Relevance of residual histologic and electrocorticographic abnormalities for surgical outcome in frontal lobe epilepsy.

PURPOSE: To estimate the significance of residual electrocorticographic and neuropathologic abnormalities on seizure control after surgery for frontal lobe epilepsy with the purpose of determining their relevance in deciding the extent of the surgical procedure. METHODS: The presence of epileptiform discharges in intraoperative electrocorticograms (ECoGs) and the nature and extent of neuropathologic abnormalities were reviewed for 35 patients who underwent frontal lobe resections for the treatment of epilepsy at our institution. The relations between surgical outcome and presence of the following features were studied: (a) presence of abnormal tissue at the limits of the resection; (b) presence of sporadic spikes and seizure patterns in the preresection ECoG; (c) their abolition in the postresection ECoG; and (d) the topography of residual discharges with respect to the margins of the resection. RESULTS: On neuropathologic examination, 18 patients showed focal cortical dysplasia (CD), and 17 showed other abnormalities (non-CD). Ten CD patients and 11 non-CD patients experienced a favourable outcome. Seizure patterns were significantly more common in patients with focal cortical dysplasia than in those without, with a sensitivity of 94% and a specificity of 75%. Abolition of seizure patterns was associated with a favourable surgical outcome (p = 0.031). Abolition of sporadic spikes or their presence in the postresection ECoG did not influence outcome. There was no clear relation between outcome and location of residual sporadic discharges. Seizure patterns persisted in the postresection ECoG in three CD patients, were located at the margins of the resection in all three, and these patients had a poor outcome. Incomplete removal of abnormal tissue was not associated with a poorer outcome in either patient group or in the complete sample. CONCLUSIONS: Seizure patterns were significantly more common in patients with cortical dysplasia, and their abolition on postresection ECoG recordings was associated with a favourable surgical outcome. Persistence of sporadic ECoG spikes and incomplete removal of histologic abnormalities did not affect outcome significantly.

Histological heterogeneity of dysembryoplastic neuroepithelial tumour: identification and differential diagnosis in a series of 74 cases.

AIMS: In a retrospective study of resected specimens from 416 patients being treated for long-standing epilepsy, 74 cases of dysembryoplastic neuroepithelial tumour (DNT) were encountered that were all characteristically composed of small round oligodendroglia-like cells (OLC), astrocytes and mature neurones in varying proportions. The architectural patterns, histological, immunohistochemical and ultrastructural features and results of cell proliferation studies and postoperative follow-up are described to facilitate the identification of DNT and to differentiate it from other intrinsic neoplasms that commonly present with seizures. METHODS AND RESULTS: The tumours presented with early onset of seizures, at a median age of 7 years, without the signs of raised intracranial pressure. A majority of the lesions were located in the temporal lobe (n = 59), with fewer cases in the frontal (n = 8), parietal (n = 6) and occipital lobes (n = 1), and ranged in size from 10 to 70 mm; 33 were cystic. Histologically three types could be distinguished, multinodular, solitary nodular and diffuse. The first type (37.8%) had the features of a typical DNT with multinodular architecture and mixed cellular composition. The second type (33.8%) consisted of a solitary nodule, while the third (28.4%) was a diffuse tumour, both composed of a similar mixture of cells as the multinodular DNT. The lesions were seen in the neocortex and white matter and tumours in the temporal lobe often involved the amygdala and hippocampus. The presence of myxoid matrix, microcystic change, calcification and leptomeningeal involvement were common. Dysplastic neurones at the periphery of the tumour and abnormalities in cortical lamination in the adjacent neocortex were found in about one-third of the resections. Rare mitotic figures were encountered in eight of the tumours and necrosis was found in two. Immunocytochemistry for glial fibrillary acidic protein (GFAP) and neuronal markers neuron-specific enolase, synaptophysin and neurofilament (RT 97) assists in establishing the diagnosis, highlighting the astrocytic and neuronal components, and the OLC, by the absence of expression of GFAP. Electron microscopy showed that in some cases OLC show neuronal differentiation. Although the proliferating cell nuclear antigen labelling index varied between 0 and 45.5%, 20 of the 51 tumours stained failed to express the antigen, in keeping with the indolent nature of this neoplasm. The response to surgery was excellent; none of the tumours have recurred, and the control of seizures remained good. CONCLUSIONS: Despite some histological heterogeneity, the clinical and pathological features and indolent biological behaviour indicate that these tumours constitute a single distinct entity. The spectrum of morphological appearances of DNT is broader than has been previously reported, the recognition of which is needed to avoid unnecessary neoadjuvant therapy.

A clinicopathological study of autism.

A neuropathological study of autism was established and brain tissue examined from six mentally handicapped subjects with autism. Clinical and educational records were obtained and standardized diagnostic interviews conducted with the parents of cases not seen before death. Four of the six brains were megalencephalic, and areas of cortical abnormality were identified in four cases. There were also developmental abnormalities of the brainstem, particularly of the inferior olives. Purkinje cell number was reduced in all the adult cases, and this reduction was sometimes accompanied by gliosis. The findings do not support previous claims of localized neurodevelopmental abnormalities. They do point to the likely involvement of the cerebral cortex in autism.

Autosomal-dominant dentatorubropallidoluysian atrophy in the United Kingdom.

Dentatorubropallidoluysian atrophy (DRPLA) has been described chiefly in Japan and appears to be rare in Europe. It is of autosomal dominant inheritance. We report the first British family with DRPLA, which contains four affected individuals in two generations. The diagnosis was made at autopsy in one case. The age of onset of symptoms ranged from 15 to 38 years, and clinical features included ataxia, dementia, chorea, and dystonia; three patients had generalized seizures. The three living patients resemble those with early Huntington's disease clinically. Three main phenotypes of DRPLA have been proposed: an ataxo-choreoathetoid type, a pseudo-Huntington type, and a myoclonic epilepsy type. The variation in clinical presentation in our family demonstrates the difficulty in applying such classifications to this and other dominantly inherited disorders with phenotypic variation. DRPLA is likely to be confused with Huntington's disease in European families.

Electrocorticography and stimulation.

Although acute electrocorticography (ECoG) is routinely used during epilepsy surgery there is little agreement as to its value nor criteria for its interpretation. Specific issues are reviewed on the basis of the literature and personal studies: does failure to resect the entire irritative zone prejudice seizure control, and are residual discharges predictive of failure; does activation of the ECoG by intravenous barbiturates provide information of clinical value; does intraoperative electrical stimulation help to improve localisation or avoid postoperative deficits; is the ECoG of value for monitoring functional procedures; can the value of ECoG be increased by new interpretive approaches? It is suggested that resection of the entire area of interictal discharge is not essential for satisfactory surgical outcome, but a distinction may need to be made between those discharging regions that function as pacemakers and those in which ECoG spikes appear secondarily. There is also evidence that, apart from any consideration of determining the area resected, the topography of epileptiform discharge may be predictive of pathology and surgical outcome. It is concluded that more detailed topographic and quantitative analysis of the ECoG is required before its value in planning surgery can be determined or objective interpretive criteria established.

Surgical treatment of epilepsy due to cortical dysplasia: clinical and EEG findings.

Seventeen patients with cortical dysplasia who had surgical resection for medically intractable partial epilepsy were studied. Compared with two groups of surgically treated patients with intractable epilepsy due to tumour (n = 20) and mesial temporal sclerosis (n = 40), patients with cortical dysplasia showed significantly more frequent extratemporal lesions, more frequent non-epileptiform EEG abnormalities and less favourable surgical outcome for seizure control. Patients with cortical dysplasia were younger at onset of seizures and had a lower detection rate of CT abnormalities compared with the tumour group, and lower IQ compared with the mesial temporal sclerosis group. MRI was abnormal in five of seven patients. Six patients became seizure-free or almost seizure-free but eight did not experience relief of seizures. Surgical outcome related to the extent of pathology but not to the histological abnormality. Lesions outside the temporal and frontal lobes were correlated with poor surgical outcome, as were generalised interictal EEG abnormalities, which may reflect extensive or multiple lesions. Ictal intracranial recordings were not useful for presurgical evaluation of cortical dysplasia.

Late fetal pontine destruction.

A child with an absent pons is described who died 8 weeks after birth. At postmortem examination, the defect was consistent with a vascular event in the last trimester.

Cerebral aspergilloma in a child with autosomal recessive chronic granulomatous disease.

A 2 year old girl presented with epilepsy 16 months after being diagnosed as having autosomal recessive chronic granulomatous disease. Computed tomography showed a cerebral mass which was surgically removed and proved histologically to be an aspergilloma. This case illustrates the application of molecular diagnostic techniques to the diagnosis of chronic granulomatous disease. The occurrence of, and unusual reaction to, cerebral aspergillus infection indicates the need to consider this possibility in the differential diagnosis of mass lesions in chronic granulomatous disease. Furthermore, it is clear that autosomal recessive chronic granulomatous disease cannot be considered to be a clinically mild form that is exempt from major neurological complications.

Control of temporal lobe epilepsy following en bloc resection of low-grade tumors.

Thirty-one patients with a mean age of 18.9 years (range 3 to 53 years) who underwent temporal lobe surgery for tumor-related epilepsy over a 14-year period are presented. All had suffered chronic drug-resistant temporal lobe seizures (mean age at onset 6.9 years, range 0 to 30 years; mean duration of condition 11.9 years, range 3 to 39 years). Preoperative interictal scalp electroencephalography tracings indicated unilateral localized epileptic foci in 90% of patients, and computerized tomography scans showed abnormalities within the temporal lobe in 87%. All patients underwent en bloc temporal lobectomy. No patient received adjuvant radiotherapy or chemotherapy. Review of the histological material showed dysembryoplastic neuroepithelial tumor in 27 (87%) of the specimens and microscopic evidence of incomplete removal of tumor in 22 (71%). At long-term follow-up evaluation (mean duration 5.8 years, range 1 to 14 years), 81% of patients were completely free of seizures (Engel grade I) and 10% were almost seizure free (Engel grade II) with no deaths reported in either early or late follow-up review. Only one patient in the series failed to benefit from the surgery. Four patients suffered permanent neurological deficit causing a mild disability. Psychological assessment showed no significant fall in verbal or performance intelligent quotient for the group, but a mild memory impairment was evident in 32%. Behavioral and social aspects improved in nearly all (94%) cases. Relief of seizures could not be predicted by intraoperative electrocorticography, and outcome was independent of the completeness of tumor resection. Postoperative electroencephalographic findings identified epileptiform potentials in 65% of patients, which were associated with a worse seizure-control outcome grade.

Prion protein immunocytochemistry helps to establish the true incidence of prion diseases.

Creutzfeldt-Jakob disease (CJD) and Gerstmann-Strüssler-Scheinker disease (GSSD) are transmissible spongiform encephalopathies or prion diseases affecting man. It has been reported that prion diseases may occur without the histological hallmarks of spongiform encephalopathies: vacuolation of the cerebral grey matter, neuronal loss and astrocytosis. These cases without characteristic neuropathology may go undiagnosed and consequently the true incidence of transmissible dementias is likely to have been under-estimated. Immunocytochemistry using antibodies to prion protein gives positive staining of these cases, albeit the pattern of immunostaining differs from that seen in typical forms. Accumulation of prion protein is a molecular hallmark of prion diseases, and thus a reproducible, speedy and cost-efficient immunocytochemical screening of unusual dementias may help to establish the true incidence of prion diseases.

Beta A4 deposition in the temporal cortex of adults with Down's syndrome.

The deposition of beta A4 has been quantified in the temporal cortex of 9 adults (4 male, 5 female) with Down's syndrome (DS), mean age (+/- SD) 54.7 +/- 8.8 years (range 41-67 years) at the time of death. Immunostaining with antibodies, raised to different portions of the beta A4 protein, showed a greater number of deposits than were seen with traditional silver impregnation or amyloid stains. Antibody to beta A4(1-10) identified fewer plaques than the antibody to beta A4(12-28), the mean ratio of beta A4(1-10)/beta A4(12-28) plaques being 0.30 +/- 0.10 (mean +/- SD). Morphologically, 'diffuse' and 'neuritic' deposits could be distinguished but there was no significant difference in the beta A4(1-10)/beta A4(12-28) ratio according to plaque morphology, nor did the ratio change with age. Quantitatively, the beta A4(12-28) load in the temporal cortex of DS patients was high, occupying some 14% of the field area, and it was not related to the age of the subject over the range studied. Similarly, the total beta A4(12-28) plaque count was high and not age-related. The proportion of morphological plaque types visualised by the Glees and Marsland silver impregnation and by beta A4(12-28) immunostaining were compared. In both techniques 'diffuse' plaques (D) were predominant in the younger subjects and the proportion of 'neuritic' plaques (N) increased with age. The relative proportions of cored plaques (Cp) and plaque cores (C) did not change significantly with age.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuropathology of biotinidase deficiency.

A patient with biotinidase deficiency and a progressive neurological disorder died just before the biochemical diagnosis was established. Post-mortem examination of the brain and spinal cord revealed necrotising lesions similar to those in Leigh's disease and Wernicke's encephalopathy. Unlike these two conditions, the regions affected included the hippocampus and parahippocampal cortex. In addition there was severe focal oedema in deep cerebral grey matter, the brain stem, and the spinal cord. These lesions appear to result from a number of severe metabolic disturbances, perhaps linked to an underlying disordered pyruvate metabolism. The nature of the pathology explains why a neurological deficit may persist despite treatment.

Rasmussen's encephalitis in surgery for epilepsy.

Nineteen patients with Rasmussen's encephalitis were studied, using light-microscopy, immunohistochemistry and in some cases electron-microscopy. Although there was inflammation, no causative agent was identified. 10 patients underwent hemispherectomy and with one exception did well, while local resection for seven produced little or no improvement. For two patients biopsy with subpial transection was beneficial, although a third had a poor response, necessitating subsequent hemispherectomy. Surgical treatment of these patients is justified by a beneficial outcome. Neuropathological study of the resected material is essential for diagnosis and management of this condition.

Predictive value of intraoperative electrocorticograms in resective epilepsy surgery.

The preresection and postresection intraoperative electrocorticograms of 76 consecutive patients undergoing resective surgery for intractable epilepsy were analyzed to see if location, configuration, and discharge rate of epileptiform activity correlated with type and location of pathology of the resected specimens and outcome in regard to seizure control. The location of the predominant spike focus did not correlate with either type of location of pathology or with seizure outcome from temporal lobe surgery (n = 58). The presence of spontaneous or activated spikes outside the resected area did not correlate with outcome from any surgery type. Positive spikes recorded from the amygdala and anterior hippocampus (n = 37) were not associated with type or location of pathology, but bursts of fast repetitive spikes on these needle recordings tended to associate with mesiotemporal pathology (p = less than 0.02) and with mesial temporal sclerosis (p = less than 0.04). A preresection spike discharge rate of 1 per 4 minutes or less was associated with a poor outcome in 5 of 6 patients (p = 0.03), whereas a rate of 18 or more per minute was associated with a good outcome in 15 of 18 patients (p less than 0.06). Persistence of 50% or more of the preresection epileptiform activity in the postresection electrocorticogram after temporal lobectomy correlated with poor outcome in 80% (p = less than 0.03), although the absolute amount of epileptiform activity remaining in the postresection electrocorticogram did not correlate with outcome. Further studies are needed to define the role of intraoperative electrocorticograms in resective epilepsy surgery.

Prion dementia without characteristic pathology.

Gerstmann-Sträussler syndrome (GSS) was diagnosed in a family with presenile dementia by prion protein gene analysis. Extensive histological examination of the brain of an affected individual from this family showed no characteristic features of GSS or Creutzfeldt-Jakob disease (CJD). Thus "spongiform encephalopathy" (GSS or CJD) cannot always be excluded on neuropathological grounds in an individual dying of a dementing condition, and the true prevalence of these diseases is likely to be underestimated. Screening by prion protein gene analysis will help to determine the full clinical and neuropathological phenotype in familial cases. This observation may be relevant to the assessment of possible transmission of bovine spongiform encephalopathy to man.

Neuropathologic correlates of leuko-araiosis.

We describe the pathologic findings in 17 persons with dementia, 12 of whom exhibited leuko-araiosis on computed tomographic scan. The presence of white matter pallor was confirmed on autopsy in 11 of these 12 cases, 9 with Alzheimer's disease and 2 with multi-infarct dementia. Two further patients, 1 with Alzheimer's disease and 1 with multi-infarct dementia, proved to have white matter changes on pathologic examination. White matter pallor coexisted with cerebral amyloid angiopathy in the brains of the patients with Alzheimer's disease. The presence of severe white matter pallor in patients with Alzheimer's disease correlated with early death, while the presence of cortical scars was associated with prolonged survival. Because early death in patients with Alzheimer's disease has been linked with severe pathologic and chemical changes, the presence of white matter pallor may be further evidence of a particularly severe process in patients with early onset of Alzheimer's disease.

Acute hippocampal recording and pathology at temporal lobe resection and amygdalo-hippocampectomy for epilepsy.

An electrocorticographic (ECoG) study is reported of patients undergoing surgery for epilepsy of temporal lobe origin. During 22 en bloc resections and six out of a total of 18 amygdalo-hippocampectomies, the activity of the hippocampus was also recorded by a multipolar strip electrode placed along its axis on the ventricular surface. Patients with mesial temporal pathology, chiefly mesial temporal sclerosis, made up the majority of those selected for amygdalo-hippocampectomy. They showed a characteristic ECoG pattern, with spikes localised to the mid part of the second and third convolutions and inferior aspect of the temporal lobe. Typically, this was associated with hippocampal discharges showing an anterior maximum. Pathology involving lateral temporal neocortex and non-specific findings were associated with more widespread temporal spikes and a maximum discharge amplitude over the mid and posterior parts of the hippocampus. It is suggested that intraoperative recording of the ECoG and hippocampal activity may provide a guide to the choice between en bloc resection and amygdalo-hippocampectomy.

Cortical Lewy body dementia: clinical features and classification.

Seven patients, aged 65-72 years, are described with dementia and cortical Lewy bodies. In one patient a Parkinsonian syndrome was followed by dementia and motor neuron disease. In the remaining six patients dementia was accompanied by dysphasia, dyspraxia and agnosia. One developed a Parkinsonian syndrome before the dementia, in three cases a Parkinsonian syndrome occurred later, and in two cases not at all. All patients showed Lewy bodies and cell loss in the substantia nigra, locus coeruleus and dorsal vagal nucleus, as in Parkinson's disease. The severity of cell loss in the nucleus basalis varied from mild to severe. Lewy bodies were also present in the parahippocampus and cerebral cortex, but Alzheimer-type pathology was mild or absent, and insufficient for a diagnosis of Alzheimer's disease. Patients with moderate or severe dementia, some with temporal or parietal features, may have cortical Lewy body disease, Alzheimer's disease, or a combination of the two. Cortical Lewy body disease may be associated with dementia in Parkinson's disease more often than realised, but is not necessarily associated with extensive Alzheimer pathology.