. Children who underwent left temporal lobectomy demonstrated no significant loss in verbal intellectual functioning and improved significantly in nonverbal intellectual functioning. Children who underwent right temporal lobectomy did not demonstrate significant changes in intellectual functioning. Although group scores showed no change in overall IQ values, an analysis of individual changes revealed that approximately 10% of the sample experienced a significant decline and 9% experienced significant improvement in verbal functioning. Significant improvement in nonverbal cognitive function was observed in 16% of the sample and only 2% of the sample showed significant declines. Risk factors for significant decline included older patient age at the time of surgery and the presence of a structural lesion other than mesial temporal sclerosis on MR imaging.Conclusions. The present study provides preliminary data for establishing the risk of cognitive morbidity posed by temporal lobectomy performed during childhood. With respect to global intellectual functioning, a slight improvement was significantly more likely to occur than a decline. However, there were several patients in whom significant declines did occur. It will be necessary to study further the factors associated with such declines. In addition, further study of more specific cognitive functions, particularly memory, is needed.
Summary: Twenty‐two patients with intractable complex partial seizures (CPS) were treated with temporal lobectomy. Eighteen of 22 (82%) are seizure‐free while receiving medication, with a mean follow‐up time of 4 years. In each case, the clinical seizure pattern, interictal and ictal scalp EEG, magnetic resonance imaging (MRI), neuropsychological testing, and results of the intracarotid amobarbital procedure (IAP) converged to indicate a localized abnormality. None of the patients in this series had mass lesions, vascular malformations, or cortical scars, but 18 of 22 had hippocampal atrophy on MRI and 20 had hippocampal sclerosis (HS) on pathologic examination. We believe it is possible, on the basis of the preoperative evaluation described, to identify a population of epileptic patients who will do very well postoperatively. Such patients do not require invasive EEG monitoring, and they represent ∼20% of the patients treated surgically in our epilepsy unit in the past several years.
We recently demonstrated statistically significant correlations between presurgical memory impairment and hippocampal volumetric cell densities (in CA3 and the hilar area only) for patients with idiopathic left temporal lobe epilepsy who exhibited marked hippocampal neuron loss. In the present research we determine whether the same relationship exists for patients with structural lesions, in whom hippocampal neuron loss was minimal. Rank-order correlations of verbal memory test results (ie, Long Term Retrieval score of the verbal Selective Reminding Test, Percent Retention index of the Logical Memory subtest of the Wechsler Memory Scale) and hippocampal volumetric cell densities (subfields CA1, CA2, CA3, the hilar area, and the granule layer of area dentata) were computed for 22 patients with structural lesions and medically refractory epilepsy of temporal lobe onset (11 left, 11 right). There were statistically significant correlations between Long Term Retrieval and the volumetric cell density of CA1 (r = 0.62, p < 0.05) and between percent retention and the volumetric cell density of CA2 (r = 0.60, p < 0.05) for patients with left hemisphere lesions. No other correlations were found for patients with left or right temporal lobe lesions.
We studied seizure localization and surgical pathology in 25 patients who developed intractable complex partial seizures following head trauma. All patients underwent an extensive presurgical evaluation that included MRI, neuropsychological evaluation, and surface EEG monitoring, and 21 had intracranial EEG monitoring. Seizures were successfully localized in nine patients; all nine underwent a surgical procedure and are seizure-free. Six of these patients had a mesial temporal lobe seizure focus, of whom five had a pathologic diagnosis of mesial temporal sclerosis. All five patients who developed mesial temporal sclerosis sustained their head injury at or before age 5 years. The three remaining patients whose seizures were successfully localized had neocortical foci and circumscribed radio-graphic abnormalities, which were presumed to be secondary to head trauma, and all had successful surgical resections of the epileptogenic focus. The remaining 16 patients sustained later trauma and did not have a focal MRI lesion, and their seizures were not adequately localized. We conclude that as a group, seizure foci secondary to head trauma are difficult to localize accurately, and this should deter surgical intervention. There was an association between early head injury (ie, at or before age 5 years) and mesial temporal sclerosis, and this association aided seizure localization and successful surgical intervention. Therefore, under the right circumstances, trauma can be a suitable historical element in the profile of patients in whom epilepsy surgery is successful.
We studied clinical seizure characteristics, seizure localization, and pathology in 38 patients who developed medically intractable partial seizures following meningitis (n = 16) or encephalitis (n = 22) and were evaluated for epilepsy surgery. Whereas meningitis in this group was commonly associated with mesial temporal sclerosis (MTS), most encephalitis patients had neocortical foci. The age of onset of the encephalitic illness was important in predicting mesial temporal or neocortical foci in that group: encephalitis before, but not after, age 4 years was associated with MTS. Since almost all meningitis occurred before age 4 years, these data support the hypothesis that the medial temporal lobe is particularly susceptible to early insults, establishing the initial pathologic entity of MTS and the subsequent cascade of partial seizures. Later-onset encephalitis produced extrahippocampal neocortical seizure foci, was rarely associated with MRI abnormality, and was difficult to localize precisely. In contrast, meningitis was commonly associated with MTS, aiding seizure localization and successful surgical intervention when seizures were medically uncontrolled.
This study evaluated the memory and intellectual function of 32 adults following minimal brain injury. All patients had a Glasgow Coma Scale score of 15 upon evaluation in the Emergency Room, negative findings on radiographic examination, and negative history of prior neurologic disease or injury. Seventeen of these had experienced a loss of consciousness. Patients suffering a loss of consciousness postinjury obtained significantly lower mean verbal intelligence quotients than those obtained by patients who remained conscious following their accidents. Both groups exhibited memory impairments. This could indicate that loss of consciousness predicts intellectual impairment, but not degree of memory dysfunction. An alternative interpretation of these data is that patients referred for examination after a head injury that did not involve a loss of consciousness included a disproportionate number of patients from upper socioeconomic levels who have greater access to medical delivery systems or greater sophistication regarding cognitive function.
Azathioprine has the longest continuing history of clinical use in the treatment of multiple sclerosis (MS) of any immunosuppressive therapy besides corticosteroids. To date, 19 clinical trials of azathioprine in MS have been reported, and another eight are under way. A review of the reported trials indicates little evidence for a therapeutic effect in MS. This and the lack of evidence for a specific immune alteration in the pathogenesis of MS are relative contraindications for the use of high risk immunosuppressive therapies in this disease. A further caveat is raised by a recent report suggesting that azathioprine may have contributed to an increased incidence of carcinomas in MS patients treated with this drug. In view of these considerations, perhaps the best position to take at the present time is to encourage investigators already engaged in controlled clinical trials of azathioprine to complete their work, so that this data can be considered before new studies of azathioprine in MS are undertaken.
Surgical manipulation in the region of the carotid sinus resulted in diffuse electroencephalographic slowing in two patients, despite the absence of bradycardia or hypotension. Direct observation confirmed the absence of carotid compression. The effect was abolished by infiltration of lidocaine hydrochloride into the carotid sinus area. Carotid clamping in one patient failed to produce similar electroencephalographic changes. We believe that this is the first observation of an influence of carotid sinus stimulation on human cerebral activity not attributable to reflex cardiovascular changes or complicated by the possibility of carotid compression.
Ictal sexual automatisms such as masturbatory activity, pelvic thrusting, or similar automatisms for which the patient is amnesic have been attributed to temporal lobe disease. Of 61 patients with medically refractory complex partial seizures, 14 had frontal lobe seizure foci. Four of these patients manifested sexual automatisms in some or all of their seizures. Frontal lobe seizure origin was documented by depth EEG in three patients. In the fourth, a calcified lesion was demonstrated radiologically. In three patients, frontal lobectomy revealed abnormal frontal lobe pathology and was followed by 75 to 100% reduction in seizure frequency. Sexual automatisms did not occur in patients with seizures originating in any area other than the frontal lobe.
Medication withdrawal is used in selected instances to precipitate seizures during evaluation of epileptic patients. Whether such medication manipulation can alter electrical seizure onset or clinical seizure type is not known. Information regarding the effects of anticonvulsant withdrawal on depth EEG onset and clinical manifestations of seizures was reviewed in 25 patients with partial complex seizures in whom intracranial electrodes were implanted. For the purposes of this study, the withdrawal period was defined as the time after abrupt cessation of medication between one and five half-lives of the drug and the base-line state as all other times. Ten patients were withdrawn from carbamazepine, 6 from phenobarbital, 2 from phenytoin, and 3 from primidone. Overall effects of anticonvulsant withdrawal in 18 patients and 21 instances of withdrawal with a total of 89 withdrawal and 71 base-line seizures were notable. Focal electrical onset and typical clinical seizure type during withdrawal were entirely consistent with electrical and/or clinical characteristics of seizures occurring during the base-line state in 13 instances. "New" clinical and/or electrical seizure types occurred during withdrawal only in a number of patients in whom bilateral or multifocal seizure onset was confirmed electrographically outside of the withdrawal period. In only 1 patient did withdrawal produce atypical clinical and electrical seizures when the base-line state showed a clinically typical seizure of clear-cut localized onset. After surgery this patient was shown to have unequivocal multifocal seizure onset. Thus, for purposes of localizing single epileptic foci, information obtained during the anticonvulsant withdrawal period provided no misleading information in this group of patients, while condensing the time needed for evaluation.