Commentary: physical approaches for the treatment of epilepsy: electrical and magnetic stimulation and cooling.

Physical approaches for the treatment of epilepsy currently under study or development include electrical or magnetic brain stimulators and cooling devices, each of which may be implanted or applied externally. Some devices may stimulate peripheral structures, whereas others may be implanted directly into the brain. Stimulation may be delivered chronically, intermittently, or in response to either manual activation or computer-based detection of events of interest. Physical approaches may therefore ultimately be appropriate for seizure prophylaxis by causing a modification of the underlying substrate, presumably with a reduction in the intrinsic excitability of cerebral structures, or for seizure termination, by interfering with the spontaneous discharge of pathological neuronal networks. Clinical trials of device-based therapies are difficult due to ethical issues surrounding device implantation, problems with blinding, potential carryover effects that may occur in crossover designs if substrate modification occurs, and subject heterogeneity. Unresolved issues in the development of physical treatments include optimization of stimulation parameters, identification of the optimal volume of brain to be stimulated, development of adequate power supplies to stimulate the necessary areas, and a determination that stimulation itself does not promote epileptogenesis or adverse long-term effects on normal brain function.

Aphasic or amnesic status epilepticus detected on PET but not EEG.

PURPOSE: To describe five patients with ictal aphasia and one patient with ictal amnesia, who had focal positron emission tomography (PET) hypermetabolism but no clear ictal activity on electroencephalography (EEG). METHODS: (18)F-Fluorodeoxyglucose (FDG)-PET scans with concomitant EEG were obtained in five patients with suspected ictal aphasia or ictal amnesia without ictal activity on EEG. We reviewed medical history, EEG, imaging data, and treatment outcome. RESULTS: Brain magnetic resonance imaging (MRI) showed no structural abnormalities in any of the patients. EEG showed left temporal irregular delta activity in three patients, with aphasia and nonspecific abnormalities in two other patients, all without clear ictal pattern. All patients demonstrated focal hypermetabolism on PET scan. The hypermetabolism was in the left frontotemporal region in patients with ictal aphasia and in the bilateral hippocampal region in the patient with amnesia. Three patients who received intravenous benzodiazepines during their episodes had transient clinical improvement. With antiepileptic drug (AED) treatment, symptoms gradually resolved in all patients. Concomitant resolution of PET hypermetabolism was documented in three patients who had follow up scans. One patient with ictal aphasia later developed recurrent episodes, each with recurrent PET hypermetabolism. This patient and one other patient required immune-modulating therapy in addition to AEDs. DISCUSSION: FDG-PET imaging should be considered as a diagnostic tool in patients with suspected ictal aphasia or amnesia, who fail to show clear evidence of ictal activity on EEG.

Effects of a static magnetic field on audiogenic seizures in black Swiss mice.

Effects of a static magnetic field (SMF) with strong gradient components were studied in black Swiss mice. Exposure to SMF (100-220 mT, 15-40 T/m for 1h) did not affect the threshold for detecting auditory brainstem responses. Serial seizures elevated the hearing threshold at some frequencies, but there was no difference between SMF-exposed and unexposed control mice. EEG changes were recorded during audiogenic seizures. Pretreatment with SMF prolonged seizure latency in response to stimulation with white noise of increasing intensity from 74 to 102 dBA (1 min interval between 2 and 4 dBA increments) without significant effects on seizure severity. Gender-related differences were not statistically significant. Stimulation with 10 min sound steps revealed prolongation of latency and reduction of seizure severity in SMF-exposed, but not unexposed, mice. Pretreatment with phenytoin (5 mg/kg) in combination with SMF had significantly greater effects on seizure latency and severity than either pretreatment alone. These findings indicate that the SMF studied here under different conditions elevated seizure threshold and had anticonvulsant properties in Black Swiss mice and increased the efficacy of a conventional anticonvulsant drug.

Clinical features of epilepsy in patients with cerebellar structural abnormalities in a referral center.

PURPOSE: The objective of this study was to describe epilepsy localization, clinical features and surgery outcome in patients with epilepsy and cerebellar structural abnormalities. METHODS: We identified 10 patients with cerebellar lesions and epilepsy from our epilepsy database. Patients with only cerebellar atrophy were excluded. Medical records were reviewed for demographic data, seizure history, examination findings, EEG findings, epilepsy treatment and course. We reviewed imaging data for cerebellar structural findings, as well as cerebral abnormalities. RESULTS: Out of 2288 epilepsy patients in the database, 10 had epilepsy and cerebellar structural abnormalities other than atrophy. Their ages ranged from 26 to 52 years. The most common cerebellar malformations included Dandy-Walker malformation, cerebellar tumors and posterior fossa arachnoid cyst. Epilepsy was classified as generalized in one patient. Nine patients had focal epilepsy: the localization was temporal in five, frontal in one, occipital in one, and unclassified in two. A cerebral structural abnormality considered responsible for epilepsy was identified in six patients; four had hippocampal sclerosis, one had a hippocampal malformation, and one had a temporal pole cortical malformation. Presurgical evaluation was done in six patients. Surgery was performed in five, with excellent outcome in four. CONCLUSION: In this small series, epilepsy associated with cerebellar malformations was usually focal, most often with a temporal lobe focus. The cerebellar lesions did not adversely affect surgical success.

Diabetic peripheral neuropathic pain: case studies.

Three case reports in this article illustrate the diagnostic methods used and the treatment course encountered for many patients with diabetic peripheral neuropathic pain (DPNP). Each case addresses an aspect of DPNP: pain that appears to be refractory to initial therapy, DPNP occurring with other medical conditions, and nondiabetlc neuropathy occurring in patients with diabetes mellitus. Together, these cases bring clarity to the confusing clinical experience for patients who have decreased sensation in combination with burning pain, and they apply the consensus guidelines for DPNP. Recently approved medications by the Food and Drug Administration for the treatment of DPNP offer hope for many patients whose pain was thought to be refractory to treatment.

Consensus guidelines: treatment planning and options. Diabetic peripheral neuropathic pain.

Despite the number of patients affected by diabetic peripheral neuropathic pain (DPNP), little consensus exists about the pathophysiology, best diagnostic tools, and primary treatment choices. Theories about the causes of DPNP are inextricably linked with the causes of diabetic neuropathles, yet most patients with such neuropathies do not experience pain. The factors that differentiate patients with pain from those without remain unknown and are the subject of much research. When choosing treatment for patients with DPNP, physicians are confronted with a myriad of choices, none of which has been shown to be effective for all patients. This article reviews the evidence for these treatments and attempts to guide physicians in choosing those treatments based on evidence from well-designed clinical trials to support their use. Two agents, duloxetine and pregabalin, are formally approved by the Food and Drug Administration for the treatment of DPNP. In addition, several other agents, including the tricyclic class of antidepressants, have been effective in clinical trials. Ultimately, treatment choice must also Include consideration of adverse effects, individual patient factors such as comorbidities, and often cost.

Devices for gradient static magnetic field exposure.

We describe devices designed for magnetic field exposures in which field amplitude and gradients are controlled simultaneously. Dosimetry based on field continuation of high resolution magnetic field scans and numerical models is compared with validation measurements. The dosimetry variables we consider are based on the assumption that the biological or chemical system under study has field transducers that are spatially isotropic, so that absolute field amplitude and two gradient components fully describe local exposure.

Gabapentin dosing in the treatment of epilepsy.

BACKGROUND: Gabapentin is considered a safe and well-tolerated antipileptic drug (AED) with a favorable pharmacokinetic profile and a broad therapeutic index. However, recent studies have used higher doses and faster titration schedules than those used in the pivotal trials that established the efficacy of gabapentin in the treatment of partial seizures. OBJECTIVE: The purposes of this review were to assess the gabapentin titration and dosing regimens that have been published in peer-reviewed journals, to develop dosing recommendations to maximize antiseizure efficacy without compromising tolerability, and to formulate guidelines for an adequate therapeutic assessment of gabapentin dosage efficacy. METHODS: In the absence of sufficient placebo-controlled, double-blind studies, a formal evidence-based assessment could not be performed. However, a MEDLINE search using the search terms gabapentin and epilepsy, spanning back to the year 1986, produced numerous published reports from randomized, placebo-controlled and open-label trials, as well as case reports. These were reviewed to assess the range of dosing and titration schedules reported. Reports that employed gabapentin doses and titration schedules were selected for review. RESULTS: Our review of this literature suggests improved seizure control at higher gabapentin maintenance dosages (< or =3600 mg/d) than are used today in clinical practice (1800 mg/d) without an increase in the incidence of adverse reactions. Most of the patients who received high dosages (eg, 3600 mg/d) or experienced fast titration rates tolerated gabapentin well. Side effects occurred around the onset of dosing and were reported in some studies to be transient. CONCLUSIONS: Based in the literature here, in most adult patients, gabapentin may be initiated at a dosage of 900 mg/d and titrated to maintenance dosages > or = 3600 mg/d. Children may be treated with gabapentin 23 to 78 mg/kg per day. Based on controlled and open trials, the majority of patients will tolerate gabapentin well enough for an adequate therapeutic assessment. Titration to effect can be accomplished rapidly, if necessary; however, as with other AEDs, optimal seizure control may take months to achieve.

Effects of non-uniform static magnetic fields on the rate of myosin phosphorylation.

The effect on myosin phosphorylation from exposure to a magnetic field generated by an array of four permanent magnets was investigated. Two lateral positions in the non-uniform field over the array were explored, each at four vertical distances over the surface of the device. The rate of myosin phosphorylation was found to depend on the position laterally over the array as well as the distance from the device surface. The square magnet array was comprised of axially magnetized, cylindrical NdFeB permanent magnets arranged with poles of alternating polarity in a plane (MagnaBloc trade mark therapeutic device). Detailed dosimetry of the magnet array was compiled: the magnetic flux density averaged over the exposure volume spanned the range 0.7-86 mT for the eight different exposure positions. The corresponding range for the absolute field gradient was 0.4-20 T/m. Comparing the dosimetry to the experimental outcome, our results imply that magnetic field amplitude alone is not sufficient to describe the influence of the field in this preparation.