Maher Hassounah

Intraoperative facial motor evoked potential monitoring with transcranial electrical stimulation during skull base surgery

OBJECTIVE To address the limitations of standard electromyography (EMG) facial nerve monitoring techniques by exploring the novel application of multi-pulse transcranial electrical stimulation (mpTES) to myogenic facial motor evoked potential (MEP) monitoring. METHODS In 76 patients undergoing skull base surgery, mpTES was delivered through electrodes 1cm anterior to C1 and C2 (M1-M2), C3 and C4 (M3-M4) or C3 or C4 and Cz (M3/M4-Mz), with the anode contralateral to the operative side. Facial MEPs were monitored from the orbicularis oris muscle on the operative side. Distal facial nerve excitation was excluded by the absence of single pulse responses and by onset latency consistent with a central origin. RESULTS M3/M4-Mz mpTES (n=50) reliably produced facial MEPs while M1-M2 (n=18) or M3-M4 (n=8) stimulation produced 6 technical failures. Facial MEPs could be successfully monitored in 21 of 22 patients whose proximal facial nerves were inaccessible to direct stimulation. Using 50, 35 and 0% of baseline amplitude criteria, significant facial deficits were predicted with a sensitivity/specificity of 1.00/0.88, 0.91/0.97 and 0.64/1.00, respectively. CONCLUSIONS Facial MEPs can provide an ongoing surgeon-independent assessment of facial nerve function and predict facial nerve outcome with sufficiently useful accuracy. SIGNIFICANCE This method substantially improves facial nerve monitoring during skull base surgery.

OPTIC GLIOMAS: A RETROSPECTIVE ANALYSIS OF 50 CASES

PURPOSE Gliomas of the optic pathways are rare childhood central nervous system tumors. The treatment approach is controversial because of its rarity and the slow and unpredictable growth rates of these lesions. METHODS AND MATERIALS We reviewed 50 patients with the diagnosis of optic pathway low-grade gliomas treated between January 1980 and December 1995 at King Faisal Specialist Hospital and Research Center, Saudi Arabia. Thirty-five patients presented with chiasmatic/hypothalamic (posterior tumors), and 15 with optic nerve gliomas with or without chiasmal involvement (anterior tumors). Evidence of neurofibromatosis was present in 18 patients. Twenty-nine patients underwent surgery (total or partial resection), and 12 of these received postoperative radiotherapy (RT). Sixteen patients were treated with primary RT. The radiation dose varied between 42 and 54 Gy (median dose 50). RESULTS The overall actuarial survival rate was 87.5% at 5 years and 75% at 10 years, and the corresponding progression-free survival (PFS) rates were 69% and 62%. Patients with anterior tumors fared better than those with posterior tumors, with a 10-year PFS rate of 72% and 58%, respectively; the difference, however, was not statistically significant (p = 0.58). A PFS advantage was found in favor of patients with posterior tumors treated with RT (primary or postoperative) compared with no RT, with 5-year PFS rates of 68% vs. 42% (p = 0.03). This, however, did not translate into a survival advantage because of the success of salvage treatment. CONCLUSION In multivariate analysis, age (<3 vs. >3 years) emerged as the only significant determinant for PFS with patients <3 years old faring worse (p = 0.03). Neurologic and endocrine dysfunction are significant problems that need to be addressed.

CRANIOPHARYNGIOMA IN CHILDREN

PURPOSE The treatment regimens at presentation and recurrence, the related morbidity, and survival rates were studied for children with craniopharyngioma who were treated at King Faisal Specialist Hospital & Research Center (KFSH&RC). METHODS & MATERIALS From 1975 to 1996, a total of 56 children younger than 18-years-old at diagnosis underwent treatment with surgery and/or radiotherapy for craniopharyngiomas at KFSH&RC. There was evidence that these patients had advanced disease at diagnosis; 36% of 51 patients whose visual status pretreatment was known were either blind or had major bilateral visual defects prior to treatment, and 36% of the 56 patients had diabetes insipidus. This report concentrates on 44 patients who had first definitive resection at KFSH&RC. Treatment policy was total resection if possible (17 patients), if not, subtotal resection (17 patients) or lesser procedures (10 patients). Five patients received postoperative irradiation after first definitive resection. RESULTS Ten-year-survival, and progression-free and event-free survival rates were 65%, 39%, and 29%, respectively. There were 9 postoperative deaths; 7 following the first procedure and 2 following resection for relapse, and 3 early deaths at home prior to relapse, following the first resection. None of the 22 patients who underwent less than total resection without postoperative radiation treatment were progression-free at 5 years, whereas the 5 patients who were irradiated remain progression-free. CONCLUSION A more selective approach to total resection, and the routine use of postoperative irradiation following lesser surgical procedures requires evaluation.

TREATMENT RESULTS FOR 149 MEDULLOBLASTOMA PATIENTS FROM ONE INSTITUTION

PURPOSE Retrospective analysis of patients with medulloblastoma to determine the effectiveness of previous treatments for medulloblastoma and plan for future management strategies. METHODS AND MATERIALS During the period March 1976 to December 1991, 172 patients with cerebellar medulloblastoma were referred to King Faisal Specialist Hospital and Research Center. One hundred and forty-nine patients were treated with curative intent. There were six postoperative deaths, and 10 patients planned for radiotherapy treatment failed to complete the prescribed course. One hundred and thirty-three patients completed a course of radiotherapy after surgery. Adjuvant chemotherapy was not used routinely (six patients only). Tumors were staged retrospectively according to the Chang staging system. There were no T1 patients, 32 patients had T2 tumors, 76 had T3 tumors, and 29 had T4 tumors. The T stage could not be allocated in 12 patients. Ninety-nine patients required a shunting procedure either pre- or postoperatively. Forty-six patients had complete resection of tumor, 91 had incomplete resection, and 6 patients had biopsy only. The extent of resection could not he determined in six patients. The median radiation dose for the whole brain was 34 Gy, spine 32.5 Gy, and posterior fossa 52.8 Gy. Fraction sizes ranged from 1.7-1.8 Gy for craniospinal fields and 2 Gy for the posterior fossa boost. Seventy percent completed the prescribed course within 7 weeks. RESULTS Actuarial survival for the whole group of 149 patients was 53% at 5 years and 38% at 10 years. On univariate analysis, patients with T2 tumors did significantly better as compared to patients with T3 and T4 tumors. Survival of patients who had clinical and radiological complete resection of tumor at surgery was significantly better than patients with incomplete tumor removal. The presence of a ventriculoperitoneal (VP) shunt had a significant negative impact on survival. Treatment failure by site was analyzed with respect to the radiation dose. Doses greater than 50 Gy for the posterior fossa, and greater than 30 Gy for craniospinal axis, resulted in significantly better survival. On multivariate analysis, the only significant prognostic factor was the presence of a VP shunt in patients with T2 tumors. CONCLUSION T stage, VP shunt, radiation doses and extent of surgery were important prognostic factors. In this study, radiation doses of more than 50 Gy to the posterior fossa and 30 Gy to the craniospinal axis resulted in improved survival.

Benign tumors from the human nervous system express high levels of survivin and are resistant to spontaneous and radiation-induced apoptosis.

Survivin, an inhibitor of apoptosis, is over-expressed in foetal tissues and human cancers, but it is almost undetectable in normal tissues. Here we have assessed the level of the survivin protein in some benign tumors of the nervous system: meningioma, schwannoma, low-grade ependymoma, pilocytic astrocytoma and pituitary adenoma. Using immuno-blot analysis we present evidence that these low-grade tumors are positive for survivin expression. In agreement, flow cytometrical analysis showed that both spontaneous and radiation-induced apoptosis levels are very low in these neoplasms. Using host cell reactivation assay we have also shown that these tumor cells are proficient in the repair of γ-ray-induced DNA damage. However, they are deficient in the removal of ultraviolet (UV) light-induced DNA photolesions, especially the shwannoma- and the pituitary adenoma-derived cells. These results suggest that survivin overexpression may be an early event in the stepwise tumoregenesis and hence could be responsible for the onset as well as the growth advantage during tumoregenic progression of malignant as well as benign neoplasms.

Expression of survivin and p16INK4a/Cdk6/pRB proteins and induction of apoptosis in response to radiation and cisplatin in meningioma cells

Although meningiomas represent the most common class of tumors of the central nervous system, the molecular events underlying their genesis and development are still not well defined, and therapeutic approaches based on the genetics of these tumors are currently lacking. In the present study we have used the immunoblotting technique to show that the p16(INK4A), Cdk6 and pRB proteins are differentially expressed in primary meningioma cells with 20-, 30- and 36-fold difference between the lowest and the highest levels of each protein, respectively. In addition, we present evidence that the level of the anti-apoptosis survivin protein is high in these benign tumors. Moreover, the annexin V-associated flow cytometry technique was used to show that 60% of meningioma cell cultures underwent apoptosis in response to both gamma-rays and cisplatin, and 50% of these cells exhibited significant sensitivity to hydroxyurea. These agents triggered apoptosis through the mitochondrial pathway, by increasing the Bax/Bcl-2 ratio. Interestingly, the induction of apoptosis following radiation and cisplatin was significant in all cells that expressed low levels of p16(INK4A), Cdk6 and pRB proteins. These data shed more light on the molecular biology of meningioma cells and suggest that survivin and proteins of the RB pathway could play a determinant role in the development and the treatment of meningiomas.

Outcome of surgery for intramedullary spinal ependymoma

BACKGROUND AND OBJECTIVES Ependymoma is the most frequently encountered intramedullary tumor. Total surgical resection is the therapeutic modality of choice whenever possible, but carries a significant risk of morbidity. This study was designed to define prognostic factors that affect clinical outcome after surgical resection of spinal intramedullary ependymoma. PATIENTS AND METHODS The medical records, radiological and pathological studies of all patients with intramedullary spinal ependymomas treated surgically in one institution were reviewed retrospectively. Spinal myxopapillary ependymomas were excluded. In a multivariable regression analyis, possible prognostic factors were correlated with the 6-month postoperative neurological status using McCormick’s grading scale. RESULTS Surgery was performed on 17 patients (14 males, 3 females, mean age of 42±15 years) with spinal ependymoma. The cervical spine was the most common tumor location (71%). Total surgical resection of the tumor was achieved in 11 cases (65%). Intraoperative neurophysiological monitoring was used in 8 cases (47%). Postoperatively, 11 patients (65%) either improved or had no change from their preoperative neurological status. None of the 11 totally resected tumors has shown evidence of recurrence in a follow-up period range from 8–120 months (median, 33 months). Of several possible prognostic factors, the only statistically significant correlation identified with the 6-month postoperative neurological status was the preoperative McCormick grading score. CONCLUSIONS Preoperative neurological status was the only statistically significant factor in determining the postoperative neurological outcome of patients with spinal intramedullary ependymomas. Early diagnosis and referral for surgery to specialized centers are recommended as controllable factors in improving outcome.

Primary angiosarcoma of the brain in a child.

We describe a pediatric case of primary angiosarcoma of the brain displaying striking intravascular papillary pattern, consistent with the “Dabska tumor,” often in continuity with a massive, multifocal intravascular papillary endothelial hyperplasia. The tumor contained small hemangioma and obliterated dysplastic arteries as well as very large thin-walled veins. The surrounding brain tissue showed scattered telangiectasias, conglomerates of calcified dysplastic arteries, old hemorrhages and gliosis. Colocalization of these lesions suggests the development of a papillary angiosarcoma in the pre-existing vascular malformation. Although never reported, the possibility of a malignant transformation of endothelial papillary hyperplasia also should be considered in this case.

Intraoperative direct cortical stimulation motor evoked potentials: Stimulus parameter recommendations based on rheobase and chronaxie

OBJECTIVE To determine optimal interstimulus interval (ISI) and pulse duration (D) for direct cortical stimulation (DCS) motor evoked potentials (MEPs) based on rheobase and chronaxie derived with two techniques. METHODS In 20 patients under propofol/remifentanil anesthesia, 5-pulse DCS thenar MEP rheobase and chronaxie with 2, 3, 4 and 5ms ISI were measured by linear regression of five charge thresholds at 0.05, 0.1, 0.2, 0.5 and 1msD, and estimated from two charge thresholds at 0.1 and 1msD using simple arithmetic. Optimal parameters were defined by minimum threshold energy: the ISI with lowest rheobase2×chronaxie, and D at its chronaxie. Near-optimal was defined as threshold energy <25% above minimum. RESULTS The optimal ISI was 3 or 4 (n=7 each), 2 (n=4), or 5ms (n=2), but only 4ms was always either optimal or near-optimal. The optimal D was ∼0.2 (n=12), ∼0.1 (n=7) or ∼0.3ms (n=1). Two-point estimates closely approximated five-point measurements. CONCLUSIONS Optimal ISI/D varies, with 4ms/0.2ms being most consistently optimal or near-optimal. Two-point estimation is sufficiently accurate. SIGNIFICANCE The results endorse 4ms ISI and 0.2msD for general use. Two-point estimation could enable quick individual optimization.