P. Sarat Chandra

Expression of CD34 as a novel marker for glioneuronal lesions associated with chronic intractable epilepsy.

The spectrum of glioneuronal lesions underlying intractable epilepsies includes malformative pathologies like focal cortical dysplasia (FCD); and neoplastic lesions like gangliogliomas (GG) and dysembryoplastic neuroepithelial tumours (DNT). These may occur either singly or as dual lesions, having simultaneous presence of both elements. Currently, the relationship between the malformative and neoplastic glioneuronal lesions is poorly understood. Recently, CD34, a stem cell marker transiently expressed during early neurulation, has been identified in these tumours. This study was undertaken to (i) evaluate the role of CD34 as a diagnostic marker for glioneuronal lesions of epilepsy, namely, GG, DNT and FCD, and (ii) attempt to define the relationship among these lesions, using CD34 as a marker.

Intra-operative electrocorticography in lesional epilepsy

Intra-operative electrocorticography (ECoG) is useful in epilepsy surgery to delineate margins of epileptogenic zone, guide resection and evaluate completeness of resection in surgically remediable intractable epilepsies. The study evaluated 157 cases (2000-2008). The preoperative evaluation also included ictal SPECT (122) and PET in 32 cases. All were lesional cases, 51% (81) of patients had >1 seizure/day and another 1/3rd (51) had >1/week. Pre and post resection ECoG was performed in all cases. A total of 372 recordings were performed in 157 cases. Second post-operative recordings (42) and third post-operative recordings (16) were also performed. Site of recordings included lateral temporal (61), frontal (39), parietal (37), hippocampal (16) and occipital (4). 129/157 cases (82%) showing improvement on ECoG, 30/42 cases showed improvement in 2nd post resection, 8/16 showed improvement in the 3rd post-operative ECoG. 116/157 (73%) patients had good outcome (Engel I and II) at follow up (12-94 months, mean 18.2 months). Of these, 104 patients (80%) showed improvement on post-operative ECoG. 12 had good outcome despite no improvement on ECoG. The improvement in ECoG correlated significantly with clinical improvement [Sensitivity: 100% (95% CI; 96-100%); specificity: 68.3% (95% CI; 51.8-81.4%); positive predictive value: 89.9% (95% CI, 83.1-94.3%); negative predictive value: 100% (95% CI, 85-100%)]. The level of agreement was 91.72% (kappa: 0.76). Concluding, pre and post resection ECoG correlated with its grade of severity and clinical outcome.

Memory and intelligence outcome following surgery for intractable temporal lobe epilepsy: relationship to seizure outcome and evaluation using a customized neuropsychological battery

The main objectives of this prospective study were to (1) assess memory and intelligence outcome following surgery for intractable temporal lobe epilepsy, (2) correlate this with seizure outcome and side of surgery, and (3) perform (1) and (2) using an indigenously developed battery customized to the Indian population. Prior to use in our epilepsy surgery program, the test-retest and interexaminer variance reliability of this battery had been established in both normal and cognitively compromised populations. The memory scores were overall rather than material-specific. The battery was administered to right-handed adults undergoing surgery for intractable temporal lobe epilepsy without any evidence of opposite temporal lobe abnormality, both presurgery and postsurgery at a mean follow-up of 8 months. Twenty-five consecutive patients were included; 13 underwent right and 12 underwent left temporal surgery. Seizure outcome was assessed using Engels classification. Among 13 patients who underwent right temporal surgery, although 4 patients with poor seizure outcome had insignificant changes in scores, 7 of 9 patients with good seizure outcome exhibited considerable (> 20% over preoperative) improvement in their memory and intelligence scores. Statistical analysis using Students t test and the Mann-Whitney test revealed that the patients who underwent right temporal surgery with good seizure outcome had significant improvement in both memory (P = 0.007) and intelligence (P = 0.043) scores compared with those with poor seizure outcome. In contrast, patients who underwent left temporal surgery had no significant change in cognitive scores irrespective of seizure outcome. Cognitive improvement seems to occur in patients with good seizure outcome following nondominant temporal lobe surgery for intractable epilepsy with no evidence of pathology in the opposite temporal lobe. The same finding was not observed in patients undergoing left temporal surgery.

Endoscopic management of intraventricular neurocysticercosis

Surgical management is the only option for patients presenting with acute hydrocephalus caused by intraventricular neurocysticercosis. Although various modalities have been described, endoscopic excision is becoming increasingly popular. The outcomes for 22 patients with intraventricular neurocysticercal cysts with hydrocephalus managed endoscopically are presented. Complete excision of cysts (fourth ventricle, 14; lateral ventricle, 4; third ventricle, 3; both lateral and third ventricles, 1) was performed in all patients. Internal procedures for cerebrospinal fluid diversion were performed in 20 patients. There were minimal perioperative complications, all patients were relieved of raised intracranial pressure and no patient has required shunting to date. Mean follow-up duration was 20.7 months. Follow-up imaging showed the absence of residual cysts and resolution of hydrocephalus in all patients.

Spontaneous Decompression of a Posterior Fossa Arachnoid Cyst: A Case Report

The authors present a case of spontaneous regression of a posterior fossa, supracerebellar arachnoid cyst causing hydrocephalus in a 7-month-old male child. The patient presented with macrocrania, bulging fontanelle and upgaze paresis of the eyes. There was complete improvement of these symptoms on the morning of the day of surgery without any obvious precipitating factors, including trauma. CT scan showed complete resolution of the cyst and hydrocephalus. The child was doing well at 1 year of follow-up. To the best of our knowledge, this is the first case report of spontaneous resolution of a posterior fossa arachnoid cyst.

Surgery for Drug-Resistant Epilepsy in Children

BACKGROUND Neurosurgical treatment may improve seizures in children and adolescents with drug‐resistant epilepsy, but additional data are needed from randomized trials. METHODS In this single‐center trial, we randomly assigned 116 patients who were 18 years of age or younger with drug‐resistant epilepsy to undergo brain surgery appropriate to the underlying cause of epilepsy along with appropriate medical therapy (surgery group, 57 patients) or to receive medical therapy alone (medical‐therapy group, 59 patients). The patients in the medical‐therapy group were assigned to a waiting list for surgery. The primary outcome was freedom from seizures at 12 months. Secondary outcomes were the score on the Hague Seizure Severity scale, the Binet–Kamat intelligence quotient, the social quotient on the Vineland Social Maturity Scale, and scores on the Child Behavior Checklist and the Pediatric Quality of Life Inventory. RESULTS At 12 months, freedom from seizures occurred in 44 patients (77%) in the surgery group and in 4 (7%) in the medical‐therapy group (P<0.001). Between‐group differences in the change from baseline to 12 months significantly favored surgery with respect to the score on the Hague Seizure Severity scale (difference, 19.4; 95% confidence interval [CI], 15.8 to 23.1; P<0.001), on the Child Behavior Checklist (difference, 13.1; 95% CI, 10.7 to 15.6; P<0.001), on the Pediatric Quality of Life Inventory (difference, 21.9; 95% CI, 16.4 to 27.6; P<0.001), and on the Vineland Social Maturity Scale (difference, 4.7; 95% CI, 0.4 to 9.1; P=0.03), but not on the Binet–Kamat intelligence quotient (difference, 2.5; 95% CI, ‐0.1 to 5.1; P=0.06). Serious adverse events occurred in 19 patients (33%) in the surgery group, including hemiparesis in 15 (26%). CONCLUSIONS In this single‐center trial, children and adolescents with drug‐resistant epilepsy who had undergone epilepsy surgery had a significantly higher rate of freedom from seizures and better scores with respect to behavior and quality of life than did those who continued medical therapy alone at 12 months. Surgery resulted in anticipated neurologic deficits related to the region of brain resection. (Funded by the Indian Council of Medical Research and others; Clinical Trial Registry–India number, CTRI/2010/091/000525.)

Surgical outcome of cortical dysplasias presenting with chronic intractable epilepsy: a 10-year experience.

BACKGROUND There has been sparse description of cortical dysplasias (CDs) causing intractable epilepsy from India. AIM Clinical retrospective study of CDs causing intractable epilepsy that underwent surgery. MATERIALS AND METHODS Fifty-seven cases of CDs reviewed (1995 till July 2006) are presented. All patients had intractable epilepsy, and underwent a complete epilepsy surgery workup (inter ictal electroencephalography (EEG), video EEG, MRI as per epilepsy protocol, SPECT {interictal, ictal with subtraction and co-registration when required}, and PET when necessary). Surgical treatment included a wide exposure of the pathology with a detailed electrocorticography under optimal anesthetic conditions. Mapping of the sensori-motor area was performed where indicated. Procedures included resection either alone or combined with multiple subpial transactions when extending into the eloquent areas. RESULTS Our study had 28 (49.12%) cases of isolated focal CDs, and 29 (50.67%) with dual pathology. Average age at the time of onset of seizures in our series was 7.04 years (three months to 24 years), and average age at the time of surgery was 10.97 years (eight months to 45 years). Among coexistent pathologies, one had associated MTS, 16 had coexistent gangliogliomas and 12 (dysembryonic neuroepithelial tumor) DNTs. At an average follow-up of 3.035 years (range 5-10 years), three patients were lost to follow-up. Fifty-one per cent (29/57) patients had a good outcome (Engel Grade I) and 26%(15/57) had a Grade II outcome. CONCLUSION Cortical dysplasias have a good outcome if evaluated and managed with concordant electrical and imaging modalities.

The role of neuronavigation-guided functional MRI and diffusion tensor tractography along with cortical stimulation in patients with eloquent cortex lesions.

Abstract Objective. To effectively combine functional MRI (fMRI), diffusion tensor tractography (both guided by neuronavigation) along with cortical stimulation (CS) for surgery of eloquent cortex (EC) lesions. Materials and methods. Fifteen patients with lesions adjacent to the eloquent motor and sensory cortex were included. Preoperative fMRI and diffusion tensor imaging were performed and then integrated into the neuronavigation system. Intraoperative CS of sensory/motor cortex was performed to localize the EC under awake condition and this was correlated with areas active on fMRI utilizing neuronavigation. For excision of the deeper structures, CS, and tractography guided by neuronavigation were utilized. Results. A total of 127 cortical sites were evaluated with CS in 15 patients. The overall sensitivity, specificity, and accuracy of fMRI were 79%, 85%, and 82%, respectively, keeping the areas positive on CS as a referential parameter. Tractography helped in resecting the deeper areas of the tumor, but was not very accurate due to brain shift. However, it was useful in roughly assessing the deeper areas close to the long tracts. The risk of developing persistent neurological deficits was 6%. Pathologies included gliomas in ten patients, cavernous malformation in two patients, meningioma in one patient, and focal cortical dysplasia and Dysembryonic neuroepithelial tumor in one patient each. Near total excision was achieved in 7/10 (> 95% excision) gliomas and a total excision in all others lesions. Conclusions. Lesions directly over the EC present a special surgical challenge. The challenge lies in excising these lesions without producing any deficits. These goals may be achieved better by combined use of multimodal neuronavigation (fMRI and tractography) and intraoperative mapping with CS under awake conditions.

A Hypothesis Regarding the Pathogenesis and Epileptogenesis of Pediatric Cortical Dysplasia and Hemimegalencephaly Based on MRI Cerebral Volumes and NeuN Cortical Cell Densities

Summary:  This study compared MRI cerebral volumes and Neuronal‐Nuclei (NeuN) cell densities in pediatric epilepsy surgery patients with cortical dysplasia (CD; n = 25) and hemimegalencephaly (HME; n = 14). Our purpose was to deduce possible mechanisms of pathogenesis and epileptogenesis based on an understanding of normal developmental corticoneurogenesis. We used MRI to measured cerebral hemisphere volumes, and NeuN staining to determine grey and white matter cell densities and cell sizes in the molecular layer, grey, and white matter. CD and HME surgical cases were compared with autopsy or non‐CD cases (n = 20). Total MRI brain volumes were similar between non‐CD, CD, and HME cases. However, in HME patients, the affected cerebral hemisphere was larger and the nonaffected side smaller than non‐CD cases. Compared with autopsy cases, NeuN cell densities and cell sizes in CD and HME patients were increased in the molecular layer, upper grey matter, and white matter. In CD and HME cases, total cerebral hemisphere volumes were normal in size and there were more cortical neurons in upper layers than expected. The increase in cortical neuronal densities is consistent with the hypothesis that CD and HME pathogenesis involves increased neurogenesis in the late (not early) phases of cortical formation. In addition, more neurons in the molecular layer and white matter supports the concept that CD and HME pathogenesis also involves incomplete programmed cell death in the remnant cells occupying the preplate and subplate regions. Based on our anatomical and previous electrophysiological findings, we propose that in CD and HME seizure generation is the consequence of incomplete cerebral development with abnormal interactions between immature and mature cells and cellular networks.

An Unusual Case of Dorsally Situated Bony Spur in a Lumbar Split Cord Malformation

A case of lumbar split cord malformation (SCM) with a bony spur situated dorsally is presented. This was associated with a hypertrophied posterior arch. The ventral dura was totally intact, and there was no fibrous septum connecting the bony arch to the dura. To our knowledge, such a case has not been reported earlier. In view of this unique finding, we propose a slight modification in Pangs unified theory of embryogenesis in the development of SCM.