Hyperbaric oxygen for persistent post-concussive symptoms: long-term follow-up.

We report results of an observational cohort study investigating long-term follow-up in participants from two completed United States military trials of hyperbaric oxygen (HBO2) for persistent post-concussive symptoms (PCS), as well as challenges in recruitment and retention in active-duty military personnel. After informed consent, participants completed an electronic survey assessing PCS, post-traumatic stress disorder (PTSD), anxiety, depression and quality of life. Of 132 HBO2 study participants, 40 (30%) completed the survey (42 could not be contacted; 50 were lost to follow-up or declined). All were male, age 28.1 ±6.6 years (mean ±1SD). Time to follow-up was 39.2 ±6.1 months. At follow-up, participants reported continued symptoms of PTSD, depression, anxiety and reduced quality of life. Among DARPA/VCU study participants, total PCS scores worsened in the 1.5 atmospheres absolute (ATA) equivalent HBO2 group (mean change 7.4 ±15.8) and improved in the sham (-8.0 ±7.7) and 2.0 atmospheres absolute equivalent HBO2 groups (-3.3 ±7.4). Individual changes varied widely, range -23 to +28 points. In participants from the HOPPS study, total PCS scores worsened in all groups: local care (10.5 ±8.7), sham (7.9 ±11.9) and 1.5 ATA HBO2 (1.0 ±19.4). In this limited, cross-sectional sample, PCS and PTSD symptoms did not appear to improve over time by descriptive analyses. Low participation rates and potential response bias limit our ability to perform statistical hypothesis testing and to draw conclusions from these data. Future studies should prospectively plan longitudinal follow-up and regular engagement with participants to minimize attrition.

Botulinum toxin type-a in the prevention of migraine: a double-blind controlled trial.

INTRODUCTION: Migraine is a frequent medical complaint. In military populations, migraine can be detrimental to productivity and troop readiness, and can be disqualifying for service in some military duty specialties. This study assessed the effectiveness of botulinum neurotoxin type-A (BTX-A) in reducing the frequency of migraines in known migraineurs. METHODS: There were 32 subjects (control = 17, test n = 15) who completed the assessment battery at baseline and monthly for 3 mo. Adult subjects with migraine headaches occurring more than 5 times/month were recruited and randomized to receive placebo saline injection vs. BTX-A. The primary efficacy parameter was the average frequency of headache days for 3 mo. Secondary outcome measures were severity of attacks and quality of life. RESULTS: Quadratic trends were noted for headache severity (F (2,29) = 14.1, p = 0.001) and headache indexes (F (2,29) = 4.5, p = 0.042) for both groups, suggesting changes in severity of head pain and overall intensity of headaches experienced over time; however, results were not significant for headache frequency and severity between groups. Paired t-tests of the headache index scores for the control group revealed a significant increase from the first to the third follow-up periods (t = -2.58, p = 0.020). Such a trend was not observed for the BTX-A group. Both groups, however, reported similarly low to moderate quality of life as a result of their migraines. CONCLUSIONS: This controlled trial failed to demonstrate efficacy of BTX-A in reducing the frequency of migraine headaches. The pattern headache index in the botox group, however, suggested a protective effect for botox against the headache severity.

Neurologic adverse events associated with smallpox vaccination in the United States, 2002-2004.

CONTEXT: Neurologic illness is an infrequent but severe adverse event associated with smallpox vaccination. The reinstatement of smallpox vaccination in the United States in response to possible bioterrorism renewed concerns about vaccine-related adverse neurologic events. OBJECTIVE: To determine rates and describe the clinical features of neurologic events associated with smallpox vaccination. DESIGN AND SETTING: We assessed reports of adverse events obtained through active case reporting and review of data reported to the Vaccine Adverse Event Reporting System among 665,000 persons vaccinated against smallpox by the Departments of Defense (n = 625,400 [corrected]) and Health and Human Services (n = 39,400 [corrected]) during the 2002-2004 US Smallpox Vaccination Program. MAIN OUTCOME MEASURE: Adverse neurologic events temporally associated with smallpox vaccination. RESULTS: Between December 16, 2002, and March 11, 2004, 214 neurologic adverse events temporally associated with smallpox vaccination were reported; 111 reports involved Department of Health and Human Services and 103 involved Department of Defense vaccinees. Fifty-four percent of these events occurred within 1 week of vaccination, and 53% were among primary vaccinees. The most common neurologic adverse event was headache (95 cases), followed by nonserious limb paresthesias (n = 17) or pain (n = 13) and dizziness or vertigo (n = 13). Serious neurologic adverse events included 13 cases of suspected meningitis, 3 cases of suspected encephalitis or myelitis, 11 cases of Bell palsy, 8 seizures (including 1 death), and 3 cases of Guillain-Barré syndrome. Among these 39 events, 27 (69%) occurred in primary vaccinees and all but 2 occurred within 12 days of vaccination. CONCLUSIONS: During the 2002-2004 smallpox vaccination campaign, reported neurologic events were generally mild and self-limited, and no neurologic syndrome was identified at a rate above baseline estimates. Serious neurologic adverse events, such as postvaccinal encephalitis, Bell palsy, and Guillain-Barré syndrome, occurred in accordance with expected ranges.

Human biovibrations: assessment of human life signs, motor activity, and cognitive performance using wrist-mounted actigraphy.

The application of miniature motion sensors (accelerometers) to study the macro- (gross) and micro- (barely discernible) activities associated with human motion has been termed actigraphy. In countless human sleep studies, actigraphy has mostly been applied to distinguish between when a person is asleep or awake. Use of sleep/wake information has been applied to the development of mathematical models that aim to predict aspects of cognitive performance. However, wrist-mounted actigraphy potentially has many more applications to cognitive and physical assessment beyond sleep/wake discrimination. For example, studies reveal that micro-miniature accelerometric sensors can discriminate heart rate, breathing, and life cessation (death) via actigraphically measured biovibration signals. This paper briefly reviews the development of wrist-mounted actigraphy; presents the data showing wrist-monitored ballistocardioimpulses, respirations, and life-signs signals; discusses the application of sophisticated signal processing for new clinical, operational, and cognitive-assessment-related applications; and concludes with recommendations for further research for demodulating the complex actigram signal.

Eight-year immunogenicity and safety of interferon beta-1a-Avonex treatment in patients with multiple sclerosis.

An open-label extension study of the phase III trial of intramuscular interferon beta-1a (IFNbeta-1a-Avonex) was conducted to evaluate the immunogenicity and safety of IFNbeta-1a-Avonex over six years in patients with relapsing multiple sclerosis (MS). Patients who participated in the pivotal phase III study were offered enrolment; entry was also open to patients who had not participated. All patients received IFNbeta-1a-Avonex 30 microg intramuscularly once weekly for six years, for a treatment duration of up to eight years in patients who received IFNbeta-1a-Avonex in the phase III trial. Serum levels of IFNbeta antibodies were measured every six months using a screening enzyme-linked immunosorbent assay (ELISA) followed by an antiviral cytopathic effect assay to detect neutralizing antibodies (NAbs) in serum samples positive on ELISA. The incidence of adverse events and laboratory test results assessed safety. Of 382 total patients, 218 had participated in the phase III study (103 placebo, 115 IFNbeta-1a-Avonex) and 164 had not participated; 24 of the 164 were IFNbeta-naïve. At baseline, 281 patients were negative for IFNbeta antibodies (NAb-). NAbs (titre > or = 20) developed at any time over six years in 5% of these patients. Of 140 patients who had been on IFNbeta-1b-Betaseron, 49 were positive for NAbs (NAb+) at baseline; 11 of 115 who had been on IFNbeta-1a-Avonex were NAb+ at baseline. Thirty-nine of 49 patients who had been on Betaseron and were NAb+ had titres < 100; 36 of these 39 seroconverted to NAb- while on IFNbeta-1a-Avonex, with a median time of approximately six months. Ten patients who had been on Betaseron had NAb titres > or = 100; five remained NAb+ during six years on IFNbeta-1a-Avonex and five seroconverted to NAb-, but only after at least two years. Five patients who had been on IFNbeta-1a-Avonex during the clinical trial were NAb+ with titres < 100 at baseline; four seroconverted to NAb-, with a median time of two to three years. Six patients who had been on IFNbeta-1a-Avonex had NAb titres > or = 100; five of these remained NAb+ at six years. No patient with a NAb titre > 1000 seroconverted to NAb-, whether initially treated with IFNbeta-1a-Avonex or -Betaseron. Adverse events were similar to those observed in the pivotal phase III trial. Results from this trial indicated that IFNbeta-1a-Avonex was associated with a low incidence of NAbs and was well tolerated for up to eight years. Further, the results indicate that persistence of NAbs is dependent on titre and IFNbeta product.

The presence of psychiatric disorders reduces the likelihood of neurologic disease among referrals to a neurology clinic.

OBJECTIVES: This study aims to explore the prevalence and impact of psychiatric disorders on the likelihood of an organic, neurological explanation for symptoms among neurology referrals. METHODS: Consecutive new adult neurology referrals were screened for psychiatric disorders (PRIME-MD) prior to evaluation by neurologists, blinded to these results. Diagnoses were stratified into three categories: no neurological diagnosis, neurological-headache, and neurological-nonheadache. RESULTS: Of 235 patients enrolled, 79 (34%) received no neurological diagnosis, 54 (23%) headache and 102 (43%) a neurological diagnosis. Overall, 39% had an underlying psychiatric disorder. Patients with psychiatric disorders were less likely to have a neurological diagnosis (RR: 0.66, 95% CI: 0.48-0.90): 25% of patients with a neurological diagnosis had an underlying psychiatric disorder, compared to 43% among those with no diagnosis and 57% among those with headaches. CONCLUSION: Psychiatric disorders are common among neurology referrals, particularly those with headaches and are associated with a decreased likelihood of an underlying neurological process.

Idiopathic intracranial hypertension and postlumbar puncture headache.

Idiopathic intracranial hypertension and low cerebrospinal pressure are 2 conditions that are thought to be on opposite ends of the cerebrospinal pressure spectrum. Headache is the prominent component of both conditions. We describe a patient whose evaluation for idiopathic intracranial hypertension resulted in a postlumbar puncture headache. Although not entirely intuitive, we suggest that the 2 conditions can be present in the same patient.

Acute Wernicke's encephalopathy following bariatric surgery: clinical course and MRI correlation.

Postoperative complications and nutritional deficits resulting from bariatric surgery can lead to severe vitamin-deficiency states, such as Wernicke's encephalopathy (WE). Patients with acute WE generally present with the classic clinical triad of inattentiveness, ataxia, and ophthalmoplegia. We describe a patient who presented with acute WE at 2 months after laparoscopic bariatric surgery. Initial MRI of the brain demonstrated the characteristic injuries of WE, and repeat imaging showed resolution after 4 months of thiamine supplementation, at which time the patient had normal gait but persistent memory deficits. Even with early recognition and aggressive therapy, acute WE commonly results in permanent disability due to the irreversible cytotoxic effects on specific regions of the brain. Since the clinical onset of acute WE follows a predictable time-course in post-bariatric surgery patients with malnutrition, we recommend prevention by administration of parenteral thiamine beginning at 6 weeks postoperatively in malnourished patients.

Transient neurologic deficits associated with carbamazepine-induced hypertension.

Carbamazepine is a well-established, effective treatment of complex partial seizures and is well tolerated in most patients. The adverse effects of carbamazepine include aplastic anemia, agranulocytosis, pancytopenia, bone marrow depression, thrombocytopenia, cardiac conduction abnormalities, congestive heart failure, and peripheral edema. Hypertension or hypotension has also rarely been documented in patients with either therapeutic or toxic blood levels of carbamazepine. It is possible that carbamazepine-induced hypertension in those with therapeutic blood levels is rarely seen because most of the patients who begin treatment are young and do not have baseline hypertension. The authors describe a patient of African-American descent with a history of controlled essential hypertension who developed severe uncontrolled hypertension when started on carbamazepine. Treatment with additional antihypertensive medications did not reduce his blood pressure. In addition, he developed two episodes of transient neurologic deficits, the symptoms of which consisted of dysarthria, vertigo, and unstable gait. A substantial reduction of his carbamazepine dose resulted in the control of his blood pressure and no recurrence of his symptoms.