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Temporal lobe epilepsy and neuropathology. Histological findings in resected temporal lobes correlated to surgical results and clinical aspects.

Neuropathological findings were studied in 74 patients with drug-resistant temporal lobe epilepsy who underwent unilateral temporal lobe resection in 1960-1969 in Denmark. In 60 per cent of the patients a well-defined neuropathological abnormality was revealed (i.e. 13 cases of focal lesions, including four small tumours, 21 cases of gliosis, and 10 cases of perivascular infiltration), in 23 per cent the findings were either questionably abnormal or without structural abnormality, while in the last 18 per cent sequelae of a previous operation dominated the histology. The general trend was for the postoperative clinical outcome to be better, the more specific and circumscribed the histological abnormality. There was no correlation between the neuropathological findings and the preoperative types of seizures. Postoperative recurrence of seizures was more often observed in patients with gliosis than in those with other histological diagnoses. A positive correlation existed between a history of cerebral infection and the presence of perivascular lymphocytic and histiocytic infiltration, and gliosis was a frequent finding in patients with epilepsy of unknown aetiology. No other significant correlation was found between the neuropathological abnormalities and the clinical, hereditary, aetiological, and social aspects.

Adolescent

Temporal lobe epilepsy. Follow-up investigation of 74 temporal lobe resected patients.

This survey covers 74 patients with temporal lobe epilepsy, resistant to medication, who underwent unilateral temporal lobectomy during the years 1960-1969 at Rigshospitalet, Copenhagen. Preoperatively all patients were socially incapacitated. In all patients a unilateral or predominantly unilateral temporal EEG focus was found. No tumour or gross vascular malformation had been recognized before or during operation. At follow-up 45 patients were free from seizures. A further 15 had obtained a reduction in their seizure frequencies by at least 75%, while the remaining 10 survivors, only obtained a slight improvement or remained unchanged. There were four deaths. The operation also favourably influenced the psychiatric status, which was found closely related to relief from seizures. Prognostically favourable factors were: i) preoperative presence of a single type of seizure, ii) duration of epilepsy of less than four years, iii) operation in or before early adulthood, iv) an anterior temporal or sphenoidal electrode focus, or both, on the EEG. The prognostically unfavourable factors regarding complete relief from seizures were: i) preoperative presence of grand mal, ii) age at onset of epilepsy or of the first grand mal seizure between 5 and 19 years of age, iii) preoperative duration of epilepsy of over ten years and of grand mal of over one year. Prognostically unfavourable factors regarding psychiatric normalization were: i) preoperative presence of psychosis, ii) ictal-affective attacks or automatisms of a complex nature, iii) impairment of intellectual functions. The eventual neuropathological conclusion was that the more specific and circumscribed the histological abnormality the better the final outcome. The social rehabilitation was found to be significantly improved by operation at an early age.

Adolescent

Neuropathological changes in resected temporal lobe of patients with cryptogenic epilepsy.

The study was performed on cerebral tissue resected during temporal lobectomy in 16 patients whose long-standing cryptogenic epilepsy did not submit to anticonvulsive drugs. Cases presenting definite etiological factors such as CNS trauma, infection or neoplasm were excluded. Neuropathological investigations disclosed microangiomas and focal vascular malformations in the meninges and tissue in 7 patients. Neuronal heterotopias in the white matter and of the white matter in the cortex were observed in 3 cases. Main cortical changes were: neuronal loss, chronic neuronal degeneration, perineuronal satellitosis, and GFAP-positive submeningeal gliosis, especially at the bottom of sulci, perivascular gliosis and laminar or diffuse gliosis. The changes in the hippocampus were most enhanced in the end-plate and in the sector H3 of the pyramidal layer. Astrocytic gliosis in the white matter presented distinct GFAP and S-100 immunostaining; the latter involved in some cases a wider area than the GFAP reaction. The above named changes are analysed with regard to the presumed epileptogenic factors and to the postepileptic damage.

Adolescent

Temporal lobe epilepsy and neuro-ophthalmology. Ophthalmological findings in 74 temporal lobe resected patients.

A survey is presented of the ophthalmological findings in 74 patients with drug-resistant temporal lobe epilepsy, who underwent unilateral anterior temporal lobectomy 1960-1969 at Rigshospitalet, Copenhagen. At follow-up, 1970-1971, one to ten years following the operation, 81% of the patients had no or only few seizures. Preoperatively 11% of the patients suffered from strabismus as compared to an expected frequency of 5%, but this trend just falls short of statistical significance. The visual acuity remained unchanged in all patients following the operation. Preoperatively a visual field defect was observed in 2 patients. At follow-up 51 patients had homonymous hemianopias, in 38 of them this was limited to the upper quadrants, and in 13 patients also included the lower quandrants, but was characterized as a total homonymous hemianopia in only 6 patients. The presence and extent of the visual field defects were correlated to surgical results, age at onset of epilepsy, age at operation, preoperative duration of epilepsy, presence of grand mal, preoperative complications, and neuropathological findings, but without observing any statistically significant conclusions. On the other hand, the extent of the postoperative visual field defect was significantly influenced by the side of the operation, with more and larger defects following right-sided lobectomies. In the 51 patients with postoperative hemianopias, this defect was either unobserved by the patient or regarded as a considerably less important handicap than the frequent and socially invalidating preoperative seizures...

Adolescent

Kinetic properties of hexokinase in resected temporal lobes of patients with drug-resistant epilepsy.

Properties of the cerebral glycolytic enzyme, hexokinase, were studied in biopsy samples of human temporal lobe, obtained during lobectomy for drug-resistant epilepsy and compared "blind" with contol biopsy samples of human cerebral cortex. No significant changes in the total activity or subcellular distribution of the enzyme were observed but the Km value for glucose was altered. The 17 control samples gave a normal mean value for Km (glucose) of 0.05 mM and the 14 epileptic samples gave a significantly higher mean value of 0.09 mM. The drugs used in previous treatment of the epilepsies were "scored" with respect to type and dose; analysis of these in relation to the kinetic results eliminated the possibility that the increase in Km value was an artifact due to the drugs. The observed change in enzyme kinetic properties is discussed in terms of potential interactions of small molecules with the isoenzymes of cerebral hexokinase.

Age Factors

Factors influencing the occurrence of schizophrenia-like psychosis in patients with temporal lobe epilepsy.

From a series of 255 patients who had undergone temporal lobectomy for the relief of intractable psychomotor epilepsy, all 47 patients with 'alien tissue' (small tumours, hamartomas, focal dysplasia) in the resected temporal lobe were contrasted with a group of 41 patients who showed mesial temporal sclerosis in their resected lobe. Five per cent of the mesial temporal sclerosis group and 23% of the alien tissue group were psychotic. A marked interaction occurred between psychosis and 'left handedness'. In the alien tissue group, females, especially left-handed females, were the most likely to have developed a schizophrenia-like psychosis.

Age Factors

[3-year experiences with surgical treatment of epilepsy at the Hvidovre hospital].

The results of a retrospective survey of 48 patients submitted to neurosurgery for medically intractable epilepsy are presented. Twenty-eight patients were treated with selective amygdalohippocampectomy, one with temporal lobe resection, 12 with anterior callosotomy and seven with a total callosotomy. Of the amygdalohippocampectomized patients and the one with temporal lobe resection (n = 29), 52% were seizure free, 17% experienced rare seizures, 7% had a worthwhile improvement while 24% observed no worthwhile improvement (follow-up time 6 to 36 months). Of the callosotomized patients, 11% were free from generalized seizures, 69% had a significant seizure reduction and 18% experienced no worthwhile improvement. The observed neurological complications were: one patient had hemianopia, one had superior quadrant anopia, four developed unilateral anosmia and one complete anosmia. The callosotomized patients, with two exceptions, were all mentally and physically handicapped. In the callosotomy group, two patients died, one from a intracerebral hematoma three months after the operation and another patient seven months postoperatively from unknown causes.

Adult

Mental aspects of temporal lobe epilepsy. Follow-up of 74 patients after resection of a temporal lobe.

Psychiatric disorders were investigated in 74 patients with drug-resistant temporal lobe epilepsy (complex partial epilepsy). In all cases unilateral anterior temporal lobectomy had been performed during the period 1960-69. At follow-up in 1970-71, 45 patients were free from seizures, and in a further group of 15 patients seizure frequency had been substantially reduced. There were four postoperative deaths. Six patients were psychiatrically normal and had no history of any such disorder. Behavioural disturbances were observed in 55 patients. Before operation 11 patients displayed schizophrenia-like psychoses, and nine others became psychotic during follow-up. Fourteen patients attempted suicide on one or more occasions. Half the patients had diminished sexual drive. Improvement in psychiatric status was clearly correlated with relief from seizures and, in those cases with only a few or no seizures after operation, led directly to social rehabilitation. The presence or absence of a psychiatric disorder was not useful as a criterion for or against surgery.

Adolescent

Electrophysiological correlates of pathology and surgical results in temporal lobe epilepsy.

Routine pre-operative EEG studies as well as direct brain recording and stimulation carried out during operations were analysed for 59 patients subjected to a standard unilateral anterior temporal lobectomy for the treatment of epilepsy. All patients in the present series were 16 years old or older at the time of operation, which was invariably carried out under local scalp analgesia only. Electrophysiological findings was correlated with pathological changes noted in the resected temporal lobes, and with the effects of surgery upon seizure activity. Pre-operative EEG data correlated with each of four pathological categories when sphenoidal electrodes and intravenous barbiturate narcosis were emplyed. Thirty of 31 patients with mesial temporal sclerosis demonstrated medial temporal primary spike foci, frequently with independent contralateral and extratemporal secondary foci. In addition, one-third of these patients demonstrated unilateral focal decreased barbiturate-induced fast activity in the corresponding sphenoidal to ear channels. Twelve patients with other specific medial focal lesions (mostly hamartomas) also had medial temporal primary foci, often with independent contralateral secondaries but never with extratemporal foci. Two patients in this group also demonstrated focal decreased fast activity in the appropriate sphenoidal-ear channel. Both of these groups did very well post-operatively with respect to their epilepsy. Five patients with large temporal convexity cicatrices antedating seizures all demonstrated lateral temporal primary spike foci without independent secondary foci or focal decreased fast activity and did not do as well post-operatively as the first two groups. Eleven patients had only non-specific changes in the resected temporal lobe and in general did not benefit from surgery. Various combinations of primary and independent secondary spike foci were seen. Only this group demonstrated diffuse or bifrontal spikes during initial EEG recording, and basal mid-line spikes with intravenous thiopentone. Pecilar sharp notched spike were also very common in this group, but not unique to it. Focal decreases in barbiturate-induced fast activity were not noted.

Adolescent

Outcome following resective surgery for temporal lobe epilepsy: a prospective follow up study of 102 consecutive cases.

The long term outcome has been assessed in a consecutive series of 102 cases undergoing resective temporal lobe surgery because of medically intractable epilepsy. Patients were followed prospectively for a median of 61 months. Actuarial statistics were used to measure the temporal patterns of remission and stability of outcome over prolonged periods of observation. The probability of achieving one year remission was 57% by one year, 70% by two years, and 77% by seven years. Once a patient was in one year remission the probability of remaining seizure free was 90%. This rose to 94% after two consecutive years of being seizure free. The majority of patients who remit following surgery have done so by two years of follow up. Outcome at the end of the second post operative year is a good predictor of long term prognosis.

Adolescent

Polygenic burden and its association with baseline cognitive function and postoperative cognitive outcome in temporal lobe epilepsy.

OBJECTIVE: Demographic and disease factors are associated with cognitive deficits and postoperative cognitive declines in adults with pharmacoresistant temporal lobe epilepsy (TLE), but the role of genetic factors in cognition in TLE is not well understood. Polygenic scores (PGS) for neurological and neuropsychiatric disorders and IQ have been associated with cognition in patient and healthy populations. In this exploratory study, we examined the relationship between PGS for Alzheimer's disease (AD), depression, and IQ and cognitive outcomes in adults with TLE. METHODS: 202 adults with pharmacoresistant TLE had genotyping and completed neuropsychological evaluations as part of a presurgical work-up. A subset (n = 116) underwent temporal lobe resection and returned for postoperative cognitive testing. Logistic regression was used to determine if PGS for AD, depression, and IQ predicted baseline domain-specific cognitive function and cognitive phenotypes as well as postoperative language and memory decline. RESULTS: No significant findings survived correction for multiple comparisons. Prior to correction, higher PGS for AD and depression (i.e., increased genetic risk for the disorder), but lower PGS for IQ (i.e., decreased genetic likelihood of high IQ) appeared possibly associated with baseline cognitive impairment in TLE. In comparison, higher PGS for AD and IQ appeared as possible risk factors for cognitive decline following temporal lobectomy, while the possible relationship between PGS for depression and post-operative cognitive outcome was mixed. SIGNIFICANCE: We did not observe any relationships of large effect between PGS and cognitive function or postsurgical outcome; however, results highlight several promising trends in the data that warrant future investigation in larger samples better powered to detect small genetic effects.

Adult

Temporal and extended temporal resections for the treatment of intractable seizures in early childhood.

In our series of 33 children who underwent temporal and extended temporal lobe resections because of seizures, the average age at surgery was 7 years, 11 months. Sixteen cases (48%) were diagnosed as having tumors: low-grade astrocytoma (6), hamartoma (5), and ganglioglioma/neuroma (5). Other pathologic diagnoses included one or more cytoarchitectural abnormalities and/or reactive changes. Due to a more aggressive and early radiologic and electrophysiologic investigation of children with seizures, a resectable focus, e.g. neoplasm or structural abnormality, was found in a much younger age group of patients than previously reported. In children who had intractable seizures but normal radiologic studies, positron emission tomography was of great value in localizing the seizure focus. In a group of children with infantile spasms, seizures were controlled following the identification and resection of a focal lesion. Prompt detection and precise localization of lesions in the temporal lobe in the pediatric population may lead to surgical management and seizure control.

Adolescent

Presurgical electroencephalographic patterns and outcome from anterior temporal lobectomy.

We reviewed data from 48 patients after anterior temporal lobe resection for medically intractable epilepsy. All had ictal electro-encephalographic (EEG) evidence of unilateral temporal lobe onset. Depth electrodes were used in 19 patients. Successful surgical outcome correlated significantly with factors that suggested a temporal lobe focus, particularly in the interictal scalp EEG. The most successful outcome occurred in patients with well-localized unilateral interictal temporal spikes (100% improved). The group with well-localized bilateral temporal spikes also did well (76% improved). Patients with extratemporal spread of the interictal spike on scalp EEG, either unilaterally or bilaterally, did less well. Only one third improved, despite extensive extracranial and intracranial monitoring, when indicated. The interictal scalp EEG may be the only EEG necessary for the presurgical evaluation of selected patients with intractable temporal lobe epilepsy.

Adolescent

Ictal spikes: a marker of specific hippocampal cell loss.

Spontaneous seizures recorded from mesial temporal depth electrodes in the human are commonly manifested by one of two onset patterns: a high frequency discharge or a periodic spike discharge morphologically similar but clearly distinguished from ongoing interictal activity. We categorized medial temporal lobe seizure onset for the presence of periodic ictal spikes at a frequency of less than 2 Hz lasting for more than 5 sec to investigate the relationship of this ictal pattern to anatomical changes in the resected temporal lobe tissue. Fifty-one patients had hippocampal depth electrode recordings of spontaneous seizures, subsequent hippocampal resection, and quantitative cell counts of hippocampal subfields. Thirty-two of these patients had ictal spikes lasting at least 5 sec in more than 50% of their seizures. The presence of ictal spikes was significantly correlated with decreased cells in CA1 only (P = 0.015). The correlation of a common ictal pattern with focal cell loss in the hippocampus suggests that electrophysiological manifestations of seizures provide a clue to the underlying pathological substrate. Ictal spikes may be a cause or result of the cell loss. These observations should be correlated with independent investigations in humans and animal models that reflect the CA1 cell loss associated with temporal lobe epilepsy.

Electroencephalography

Psychomotor-psychic seizures treated with bilateral amygdalotomy and orbitotomy.

A 26-year-old woman developed seizures and psychiatric disorders after having been in coma with encephalitis for a protracted period at age 11. Seizures were psychomotor, minor motor, and major motor with auras of fear, panic, and olfaction. The patient hallucinated, had paranoid ideas, was depressed, and attempted suicide. Medical and psychiatric treatment with anticonvulsants and tranquilizers was ineffective. Depth and surface EEG recordings revealed bilateral discharge abnormality in temporal, frontal, and thalamic areas. Lesions were placed in the temporal and orbitofrontal area bilaterally for the psycho-motor-psychic seizures and in the left thalamus for the minor motor seizure. The seizures were relieved without the incapacitating complications that occur with standard lobotomy and temporal lobe resection. Improvement of the psychic component of the seizures is believed due to interrupting seizure discharging circuitry in the temporal and frontal areas. The term temporofrontal seizures is proposed for the anatomic designation of psychomotor-psychic seizures.

Adult

Magnetic resonance imaging-based volume studies in temporal lobe epilepsy: pathological correlations.

We performed a prospective study correlating magnetic resonance imaging volume measurements of the hippocampal formation with histopathology in 24 patients with intractable partial epilepsy who subsequently underwent an anterior temporal lobectomy for their seizure disorder. Patients with mass lesions verified pathologically were excluded from this study. In 71% of patients, quantitative hippocampal formation atrophy correctly lateralized the temporal lobe of seizure origin; in 29%, the volume study was indeterminant. The severity of the pathological alterations in the hippocampus correlated with the hippocampal formation volume determination. Mesial temporal sclerosis was identified in the surgically excised temporal lobe in 15 patients. The magnetic resonance imaging volume studies indicated hippocampal atrophy in the temporal lobe resected in 14 of the 15 patients. Magnetic resonance imaging-based volume measurements of the hippocampal formation increase the diagnostic yield of magnetic resonance imaging scanning in patients with intractable partial epilepsy related to mesial temporal sclerosis.

Adolescent