The term epileptic seizures is used to describe a variety of paroxysmal signs and symptoms resulting from a large number of underlying pathological processes. Generalized tonic-clonic convulsions, therefore, reflect entirely different basic neuronal mechanisms than those of typical absences. Animal research suggests that the former result from disturbances that involve disinhibilion, whereas the abnormality giving rise to the latter requires intact, if not enhanced, inhibition in order to sustain hypersynchronous neuronal discharges. Investigations in human mesial temporal lobe epilepsy and chronic experimental animal models indicate that partial seizures can also reflect multiple underlying mechanisms, with some disinhibitory in type, while others appear to be hypersynchronous and associated with enhanced inhibition. Just as more than one epileptogenic disturbance can result in transition to ictus, it is likely that more than one mechanism can be engaged to terminate epileptic seizures, that these diverse processes could result in different postictal manifestations, and that they could conceivably contribute differently to the development of interictal behavioral disturbances. An appreciation for the fact that epilepsy is not merely an increase in excitation and/or a decrease in inhibition, but a variety of complicated neuronal interactions in different patients, or even at different times in the same patient or same seizure, is essential to the development of effective treatments to control epileptic seizures and prevent their consequences.

Background and Purpose: We examined the efficacy of the antioxidant LY231617 administered five hours following middle cerebral artery (MCA) occlusion in rats. Methods: The treatment was contrived for a two hour interval. Group A (n=16) was left untreated. Group B (n=16) received an intravenous infusion of LY231617. Group C (n=6) received saline (86 μI/min) by retrograde infusion of the cerebral vein (RICV). Group D (n=22) was administered LY231617 (10mg/kg/2hr) in saline (86μI/min) by RICV. Local cerebral blood flow with [14C]-iodoantipyrine and blood-brain transfer constant with 14C-α-amino-isobutyric acid were examined. Early ischemic damage was histologically examined with cresyl violet and Luxol fast blue and with triphenyl-tetrazolium chloride. Results: The results revealed a marked increase in local cerebral blood flow (over 600%, p < 0.01) after RICV with LY231617, with a significant improvement of BBB permeability in rats from group D. Ischemic brain damage measured with Luxol fast blue and triphenyl-tetrazolium chloride methods showed a significant improvement (50-91 %) of ischemic damage in group D, as compared to groups B and C. Conclusion: Retrograde infusion of the cerebral vein with LY231617 resulted in a significant amelioration at seven hours post MCA occlusion.

Background: Using a population-based register of the Saguenay-Lac-Saint-Jean region (Quebec, Canada), the genealogical reconstruction of 533 individuals with intracranial aneurysm (IA) showed a familial aggregation (the presence of aneurysm in two or more first- to third-degree relatives) for 159 (29.8%) of them; this proportion is much higher than reported elsewhere. Objective: As part of an ongoing project to assess a genetic predisposition to intracranial aneurysms in the Saguenay-Lac-Saint-Jean population, the objective of the present study was to determine whether age-specific rates of ruptured cerebral aneurysms were higher than in other populations. Design: A retrospective study of cases of proven ruptured I As which were hospitalized during the 1973 to 1992 period was conducted. Age-adjusted rates were computed and compared to those reported in the Helsinki population. Results: We identified 412 cases of ruptured aneurysms. The age-adjusted incidence rate was 7.2/100,000/year (6.2 for men, 8.1 for women), which is similar to the incidence rates reported in other studies. Although the mean age at time of rupture was younger (46.6 years ± 13.8) than usually reported, no increase in age-specific incidence rates was detected. Conclusions: The results of this epidemiological study neither support nor reject the hypothesis of a genetic predisposition to intracranial aneurysms in the Saguenay-Lac-Saint-Jean population.

Background: No clinical parameter other than “sufficient” dopamine denervation and exposure to exogenous levodopa has been unquestionably linked to dyskinesia in levodopa-treated Parkinson’s disease patients. Methods: We retrospectively analyzed data on 100 consecutive patients treated with levodopa for 1 to 18 years to identify clinical risk factors for dyskinesia. The cumulative dyskinesia-free survival probability in relation to levodopa therapy was assessed using the Kaplan-Meier method. Results: Overall, 56% of patients developed dyskinesia after a mean of 2.9 years, a figure similar to the average duration of levodopa treatment in the non-dyskinetic group. Dyskinetic patients were significantly younger at disease onset, but their mean latency to dyskinesia induction after levodopa initiation was not different from older dyskinetic individuals and the overall dyskinesia-free survival of younger subjects was not worse either. Dyskinetic patients were on a higher daily levodopa dose than non-dyskinetic subjects when dyskinesia emerged, but the cumulative levodopa dose used prior to dyskinesia did not discriminate dyskinetic from non-dyskinetic patients. A delay in initiating levodopa therapy of more than three years after disease onset and levodopa treatment initiation in Hoehn-Yahr stage II compared to stage I patients did not increase the probability of developing dyskinesia over time. Conclusions: Since withholding levodopa therapy did not increase the risk for dyskinesia in our patients and can delay the emergence of dyskinesia after onset of parkinsonian symptom, a trial with a dopaminomimetic agonist as initial treatment appears logical.

Background: There is currently no consensus on the best way to localize muscles in the forearm for botulinum toxin (BTX) injection. We devised a study to compare electromyography (EMG) with local stimulation through a cannula for localizing forearm muscles for botulinum toxin (BTX) injection, and for predicting the risk of unwanted weakness in non-target muscles. Methods: In 12 patients with focal hand dystonia a single “target” muscle, determined by clinical examination to contribute most to the dystonic hand posture, was selected for botulinum toxin injection. The patients were randomized into 2 treatment groups, one in which the target muscle was localized by recording the EMG signals during voluntary contractions (8 patients) and the other in which the target muscle was localized by local electrical stimulation (4 patients). The target muscle was then injected with a standardized dose of BTX. Results: At follow-up 3 weeks after BTX injection the target muscle was weakened in 7/12 patients (4/8 of the EMG group, and 3/4 of the stimulation group). Additional non-injected muscles, adjacent to the target muscle, were weakened in 5 of these 7 patients, presumably from diffusion of the toxin. Conclusions: Localization by stimulation is probably at least as good as EMG. Each technique has certain advantages. Weakness of “non-target” muscles was not consistently predicted by either EMG or stimulation suggesting that BTX diffuses farther than the volume conduction of EMG signals or the spread of effective stimulus current.

Objective: To present guidelines on the use of apomorphine in combination with rectal domperidone in Parkinson’s disease (PD) patients undergoing abdominal surgery and to review the perioperative problems encountered in such patients. Background: PD patients undergoing abdominal surgery present a major therapeutic challenge. Because most antiparkinsonian medications must be withheld until the patient is able to resume oral intake, resulting rigidity and akinesia as well as alterations in gastrointestinal motility, respiratory function and swallowing mechanisms predispose these patients to numerous serious postoperative complications. We have found that parenteral apomorphine in combination with rectal domperidone markedly facilitates the care of these difficult patients. Methods: Presentation of two illustrative cases with review of the literature. Results: A standardized protocol using subcutaneous apomorphine and rectal domperidone was used in two PD patients who underwent abdominal surgery. Excellent control of parkinsonian symptomatology was obtained without side effects. The simplicity of the protocol was emphasized in our second patient who required urgent reoperation; the surgery nursing staff was able to restart the apomorphine immediately without having to wait for neurological follow-up assessment. Conclusions: The use of parenteral apomorphine with rectal domperidone in the immediate postoperative period for patients unable to take oral antiparkinson drugs increases patient comfort, facilitates nursing care and may reduce serious postoperative complications.

Background: Focal gliomas involving the midbrain tectum and tegmentum have been identified as having a better prognosis than diffuse tumors affecting the brain stem. However, only limited information is available concerning treatment effectiveness and long term outcome for these patients. Methods: A retrospective, population-based cancer registry survey was performed to assess the clinical features and treatment courses of patients with focal midbrain tumors. Results: Sixteen patients with midbrain gliomas were identified; eight had tectal gliomas and eight tegmental gliomas. Thirteen patients presented with symptoms related to hydrocephalus, and 12 required a ventriculoperitoneal shunt. Seven patients underwent surgery directed at the tumor. Eight patients underwent initial radiation therapy and none had initial chemotherapy. One patient diagnosed at age 18 months had a rapidly growing tumor after 14 months of follow up which has responded to chemotherapy. The mean survival of this patient population was 84 months (range 3-280 months) after diagnosis, with only one tumor related death occurring (280 months after diagnosis). Survival was not affected by tumor location within the midbrain (tegmental or tectal) or by whether radiation therapy was or was not administered. Conclusions: Patients with focal midbrain gliomas require symptom control aimed at treatment of hydrocephalus, or mass effect from the tumor. However the extended survival of this population suggests that routine aggressive surgical debulking is often not required. Furthermore, the routine use of radiation therapy or chemotherapy for all such patients is questioned.

Background: The term, “triphasic wave” originally described an EEG pattern believed to be a marker for a specific stage of hepatic coma. For 4 decades, the diagnostic and prognostic specificity of the pattern remains controversial. Its pathophysiology also continues to be elusive. Methods: EEG recordings were obtained in three patients known or suspected to have primary generalized epilepsy. In 2 patients, the EEGs were part of long-term monitoring using simultaneous video-EEG telemetry. For the third patient, the EEG was secured only during the post-ictal unconsciousness. These 3 patients were specifically selected because of the presence of triphasic waves in their EEGs. Results: Triphasic waves were observed in the EEG of the 3 patients only during post-ictal unconsciousness. The pattern was transient, being preceded by generalized suppression and delta slow waves and followed by theta activities. Alpha rhythms supervened when the patients became fully alert. Conclusion: A post-ictal state should be considered in unconscious patients with triphasic EEG waves.

Background: Localizing critical brain functions such as language in children is difficult and generally requires invasive techniques. Recently sensory, motor and language functions in adults have been mapped to specific brain locations using functional imaging techniques. Of these techniques, functional MRI (fMRI) is the least invasive and has the highest spatial and temporal resolution. Its use in adults is well documented but application to children has not been as well described. In the present study lateralization and localization of language was evaluated with fMRI prior to epilepsy surgery in a nine-year-old male with complex partial seizures, attentional difficulty and decreased verbal proficiency. Methods: Two language paradigms well studied in adults (read, verb generation) and two additional language paradigms (antonym generation, letter fluency) were studied using whole brain fMRI after stimulus items and timing were adjusted to achieve the desired performance level during imaging. The patient was also conditioned to the magnet environment prior to imaging. Results: Word reading and letter fluency tasks produced lateralized and localized activation similar to that seen in adults. The patient had no language deficits following an anterior 2/3 dominant temporal lobe resection. Conclusions: With modifications of protocols such as those detailed in this report, this non-invasive method for localizing language function is feasible for the presurgical evaluation of children as well being applicable for a variety of developmental language issues.

Background: Intramedullary spinal cord abscess due to Listeria Monocytogenes is an uncommon condition usually affecting immunocompromised patients. Method: Case study. Results: A 69-year-old man presented with 3 weeks history of subacute paralysis of both lower limbs and the left upper limb. Myelogram and CT scan showed a widened upper cervical cord. CSF revealed lymphocytosis, moderately elevated protein and depressed glucose. A gadolinium-enhanced MRI showed diffuse cervical cord edema with two ring-enhancing lesions at C2-C3. Blood and CSF cultures grew Listeria Monocytogenes. He received IV ampicillin and gentamycin; the latter was discontinued after 1 month due to nephrotoxicity. Serial MRI over the next 3 months showed significant reduction in the size of these abscesses. The patient made a modest improvement in the power of his lower limbs, however he remained bed-ridden. Aside from being a mild, diet-controlled diabetic, there was no evidence of immunosuppression. Conclusion: Listeria spinal cord abscess is a treatable disorder and should be considered in the differential diagnosis in patients with a subacute onset of spinal cord dysfunction.

Background: Major neurological complications of sickle cell disease include cerebral infarction and intracranial hemorrhages. Methods: We describe the case of a 25-year-old man with sickle cell disease who developed a severe headache of acute onset, located at the vertex. There was associated pitting edema of the scalp. Results: Technetium and gallium bone imaging showed focal decreased uptake of the tracers, consistent with a recent fronto-parietal skull infarction. Management included intravenous hydration and analgesic medication. Conclusions: In addition to the more common intracranial vaso-occlusive complications, skull infarction should be considered as a cause of new-onset headache in patients with sickle cell disease, especially if scalp edema is present.

Background: Periodontoid synovial cysts are rare lesions which may produce symptomatic cervico-medullary compression. Method: We report such a patient, whose progressive neurological deterioration required surgical treatment by transoral odontoidectomy and decompression. Results: The diagnostic and theraputic interventions are described, including a lumbar puncture which precipitated a transient loss of consciousness and respiratory arrest. Surgery achieved clinical improvement, without complications or need for operative stablization. Detailed neuropathology is presented, as well as a literature review. Conclusion: Appropriate neuroradiological assessment is required in patients with suspected cervico-medullary compression, and symptomatic periodontoid synovial cysts may respond well to transoral surgical decompression.

Neurology has a proud tradition, built on the established principles of medicine, the scientific method of the 17th century and the clinical approach of the French and later the English schools of neurology in the 19th century and the first half of this century. In the post World War II era neurology was advanced by the development of neurological training centers, the discovery of new pharmacological and neurosurgical therapies, and most recently by in the exciting advances in neurogenetics. These changes have broadened and advanced the scope of our discipline by focusing on the disease processes that affect the nervous system. I would like to suggest an additional conceptual framework to broaden it further. That concept is a population health perspective that should place our various approaches in closer relationship to the communities they serve.