Novel in vivo Assessment of Unruptured Intracranial Aneurysm Inflammatory Factors.

Background and Purpose: The growth and eventual rupture of intracranial aneurysms may be due to an underlying inflammatory process as evidenced by pathological examination of aneurysm walls. We hypothesize that unruptured aneurysms have an increased inflammatory milieu within their lumen in comparison to the rest of the cerebral arterial vascular system. Methods: Blood was sampled from unruptured aneurysms in patients presenting for aneurysm coil embolization and C3 and C4 complement values from this serum were compared with complement values in the parent artery. Results: Ten patients were enrolled over 32 months with a mean aneurysm size of 9.1 mm. Compared to control samples drawn from peripheral circulation, there were significant decreases of both C3 (p = 0.0003) and C4 (p = 0.0063) levels in aneurysmal blood samples. Conclusions: A state of decreased complement indicative of classic pathway activation was found in all tested aneurysms, thus providing evidence of an ongoing process of complement activation in the blood of live, unruptured aneurysm sacs.

Neuronal Entropy-Rate Feature of Entopeduncular Nucleus in Rat Model of Parkinson's Disease.

The function of the nigro-striatal pathway on neuronal entropy in the basal ganglia (BG) output nucleus, i.e. the entopeduncular nucleus (EPN) was investigated in the unilaterally 6-hyroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease (PD). In both control subjects and subjects with 6-OHDA lesion of dopamine (DA) the nigro-striatal pathway, a histological hallmark for parkinsonism, neuronal entropy in EPN was maximal in neurons with firing rates ranging between 15 and 25 Hz. In 6-OHDA lesioned rats, neuronal entropy in the EPN was specifically higher in neurons with firing rates above 25 Hz. Our data establishes that the nigro-striatal pathway controls neuronal entropy in motor circuitry and that the parkinsonian condition is associated with abnormal relationship between firing rate and neuronal entropy in BG output nuclei. The neuronal firing rates and entropy relationship provide putative relevant electrophysiological information to investigate the sensory-motor processing in normal condition and conditions such as movement disorders.

Using a virtual training program to train community neurologist on EEG reading skills.

BACKGROUND: EEG training requires iterative exposure of different patterns with continuous feedback from the instructor. This training is traditionally acquired through a traditional fellowship program, but only 28% of neurologists in training plan to do a fellowship in EEG. PURPOSE: The purpose of this study was to determine the value of online EEG training to improve EEG knowledge among general neurologists. METHODS: The participants were general neurologists invited through bulk e-mail and paid a fee to enroll in the virtual EEG program. A 40-question pretest exam was performed before training. The training included 4 online learning units about basic EEG principles and 40 online clinical EEG tutorials. In addition there were weekly live teleconferences for Q&A sessions. At the end of the program, the participants were asked to complete a posttest exam. RESULTS: Fifteen of 20 participants successfully completed the program and took both the pre- and posttest exams. All the subjects scored significantly higher in the posttest compared to their baseline score. The average score in the pretest evaluation was 61.7% and the posttest average was 87.8% (p = .0002, two-tailed). CONCLUSIONS: Virtual EEG training can improve EEG knowledge among community neurologists.

Development of a therapeutics curriculum to enhance knowledge of fourth-year medical students about clinical uses and adverse effects of drugs.

BACKGROUND: Enhanced clinical pharmacology and therapeutics education of medical students is important for improving effective and safe drug therapy. Increased education about pharmacovigilance is needed because serious drug-induced adverse effects are increasing. Fostering the needed scientific approach to prescribing requires knowledge of evidence-based drug therapy, based on understanding clinical trials. Therapeutic agents with novel mechanisms of action are increasingly available, and an unbiased understanding of the risks and benefits of novel agents is also important. These issues can be addressed in clinical pharmacology courses. However, many medical schools lack sufficient clinical pharmacologists to teach such courses. The Southern Illinois University Medical School faculty implemented an Advanced Therapeutics course to address these issues. DESCRIPTION: Development of this course involved defining appropriate content and organizing preclinical pharmacology and clinical faculty into teaching teams. The course was offered to 4th-year medical students and covered clinical trial information, and cutting-edge therapeutic developments. The "ABCs of Pharmacology" is a mental algorithm that was presented in the sophomore year and reintroduced in this course. This algorithm emphasizes pharmacovigilance, which stresses the balance between positive and negative effects of pharmacological agents. General principles of clinical pharmacology and therapeutics were covered by a clinical pharmacologist. Most sessions on specific disease treatment involved an integrated presentation by a preclinical pharmacologist and a clinician with expertise in that topic, often in the context of clinical cases. Other important topics were emphasized, which reinforce individualization of therapy, including pharmacogenomics that may determine idiosyncratic responses. Feedback during and following the course was obtained via questionnaires. EVALUATION: This approach was well received by participating students and graduates. Most students rated this course as a valuable experience. CONCLUSION: This approach appears useful for educating medical students about therapeutics at medical schools that lack sufficient clinical pharmacology faculty to mount such a course.

Metabolic changes in rat striatum following convulsive seizures.

Generalized convulsive seizures increase glucose utilization within the brain but their impact on metabolism is not well known. The striatum receives excitatory input from widespread sources in the brain and could potentially reflect energy depletion in the brain resulting from generalized seizures. We utilized multiprobe microdialysis in freely moving rats subjected to maximal electroshock to simultaneously measure glucose, lactate, and pyruvate levels in the interstitial space within striatum and in peripheral subcutaneous tissue. A brief convulsive seizure was associated with marked changes in striatal and peripheral metabolism during the post-ictal state that lasted up to 1 h. There were significant central and peripheral elevations of glucose, pyruvate, and lactate, reflecting increased glucose metabolism. Interestingly, the lactate-to-pyruvate ratio increased significantly in the periphery but remained unchanged in the striatum. Thus, there appears to be brain mechanisms that maintain adequate energy sources and prevent anaerobic shift during the post-ictal state.

Effect of cotherapy reduction on tolerability of epilepsy add-on therapy: a randomized controlled trial.

BACKGROUND: Adverse effects are the most common cause for failure of an antiepileptic drug (AED), especially when an AED is added to existing therapy. With the increased drug load, it may not be possible to titrate the newly added AED to effective doses. Reducing the dosage of AED cotherapy as the new drug is introduced may improve tolerability. OBJECTIVE: To evaluate reduction of AED cotherapy as a strategy to improve tolerability and patient retention when a new AED is added to existing therapy. METHODS: In a 20-week, randomized, open-label study, topiramate was initiated as add-on therapy in adults and adolescents (> or =12 y of age) with inadequately controlled partial-onset seizures. Patients were randomized to receive treatment in which adverse events could be managed by adjustments in AED cotherapy (flex-dose group) or treatment in which AED cotherapy dosages remained fixed (fixed-dose group). Topiramate could be adjusted as needed in both groups. In the flex-dose group, patients exited randomized treatment when topiramate was discontinued. In the fixed-dose group, patients exited when AED cotherapy was reduced due to adverse events or when topiramate was discontinued. The primary study outcome was the percentage of patients exiting randomized treatment due to adverse events. RESULTS: The flex-dose group comprised 297 patients; 302 patients were in the fixed-dose group. Significantly fewer patients in the flex-dose group exited the study due to adverse events (16% vs 23% in the fixed-dose group; p = 0.02). In the flex-dose group, 10% (17 of 168) of patients discontinued topiramate due to adverse events after AED cotherapy was reduced versus 22% (29 of 129) when AED cotherapy was not reduced. CONCLUSIONS: Reduction of AED cotherapy is a useful strategy to improve tolerability and retention when topiramate is initiated as adjunctive therapy.

The effect of vagus nerve stimulation on migraines.

Vagus nerve stimulation (VNS) inhibits nociceptive behavior in animals. VNS might reduce pain in patients with VNS device implanted for intractable seizures. One case report described possible benefits on migraines. We contacted all patients who received VNS therapy for intractable epilepsy between 1993 and 1999 at Southern Illinois University, Springfield, Illinois. Patients who had concomitant chronic pain were subsequently interviewed. Pain intensity before and after VNS implantation was rated by the patient as average, worst, and least and on numeric rating scale from 1 to 10. Current pain measurements were compared to preimplantation by using Global Pain Relief Rating Scale. Of 62 patients who received VNS, 27 patients were interviewed; 4 patients had common migraine, and no other chronic pain syndromes were identified. All patients with migraine reported reductions in headache frequency and numeric rating scale score for average and least headache intensity. One patient reported complete relief of headaches. Improvement was reported to start 1 to 3 months after initiation of therapy. On Global Pain Relief Rating Scale, 1 patient reported complete pain relief, 2 reported a lot of pain relief, and 1 reported slight pain relief. Concomitant antiepileptic drugs were decreased in 3 patients and slightly increased in 1. VNS might be beneficial for prophylactic therapy of migraine.

Effects of seizure repetition on postictal and interictal neurocardiac regulation in the rat.

PURPOSE: Human epilepsy is associated with abnormalities in cardiac regulation, as measured by reductions of heart rate variability (HRV) and approximate entropy (ApEn), but it is not known how these abnormalities are related to seizure experience. METHODS: Baseline electrocardiogram (ECG) was recorded from seizure-naive rats. They were subjected daily to maximal electroshock (MES), which induced tonic seizures with hindlimb extension, for a total of 10 days. ECG was obtained for 30 min before and after the first and last seizure. R-R variability, spectral variability, and ApEn were calculated to determine changes in pre- and postictal cardiac regulation. Before the last seizure, interictal parameters were compared with baseline values to determine changes in interictal HRV as a consequence of seizure repetition. Postictal values obtained after the last seizure were compared with the initial postictal data to look for changes in postictal cardiac regulation. RESULTS: During the postictal state, a mild, but significant, loss of ApEn was present after either the first or last seizure. Seizure repetition induced loss of R-R variability and high-frequency spectral band, which was present both interictally and postictally. CONCLUSIONS: The results suggest that convulsive seizures are associated with an immediate reduction of the complexity of cardiac rhythm regulation, as reflected by reductions of ApEn. Seizure repetition may induce long-term neural abnormalities in neurocardiac regulatory systems, especially parasympathetic, which limit appropriate autonomic responses. These acquired abnormalities may, in turn, predispose individuals to cardiac arrhythmia and sudden unexpected death in epilepsy.

Self-inflicted vocal cord paralysis in patients with vagus nerve stimulators. Report of two cases.

Vagus nerve stimulation for treatment of epilepsy is considered safe; reports of severe complications are rare. The authors report on two developmentally disabled patients who experienced vocal cord paralysis weeks after placement of a vagus nerve stimulator. In both cases, traction injury to the vagus nerve resulting in vocal cord paralysis was caused by rotation of the pulse generator at the subclavicular pocket by the patient. Traumatic vagus nerve injury caused by patients tampering with their device has never been reported and may be analogous to a similar phenomenon reported for cardiac pacemakers in the literature. As the use of vagus nerve stimulation becomes widespread it is important to consider the potential for this adverse event.

Cardiac dysrhythmia associated with the immediate postictal state after maximal electroshock in freely moving rat.

PURPOSE: Cardiac autonomic changes accompany complex partial seizures and generalized tonic-clonic seizures, and participate, at least partially, in the sudden and unexpected death in epilepsy (SUDEP). The analysis of the heart rate variability (HRV) is one of the simplest ways of providing insight into autonomic functions. The entropy quantifies the repetition of complex patterns in a signal and refers to systems randomness, regularity, and predictability. Clinical investigations have reported that entropy decreases in patients with a high risk of sudden cardiac death. The goal of this study was to evaluate the effects of the maximal electroshock (MES) on the entropy of HRV, monitored in the immediate postictal stage in the model of the freely moving rat. METHODS: Entropy changes were correlated with the high and low frequencies of spectral analysis, which reflect the participation of the sympathetic and parasympathetic activities. RESULTS: MES-induced arrhythmia is characterized by an HRV increase, an imbalance in favor of the parasympathetic activity, and a decrease in the entropy. Entropy decrease was restricted to the duration of the arrhythmia, suggesting that the postictal arrhythmia may be associated with a higher risk of lethal cardiac complications. Nevertheless, entropy changes did not correlate with spectral changes. CONCLUSIONS: The results suggest that the imbalance demonstrated in the spectral domain explains only partially the contribution of each autonomic system in the complexity of the heart rate during the postictal state.