Donald A. Ross

Lamotrigine for HIV-associated painful sensory neuropathies: A placebo-controlled trial

Objective: To evaluate the efficacy and tolerability of lamotrigine (LTG) for the treatment of pain in HIV-associated sensory neuropathies. Methods: In a randomized, double-blind study, patients with HIV-associated distal sensory polyneuropathy (DSP) received LTG or placebo during a 7-week dose escalation phase followed by a 4-week maintenance phase. Randomization was stratified according to whether or not patients were currently using neurotoxic antiretroviral therapy (ART). Results: The number of patients randomized was 92 (62 LTG, 30 placebo) in the stratum receiving neurotoxic ART and 135 (88 LTG, 47 placebo) in the stratum not receiving neurotoxic ART. Mean change from baseline in Gracely Pain Scale score for average pain was not different between LTG and placebo at the end of the maintenance phase in either stratum, but the slope of the change in Gracely Pain Scale score for average pain reflected greater improvement with LTG than with placebo in the stratum receiving neurotoxic ART (p = 0.004), as did the mean change from baseline scores on the Visual Analogue Scale for Pain Intensity and the McGill Pain Assessment Scale and patient and clinician ratings of global impression of change in pain (p ≤ 0.02). The incidence of adverse events, including rash, was similar between LTG and placebo. Conclusions: Lamotrigine was well-tolerated and effective for HIV-associated neuropathic pain in patients receiving neurotoxic antiretroviral therapy. Additional research is warranted to understand the differing response among patients receiving neurotoxic antiretroviral therapy compared with those not receiving neurotoxic antiretroviral therapy.

A direct brain interface based on event-related potentials

Cross-correlation between a trigger-averaged event-related potential (ERP) template and continuous electrocorticogram was used to detect movement-related ERPs. The accuracy of ERP detection for the five best subjects (of 17 studied), had hit percentages >90% and false positive percentages <10%. These cases were considered appropriate for operation of a direct brain interface.

In vivo cerebral metabolism and central benzodiazepine‐receptor binding in temporal lobe epilepsy

Positron emission tomography measured interictal cerebral glucose metabolism with [18F]fluorodeoxyglucose and central benzodiazepine-receptor binding with [11C]flumazenil in 10 mesial temporal lobe epilepsy (TLE) patients and in normal subjects. Eight TLE patients had mesial temporal, lateral temporal, and thalamic hypometabolism ipsilateral to EEG ictal onsets, with additional extratemporal hypometabolism in four. One had unilateral anterior mesial temporal hypometabolism only, and one had normal metabolism. Each patient had decreased benzodiazepine-receptor binding in the ipsilateral anterior mesial temporal region, without neocortical changes. Thus, interictal metabolic dysfunction is variable and usually extensive in TLE, whereas decreased central benzodiazepine-receptor density is more restricted to mesial temporal areas. Metabolic patterns in TLE may reflect diaschisis, while benzodiazepine-receptor changes may reflect localized neuronal and synaptic loss that is specific to the epileptogenic zone. [11C]Flumazenil imaging maybe useful in presurgical evaluation of refractory complex partial seizures.

Radiologic characteristics and results of surgical management of rathke's cysts in 43 patients

Although Rathkes cysts are a relatively common autopsy finding, rarely have they been reported as a clinical entity. Because of recent improvements in neuroradiological imaging, cystic intrasellar and suprasellar lesions are discovered often, leading to questions about proper management. Against this background, we reviewed the data from 43 patients with Rathkes cysts treated by one neurosurgeon over a 13-year period, and present the results here. The 43 patients had a mean age of 34 years, and 77% were female. Headache was the most common symptom, followed by galactorrhea, visual field loss, and hypopituitarism. Computed tomographic (CT) scans were reviewed in 20 cases, magnetic resonance (MR) images were reviewed in 15, and both CT and MR studies were reviewed in 5 cases. Although all Rathkes cysts were discrete and well-defined by both CT and MR imaging, the diversity of locations, CT attenuations, and MR signal intensity make it difficult to establish the diagnosis by radiological criteria. Forty patients underwent transsphenoidal surgery and three underwent craniotomy. There was one recurrence at 25 months requiring a second operation, and the mean follow-up period was 62 months. Seven patients had persistent headaches. For symptomatic lesions suspected to be Rathkes cysts, the recommended treatment is simple drainage of the cyst with biopsy of the wall, when this can be done safely. Follow-up imaging should be minimal for asymptomatic patients, and radiation therapy is not indicated.

Vagus nerve stimulation reduces daytime sleepiness in epilepsy patients

Background: Given that vagal afferents project to brainstem regions that promote alertness, the authors tested the hypothesis that vagus nerve stimulation (VNS) would improve daytime sleepiness in patients with epilepsy. Methods: Sixteen subjects with medically refractory seizures underwent polysomnography and multiple sleep latency tests (MSLT) and completed the Epworth Sleepiness Scale (ESS), a measure of subjective daytime sleepiness, before and after 3 months of VNS. Most subjects (>80%) were maintained on constant doses of antiepileptic medications. Results: In the 15 subjects who completed baseline and treatment MSLT, the mean sleep latency (MSL) improved from 6.4 ± 4.1 minutes to 9.8 ± 5.8 minutes (± SD; p = 0.033), indicating reduced daytime sleepiness. All subjects with stimulus intensities of ≤1.5 mA showed improved MSL. In the 16 subjects who completed baseline and treatment ESS, the mean ESS score decreased from 7.2 ± 4.4 to 5.6 ± 4.5 points (p = 0.049). Improvements in MSLT and ESS were not correlated with reduction in seizure frequency. Sleep-onset REM periods occurred more frequently in treatment naps as compared to baseline naps (p < 0.008; Cochran-Mantel-Haenszel test). The amount of REM sleep or other sleep stages recorded on overnight polysomnography did not change with VNS treatment. Conclusions: Treatment with VNS at low stimulus intensities improves daytime sleepiness, even in subjects without reductions in seizure frequency. Daytime REM sleep is enhanced with VNS. These findings support the role of VNS in activating cholinergic and other brain regions that promote alertness.

Spinal cord astrocytomas : results of therapy

Spinal cord astrocytomas are rare lesions, usually of low grade, with a long natural history. Because of this, it is difficult to define the optimum approach to therapy based on available data. To provide more data, a retrospective review was performed. From 1975 through 1989, 21 patients were seen and treated (median age, 21 years), and 15 patients received radiation therapy after undergoing either biopsy or resection. The median time until death or the last follow-up examination was 41 months. The actuarial survival of all patients was 68% at 5 years. Of the five deaths, four were related to local tumor recurrence. The overall survival and recurrence-free survival of irradiated patients at 5 years was 57% and 44%, respectively. The age of the patient was a prognostic factor, with younger patients surviving substantially longer before recurrence. Of the 15 irradiated patients, 7 experienced recurrence of the tumor, which occurred within the irradiated portion of the spinal cord in all 7. Gross total resections were rarely achieved and, also, the extent of resection did not influence the risk for recurrence. In summary, we observed a long natural history for this disease, and although additional local therapy appears needed, it is unclear that either higher doses of radiation or more extensive surgery will decrease the risk of recurrence.

Temporal lobe central benzodiazepine binding in unilateral mesial temporal lobe epilepsy

Article abstract—PET-demonstrated decreases in [11C]flumazenil binding occur in anterior mesial temporal structures on the side of epileptogenesis in unilateral mesial temporal lobe epilepsy. We performed quantitative autoradiog-raphy on anterior mesial and lateral temporal specimens from 11 subjects with unilateral mesial temporal lobe epilepsy and six neurologically normal controls to identify the predominant in vitro correlates of the decreased [11C]flumazenil binding. In anterior mesial temporal regions exhibiting the greatest neuronal cell loss, decreases in agonist and antagonist binding to type 1 and 2 (central) benzodiazepine binding sites were highly correlated with neuronal cell counts. Cell loss and decreased binding were particularly prominent in the lateral portion of hippocampal region CA1, adjacent to CA2. Lateral temporal central benzodiazepine binding was diffusely increased, achieving statistical significance in cortical laminae V and VI. These findings suggest that the predominant source of PET-demonstrated decreases in [11C]flumazenil binding in mesial temporal epilepsy is hippocampal sclerosis, rather than down-regulation of central benzodiazepine binding sites on surviving hippocampal neurons.

Intracerebral depth electrode monitoring in partial epilepsy: the morbidity and efficacy of placement using magnetic resonance image-guided stereotactic surgery.

OBJECTIVE To determine the indications for, efficacy of, and safety of depth electrode placement using magnetic resonance imaging (MRI)-guided stereotactic surgery in patients with intractable epilepsy. METHODS We analyzed retrospectively the results of depth electrode usage in 50 consecutive patients at the University of Michigan Hospitals studied in the years 1991 through 1994, using MRI-guided stereotactic implantation, in conjunction with simultaneous subdural strip electrode recordings. RESULTS There were no deaths, no infections, and no new neurological deficits. One small subdural hematoma adjacent to a subdural strip electrode was evacuated to prevent interference with ictal recording. Two cylindrical subdural electrodes were found to be intraparenchymal, as revealed by postoperative MRI, and were removed. One patient was unintentionally left alone briefly, and he pulled out the electrodes while confused postictally, requiring a subsequent operation for replacement. Ictal onset zones were successfully localized in 47 patients. CONCLUSION We have found intracerebral electrode placement to be as safe as subdural strip electrode placement and have found combined depth and strip electrode monitoring to be highly effective in localizing the onset zones of complex partial seizures. Intracranial monitoring was particularly useful in the detection of a single ictal onset zone in the absence of neuroimaging abnormality and in the definitive diagnosis of bilateral independent ictal onset zones in the temporal lobe epilepsy syndrome. The specific technical aspects of the procedure that contribute to a successful outcome are reviewed. A comparison with earlier reported series suggests that MRI-guided stereotaxy and pial inspection may reduce complications of depth electrode placement.

Serial Cognitive Testing in Temporal Lobe Epilepsy: Longitudinal Changes with Medical and Surgical Therapies

Summary: Cognitive testing was repeated at intervals ranging from 1 to 8 years in 47 adult patients with temporal lobe epilepsy (TLE). Each patient underwent standardized batteries, including the Wechsler Adult Intelligence Scale, Revised (WAIS‐R), and Wechsler Memory Scale (WMS). Both surgically treated and nonsurgical patients were examined. The nonsurgical group underwent serial testing for clinical indications, usually for complaints of memory dysfunction. Longitudinal testing could not verify any mean deterioration of intellect or memory in this group; variance over time was similar to test‐retest norms in healthy controls. WAIS‐R scores before and after resection in the surgical group were similar to our serial WAIS‐R data in nonsurgical patients. When we divided surgical patients according to side of epileptogenesis, we noted the expected differences in verbal and visual memory. Right‐sided surgery patients improved significantly in Full‐scale IQ (FSIQ) and tended to improve in logical memory on postoperative testing. Patients undergoing left resections had no retest improvement and tended to show decrease in several measures of verbal memory. Our findings should stimulate continued investigation into the natural history of lateralized memory and intellectual function in epilepsy, particularly to clarify longterm cognitive outcome in nonsurgical patients.

Identification of electrocorticogram patterns as the basis for a direct brain interface.

This study reports on the first step in the development of a direct brain interface based on the identification of event-related potentials (ERPs) from an electrocorticogram obtained from the surface of the cortex. Ten epilepsy surgery patients, undergoing monitoring with subdural electrode strips and grid arrays, participated in this study. Electrocorticograms were continuously recorded while subjects performed multiple repetitions for each of several motor actions. ERP templates were identified from action-triggered electrocorticogram averages using an amplitude criterion. At least one ERP template was identified for all 10 subjects and in 56% of all electrode-recording sets resulting from a subject performing an action. These results were obtained with electrodes placed solely for clinical purposes and not for research needs. Eighty-two percent of the identified ERPs began before the trigger, indicating the presence of premovement ERP components. The regions yielding the highest probability of valid ERP identification were the sensorimotor cortex (precentral and postcentral gyri) and anterior frontal lobe, although a number were recorded from other areas as well. The recording locations for multiple ERPs arising from the performance of a specific action were usually found on close-by electrodes. ERPs associated with different actions were occasionally identified from the same recording site but often had noticeably different characteristics. The results of this study support the use of ERPs recorded from the cortical surface as a basis for a direct brain interface.