Premature mortality in refractory partial epilepsy: does surgical treatment make a difference?

BACKGROUND: Epilepsy carries an increased risk of premature death. For some people with intractable focal epilepsy, surgery offers hope for a seizure-free life. The authors aimed to see whether epilepsy surgery influenced mortality in people with intractable epilepsy. METHODS: The authors audited survival status in two cohorts (those who had surgery and those who had presurgical assessment but did not have surgery). RESULTS: There were 40 known deaths in the non-surgical group (3365 person years of follow-up) and 19 in the surgical group (3905 person-years of follow-up). Non-operated patients were 2.4 times (95% CI 1.4 to 4.2) as likely to die as those who had surgery. They were 4.5 times (95% CI 1.9 to 10.9) as likely to die a probable epilepsy-related death. In the surgical group, those with ongoing seizures 1 year after surgery were 4.0 (95% CI 1.2 to 13.7) times as likely to die as those who were seizure-free or who had only simple partial seizures. Time-dependent Cox analysis showed that the yearly outcome group did not significantly affect mortality (HR 1.3, 95% CI 0.9 to 1.8). CONCLUSION: Successful epilepsy surgery was associated with a reduced risk of premature mortality, compared with those with refractory focal epilepsy who did not have surgical treatment. To some extent, the reduced mortality is likely to be conferred by inducing freedom from seizures. It is not certain whether better survival is attributable only to surgery, as treatment decisions were not randomised, and there may be inherent differences between the groups.

Surveillance neuroimaging in childhood intracranial ependymoma: how effective, how often, and for how long?

OBJECT: The authors examined images obtained in 52 children with intracranial ependymomas to determine risk factors for tumor recurrence and to assess the impact of surveillance imaging on patient outcome. METHODS: Data obtained in all children with intracranial ependymomas were prospectively entered into a database from January 1987 to June 2000. The imaging and clinical details in all patients were reviewed. Fifty-two children with histologically proven intracranial ependymomas were treated at the authors' institution; recurrences developed in 28 (54%) of them, with a median time from surgery to first recurrence of 14.5 months (range 3-65 months). Of these tumor recurrences, 43% were asymptomatic and were noted on surveillance imaging. Seventeen children died, all of whom had recurrences. Incomplete excision of the primary tumor was significantly associated with reduced time to recurrence (p = 0.0144) and time to death (p = 0.0472). The age of the patient, location of the primary tumor, histological findings, and the presence or absence of spinal metastases on preoperative imaging were not significantly associated with outcome. The risk of death at any given time was 12-fold greater in patients in whom a recurrence was identified due to symptoms rather than on surveillance images (p = 0.016). CONCLUSIONS: Recurrent childhood ependymoma has a poor prognosis. The extent of the initial local tumor resection is the factor most closely associated with outcome. Surveillance imaging reveals a substantial number of asymptomatic recurrences, and survival appears to be improved in these patients compared with those identified by symptoms. The improvement in survival is thought to be greater than that expected just from earlier diagnosis.

Benign central neurocytoma.

BACKGROUND: "Central neurocytoma" is classically considered as an intraventricular benign tumor, largely based on data from small retrospective series. The authors present prospective data on 12 patients with tumors diagnosed as central neurocytoma, to highlight the diverse nature of this tumor and challenge the classic notion. METHODS: Between 1991 and 1997, 12 patients had tumors diagnosed prospectively as "central neurocytoma". Clinical, radiologic, and histologic data were collected, and Karnofsky performance score was evaluated for each patient. Proliferation marker studies were performed using Ki-67 labeling index. RESULTS: In two patients, the tumors were located in atypical locations, namely, the parietal lobe and the spine. Aggressive behavior characterized by clinical and radiologic evidence of tumor progression was noted in two additional patients. In both these cases, unusually high proliferation rates of 5.3% and 11.2% were noted. Total excision of the tumor, when possible, was the treatment of choice. Postoperative radiotherapy to the residual tumor may be of benefit in patients with clinically aggressive tumors, or those with high proliferation rates. CONCLUSIONS: Given the findings of this study, it is suggested that the traditional concept of central neurocytoma as a benign intraventricular tumor warrants reconsideration.

Intracranial neoplasms in the first year of life: results of a second cohort of patients from a single institution.

The objective of this study was to describe the presentation and outcome of children with intracranial tumours under 1 year of age, and to compare the results with a previous cohort from the same paediatric neurosurgical unit. It is a retrospective review of all children under 1 year of age presenting with intracranial tumours between 1982 and 1997, with follow-up data from a multidisciplinary paediatric neuro-oncology clinic. Seventy-five children were diagnosed during the period of study. Overall survival at 5 years was 56% (31 of 55 eligible children), half of whom are in mainstream education. Earlier diagnosis and a dramatic reduction in peri-operative mortality compared to our previous cohort account for the improvements in the results of treatment for these children whose care can only be properly managed in a specialized paediatric oncology centre.

Disproportion in the distribution of gray and white matter: neuropsychological correlates.

OBJECTIVE: To examine the relationship between measures of disproportion in the regional distribution of gray and white matter and preoperative neuropsychological function in temporal lobe epilepsy patients with proved hippocampal sclerosis (HS). BACKGROUND: Subtle cerebral structural disruption, not evident on routine inspection of high-resolution MRI, is associated with poor surgical outcome in patients with histologically proved HS. Preoperative global memory dysfunction is also associated with poor postoperative seizure control. The authors hypothesize that patients with HS and abnormal regional distributions of gray and white matter would show more diffuse neuropsychological deficits preoperatively than patients with isolated HS alone. METHODS: A total of 28 adults with lateralized temporal lobe epilepsy and hippocampal volume loss measured on MRI were assessed preoperatively on neuropsychological tests of general intellect and the learning and recall of both verbal and nonverbal material. Quantitative MRI analysis of the regional distribution of gray and white matter was performed. Chi-square analyses were used to examine the relation between the presence or absence of cerebral abnormalities and preoperative performance on the neuropsychological tests. RESULTS: A total of 15 of 28 patients had extrahippocampal abnormalities on quantitative MRI analysis. Thirteen patients had global memory impairment. Bilateral memory deficits were significantly associated with both the presence of cerebral abnormalities (p < 0.02) and poor postoperative seizure control (p < 0.05). CONCLUSIONS: Disproportion in the regional distribution of gray and white matter in patients with HS may form the structural basis of global memory disturbance in a distinct group of patients with temporal lobe epilepsy.

Presurgical evaluation of patients with epilepsy and normal MRI: role of scalp video-EEG telemetry.

When considering surgery for intractable partial seizures, even with high resolution MRI, some patients do not show structural abnormalities. The aim was to consider whether these patients were likely to proceed to surgical treatment after scalp video-EEG telemetry. All patients undergoing presurgical evaluation at the National Hospital for Neurology and Neurosurgery between 1995 and 1997 were reviewed and 40 were identified without definite MRI abnormalities. None of 40 disclosed a well localised epileptogenic zone concordant with other tests that would have allowed the patient to proceed directly to surgery. In five of the 40, evaluation led to a hypothesis that could be tested by intracranial studies; three proceeded to surgery. It is suggested that high quality MRI is performed first when surgical evaluation is undertaken and if negative the patient carefully counselled before proceeding with any investigations, as successful resective surgery is an unlikely outcome in such MRI negative cases.

The relationship between quantitative MRI and neuropsychological functioning in temporal lobe epilepsy.

PURPOSE: Quantitative MRI techniques provide an unparalleled opportunity to examine in vivo the relationship between the extent and laterality of hippocampal pathology and associated neuropsychological deficits. The purpose of this study was to examine the nature of the relationship between quantitative measures of hippocampal pathology and neuropsychological measures, using a multivariate approach. METHODS: We examined the relationship between two MRI measures of hippocampal structure; hippocampal volumes (HCvol) and T2 relaxation times (HCT2), and memory performance, in 80 presurgical temporal lobe epilepsy patients. RESULTS: As a group, patients with left hippocampal sclerosis (LHS) performed more poorly that those with right hippocampal sclerosis (RHS) on immediate and delayed prose recall. In the group as a whole, right hippocampal volume was significantly correlated with the delayed recall of a complex figure. None of the verbal memory test scores were significantly correlated with the right or left HCvol or HCT2 measures. However, stepwise multiple regression analyses indicated that up to a third of the variation in specific test scores could be explained by the quantitative MRI hippocampal measures in conjunction with chronological age, and age at onset of habitual epilepsy. Left hippocampal measures explained 24% of the variance in the story-recall tasks, while right hippocampal measures explained 18% of the variance in a design-learning task and 32% of the variance in a figure-recall task. CONCLUSIONS: Our results provide some support for the lateralised model of material specific memory deficits, but suggest that a number of demographic and epilepsy-related factors may interact with the extent and laterality of hippocampal pathology in shaping the nature of the associated neuropsychological deficit.

Hippocampal cell loss and gliosis: relationship to preoperative and postoperative memory function.

The authors examined the relationship between neuronal densities, glial cell densities, and the glial cell/neuron ratio in the CA1 and CA4 hippocampal subfields and preoperative and postoperative memory function in 47 patients who had undergone a temporal lobectomy (23 right, RTL; 24 left, LTL) for the relief of medically intractable epilepsy. The LTL group performed more poorly than the RTL group on a list learning and story recall task, preoperatively and postoperatively. Both the RTL and LTL groups performed more poorly on the story recall task postoperatively. In the LTL group, neuronal densities in the CA1 subfield were significantly correlated with the preoperative scores on the immediate (r = 0.53, p < 0.01) and delayed (r = 0.53, p < 0.01) recall of the story. There were no significant correlations in the LTL group between the CA1 and CA4 cell counts and Verbal IQ or scores on a measure of naming ability. None of the cell density measures in the CA1 and CA4 subfields were significantly correlated with the preoperative neuropsychological test scores in the RTL group. Postoperative decline in verbal recall was associated with the excision of a relatively intact left hippocampus, with high neuronal and low glial cell densities in the CA1 subfield. The excision of a relatively intact right hippocampus was also associated with a postoperative deterioration in verbal recall.

Postimaging brain distortion: magnitude, correlates, and impact on neuronavigation.

OBJECT: This prospective study was conducted to quantify brain shifts during open cranial surgery, to determine correlations between these shifts and image characteristics, and to assess the impact of postimaging brain distortion on neuronavigation. METHODS: During 48 operations, movements of the cortex on opening, the deep tumor margin, and the cortex at completion were measured relative to the preoperative image position with the aid of an image-guidance system. Bone surface offset was used to assess system accuracy and correct for registration errors. Preoperative images were examined for the presence of edema and to determine tumor volume, midline shift, and depth of the lesion below the skin surface. Results were analyzed for all cases together and separately for four tumor groups: 13 meningiomas, 18 gliomas, 11 nonglial intraaxial lesions, and six skull base lesions. For all 48 cases the mean shift of the cortex after dural opening was 4.6 mm, shift of the deep tumor margin was 5.1 mm, and shift of the cortex at completion was 6.7 mm. Each tumor group displayed unique patterns of shift, with significantly greater shift at depth in meningiomas than gliomas (p = 0.007) and significantly less shift in skull base cases than other groups (p = 0.003). Whereas the preoperative image characteristics correlating with shift of the cortex on opening were the presence of edema and depth of the tumor below skin surface, predictors of shift at depth were the presence of edema, the lesion volume, midline shift, and magnitude of shift of the cortex on opening. CONCLUSIONS: This study quantified intraoperative brain distortion, determined the different behavior of tumors in four pathological groups, and identified preoperative predictors of shift with which the reliability of neuronavigation may be estimated.

Central benzodiazepine receptor autoradiography in hippocampal sclerosis.

1. The gamma-aminobutyric acid (GABA)A/central benzodiazepine receptor (cBZR) complex is a major inhibitory receptor in the vertebrate CNS. Binding of [11C]-flumazenil to this complex in vivo is reduced in hippocampal sclerosis (HS). It has been uncertain whether reduced cBZR binding is entirely due to neuronal loss in HS. 2. The objective of this study was to characterize abnormalities of the cBZR in HS with a correlative autoradiographic and quantitative neuropathological study. 3. Saturation autoradiographic studies were performed with [3H]-flumazenil to investigate relationships between neuronal density and receptor availability (Bmax) and affinity (Kd) in HS. Hippocampal tissue was obtained at surgery from 8 patients with intractable temporal lobe epilepsy (TLE) due to HS and autopsies of 6 neurologically normal controls. Neuronal densities were obtained by means of a 3-D counting method. 4. Bmax values for [3H]-flumazenil binding in the subiculum, CA1, CA2, CA3, hilus and dentate gyrus were all found to be significantly reduced in HS compared with controls and significant increases in affinity were observed in the subiculum, hilus and dentate gyrus. In HS, cBZR density in the CA1 region was significantly reduced (P < 0.05) to a greater extent than could be attributable to neurone loss. In other regions, Bmax was reduced in parallel with neuronal density. 5. In HS, there is a loss of cBZR in CA1 over and above loss of neurones. This finding and increases in affinity for flumazenil in subiculum, hilus and dentate gyrus imply a functional abnormality of the GABAA/cBZR complex that may have a role in the pathophysiology of epileptogenicity in HS.

"Dural tail" adjacent to a giant posterior cerebral artery aneurysm: case report and review of the literature.

The "dural tail" sign on gadolinium (Gd-DTPA)-enhanced MRI has been described in association with meningiomas. Various series with histopathological correlation have shown that in some cases there is tumour invasion into the dura mater, but in the majority of cases it represents a hypervascular, non-neoplastic reaction. While this sign was originally thought to be specific for meningioma, subsequent case reports have described the presence of a dural tail in other intra- and extra-axial lesions. We present a patient with a giant aneurysm arising from the P2 segment of the right posterior cerebral artery, adjacent to the tentorium, with a prominent dural tail on Gd-DTPA-enhanced MRI. In this location, differentiation of an aneurysm from a meningioma was critical.

The long-term outlook for hydrocephalus in childhood. A ten-year cohort study of 155 patients.

Despite the fact that ventriculoperitoneal shunt insertion is the most commonly performed surgical operation in the pediatric neurosurgeon's repertoire, there is a surprising paucity of long-term outcome studies for these patients detailing either the complication rate over a predetermined time period or more importantly their intellectual outcome. The aims of this study, therefore, were to determine the 10-year outcome in a cohort of 155 children with shunted hydrocephalus, both in terms of the number and time sequence of shunt complications and also the long-term academic (schooling) outcome of these individuals. This was a cohort study of 155 hydrocephalic children who underwent first-time ventriculoperitoneal shunt insertion between the years 1978 and 1983, who were then followed up on an annual outpatient basis for a period of 10 years or until death. Their academic records and the surgical morbidity and mortality encountered over the 10-year study period were used as the main outcome measures. For those children surviving until schoolage, 59% were able to attend a normal school. The academic outlook for those children with hydrocephalus secondary to infection (postmeningitic) or intraventricular hemorrhage was less favorable with 52 and 60% requiring special schooling compared to those children with congenital hydrocephalus (29%; p = 0.036). 44% (68/155) of patients in this cohort did not require a shunt revision. The commonest reasons for shunt revision were blockage (49%) and infection (19%) which predominantly occurred within the first year of their original shunt procedure. Overall the infection rate was 12% (44/380 procedures). Furthermore an increased incidence of shunt infection was noted in those under 6 months old (p = 0.040). There was an 11 % mortality during the 10-year follow-up period for those with nontumor-related hydrocephalus.

Correlation of widespread preoperative magnetic resonance imaging changes with unsuccessful surgery for hippocampal sclerosis.

Despite meticulous preoperative assessment, about 30% of patients with refractory partial epilepsy due to hippocampal sclerosis fail to become seizure free after appropriate temporal lobe surgery. Perioperative complications, hippocampal remnants, and bitemporal disease do not account for all failures; extrahippocampal epileptogenic tissue must persist in some patients. Such dual pathology is detected on routine visual inspection of magnetic resonance images in about 15% of patients with hippocampal sclerosis, but most such patients are excluded from surgery. We postulated that some patients have occult extrahippocampal cerebral structural abnormalities (i.e., subtle dual pathology) and that the presence of these abnormalities would be associated with a poor surgical outcome. Quantitative postprocessing of preoperative magnetic resonance images from 27 patients subsequently proved to have hippocampal sclerosis demonstrated extrahippocampal structural abnormalities in 14, 10 of whom did not become seizure free, while 11 of 13 patients without such changes did become seizure free (chi2, p < 0.005). Such structural information may supplement clinical decision making in some patients being evaluated for epilepsy surgery and help to explain the biological basis of poor outcome from such surgery.

Surgical treatment of severe autistic regression in childhood epilepsy.

We report 2 children with partial epilepsy who manifested social and language regression and partial recovery after surgical treatment. One child had seizures since the first 2 weeks of life, caused by a right temporal dysembryoplastic neuroepithelial tumor and regression in the latter part of the first year; seizures were relieved and some functions were recovered after temporal lobe resection at 12 months of age. The second child developed epilepsy at 3 years 3 months, and between 5 years 9 months and 6 years 1 month he became aphasic (Landau-Kleffner syndrome) and lost social functioning, manifesting a very severe behavior disorder. He exhibited a significant improvement in communication, social functioning, and behavior after left multiple subpial transections. Both children manifested evidence of subclinical seizure activity in both temporal lobes. Their clinical picture was one of combined language and autistic regression, and the autistic features demonstrated a clear response to surgical treatment. We suggest that in pediatric epilepsy surgical programs, autistic regression should prompt urgent investigation if drug treatment is not effective.

Medulloblastoma: is the 5-year survival rate improving? A review of 80 cases from a single institution.

A series of 80 cases of medulloblastomas in children undergoing operation and postoperatively followed between 1980 and 1990 at Great Ormond Street Hospital for Children (GOSH) has been reviewed and compared to an earlier series reported from the same institution by McIntosh. The overall 5-year survival rate for the present series was 50%, although three patients died after surviving 5 years. The operative mortality rate was 5%. Survival analysis revealed that the presence or absence of spinal metastases and the necessity for some form of cerebrospinal fluid diversion within 30 days of the operation independently significantly affected survival in this series. Those patients with no spinal metastasis and total tumor removal had a 5-year survival rate of 73%, making this the most favorable subgroup in the series. Patient age and gender, duration of symptoms, Chang T stages, tumor volume, extent of resection, and postoperative chemotherapy were not significant variables. Although these results are better than those reported in the earlier GOSH series, they are not significantly different from the results of the second 5-year cohort of patients described in that article. Radiotherapy remains the greatest advance in treatment, although it is hoped that further improvement will result from the various chemotherapy protocols now being studied and from increasing knowledge of the biological behavior of these tumors.

Split cord malformations of the lumbar region. A model for the neurosurgical management of all types of 'occult' spinal dysraphism?

From a group of 84 patients with split cord malformations presenting to our Department between 1976 and 1990, we have selected 47 cases in whom the split cord was confined to the lower dorsal-lumbar region and in whom there were no other dysraphic features such as meningocele, lipoma or dermoid cyst. We have studied these cases of 'pure split cord malformation' in an attempt to decipher its natural history and the effects of surgical procedures designed to untether the spinal cord. We conclude that the 'neuro-orthopaedic syndrome' (which includes lower limb asymmetry, talipes and modest sensory and motor problems) is, in most cases, an inevitable consequence of the abnormal functional anatomy of the split cord and is not due to any mechanical effects of tethering of the spinal cord. Its emergence as a child grows (assuming that it was not obvious at birth) is not influenced by surgery. True neurological deterioration (defined as the loss of a previously established neurological or urological function) is a rarer event. It may occur at any age--including well into adulthood--but in children the average age at presentation is 6.8 years (range 2 years 9 months to 11 years). It is due to the mechanical effects of tethering of the spinal cord and is more likely to be arrested than improved by surgery. 'True' deterioration did not occur in any of our cases who had undergone prophylactic untethering of the spinal cord and we have concluded, therefore, that surgery has a role in the prevention of late neurological problems affecting the lower limbs and bladder. Surgery to untether the spinal cord will not, however, have any affect upon the emergence of the neuro-orthopaedic syndrome.

The beaten copper cranium: a correlation between intracranial pressure, cranial radiographs, and computed tomographic scans in children with craniosynostosis.

OBJECTIVE: The beaten copper appearance of the cranium, as well as other cranial radiographic and computed tomographic findings in children with craniosynostosis, is often interpreted by clinicians as evidence of elevated intracranial pressure (ICP). However, a correlation between radiological findings and ICP measurements has not been previously demonstrated, and their usefulness in detecting elevated ICP has not been defined. METHODS: To address those issues, 123 children with craniosynostosis who had cranial radiographs and ICP monitoring were studied. To assess the specificity of certain radiological findings to patients with craniosynostosis, cranial radiographs of patients with craniosynostosis were compared to those of age- and sex-matched controls. In patients with craniosynostosis, findings on cranial radiographs were compared to computed tomographic scans of the brain. Radiographic findings were then correlated with ICP measurements obtained while the patient was sleeping, which was measured using a Camino fiberoptic ICP monitor (Camino Laboratories, San Diego, CA). All radiographs were independently analyzed by two radiologists who were blinded to clinical and ICP data. RESULTS: A diffuse beaten copper pattern, erosion of the dorsum sellar, and suture diastasis were seen more commonly in patients with craniosynostosis than in controls (P < 0.05), but the presence of the beaten copper pattern was no more common in children with craniosynostosis. ICP was greater when a diffuse beaten copper pattern, dorsum sellar erosion, suture diastasis, or narrowing of basal cisterns was present (P < 0.05). CONCLUSION: Although this study demonstrates that some cranial radiographic and computed tomographic findings do correlate with elevated ICP, the sensitivity of radiological methods for detecting elevated ICP is universally low and they are not recommended to screen for elevated ICP in children with craniosynostosis.