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.

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.

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.

Use of intracranial pressure monitoring in the management of childhood hydrocephalus and shunt-related problems.

Although the clinical and radiological diagnosis of hydrocephalus in children is usually straightforward, there exists a minority of patients in whom the decision to shunt can be extremely difficult. Similarly, although the diagnosis of shunt malfunction usually presents little difficulty in the context of an acute blockage, a child can present with a confusing and unpredictable constellation of symptoms that might be caused by conditions separate from shunt malfunction. Continuous intraparenchymal intracranial pressure (ICP) monitoring was used to assess 41 patients with hydrocephalus, either as part of the initial diagnostic evaluation of ventriculomegaly (18 patients) or in the assessment of presumed shunt malfunction (23 patients). In 9 of 18 patients with ventriculomegaly, the ICP was within normal limits and surgical insertion of shunts was avoided. Of the 23 patients being assessed for shunt malfunction, the change in ICP profile indicated a siphoning or overdrainage process in 13. In no patient was there significant attendant morbidity, and the process was well tolerated and simple to perform. Clinical and radiological criteria alone can afford insufficient information in the initial evaluation and the subsequent management of the child with hydrocephalus. ICP monitoring provides a safe means of investigating such patients and provides valuable information upon which to base surgical management.

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.

The effectiveness of papilledema as an indicator of raised intracranial pressure in children with craniosynostosis.

Craniosynostosis management partially depends on the detection and treatment of elevated intracranial pressure (ICP). Examination for papilledema is considered to be the most reliable screening method for identifying raised ICP, but its effectiveness has not been defined. One hundred and twenty-two children with craniosynostosis who underwent funduscopic examinations and then Camino ICP monitoring were studied. All eye examinations were performed by an ophthalmologist after pharmacological pupillary dilation. Fifteen patients (12%) had papilledema. Subsequent ICP monitoring showed that the median ICP was 12.7 mm Hg, with 41 patients (34%) having elevated ICPs (> 15 mm Hg). Those with papilledema had higher ICPs (17.5 +/- 3.2 versus 12.7 +/- 5.5 mm Hg), were older (5.9 +/- 4.7 versus 1.9 +/- 2.6 years), and were more likely to have craniofacial syndromes (73 versus 41%) than those without papilledema (P < 0.05). Patients with both elevated ICPs and papilledema were older (5.9 +/- 4.7 versus 1.6 +/- 1.4 years) and more likely to have multiple-suture synostosis (92 versus 61%) than those with elevated ICPs and no papilledema (P < 0.05). The presence of papilledema was a specific (98%) indicator of raised ICP, but its sensitivity was age-dependent. It was 100% sensitive in children older than 8 years, but it indicated elevated ICP in only 22% of younger patients. These results suggest that ICP monitoring to document elevated ICP is unnecessary in children older than 8 years who have detailed ophthalmological examinations. In the younger child, the presence of papilledema reliably indicates elevated ICP but its absence does not rule out elevated ICP; formal ICP measurement has a greater role in detecting elevated ICP in these patients.

Accurate placement of the atrial catheter in ventriculoatrial shunts. Technical note.

A combined radiological and surgical technique that permits identification of appropriate recipient vessels and accurate placement of the atrial catheter in ventriculoatrial shunts is described. The procedure uses readily available radiological skills and reduces operation time and morbidity related to malpositioning of the distal catheter.

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.

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.

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.

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.

The use of autologous skull bone grafts for posterior fusion of the upper cervical spine in children.

STUDY DESIGN: Traditionally bone grafts used in posterior cervical fusion have been harvested from the iliac crest, rib, tibia, or fibula. Their use is not without significant morbidity, and it is often difficult to harvest suitable quantities of good quality bone in children. We have used autologous calvarial bone secured by sublaminar wires in seven patients with congenital spinal anomalies to achieve craniocervical stabilization and fusion. OBJECTIVES: To detail our experiences with this new method of harvesting autologous bone grafts from the patient's skull for occipitocervical fusion in a pediatric practice. SUMMARY OF BACKGROUND DATA: Calvarial bone has been used extensively in craniofacial reconstructive work with good long-term results and with no significant bone resorption. The use of membranous bone is supported by several basic science studies reported in the plastic surgery literature that claim a superiority over endochondral bone regarding fusion. In the present study, autologous calvarial bone has been used in the treatment of seven cases of congenital upper cervical spine instability associated with neurologic deficit. This method circumvents many of the problems attached to the use of traditional donor sites and provides good quality bone in large quantity that can be specifically tailored to match the contours of the craniocervical junction. METHOD: We used autologous calvarial bone secured by sublaminar wires in seven children with congenital spinal anomalies to achieve craniocervical stabilization and fusion. The ensuing calvarial defect was repaired using split-thickness parietal bone with the bone graft, which was ultimately used for the cervical fusion and acted as a template to obtain a mirror image and exact match to achieve good cosmetic results. The patients were immobilized after surgery in a halo orthosis for 3 months. RESULTS: Satisfactory results (100% fusion) were achieved in all seven cases with no attendant morbidity related to the method of graft procurement. CONCLUSIONS: We recommend this technique as a safe and effective alternative to the more traditional means of graft procurement previously used in cases of craniocervical instability in children.

Air embolism during awake craniotomy.

A case of venous air embolism during awake craniotomy is described. Chest pain and electrocardiographic changes were the major presenting features. Capnography detected a decrease in end-tidal carbon dioxide and demonstrates its use as an aid in the diagnosis of air embolism in the awake patient. Following this episode persistent hypoxaemia developed secondary to acute pulmonary oedema and a pleural effusion.

Intracranial ependymomas in childhood: a report of 24 cases followed for 5 years.

The management and outcome of 24 patients with intracranial ependymomas admitted to our institution between January 1979 and May 1988 have been analysed. Four patients out of the ten with infratentorial ependymomas who underwent a visible total resection were alive and free of disease at 5 years, whereas all those who had had an incomplete resection were dead. The prognosis in the supratentorial group was worse; only one patient out of seven was alive and free of disease at 5 years. Nine patients (six infratentorial and three supratentorial ependymomas) were investigated with myelography for occult spinal metastases, and apart from one who had a direct extension of an infratentorial tumour into the upper cervical spine, none had detectable metastases. Eight patients with infratentorial tumours underwent a ventriculo-peritoneal shunt insertion, and in three of them this followed a visible total resection of the tumour. Comparison of our results with those from other series suggests that any improvement in outlook is related primarily to an increased number of children surviving their initial surgical treatment, rather than to better methods of postoperative tumour control.

Myelography in the assessment of children with medulloblastoma.

Forty-seven out of 49 patients with a histologically-proven diagnosis of medulloblastoma admitted to our institution between 1 January 1984 and 13 December 1990 were examined post-operatively using either myelography or gadolinium-enhanced magnetic resonance imaging in an attempt to detect clinically occult spinal metastatic disease. Spinal spread of the tumour was identified in nine (19%) patients. Of the 16 patients for whom a 5-year follow-up has been available 12 had no myelographic evidence of spinal disease and of these 10 (83%) remain disease-free. Of the six who have died during this period four had evidence of spinal metastases at presentation. Of all the children in the series with spinal spread identified at the time of their initial hospitalization, only one survives to date (15 months after diagnosis). The remainder had an average life expectancy of 18 months.

Stereotactically-guided craniotomy for cavernous angiomas presenting wit epilepsy.

With the wider availability of magnetic resonance imaging cavernous malformations are being recognised with increasing frequency in those patients presenting with intractable epilepsy. Surgical resection is the treatment of choice. However, because these lesions are usually small and may be located in eloquent areas stereotactic resection should be considered. Stereotactically-guided resection of pathologically verified cavernous angiograms was performed in 10 patients in this series presenting with epilepsy (8 males, 2 females, mean age 32 years). Eight patients presented with medically intractable epilepsy (5 complex partial seizures, 3 grand mal seizures). Of the remaining patients one experienced multiple episodes of haemorrhage and the other headaches (with a non-diagnostic scan) both in association with epilepsy. Pre-operative localisation of the motor strip was determined in one case by functional MRI. Following resection of these lesions all patients experienced improved seizure control with a mean follow-up period of 22 months. The mean postoperative hospital stay was 5.1 days with no surgical complications recorded. We conclude that stereotactically-guided resection offers significant advantages in the management of cavernous malformations. Surgical indications for operative resection would include medically refractory epilepsy, repeated haemorrhage and those cases where there is diagnostic uncertainty.

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.

"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.