The effect of prophylactic medications on TMS for migraine aura.

PURPOSE: Low frequency transcranial magnetic stimulation (TMS) has recently been shown to be effective for the acute treatment of migraine with aura. TMS has recently been shown to inhibit cortical spreading depression (CSD). Prophylactic medications (PM) may reduce the frequency of migraine attacks by elevating CSD threshold. The interaction between PM and TMS is unknown. METHODS: Subgroup analysis was performed on a double-blind, Sham-controlled study that evaluated the efficacy and safety of TMS for the acute treatment of migraine with aura. Analysis of the primary efficacy endpoint pain-free at 2 hours (pain-free rate [PFR]) between TMS and Sham groups was performed based on the non-randomized use of PM. RESULTS: A total of 164 subjects eligibly treated at least 1 migraine with aura attack with TMS (n = 82) or Sham stimulation (n=82). Baseline pain intensity at the time of treatment for the first attack was no pain (31%), mild (40%), moderate (23%), or severe pain (6%). PM were used by 37% (31/82) and 41.5% (34/82) in the Sham- and TMS-treated patients, respectively. Sham patients on no PM (Sham without) had significantly higher PFR than Sham-treated patients on PM (Sham with) (P = .0014). There was no difference in PFR between TMS-treated patients on (TMS with) or off (TMS without) PM (P = .5513). However, TMS with had significantly higher PFR than Sham with patients (P= .002). There was no difference in PFR between TMS without and Sham without patients (P = .4061). CONCLUSION: Prophylactic medications do not appear to influence the treatment response to TMS. The better response in Sham-treated patients not on PM may indicate a more responsive subgroup or different patient phenotype than those currently using PM. These findings will need to be verified in a larger patient sample randomized by presence or absence of PM.

Efficacy of rivastigmine for cognitive symptoms in Parkinson disease with dementia.

BACKGROUND: Impairment of multiple neurotransmitter networks, including acetylcholine, may contribute to the cognitive impairment in patients with Parkinson disease with dementia (PDD). Therefore, cholinesterase inhibitors might improve cognitive function in PDD. On the other hand, enhancing cholinergic function could plausibly worsen features of parkinsonism. OBJECTIVE: To determine if oral cholinesterase inhibitors improve measures of cognitive outcome and are tolerated by people with PDD. METHODS: We addressed the question through the development of a critically appraised topic. Participants included consultant and resident neurologists, clinical epidemiologists, a medical librarian, and behavioral neurology and movement disorder specialists. Participants began with a structured clinical question, devised search strategies, compiled the best evidence, performed a critical appraisal, summarized the evidence, provided commentary, and declared bottom-line conclusions. RESULTS: A randomized controlled trial (n = 541) showed that, compared with placebo, rivastigmine (mean, 8.6 mg/d) significantly improved scores on 2 coprimary cognitive outcome scales in PDD, including the Alzheimer disease Cooperative Study-Clinician's Global Impression of Change. When dichotomized to evaluate clinically significant benefit (moderate or marked improvement), this outcome was not significant (risk difference = 5.3%; 95% confidence interval (CI) = -1.6 to 12.1). The number needed to treat (NNT) to avoid clinically significant worsening of cognition was 10 (95% CI = 6-28). The NNT for the combined outcome of either achieving clinically significant benefit or avoiding significant worsening was 7. The numbers needed to harm for cholinergic side effects were 9 (95% CI = 5-24) for parkinsonian symptoms and 11 (95% CI = 6-32) for rivastigmine discontinuation due to any side effect. CONCLUSION: Rivastigmine therapy for PDD is associated with significant tradeoffs in efficacy and adverse effects. Carefully monitored trials of rivastigmine may provide meaningful benefits for a minority of PDD patients.

Serum neuron specific enolase to predict neurological outcome after cardiopulmonary resuscitation: a critically appraised topic.

BACKGROUND: Despite a large body of resuscitation research, the optimal timing and approach to prognosticating futility after nontraumatic cardiac arrest remains controversial. Postresuscitation anoxic-ischemic encephalopathy may leave patients cognitively disabled and dependent, minimally conscious, or in a persistent vegetative state. Neurologists are frequently called upon to assess comatose postcardiac arrest patients to communicate accurate prognostic information and to assist in planning the most appropriate level of care. Serum neuron specific enolase (NSE), when used in conjunction with other available prognostic tools, may be a useful tool for predicting clinical outcome in this patient population. OBJECTIVE: Determine the clinical utility of a serum NSE measurement for predicting the neurologic outcome of a survivor after resuscitation from a nontraumatic cardiac arrest. METHODS: We addressed the question through the development of a structured, critically appraised topic. Participants included consultant and resident neurologists, clinical epidemiologists, medical librarian, and clinical content experts in the fields of emergency medicine, cardiac resuscitation, and critical care neurology. Participants started with a clinical scenario and a structured question, devised search strategies, located and compiled the best evidence, performed a critical appraisal, synthesized the results, summarized the evidence, provided commentary, and declared bottom-line conclusions. RESULTS: A single recent prospective cohort study, which assessed the predictive value of serum NSE was selected and appraised. A level of 80 ng/mL was determined to predict persistent coma with a sensitivity of 63% (95% CI, 49%-75%), and a specificity of 100% (95% CI, 97%-100%), positive predictive value (PPV) of 100%, negative predictive value (NPV) of 84%, and a negative LR of 0.37. CONCLUSIONS: The specificity of serum NSE levels >80 ng/mL is sufficiently high that, when it is used with other clinical and electrophysiological data, it could be useful as a prognostic indicator of neurologic outcome after cardiac arrest. Although serum NSE is an appealing, simple, readily available test, prediction of neurologic outcome after resuscitation from cardiac arrest must not rely solely on a serum biomarker, but must be determined in the context of other patient characteristics and neurologic examination findings.