John McKean

Pediatric Temporal Lobectomy for Epilepsy

Background: Temporal lobectomy in adults is an accepted form of treatment for patients with intractable complex partial seizures. There have been few long-term studies of children undergoing temporal lobectomy for epilepsy. Methods: We reviewed the pediatric cases of temporal lobectomy for intractable epilepsy performed by the Comprehensive Epilepsy Program at the University of Alberta Hospitals between 1988 and 2000. All patients had preoperative and postoperative clinical evaluations, seizure charts, drug levels, EEG, CT/MRI, long-term video EEG monitoring and neuropsychological testing. The patients were reassessed at 6 weeks, 6 months and 1 year postoperatively, then yearly. The duration of follow up was 1–10 years (mean 5 years). Results: Forty-two patients were studied (25 males and 17 females). Age at surgery ranged from 18 months to 16 years. The interictal EEG was abnormal in 38 of the 42 patients. Twenty-two patients had focal epileptic discharge and 1 had generalized epileptic discharge. Focal slowing was seen in 9 patients and diffuse slowing in 5 patients. CT scan was abnormal in 17 of 39 patients and normal in 22 of 39. MRI was abnormal in 34 of 42 patients and normal in 8 of 42. Pathology included brain tumors in 14 patients, mesial temporal sclerosis in 8, focal cortical dysplasia in 4, tuberous sclerosis in 4, dual pathology in 4, porencephalic cyst in 1 and normal pathology or gliosis in 6. Thirty-three of 42 patients (78%) were seizure-free following surgery and an additional 5 (12%) had a decrease in seizure frequency. Three patients had complications, but there were no deaths. Conclusion: Temporal lobectomy is a safe and effective treatment for children with intractable complex partial seizures. Seventy-eight percent of patients are seizure-free following the surgery and there are few complications. MRI is superior to CT scan for detection of temporal lobe pathology yet failed to detect abnormalities in some patients. The most common pathologies found were brain tumors, mesial temporal sclerosis and developmental lesions. In addition to seizure control, many patients experienced improvement in cognitive and psychosocial function following surgery.

Effects of Photoradiation Therapy on Normal Rat Brian

Laser photoradiation of the brain via an optical fiber positioned 5 mm above a burr hole was performed after the injection of hematoporphyrin derivative (HpD) in 33 normal rats and 6 rats with an intracerebral glioma. Normal rats received HpD, 5 or 10 mg/kg of body weight, followed by laser exposure at various doses or were exposed to a fixed laser dose after the administration of HpD, 2.5 to 20 mg/kg. One control group received neither HpD nor laser energy, and another was exposed to laser energy only. The 6 rats bearing an intracranial 9L glioma were treated with HpD, 5 mg/kg, followed by laser exposure at various high doses. The temperature in the cortex or tumor was measured with a probe during laser exposure. The rats were killed 72 hours after photoradiation, and the extent of necrosis of cerebral tissue was measured microscopically. In the normal rats, the extent of brain damage correlated with increases in the dose of both the laser and the HpD. In all 6 glioma-bearing rats, the high laser doses produced some focal necrosis in the tumors but also damaged adjacent normal brain tissue. We conclude that damage to normal brain tissue may be a significant complication of high dose photoradiation therapy for intracranial tumors.

Pediatric epilepsy surgery at the University of Alberta: 1988-2000

Epilepsy surgery is considered a treatment option for patients with intractable seizures. Relatively few studies of efficacy, safety, and long-term outcome are available for the pediatric age group. This study describes a 12-year experience with pediatric epilepsy surgery at the University of Alberta. Records of pediatric epilepsy surgery patients admitted to the Comprehensive Epilepsy Program at the University of Alberta between 1988 and 2000 were reviewed. All patients received preoperative and postoperative clinical evaluation, seizure charts, testing of drug levels, electroencephalogram, computed tomography/magnetic resonance imaging, neuropsychologic testing, and long-term video electroencephalogram monitoring. The patients were reassessed after surgery at 6 weeks, 6 months, and 1 year and then yearly. The duration of follow-up was 1 year to 12 years. Forty-two patients underwent temporal lobectomies; 35, extratemporal resection. The age at surgery ranged from 6 months to 16 years. Thirty-two (76%) of temporal lobe patients became seizure-free (Engel Class I) vs 24 (68%) for the extratemporal group (Engel Class I). One patient (2%) in the temporal group had an Engel Class II outcome and one patient (3%) in the extratemporal group had the same Engel Class II outcome. Three patients (4%) manifested postoperative complications, and there were no deaths. Patients reported improvement in cognitive abilities, behavior, and quality of life after the surgery. Epilepsy surgery in children is effective and safe. Many children are seizure-free after the operation and remain so, although the results of temporal lobectomy are better than for extratemporal resections. There are few complications, and children often have an improved quality of life.

Photoradiation therapy: Current status and applications in the treatment of brain tumors

Photoradiation therapy is achieved when a photosensitizing drug is activated by light to form products that are lethal to tumor cells. The most commonly used drug is hematoporphyrin derivative, which is preferentially taken up and retained by malignant tissue. Photoactivation is usually produced by using a dye laser tuned at 630 nm (red light). The primary mechanism of neoplastic cell damage in photoradiation therapy involves the production of free radicals formed during illumination of hematoporphyrin derivative by light of this wavelength. The treatment would seem to damage first the tumor cell membrane, then the cytoplasmic inclusions, and finally the nucleus. Photoradiation therapy has been quite effective in the treatment of superficial malignancies, especially in skin, breast, eye, bladder, bronchus, and stomach. Experience with brain tumors is still limited. Important unresolved problems in the application of photoradiation therapy to gliomas include relative uptake of hematoporphyrin derivative into the tumor, limited light penetration of the tissue, local heating, and damage induced in normal brain by photoradiation therapy.

Pathology and Neuroimaging in Pediatric Temporal Lobectomy for Intractable Epilepsy

Objectives: Firstly, to study the pathology at surgery in children undergoing temporal lobectomy for intractable partial epilepsy. Secondly, to compare neuroimaging techniques (CT, MRI) in the preoperative detection of pathology. Lastly, to examine the surgical outcome in children. Methods: Forty-two pediatric patients undergoing temporal lobectomy for intractable epilepsy at the Comprehensive Epilepsy Program at the University of Alberta Hospital between the years 1988–1998 were studied. Patients had extensive preoperative investigations including CT and MRI. The pathology at surgery was reviewed and compared to preoperative neuroimaging. Charts were reviewed to determine surgical outcome. Results: Brain tumors were the most common pathology, found in 13/42 patients. Mesial temporal sclerosis (MTS) was found in 8 patients and dual pathology in an additional 5. Focal cortical dysplasia (FCD) was seen in 4 patients, 1 patient had a porencephalic cyst and 4 patients had tubers of tuberous sclerosis. Seven patients had no specific pathology detected. MRI was clearly more sensitive than CT in the detection of pathology. MRI was abnormal in 27/42 cases (64%), while CT scan was found to be abnormal in only 12/39 (31%). Surgical outcome was excellent, with 34/42 patients (80%) having an Engel class I outcome. One patient had significant improvement with an Engel class II outcome, 3 (7%) had little improvement (Engel class III) and 4 (10%) were unchanged (Engel class IV). Three patients (7%) had surgical complications. Conclusions: A wide variety of developmental pathology is seen following temporal lobectomy for intractable epilepsy of childhood. Brain tumors, FCD and MTS are common. MRI is superior to CT in the detection of pathology, which may be subtle in children. Surgical outcome is excellent, with most children being seizure free and few complications being seen.

First Report of Schistosoma mekongi Infection with Brain Involvement

We describe, to our knowledge, the first reported case of Schistosoma mekongi infection with brain involvement. S. mekongi is a distinct species most closely related to Schistosoma japonicum that is endemic in a defined area of the Mekong River in Laos and Cambodia and characteristically associated with hepatosplenic disease. The patient had an excellent response to praziquantel therapy but required repeated courses of corticosteroid therapy to suppress recrudescent neurological symptoms.

Penetration of hematoporphyrin derivative into rat brain and intracerebral 9L glioma tissue.

SummaryBrain and glioma tissue levels of tritiated hematoporphyrin derivative (3H-HPD) were measured in normal and 9L intracerebral glioma-bearing rats at 24 hours following administration of3H-HPD 2–20 mg/kg and at 24–120 hours after3H-HPD 10 mg/kg. Levels of3H-HPD in blood, liver, spleen and muscle were also measured.Tissue levels of3H-HPD increased progressively as the dose was increased. In animals given 10 mg/kg, gradual decreases in tissue levels occurred between 24 and 72 hours but thereafter remained stable. The3H-HPD level in gliomas was consistently 2–3 × greater than in brain tissue, despite changes in dosage and time interval. High levels of activity were measured in normal brain tissue at all dosage levels, and subsequent clearance of the3H-HPD from brain, glioma, and other tissues was slow; at 120 hours after administration of 10 mg/kg, approximately 50% of the 24 hour level was still present.These results indicate that although a dose- and time-independent preferential uptake of hematoporphyrin derivative occurs in intracerebral gliomas, persistent high levels may be present in the surrounding brain. The disadvantages of using hematoporphyrin derivative rather than its individual components in studies of HPD uptake and photosensitization in the brain are discussed.

Photoradiation therapy of 9L-gliosarcoma in rats: hematoporphyrin derivative (types I and II) followed by laser energy

SummarySuspensions of 9L-gliosarcoma cells were inoculated into the brain or flank of rats and photoradiation therapy (PRT) was applied to the resulting tumors. The PRT consisted of hematoporphyrin derivative (HpD), type I or II, followed by single-fiber laser energy 24, 48, or 72 h later. Necrotic foci in brain tumors were most numerous following laser exposure 24 h after HpD; they were more than twice as common, and with less damage to healthy tissue, after HpD II than after HpD I with the same laser dose. Neither lifespan nor the final weight of brain tumor was affected by the type of HpD or whether PRT was applied once or twice. In rats with flank tumor, multiple PRT (up to × 4) did not delay tumor growth; also, 11 of 12 PRT-treated flank tumors grew after implantation at various sites in healthy rats. We conclude that HpD II is a more effective photosensitizer than HpD I. However, the value of PRT will be limited until a lethal dose of laser energy can be delivered throughout a tumor without destroying vital healthy tissue.

Glutathione levels and chemosensitizing effects of buthionine sulfoximine in human malignant glioma cells

SummaryBiopsy samples and cultured cells derived from them were obtained from 39 patients with malignant glioma and were analyzed for 1) glutathione (GSH) content; 2) sensitivity to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and/or nitrogen mustard (HN2) treatment and 3) the effect of buthionine sulfoximine (BSO) treatment on BCNU and/or HN2 cytotoxicity. The average GSH concentration of biopsy specimens was lower than those of cultured cells (2.36±0.44 vs. 11.42±2.32 nmol/106 cells). While some of the tumor specimens were sensitive to either BCNU or HN2, the majority were resistant to both. However, 8 of 23 tumors tested showed enhanced sensitivity to BCNU following treatment with BSO. Five of 17 tumors were similarly sensitized to HN2 by BSO. These results suggest that BSO chemosensitization may be of value for certain patients and that screening assays may help identify treatment-sensitive individuals.

Misonidazole combined with photodynamic therapy of rat 9L gliosarcoma tumours

Fifty-six Fischer 344 rats bearing subcutaneous 9L-gliosarcoma tumours were studied to determine if Misonidazole (MISO), combined with photodynamic therapy (PDT), would be more effective than PDT alone. PDT, like conventional radiation, is potentiated by oxygen, and if there are areas of hypoxic cells within the tumour it is possible that the addition of the radiosensitizing drug should make the treatment more effective. Thirty-nine rats were divided into eight groups as controls. Seventeen rats were divided into three groups and received MISO combined with PDT, five rats were exposed to a laser dose of (nm = 630) 300 J at 300 mW, seven rats to a laser dose of 600 J at 600 mW and five rats to a laser dose of 2160 J at 600 mW. The tumours were approximately 1 cm3 when treated. Animals treated with either PDT at 300 J or 600 J failed to show any effect on growth of the tumour. At 2160 J a definite delay in growth was observed but addition of MISO did not potentiate this effect. The results indicate this combined therapy did not slow the growth rate of the tumours in this model. The implication of these results are discussed.