Kimberlee J. Sass

Verbal memory impairment correlates with hippocampal pyramidal cell density

Thirty-five patients with medically refractory epilepsy localized to the temporal lobe (18 left, 17 right) completed the verbal Selective Reminding Test before surgery. Verbal memory impairments existed before surgery regardless of the lateralization of the seizure focus, but patients with left temporal seizure foci were significantly more impaired. After surgical removal of the mesial temporal lobe structures, 2 blinded observers established volumetric cell densities for hippocampal subfields CA1, CA2, CA3, the hilar area, and the granule cell layer of the area dentata. Statistically significant correlations existed between presurgical memory impairment and cell counts (in CA3 and the hilar area, only) for patients with left temporal seizure foci. These findings support the hippocampal model of memory and complement prior research documenting the memory impairments present after surgical removal of the mesial temporal structures.

Corpus callosotomy for epilepsy.: I. Seizure effects

Twenty-two patients were analyzed 2 or more years after corpus callosum section (9 partial, 13 total). Forty-one percent had class 1 outcome (elimination of secondarily generalized and complex partial seizures), 32% had class 2 outcome (elimination of secondarily generalized seizures), and 27% had class 3 outcome (no appreciable change). Total section was twice as effective in abolishing secondarily generalized seizures as was partial section (77% versus 35%). Statistically significant associations were seen between focal CT lesions and class 1 outcome, and between IQ less than 45 and class 2 or 3 outcome.

Specificity in the correlation of verbal memory and hippocampal neuron loss : dissociation of memory language, and verbal intellectual ability

Fifty-nine patients with temporal-lobe epilepsy (28 left, 31 right) completed the Boston Naming Test (BNT), verbal subtests of the Wechsler Adult Intelligence Scale-Revised, and the Logical Memory Subtest of the Wechsler Memory Scale (WMS) before surgery. Performances by patients with left temporal seizure foci were significantly more impaired than those of patients with right seizure foci on the WMS Logical Memory subtest and the BNT. After surgical removal of the mesial temporal lobe structures, two blinded observers established volumetric cell densities for hippocampal subfields CA1, CA2, CA3, the hilar area, and the granule cell layer of area dentata. Statistically significant correlations existed only between percent retention scores and hippocampal neuron loss in CA3 and the hilar area for patients with left temporal seizure foci. None of the other dependent measures was significantly correlated with hippocampal neuron density in any subfield. These results support the hypothesis that certain verbal memory impairments are attributable to hippocampal damage specifically, and not to temporal lobe damage in general.

Successful epilepsy surgery without intracranial EEG recording : criteria for patient selection

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.

Wada memory disparities predict seizure laterality and postoperative seizure control

Summary: We examined the efficacy of a memory difference score (DS: right minus left hemisphere memory) during the Wada test (intracarotid amobarbital procedure, IAP) for predicting seizure laterality and postoperative seizure outcome in 70 left speech dominant patients from two epilepsy centers. DS ≥2, after addition of 1 point to the left hemisphere injection score to account for aphasia, were noted in 71. 4% of patients and correctly predicted surgery side for 98. 0% of these patients. The DS related significantly to seizure outcome at 1–year follow‐up (p < 0.002) and correctly predicted 80% of patients who were The Wada test, or intracarotid amobarbital procedure (IAP), is traditionally used to determine the laterality of language dominance and to assess the memory competence in the hemisphere contralateral to the proposed temporal lobectomy in an effort to avoid postoperative amnesia (1–6). Ipsilateral memory testing (adequacy of the hemisphere ipsilateral to anticipated resection) also is frequently examined. The validity of IAP memory testing as a measure of temporal lobe function is demonstrated by correlating IAP memory scores of the affected hemisphere with hippocampal cell counts (7,8) and with hippocampal volume assessed by magnetic resonance imaging (MRI) (9). The disparity between ipsilateral and contralateral memory scores is often predictive of seizure focus laterality (1 1–18). However, most studies have examined group means rather than the utility of the DS for predicting the seizure focus in specific patients. To date, only Loring et al. (9) have reported Presented in part at the Annual Meeting of the International Neuropsychological Society, Galveston, Texas, February 1993. seizure‐free. Patients whose DS did not correctly predict seizure laterality more frequently required invasive studies to establish seizure onset. The relationship of the DS to laterality did not differ significantly by class of IAP memory stimuli. When seizures originate from the temporal lobe, the IAP memory DS predicts seizure laterality by assessing the functional adequacy of the involved hemisphere and is predictive of seizure control.

Degree of Hippocampal Neuron Loss Determines Severity of Verbal Memory Decrease After Left Anteromesiotemporal Lobectomy

Summary: Fifty‐eight left speech dominant adults with medically refractory epilepsy originating from the temporal lobe (28 left, 30 right) were examined using the verbal Selective Reminding Test before and after anteromesiotemporal lobectomy. After neuron density in the excised hippocampal tissue was established, a median split procedure was performed to distinguish patients with severe neuron loss (13 left, 16 right) from those with only mild or moderate neuron loss (15 left, 14 right). The memory of patients with severe left hippocampal neuron loss did not decrease significantly postoperatively. Patients with mild or moderate left hippocampal neuron loss experienced significant verbal memory decrease postoperatively. The magnitude of the verbal memory decrease was not related to recurrence of seizures after operation. Patients undergoing right anteromesiotemporal lobectomy exhibited significant improvements in verbal memory, regardless of the condition of the excised hippocampal tissue. The degree of hippocampal neuron loss determines to a great extent the severity of the verbal memory decrease that follows dominant anteromesiotemporal lobectomy.

Corpus callosotomy for epilepsy. II. Neurologic and neuropsychological outcome.

Eighteen uncontrolled epileptic patients had neuropsychological evaluation before and after partial or total corpus callosotomy. In patients with early-onset seizures and signs of severe unilateral CNS dysfunction, callosotomy produced no deficits and several improvements. AH patients whose language-dominant hemisphere did not control their dominant hand had impairments in some aspect of speech and language function after callosotomy. In some patients, unilateral deterioration of motor function was observed, and was associated with mild to moderate dysfunction in the contralateral hemisphere (ie, memory impairment or preexisting hemiparesis). Postoperative deficits occurred with partial, as well as total, section.

Anterior, Total, and Two‐Stage Corpus Callosum Section: Differential and Incremental Seizure Responses

Summary: Published reports suggest that control of generalized seizures is improved by callosotomy but do not necessarily indicate that completion of failed anterior callosotomy is beneficial. We studied 42 patients after anterior callosotomy and 22 after total callosotomy, of whom 14 underwent a two‐stage procedure. Cure or marked diminution of seizures was most dramatic for atonic and tonic‐clonic seizures after anterior callosotomy (100 and 83%), and for tonic‐clonic and tonic seizures after total callosotomy (68 and 57%). For the 14 patients who failed to improve after anterior section and then underwent total section, incremental responses were noted for all seizure types, with cure or marked diminution of partial seizures in 2 of 14 patients, of tonic‐clonic seizures in 6 of 10, of tonic seizures in 2 of 4, of atonic seizures in 2 of 5, and of myoclonic seizures in 1 of 1. More than two seizure types, verbal IQ <80, and diffuse ictal EEG patterns were significantly more common in the anterior callosotomy failures. Total callosotomy can be of benefit when anterior callosotomy fails, especially for persistent tonic‐ clonic and tonic seizures, and will most often be necessary in patients with diffuse cerebral abnormalities.

Verbal memory impairment resulting from hippocampal neuron loss among epileptic patients with structural lesions

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 equals 0.62, p less than 0.05) and between percent retention and the volumetric cell density of CA2 (r equals 0.60, p less than 0.05) for patients with left hemisphere lesions. No other correlations were found for patients with left or right temporal lobe lesions. NEUROLOGY 1995;45: 2154-2158

Russell's adaptation of the Wechsler Memory Scale as an index of hippocampal pathology

Fifty-nine patients with temporal lobe epilepsy (28 left, 31 right) completed the Visual Reproduction Subtest of the Wechsler Memory Scale before surgery. Patients with right temporal seizure foci were significantly more impaired than those with left seizure foci in their performance on the Immediate Recall measure. Group differences were not found on the measures of Delayed Recall and Percent Retention. After surgical removal of the mesial temporal lobe structures, two blinded observers established volumetric cell densities for hippocampal subfields CA1, CA2, CA3, the hilar area, and the granule cell layer of the area dentata. No statistically significant correlations existed between Visual Reproduction Subtest scores and hippocampal neuronal density. These findings were discussed in combination with those of a prior study concerning the correlation of hippocampal neuron loss and impairment on the Logical Memory Subtest. The authors conclude that when testing patients with epilepsy, the Immediate Recall and Delayed Recall scores of the Logical Memory and Visual Reproduction Subtests should not be considered indices of hippocampal injury or disease. Logical Memory Percent Retention may be an index of left hippocampal injury or disease.