Electroencephalographic features of moyamoya in adults.

OBJECTIVE: Electroencephalography is useful for evaluating transient neurological events in the setting of moyamoya disease. METHODS: EEG findings of adults with moyamoya seen at a large moyamoya referral center are summarized. Patients were identified by retrospective chart review. RESULTS: EEGs were ordered after cerebral revascularization for altered mental status, aphasia, limb shaking, or facial twitching. Among the study population of 103 patients having EEGs, 24% of adults with moyamoya had a history of clinical seizures. Ischemic or hemorrhagic strokes were associated with a twofold relative risk of seizures. Overall, 90% of EEGs were abnormal, most commonly focally (78%), or diffusely slow (68%). Epileptiform EEG discharges were seen in 24%. Whereas hemispheres with an ischemic stroke had a 19% risk of epileptiform discharges and an 8% risk of seizures on EEG, hemispheres with hemorrhagic stroke had a 35% risk of epileptiform discharges and 19% risk of seizures on EEG. Focal amplitude attenuation was seen in 19%, breach rhythm in 15%, rhythmic delta in 14%, and electrographic seizures in 12%. CONCLUSIONS: Seizures and epileptiform EEG changes are common in patients with moyamoya disease. SIGNIFICANCE: Transient events in patients with moyamoya can result from seizures as well as ischemia.

Vagus nerve stimulation magnet activation for seizures: a critical review.

Some patients receiving VNS Therapy report benefit from manually activating the generator with a handheld magnet at the time of a seizure. A review of 20 studies comprising 859 subjects identified patients who reported on-demand magnet mode stimulation to be beneficial. Benefit was reported in a weighted average of 45% of patients (range 0-89%) using the magnet, with seizure cessation claimed in a weighted average of 28% (range 15-67%). In addition to seizure termination, patients sometimes reported decreased intensity or duration of seizures or the post-ictal period. One study reported an isolated instance of worsening with magnet stimulation (Arch Pediatr Adolesc Med, 157, 2003 and 560). All of the reviewed studies assessed adjunctive magnet use. No studies were designed to provide Level I evidence of efficacy of magnet-induced stimulation. Retrospective analysis of one pivotal randomized trial of VNS therapy showed significantly more seizures terminated or improved in the active stimulation group vs the control group. Prospective, controlled studies would be required to isolate the effect and benefit of magnet mode stimulation and to document that the magnet-induced stimulation is the proximate cause of seizure reduction. Manual application of the magnet to initiate stimulation is not always practical because many patients are immobilized or unaware of their seizures, asleep or not in reach of the magnet. Algorithms based on changes in heart rate at or near the onset of the seizure provide a methodology for automated responsive stimulation. Because literature indicates additional benefits from on-demand magnet mode stimulation, a potential role exists for automatic activation of stimulation.

Symptoms and esophageal motility based on phenotypic findings of scleroderma.

Scleroderma esophagus is characterized by ineffective peristalsis and reduced esophageal sphincter pressure. Esophageal disease in scleroderma can precede cutaneous manifestations and has been associated with Raynaud's phenomenon (RP) and pulmonary fibrosis (PF). The objective of the study is to evaluate the impact of cutaneous findings, RP, and PF on demographics, symptoms, and esophageal motility in patients with scleroderma. Scleroderma patients with esophageal involvement were included after review of esophageal manometries and charts over a 6-year period. High-resolution esophageal manometry was performed. Patients completed a symptom questionnaire. The study enrolled 28 patients (22 females; mean age 50.3 ± 12.8 years) with scleroderma esophagus. Patients without skin involvement (n= 12) reported more severe heartburn (P= 0.02), while those with cutaneous findings (n= 16) had more frequent dysphagia with solids (P= 0.02). Patients with RP (n= 22) had lower amplitude of distal esophageal contractions (P= 0.01) than those without RP (n= 6). Patients with PF (n= 11) reported more severe coughing and wheezing (both P= 0.03) than those without lung disease (n= 17). This study highlights subgroups of patients with scleroderma esophagus according to phenotypic findings of dermatologic changes, RP, and PF. Heartburn and dysphagia are important symptoms that may be associated with different stages of disease progression based on skin changes in scleroderma. RP was associated with greater esophageal dysmotility. Coughing and wheezing were more severe in patients with PF.

Slow esophageal propagation velocity: association with dysphagia for solids.

BACKGROUND: Spastic disorders of the esophagus, associated with rapid esophageal propagation velocity, are classically associated with dysphagia and/or chest pain. The aim of this study was to characterize patients with slow esophageal propagation velocity (SPV) on high-resolution esophageal manometry (HRM). METHODS: A review of patients undergoing HRM was conducted during 1-year study period. Patients with achalasia, aperistalsis, and diffuse esophageal spasm were excluded. Patients with contractile front velocity (CFV) ≤ 2.3 cm s(-1) were defined as having SPV, whereas normal propagation velocity (NPV) was defined as ≥ 2.6 cm s(-1). A composite isobaric contour of all swallows for each patient was generated to determine composite distal contraction latency (cDL). KEY RESULTS: A total of 650 HRMs were reviewed and 552 met inclusion criteria. 173 patients had SPV and 339 had NPV. There was a greater female predominance in the SPV group compared with NPV (75.7%vs 66.4%, P = 0.03). Patients in the SPV group reported more dysphagia for solids (66.3%vs 53.3%; P = 0.004) and nausea (68.6%vs 59.0%; P = 0.04) than NPV group. Dysphagia for solids was the only symptom significantly associated with SPV group (OR = 2.21, CI = 1.21-4.02; P = .01). There was a negative correlation between CFV and cDL, r = -0.494, P < 0.001. CONCLUSIONS & INFERENCES: Patients with SPV have a higher prevalence of dysphagia for solids and nausea when compared with NPV. Dysphagia for solids was the only symptom significantly associated with SPV group. Thus, abnormal esophageal propagation velocity (both slow and rapid) is associated with dysphagia.

Variation of symptoms during the menstrual cycle in female patients with gastroparesis.

BACKGROUND: Gastroparesis, a chronic gastric motility disorder with symptoms of nausea, vomiting, early satiety, postprandial fullness and bloating, predominantly affects women. Some studies suggest that gastric emptying may be slower in females especially during the luteal phase of the menstrual cycle when estrogen and progesterone levels are elevated. In females with irritable bowel syndrome, symptoms may worsen during the luteal phase. The aim of this study was to determine if symptoms of gastroparesis vary along the menstrual cycle and to determine the effect of oral contraceptive agents (OCPs) on symptoms. METHODS: Thirty-nine premenopausal women were studied (10 gastroparesis patients not on OCPs, 10 gastroparesis on OCPs, nine healthy women not on OCPs and 10 healthy women on OCPs). The Gastroparesis Cardinal Symptom Index Daily Diary was used to assess daily symptoms (0=none and 5=very severe). KEY RESULTS: Gastroparesis patients not on OCPs had significantly worse symptoms during the luteal phase compared to the follicular phase for nausea (2.25±0.68 vs 1.58±1.06; P<0.001) and early satiety (2.80±0.50 vs 1.70±1.50; P<0.001), but not for vomiting, bloating, abdominal pain, fullness, or loss of appetite. Gastroparesis patients on OCPs showed little day-to-day variation of symptoms. Vomiting was more severe in patients off OCPs (2.00±0.80 vs 1.20±0.83; P=0.040). Healthy women exhibited little to no symptoms regardless of OCP use. CONCLUSIONS & INFERENCES: Increased symptoms, particularly nausea and early satiety, occurred in the luteal phase of the menstrual cycle in female patients with gastroparesis. A variation in symptoms was not seen in gastroparesis female patients on hormonal contraception.

Assessment of symptoms during gastric emptying scintigraphy to correlate symptoms to delayed gastric emptying.

BACKGROUND: Symptoms of gastroparesis based on patient recall correlate poorly with gastric emptying. The aim of this study is to determine if symptoms recorded during gastric emptying scintigraphy (GES) correlate with gastric emptying and with symptoms based on patient recall. METHODS: Patients undergoing GES completed the Patient Assessment of GI Symptoms (PAGI-SYM) assessing symptoms over the prior 2 weeks and a questionnaire for which patients graded six symptoms during GES. A Symptom Severity Index (SSI) represented the mean of six symptoms at each time point. KEY RESULTS: A total of 560 patients underwent GES for clinical evaluation of symptoms. Of 388 patients included in the study: 232 patients had normal GES (NGES), 156 delayed GES (DGES), and 11 rapid GES (RGES). Symptom severity index increased pre to postprandial for each group: NGES: 0.51 +/- 0.07 to 0.92 +/- 0.03, DGES: 0.60 +/- 0.09 to 1.13 +/- 0.05, and RGES: 0.56 +/- 0.12 to 0.79 +/- 0.13. Delayed gastric emptying scintigraphy patients had a higher postprandial SSI than NGES patients (1.13 +/- 0.05 vs 0.92 +/- 0.03, P < 0.05). Postprandial symptoms of stomach fullness (1.9 +/- 0.12 vs 1.5 +/- 0.09; P = 0.011), bloating (1.4 +/- 0.11 vs 1.1 +/- 0.09; P = 0.033), and abdominal pain (1.1 +/- 0.08 vs 0.7 +/- 0.12; P = 0.012) were higher in DGES than NGES. Symptom severity based on PAGI-SYM for 2 weeks prior to GES correlated with symptoms during the test for nausea (NGES, r = 0.61; DGES, r = 0.70), stomach fullness (NGES, r = 0.47; DGES, r = 0.60), and bloating (NGES, r = 0.62, DGES, r = 0.66). CONCLUSIONS & INFERENCES: Stomach fullness, bloating, and abdominal pain recorded during GES were higher in patients with delayed gastric emptying than in patients with normal gastric emptying. Symptoms recorded during GES correlated with those during daily life by patient recall.

Group therapy for patients with psychogenic nonepileptic seizures: a pilot study.

Great advances have been made in the diagnosis of people with psychogenic nonepileptic seizures (PNES) since the advent of video/EEG monitoring. However, treatment options for this population have lagged significantly. This pilot study was undertaken to evaluate whether group therapy done with a psychodynamic focus would offer a useful intervention. Twelve patients entered the study and seven completed at least 75% of the 32 weekly sessions. The Beck Depression Inventory and the Global Severity Index of the Symptom Checklist-90 showed improvement as well as an overall decrease in PNES frequency. The data suggest that group therapy focusing on interpersonal issues may benefit patients with PNES.

Gastric emptying of a non-digestible solid: assessment with simultaneous SmartPill pH and pressure capsule, antroduodenal manometry, gastric emptying scintigraphy.

Gastric emptying of digestible solids occurs after trituration of food particles. Non-digestible solids are thought to empty with phase III of the migrating motor complex (MMC). The aim of this study was to determine if a non-digestible capsule given with a meal empties from the stomach with return of the fasting phase III MMC or during the fed pattern with the solid meal. Fifteen normal subjects underwent antroduodenal manometry and ingestion of a radiolabelled meal and SmartPill wireless pH and pressure capsule. In five subjects, emptying of the SmartPill was studied in the fasting period by ingesting the SmartPill with radiolabelled water. The SmartPill emptied from the stomach within 6 h in 14 of 15 subjects. SmartPill pressure recordings showed high amplitude phasic contractions prior to emptying. SmartPill gastric residence time (261 +/- 22 min) correlated strongly with time to the first phase III MMC (239 +/- 23 min; r = 0.813; P < 0.01) and correlated moderately with solid-phase gastric emptying (r = 0.606 with T-50% and r = 0.565 with T-90%). Nine of 14 subjects emptied the capsule with a phase III MMC. In five subjects, the SmartPill emptied with isolated distal antral contractions. In five subjects ingesting only water, SmartPill gastric residence time (92 +/- 44 min) correlated with the time to the first phase III MMC (87 +/- 30 min; r = 0.979; P < 0.01). The non-digestible SmartPill given with a meal primarily empties from the stomach with the return of phase III MMCs occurring after emptying the solid-phase meal. However, in some subjects, the SmartPill emptied with isolated antral contractions, an unappreciated mechanism for emptying of a non-digestible solid.

Rapid protection of the gastroduodenal mucosa against aspirin-induced damage by rabeprazole.

BACKGROUND: The ability of a proton pump inhibitor to reduce or prevent NSAID-induced gastroduodenal damage during the first 24 h has not been tested. AIM: To determine, whether oral rabeprazole, administered 5 h before the initiation of therapeutic dosing of aspirin protects the gastroduodenal mucosa. METHODS: Normal subjects were randomized into two groups - one received rabeprazole, 20 mg at 07:00 hours and the other placebo, before initiation of aspirin 650 mg at 12:00 hours, and then q4 h for 3 days. Upper endoscopic examinations were performed on all subjects at baseline, 24 and 72 h after initiation of aspirin. Gastroduodenal mucosal damage was scored. RESULTS: Thirty subjects were compliant with study medications and underwent three endoscopic examinations. Salicylate concentrations were similar for the placebo and the rabeprazole groups at all times. On rabeprazole, the Lanza scores were significantly lower compared with placebo at 24 h (1.3 +/- 0.26 vs. 2.1 +/- 0.26, P < 0.05) and at 72 h (1.3 +/- 0.29 vs. 2.3 +/- 0.28, P < 0.05). Gastric antral erosion counts were less with rabeprazole than placebo at 24 (4.1 +/- 1.3 vs. 7.6 +/- 2.0, P > 0.05) and 72 h (5.3 +/- 1.8 vs. 8.0 +/- 1.5; P > 0.05). CONCLUSIONS: Rabeprazole, initiated 5 h before the start of therapeutic dosing with aspirin, decreased Lanza scores and antral erosion counts at 24 h. These findings suggest that prophylaxis with rabeprazole could start concurrently with aspirin administration.

High-resolution solid-state manometry of the antropyloroduodenal region.

Manometric recording from the pyloric channel is challenging and is usually performed with a sleeve device. Recently, a solid-state manometry system was developed, which incorporates 36 circumferential pressure sensors spaced at 1-cm intervals. Our aim was to use this system to determine whether it provided useful manometric measurements of the pyloric region. We recruited 10 healthy subjects (7 males:3 females). The catheter (ManoScan(360)) was introduced transnasally and, in the final position, 15-20 sensors were in the stomach and the remainder distributed across the pylorus and duodenum. Patients were recorded fasting and then given a meal and recorded postprandially. Using pressure data and isocontour plots, the pylorus was identified in all subjects. Mean pyloric width was 2.1 +/- 0.1 cm (95% CI: 1.40-2.40). Basal pyloric pressure during phase I was 9.4 +/- 1.1 mmHg, while basal antral pressure was significantly lower (P = 0.003; 95% CI: 2.4-8.4). Pyloric pressure was always elevated relative to antral pressure in phase I. For phases II and III, pyloric pressure was 7.7 +/- 2.3 mmHg and 9.4 +/- 1.1 mmHg, respectively. Pyloric pressure increased similarly after both the liquid and solid meal. In addition, isolated pressure events and waves, which involve the pylorus, were readily identified.

Regional gastric emptying abnormalities in functional dyspepsia and gastro-oesophageal reflux disease.

To characterize proximal and distal stomach emptying in functional dyspepsia (FD) and gastro-oesophageal reflux disease (GORD). Eighty-three patients underwent gastric emptying (GE) scintigraphy and symptom scoring for the evaluation of upper gastrointestinal symptoms and were divided into three groups: FD (n = 25), GORD (n = 20) and FD + GORD (n = 38). Total, proximal and distal gastric retention were determined scintigraphically and compared with normal controls. Delayed total GE was observed in each subgroup: FD (56%), GORD (45%) and FD + GORD (55%). Greater proximal gastric retention was observed after meal ingestion in GORD compared to FD. Greater distal gastric retention was observed in FD and FD + GORD but it was only mild in GORD. Nausea, vomiting, early satiety, distention and regurgitation were associated with proximal gastric retention whereas there was no symptom associated with distal gastric retention. Multiple regression demonstrated total gastric retention at 30 min and 1 h was positively correlated with regurgitation whereas early proximal gastric retention was positively correlated with regurgitation and negatively correlated with nausea. Selective abnormalities of proximal and distal stomach emptying were demonstrated in GORD and FD. GORD and FD symptoms were associated with proximal gastric retention suggesting that proximal stomach motor function may be important in the pathogenesis of symptoms associated with these disorders.

The effect of rabeprazole on regional gastric acidity and the postprandial cardia/gastro-oesophageal junction acid layer in normal subjects: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Postprandial intragastric acidity is not uniform. Postprandial proximal gastric acid pockets have been described in the present study. AIM: To determine the effects of rabeprazole on regional intragastric acidity and proximal acid pockets. METHODS: Ten normal subjects underwent two 8-day oral dosing regimens with placebo or rabeprazole 20 mg each morning in a randomized, double-blind protocol. Oesophago-gastric pH monitoring was performed on days 1 and 8. RESULTS: Rabeprazole increased fasting and postprandial gastric pH to above 4 in each area of the stomach on days 1 and 8. With placebo, acid pockets were identified at the cardia/gastro-oesophageal junction in 62 and 50 of 150 pull-throughs on days 1 and 8, respectively. Acid pockets were detected postprandially 3.1 +/- 0.2-5.8 +/- 0.1 cm below the proximal border of the lower oesophageal sphincter with a mean pH drop from 4.6 +/- 0.1 to 1.5 +/- 0.1. Rabeprazole decreased the number of acid pockets to 30 and 27 on days 1 and 8, respectively. Rabeprazole also decreased their length and magnitude of the pH drop. CONCLUSIONS: Rabeprazole increased intragastric pH on day 1 and 8 and maintained an elevated pH during and after meals. Postprandial acid pockets, identified in the region of the cardia/gastro-oesophageal junction area postprandially, were decreased in number, length and magnitude by rabeprazole.

Tachykinin expression and localization in developing feline neocortex.

Developmental patterns of expression and localization of tachykinins in feline neocortex were determined by qualitative immunohistochemical means. Three observations were obtained. (1) By midgestation, tachykinins were progressively accumulated in an infrequent (<1%) population of interneurons (sparse dendritic spines) settled mainly in superficial and deep sites. (2) Tachykinins were in a sparse axonal innervation showing horizontal elaboration in layers I and VI and vertical elaboration within the intervening layers (II-V) of true cortical plate. (3) Tachykinin innervation of the capillary beds arose in conjunction with tachykinin interneurons instead of extending from basal cerebral or meningeal vasculature. These patterns indicate that tachykinin local circuit neurons of feline neocortex are derived, at least in part, from early-generated neocortical preplate neurons that initiate tachykinin expression after they settle into the marginal zone of primitive neocortex. In addition to their roles in peptidergic modulation of synaptic connectivity in neocortex, this innervation may participate in trophic developmental interactions leading to the establishment of neocortical vasculature.

Electrophysiological and morphological changes in striatal spiny neurons in R6/2 Huntington's disease transgenic mice.

We examined passive and active membrane properties and synaptic responses of medium-sized spiny striatal neurons in brain slices from presymptomatic (approximately 40 days of age) and symptomatic (approximately 90 days of age) R6/2 transgenics, a mouse model of Huntington's disease (HD) and their age-matched wild-type (WT) controls. This transgenic expresses exon 1 of the human HD gene with approximately 150 CAG repeats and displays a progressive behavioral phenotype associated with numerous neuronal alterations. Intracellular recordings were obtained using standard techniques from R6/2 and age-matched WT mice. Few electrophysiological changes occurred in striatal neurons from presymptomatic R6/2 mice. The changes in this age group were increased neuronal input resistance and lower stimulus intensity to evoke action potentials (rheobase). Symptomatic R6/2 mice exhibited numerous electrophysiological alterations, including depolarized resting membrane potentials, increased input resistances, decreased membrane time constants, and alterations in action potentials. Increased stimulus intensities were required to evoke excitatory postsynaptic potentials (EPSPs) in neurons from symptomatic R6/2 transgenics. These EPSPs had slower rise times and did not decay back to baseline by 45 ms, suggesting a more prominent component mediated by activation of N-methyl-D-aspartate receptors. Neurons from both pre- and symptomatic R6/2 mice exhibited reduced paired-pulse facilitation. Data from biocytin-filled or Golgi-impregnated neurons demonstrated decreased dendritic spine densities, smaller diameters of dendritic shafts, and smaller dendritic fields in symptomatic R6/2 mice. Taken together, these findings indicate that passive and active membrane and synaptic properties of medium-sized spiny neurons are altered in the R6/2 transgenic. These physiological and morphological alterations will affect communication in the basal ganglia circuitry. Furthermore, they suggest areas to target for pharmacotherapies to alleviate and reduce the symptoms of HD.

Gamma oscillation underlies hyperthermia-induced epileptiform-like spikes in immature rat hippocampal slices.

BACKGROUND: Recently a hyperthermic rat hippocampal slice model system has been used to investigate febrile seizure pathophysiology. Our previous data indicates that heating immature rat hippocampal slices from 34 to 41 degrees C in an interface chamber induced epileptiform-like population spikes accompanied by a spreading depression (SD). This may serve as an in vitro model of febrile seizures. RESULTS: In this study, we further investigate cellular mechanisms of hyperthermia-induced initial population spike activity. We hypothesized that GABA(A) receptor-mediated 30-100 Hz gamma oscillations underlie some aspects of the hyperthermic population spike activity. In 24 rat hippocampal slices, the hyperthermic population spike activity occurred at an average frequency of 45.9 +/- 14.9 Hz (Mean +/- SE, range = 21-79 Hz, n = 24), which does not differ significantly from the frequency of post-tetanic gamma oscillations (47.1 +/- 14.9 Hz, n = 34) in the same system. High intensity tetanic stimulation induces hippocampal neuronal discharges followed by a slow SD that has the magnitude and time course of the SD, which resembles hyperthermic responses. Both post-tetanic gamma oscillations and hyperthermic population spike activity can be blocked completely by a specific GABA(A) receptor blocker, bicuculline (5-20 microM). Bath-apply kynurenic acid (7 mM) blocks synaptic transmission, but fails to prevent hyperthermic population spikes, while intracellular diffusion of QX-314 (30 mM) abolishes spikes and produces a smooth depolarization in intracellular recording. CONCLUSION: These results suggest that the GABA(A) receptor-governed gamma oscillations underlie the hyperthermic population spike activity in immature hippocampal slices.

Diagnostic modalities for achalasia.

Diagnostic evaluation for achalasia in patients with dysphagia begins with barium esophagography to evaluate for an anatomic lesion of the esophagus or the gastric fundus. Most of the patients with achalasia can be detected with an initial radiologic approach. Esophageal manometry, however, remains the gold standard for the diagnosis of achalasia and is important for patients for whom a correct diagnosis is uncertain or essential. The article reviews these and other diagnostic tests that may be used in evaluating patients suspected of having achalasia.

Extending gastric emptying scintigraphy from two to four hours detects more patients with gastroparesis.

Gastric emptying scintigraphy (GES) is usually performed for up to 2 hr to measure the gastric emptying (GE) of solids. Symptomatic patients, however, may have borderline results at 2 hr, making it difficult to determine whether a gastric motor disorder is present. The aim of this study was to assess whether extending GES to 4 hr is useful in evaluating patients for gastroparesis and to correlate the results of GES with patient symptoms. We studied 129 patients undergoing GES at Temple University Hospital between July 1998 and March 1999. Solid-phase GE was measured at 0, 0.5, 1, 2, 3, and 4 hr after ingestion of a 99mTc sulfur colloid-labeled egg meal. Dyspeptic symptoms of upper abdominal discomfort, early satiety, postprandial abdominal bloating, nausea, vomiting, and anorexia were graded as none, mild, moderate and severe (0, 1, 2 and 3, respectively) with the sum representing a total symptom score. Of 129 patients, 86 had normal GE at 2 hr; 26 of the 86 normal scans at 2 hr were delayed at 3 hr. Six of the 60 scans normal at 2 and 3 hr were delayed at 4 hr. Of 43 patients with delayed GE at 2 hr, 39 were delayed at 3 hr and 35 were delayed at 4 hr. Overall, the percentage of patients with delayed GE increased from 33% at 2 hr only to 58% using the results of the 2-, 3-, and 4-hr scans (P < 0.05). There was a significantly greater symptom score in patients with delayed GE compared to patients with normal GE (8.4 +/- 0.5 vs 7.1 +/- 0.5; P < 0.05). Conclusion, prolonging GES after ingestion of a 99mTc-labeled egg meal from 2 to 4 hr increased the number of symptomatic patients found to have delayed GE. These results suggest that GES should be performed for up to 4 hrs when the 2-hr result is normal.

Rapid initiation of gabapentin: a randomized, controlled trial.

OBJECTIVE: To compare the tolerability of two different dose-initiation regimens of gabapentin for the adjunctive treatment of partial seizures. BACKGROUND: Patient compliance is a key feature of successful outpatient pharmacologic therapy for epilepsy, and one aspect of compliance is simplicity of initiation. By using a rapid titration rate, leading to a rapid therapeutic gabapentin dose, perhaps there could be an improvement with compliance. METHODS: Male or female patients, at least 12 years old, with a recent history of partial seizures with or without secondary generalization, were randomized to receive gabapentin (following a blinded placebo period of an undisclosed number of days) as either a Slow initiation (300 mg day 1, 600 mg day 2, then 900 mg/day) or a Rapid initiation (900 mg/day immediately following the placebo lead-in). RESULTS: Starting gabapentin therapy at an initial therapeutic dosage of 900 mg/day is well tolerated by patients with epilepsy and is as safe as initiating with a titration schedule over 3 days. Of the four most common adverse events (somnolence, dizziness, ataxia, fatigue), only one, dizziness, occurred more often in the nontitrated (Rapid initiation) group than in the titrated (Slow initiation) group. CONCLUSION: Initiation of gabapentin at 900 mg/day is as well tolerated as is a 3-day titration, except for a higher incidence of dizziness.