Standard procedures for the diagnostic pathway of sleep-related epilepsies and comorbid sleep disorders: A European Academy of Neurology, European Sleep Research Society and International League against Epilepsy-Europe consensus review.

BACKGROUND: Some epilepsy syndromes (sleep-related epilepsies [SRE]) have a strong link with sleep. Comorbid sleep disorders are common in patients with SRE and can exert a negative impact on seizure control and quality of life. PURPOSES: To define the standard procedures for the diagnostic pathway of patients with possible SRE (scenario 1) and the general management of patients with SRE and comorbidity with sleep disorders (scenario 2). METHODS: The project was conducted under the auspices of the European Academy of Neurology (EAN), the European Sleep Research Society (ESRS) and the International League against Epilepsy (ILAE) Europe. The framework of the document entailed the following phases: conception of the clinical scenarios; literature review; statements regarding the standard procedures. For literature search a step-wise approach starting from systematic reviews to primary studies was applied. Published studies were identified from the National Library of Medicine's MEDLINE database and Cochrane Library. RESULTS: Scenario 1: despite a low quality of evidence, recommendations on anamnestic evaluation, tools for capturing the event at home or in the laboratory are provided for specific SRE. Scenario 2: Early diagnosis and treatment of sleep disorders (especially respiratory disorders) in patients with SRE are likely to be beneficial for seizures control. CONCLUSIONS: Definitive procedures for evaluating patients with SRE are lacking. We provide advice that could be of help for standardising and improving the diagnostic approach of specific SRE. The importance of identifying and treating specific sleep disorders for the management and outcome of patients with SRE is underlined.

Hiding in Plain Sight: Functional Neurological Disorders in the News.

OBJECTIVE: Functional movement and seizure disorders are still widely misunderstood and receive little public and academic attention. This is in stark contrast to their high prevalence and levels of associated disability. In an exploratory observational study, the authors examined whether the relative lack of media coverage of functional neurological disorders is in part due to misidentification in "human interest" news stories. METHODS: Thirteen recent news stories from high-impact English-language media outlets that portrayed patients with complex symptoms either attributed to other diagnoses or presented as medical mysteries were identified using online keyword searches. All selected news stories contained video or still images displaying relevant symptoms. Cases were categorized into movement disorders or seizure disorders and were then independently assessed by 10 respective expert raters. For each category, one story of a patient whose symptoms were due to a well-recognized neurological disease was also included. Both the diagnostic category and the respective confidence level were reported by each rater for each case. The interrater agreement was calculated for each group of disorders. RESULTS: The raters confirmed almost unanimously that all presented news stories except the negative control cases portrayed misidentified functional movement or seizure disorders. The interrater agreement and average diagnostic confidence were high. CONCLUSIONS: Functional neurological disorders are often wrongly considered a rare medical curiosity of the past. However, these findings suggest that, while they are largely absent from public discourse, they often appear in the news incognito, hiding in plain sight.

Caffeine as an analgesic adjuvant for acute pain in adults.

BACKGROUND: This is an updated version of the original Cochrane review published in Issue 3, 2012. Caffeine has been added to common analgesics such as paracetamol, ibuprofen, and aspirin, in the belief that it enhances analgesic efficacy. Evidence to support this belief is limited and often based on invalid comparisons. OBJECTIVES: To assess the relative efficacy of a single dose of an analgesic plus caffeine against the same dose of the analgesic alone, without restriction on the analgesic used or the pain condition studied. We also assessed serious adverse events. SEARCH METHODS: We searched CENTRAL, MEDLINE, and EMBASE from inception to 28 August 2014, the Oxford Pain Relief Database, and also carried out Internet searches and contacted pharmaceutical companies known to have carried out trials that have not been published. SELECTION CRITERIA: We included randomised, double-blind studies that compared a single dose of analgesic plus caffeine with the same dose of the analgesic alone in the treatment of acute pain. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility and quality of studies, and extracted data. Any disagreements or uncertainties were settled by discussion with a third review author. We sought any validated measure of analgesic efficacy, but particularly the number of participants experiencing at least 50% of the maximum possible pain relief over four to six hours, participants reporting a global evaluation of treatment of very good or excellent, or headache relief after two hours. We pooled comparable data to look for a statistically significant difference, and calculated numbers needed to treat to benefit (NNT) with caffeine. We also looked for any numerical superiority associated with the addition of caffeine, and information about any serious adverse events. MAIN RESULTS: We identified no new studies with available results for this update. The earlier review included 20 studies (7238 participants) in valid comparisons, but because we used different outcomes for some headache studies, the number of participants in the analyses of the effects of caffeine is now 4262 when previously it was 5243. The studies were generally of good methodological quality, using standard designs and mostly standard scales of pain measurement, although many of those treating postoperative pain were small.Most studies used paracetamol or ibuprofen, with 100 mg to 130 mg caffeine, and the most common pain conditions studied were postoperative dental pain, postpartum pain, and headache. There was a small but statistically significant benefit with caffeine used at doses of 100 mg or more, which was not dependent on the pain condition or type of analgesic. About 5% to 10% more participants achieve a good level of pain relief (at least 50% of the maximum over four to six hours) with the addition of caffeine, giving a NNT of about 14 (high quality evidence).Most comparisons individually demonstrated numerical superiority with caffeine, but not statistical superiority. One serious adverse event was reported with caffeine, but was considered unrelated to any study medication.We know of the existence of around 25 additional studies with almost 12,500 participants for which data for analysis were not obtainable. The additional analgesic effect of caffeine remained statistically significant but clinically less important even if all the known missing data had no effect; the bulk of the unobtainable data are reported to have similar results as this review. AUTHORS' CONCLUSIONS: The addition of caffeine (≥ 100 mg) to a standard dose of commonly used analgesics provides a small but important increase in the proportion of participants who experience a good level of pain relief.

Sumatriptan (all routes of administration) for acute migraine attacks in adults - overview of Cochrane reviews.

BACKGROUND: Migraine is a highly disabling condition for the individual and also has wide-reaching implications for society, healthcare services, and the economy. Sumatriptan is an abortive medication for migraine attacks, belonging to the triptan family. It is available for administration by four different routes: oral, subcutaneous, intranasal, and rectal. OBJECTIVES: To summarise evidence from four Cochrane intervention reviews on the efficacy and tolerability of sumatriptan in the treatment of acute migraine attacks in adults by four routes of administration (oral, subcutaneous, intranasal, and rectal) compared with both placebo and active comparators. METHODS: The included reviews were written by the authors of this overview; no additional searching was carried out. All included reviews were conducted according to a standard protocol and reported a standard set of outcomes. From each individual review we extracted results for pain relief at different levels, and adverse events. No additional statistical comparison was undertaken as part of the overview. We focused on the most important findings for doses and routes licensed in North America or Europe (oral 25 mg, 50 mg, 100 mg; subcutaneous 4 mg, 6 mg; intranasal 5 mg, 10 mg, 20 mg; rectal 25 mg). MAIN RESULTS: Included reviews provided data for 18 different dose and route of administration combinations in 52,236 participants. Data for the primary outcomes sought were generally well reported, and involved adequate numbers of participants to give confidence in the results, except for the rectal route of administration, where numbers were low.Subcutaneous administration was the most effective, with pain reduced from moderate or severe to none by two hours in almost 6 in 10 people (59%) taking 6 mg sumatriptan, compared with approximately 1 in 7 (15%) taking placebo; the number needed to treat (NNT) was 2.3 (95% confidence interval 2.1 to 2.4) with 2522 participants in the analysis. The most commonly used doses of oral, rectal, and intranasal sumatriptan also provided clinically useful pain relief, with the oral 50 mg dose providing complete relief of pain in almost 3 in 10 people (28%) compared with about 1 in 10 (11%) after placebo (NNT 6.1 (5.5 to 6.9) in 6447 participants). Subcutaneous administration provided more rapid pain relief than the other routes. Taking medication early, when pain was mild, was more effective than waiting until the pain was moderate or severe.The most effective dose of sumatriptan for each route of administration for the outcome of headache relief (pain reduced from moderate or severe to none or mild) at two hours was oral 100 mg (NNT 3.5 (3.2 to 3.7) in 7811 participants), subcutaneous 6 mg (NNT 2.1 (2.0 to 2.2) in 2738 participants), intranasal 20 mg (NNT 3.5 (3.1 to 4.1) in 2020 participants), and rectal 25 mg (NNT 2.4 (1.9 to 3.4) in 240 participants).Adverse events were generally of mild or moderate severity, of short duration, and more common with subcutaneously administered sumatriptan and higher doses of oral and intranasal sumatriptan than with other dose and route combinations. AUTHORS' CONCLUSIONS: Sumatriptan is an effective abortive treatment for acute migraine attacks, but is associated with increased adverse events relative to placebo. The route of administration influences efficacy, particularly within the first hour after administration. Subcutaneous sumatriptan shows the greatest efficacy in terms of pain relief, but at the expense of relatively high levels of adverse events, and with a high financial cost compared with other routes. Information about the relative efficacy of the different routes of administration for different outcomes should help to inform decisions about the suitability of sumatriptan as a migraine treatment, as well as about the most appropriate way to administer the treatment for individual patients.

Sleeping in fits and starts: a practical guide to distinguishing nocturnal epilepsy from sleep disorders.

Accurately diagnosing sleep-related events, and particularly distinguishing nocturnal frontal lobe seizures from other sleep disorders such as parasomnias, can be challenging. This article reviews the differential diagnosis of paroxysmal events from sleep, epileptic and non-epileptic, considers important diagnostic points in the history, and evaluates the role of investigations in this setting.

Factors that influence field hockey footwear selection: An online survey.

BACKGROUND: Little is known about factors that influence footwear selection by field hockey players. METHODS: An online survey was used to collect data on participant demographics and physical characteristics, factors influencing footwear selection, perceptions regarding footwear design features on injury and performance, and experiences regarding usability. Nominal and ordinal data were described as absolute frequencies and relative frequencies. Free text responses were analysed using content analysis. Sex-related differences in quantitative and qualitative data were explored. RESULTS: A total of 401 hockey players completed the survey. Participants reported that fit, comfort, support, and cushioning were the most important factors when selecting hockey footwear. Most hockey players believed that stud design could influence athletic performance (65%) and injury risk (63%) but reported having no preference on outsole design or stud shape. Most participants (63%) used hockey-specific footwear, but 46% of female hockey players did not, with 40% using trail running footwear instead. Qualitative analysis revealed that hockey players, particularly female participants, encounter difficulties finding properly fitting footwear. They desire more options for wide or narrow feet and face challenges in accessing suitable hockey shoes due to limited choices and availability. CONCLUSIONS: With over a third of field hockey players not using hockey-specific footwear, future research should attempt to understand the reasons and assess the impact of different footwear features on comfort, performance, injury risk, and usability.

Analysis of sequence variation underlying tissue-specific transcription factor binding and gene expression.

Although mutations causing monogenic disorders most frequently lie within the affected gene, sequence variation in complex disorders is more commonly found in noncoding regions. Furthermore, recent genome- wide studies have shown that common DNA sequence variants in noncoding regions are associated with "normal" variation in gene expression resulting in cell-specific and/or allele-specific differences. The mechanism by which such sequence variation causes changes in gene expression is largely unknown. We have addressed this by studying natural variation in the binding of key transcription factors (TFs) in the well-defined, purified cell system of erythropoiesis. We have shown that common polymorphisms frequently directly perturb the binding sites of key TFs, and detailed analysis shows how this causes considerable (~10-fold) changes in expression from a single allele in a tissue-specific manner. We also show how a SNP, located at some distance from the recognized TF binding site, may affect the recruitment of a large multiprotein complex and alter the associated chromatin modification of the variant regulatory element. This study illustrates the principles by which common sequence variation may cause changes in tissue-specific gene expression, and suggests that such variation may underlie an individual's propensity to develop complex human genetic diseases.

Sleep and epilepsy.

The intimate relationship between sleep and epilepsy has long been recognized, yet our understanding of the relationship is incomplete. In this article we address four key issues in this area. First, we consider the reciprocal interaction between sleep and epilepsy. Sleep state clearly influences seizure onset, particularly in certain epilepsy syndromes. The converse is also true; epilepsy may disrupt sleep, either directly through seizures and epileptiform activity, or indirectly through medication-related effects. Unraveling the influences of sleep stage, epilepsy syndrome, and drug effects is challenging, and the current state of knowledge is reviewed. Secondly, accurate diagnosis of sleep-related epilepsy can be difficult, particularly the distinction of nocturnal frontal lobe epilepsy (NFLE) from arousal parasomnias. The challenges in this area, along with work from the authors, are discussed. Thirdly, we will explore the putative relationship between obstructive sleep apnea (OSA) and epilepsy, including the effect of OSA on quality of life; this will lead us to a brief exploration of the effects of OSA on neuroendocrine function. Finally, we will review the evidence surrounding the role of sleep in sudden unexpected death in epilepsy (SUDEP).

Single dose oral ibuprofen plus paracetamol (acetaminophen) for acute postoperative pain.

BACKGROUND: Combining two different analgesics in fixed doses in a single tablet can provide better pain relief than either drug alone in acute pain. This appears to be broadly true across a range of different drug combinations, in postoperative pain and migraine headache. Some combinations of ibuprofen and paracetamol are available for use without prescription in some acute pain situations. OBJECTIVES: To assess the efficacy and adverse effects of single dose oral ibuprofen plus paracetamol for acute postoperative pain using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 4 of 12, 2013), MEDLINE (1950 to May 21st 2013), EMBASE (1974 to May 21st 2013), the Oxford Pain Database, ClinicalTrials.gov, and reference lists of articles. SELECTION CRITERIA: Randomised, double-blind clinical trials of single dose, oral ibuprofen plus paracetamol compared with placebo or the same dose of ibuprofen alone for acute postoperative pain in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently considered trials for inclusion in the review, assessed quality, and extracted data. We used validated equations to calculate the area under the pain relief versus time curve and derive the proportion of participants with at least 50% of maximum pain relief over six hours. We calculated relative risk (RR) and number needed to treat to benefit (NNT) for ibuprofen plus paracetamol, ibuprofen alone, or placebo. We used information on use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse events. MAIN RESULTS: Searches identified three studies involving 1647 participants. Each of them examined several dose combinations. Included studies provided data from 508 participants for the comparison of ibuprofen 200 mg + paracetamol 500 mg with placebo, 543 participants for the comparison of ibuprofen 400 mg + paracetamol 1000 mg with placebo, and 359 participants for the comparison of ibuprofen 400 mg + paracetamol 1000 mg with ibuprofen 400 mg alone.The proportion of participants achieving at least 50% maximum pain relief over 6 hours was 69% with ibuprofen 200 mg + paracetamol 500 mg, 73% with ibuprofen 400 mg + paracetamol 1000 mg, and 7% with placebo, giving NNTs of 1.6 (1.5 to 1.8) and 1.5 (1.4 to 1.7) for the lower and higher doses respectively compared with placebo. For ibuprofen 400 mg alone the proportion was 52%, giving an NNT for ibuprofen 400 mg + paracetamol 1000 mg compared with ibuprofen alone of 5.4 (3.5 to 12).Ibuprofen + paracetamol at the 200/500 mg and 400/1000 mg doses resulted in longer times to remedication than placebo. The median time to use of rescue medication was 7.6 hours for ibuprofen 200 mg + paracetamol 500 mg, 8.3 hours with ibuprofen 400 mg + paracetamol 1000 mg, and 1.7 hours with placebo. Fewer participants needed rescue medication with ibuprofen + paracetamol combination than with placebo or ibuprofen alone. The proportion was 34% with ibuprofen 200 mg + paracetamol 500 mg, 25% with ibuprofen 400 mg + paracetamol 1000 mg, and 79% with placebo, giving NNTs to prevent use of rescue medication of 2.2 (1.8 to 2.9) and 1.8 (1.6 to 2.2) respectively compared with placebo. The proportion of participants using rescue medication with ibuprofen 400 mg was 48%, giving an NNT to prevent use for ibuprofen 400 mg + paracetamol 1000 mg compared with ibuprofen alone of 4.3 (3.0 to 7.7).The proportion of participants experiencing one or more adverse events was 30% with ibuprofen 200 mg + paracetamol 500 mg, 29% with ibuprofen 400 mg + paracetamol 1000 mg, and 48% with placebo, giving NNT values in favour of the combination treatment of 5.4 (3.6 to 10.5) and 5.1 (3.5 to 9.5) for the lower and higher doses respectively. No serious adverse events were reported in any of the included studies. Withdrawals for reasons other than lack of efficacy were fewer than 5% and balanced across treatment arms. AUTHORS' CONCLUSIONS: Ibuprofen plus paracetamol combinations provided better analgesia than either drug alone (at the same dose), with a smaller chance of needing additional analgesia over about eight hours, and with a smaller chance of experiencing an adverse event.

Single dose oral ibuprofen plus oxycodone for acute postoperative pain in adults.

BACKGROUND: Combining two different analgesics in fixed doses in a single tablet can provide better pain relief than either drug alone in acute pain. This appears to be broadly true across a range of different drug combinations, in postoperative pain and migraine headache. Fixed-dose combinations of ibuprofen and oxycodone are available, and the drugs may be separately used in combination in some acute pain situations. OBJECTIVES: To assess the analgesic efficacy and adverse effects of a single oral dose of ibuprofen plus oxycodone for moderate to severe postoperative pain. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, (CENTRAL), on The Cochrane Library, (Issue 4 of 12, 2013), MEDLINE (1950 to 21st May 2013), EMBASE (1974 to 21st May 2013), the Oxford Pain Database, ClinicalTrials.gov, and reference lists of articles. SELECTION CRITERIA: Randomised, double-blind clinical trials of single dose, oral ibuprofen plus oxycodone compared with placebo or the same dose of ibuprofen alone for acute postoperative pain in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently considered trials for inclusion in the review, assessed quality, and extracted data. We used the area under the pain relief versus time curve to derive the proportion of participants prescribed ibuprofen plus oxycodone, ibuprofen alone, oxycodone alone, or placebo with at least 50% pain relief over six hours, using validated equations. We calculated relative risk (RR) and number needed to treat to benefit (NNT). We used information on use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse events. MAIN RESULTS: Searches identified three studies involving 1202 participants. All examined the same dose combination. Included studies provided data from 603 participants for the comparison of ibuprofen 400 mg + oxycodone 5 mg with placebo, 717 participants for the comparison of ibuprofen 400 mg + oxycodone 5 mg with ibuprofen 400 mg alone, and 471 participants for the comparison of ibuprofen 400 mg + oxycodone 5 mg with oxycodone 5 mg alone.The proportion of participants achieving at least 50% pain relief over 6 hours was 60% with ibuprofen 400 mg + oxycodone 5 mg and 17% with placebo, giving an NNT of 2.3 (2.0 to 2.8). For ibuprofen 400 mg alone the proportion was 50%, producing no significant difference between ibuprofen 400 mg + oxycodone 5 mg and ibuprofen 400 mg alone. For oxycodone 5 mg alone the proportion was 23%, giving an NNT for ibuprofen 400 mg + oxycodone 5 mg compared with oxycodone alone of 2.9 (2.3 to 4.0).Ibuprofen + oxycodone resulted in longer times to remedication than with placebo. The median time to use of rescue medication was more than 5 hours for ibuprofen 400 mg + oxycodone 5 mg, and 2.3 hours or less with placebo. Fewer participants needed rescue medication with ibuprofen + oxycodone combination than with placebo or ibuprofen alone. The proportion was 40% with ibuprofen 400 mg + oxycodone 5 mg, 83% with placebo, 53% with ibuprofen alone, and 83% with oxycodone alone, giving NNT to prevent one patient needing rescue medication of 2.4 (2.0 to 2.9), 11 (6.1 to 56), and 2.6 (2.1 to 3.4) for comparisons of ibuprofen 400 mg + oxycodone 5 mg with placebo, ibuprofen alone, and oxycodone alone, respectively.The proportion of participants experiencing one or more adverse events was 25% with ibuprofen 400 mg + oxycodone 5 mg, 25% with placebo, 26% with ibuprofen alone, and 35% with oxycodone alone; they were not significantly different. Serious adverse events were reported only after abdominal surgery 6/169 with the combination, 1/175 with ibuprofen alone, 3/52 with oxycodone alone, and 1/60 with placebo. Withdrawals for reasons other than lack of efficacy were fewer than 5% and balanced across treatment arms. AUTHORS' CONCLUSIONS: The combination of ibuprofen 400mg + oxycodone 5mg provided analgesia for longer than oxycodone alone, but not ibuprofen alone (at the same dose). There was also a smaller chance of needing additional analgesia over about eight hours, and with no greater chance of experiencing an adverse event.

Caffeine as an analgesic adjuvant for acute pain in adults.

BACKGROUND: Caffeine has been added to common analgesics such as paracetamol, ibuprofen, and aspirin, in the belief that it enhances analgesic efficacy. Evidence to support this belief is limited and often based on invalid comparisons. OBJECTIVES: To assess the relative efficacy in acute pain of a single dose of any analgesic plus caffeine against the same dose of analgesic alone. SEARCH METHODS: We searched CENTRAL, MEDLINE, EMBASE, and the Oxford Pain Relief Database to January 2012, and also carried out Internet searches and contacted pharmaceutical companies known to have carried out trials that have not been published. SELECTION CRITERIA: We included randomised, double-blind studies that compared a single dose of analgesic plus caffeine with the same dose of the analgesic alone in the treatment of acute pain. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility and quality of studies, and extracted data. Any disagreements or uncertainties were settled by discussion with a third review author. We sought any validated measure of analgesic efficacy, but particularly the number of participants experiencing at least 50% of the maximum possible pain relief over four to six hours, participants reporting a global evaluation of treatment of very good or excellent, or headache relief after two hours. We pooled comparable data to look for a statistically significant difference, and calculated numbers needed to treat to benefit (NNT) with caffeine. We also looked for any numerical superiority associated with the addition of caffeine, and information about any serious adverse events. MAIN RESULTS: We identified 19 studies (7238 participants) in valid comparisons. Most studies used paracetamol or ibuprofen, with 100 mg to 130 mg caffeine, and the most common pain conditions studied were postoperative dental pain, postpartum pain, and headache. There was a small but statistically significant benefit with caffeine used at doses of 100 mg or more, which was not dependent on the pain condition or type of analgesic. About 5% to 10% more participants achieve a good level of pain relief (at least 50% of the maximum) with the addition of caffeine, giving a NNT of about 15.Most comparisons individually demonstrated numerical superiority with caffeine, but not statistical superiority. One serious adverse event was reported with caffeine, but was considered unrelated to any study medication.We know or suspect of the existence of 20 additional studies with 9785 participants for which data for analysis were not obtainable. The additional analgesic effect of caffeine remained statistically significant but clinically less important even if all the known missing data had no effect; that is not likely to be the case. AUTHORS' CONCLUSIONS: The addition of caffeine (≥ 100 mg) to a standard dose of commonly used analgesics provides a small but important increase in the proportion of participants who experience a good level of pain relief.

Sumatriptan (oral route of administration) for acute migraine attacks in adults.

BACKGROUND: Migraine is a highly disabling condition for the individual and also has wide-reaching implications for society, healthcare services, and the economy. Sumatriptan is an abortive medication for migraine attacks, belonging to the triptan family. OBJECTIVES: To determine the efficacy and tolerability of oral sumatriptan compared to placebo and other active interventions in the treatment of acute migraine attacks in adults. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, online databases, and reference lists for studies through 13 October 2011. SELECTION CRITERIA: We included randomised, double-blind, placebo- and/or active-controlled studies using oral sumatriptan to treat a migraine headache episode, with at least 10 participants per treatment arm. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. We used numbers of participants achieving each outcome to calculate relative risk (or 'risk ratio') and numbers needed to treat to benefit (NNT) or harm (NNH) compared to placebo or a different active treatment. MAIN RESULTS: Sixty-one studies (37,250 participants) compared oral sumatriptan with placebo or an active comparator. Most of the data were for the 50 mg and 100 mg doses. Sumatriptan surpassed placebo for all efficacy outcomes. For sumatriptan 50 mg versus placebo the NNTs were 6.1, 7.5, and 4.0 for pain-free at two hours and headache relief at one and two hours, respectively. NNTs for sustained pain-free and sustained headache relief during the 24 hours postdose were 9.5 and 6.0, respectively. For sumatriptan 100 mg versus placebo the NNTs were 4.7, 6.8, 3.5, 6.5, and 5.2, respectively, for the same outcomes. Results for the 25 mg dose were similar to the 50 mg dose, while sumatriptan 100 mg was significantly better than 50 mg for pain-free and headache relief at two hours, and for sustained pain-free during 24 hours. Treating early, during the mild pain phase, gave significantly better NNTs for pain-free at two hours and sustained pain-free during 24 hours than did treating established attacks with moderate or severe pain intensity.Relief of associated symptoms, including nausea, photophobia, and phonophobia, was greater with sumatriptan than with placebo, and use of rescue medication was lower with sumatriptan than with placebo. For the most part, adverse events were transient and mild and were more common with the sumatriptan than with placebo, with a clear dose response relationship (25 mg to 100 mg).Sumatriptan was compared directly with a number of active treatments, including other triptans, paracetamol (acetaminophen), acetylsalicylic acid, non-steroidal anti-inflammatory drugs (NSAIDs), and ergotamine combinations. AUTHORS' CONCLUSIONS: Oral sumatriptan is effective as an abortive treatment for migraine attacks, relieving pain, nausea, photophobia, phonophobia, and functional disability, but is associated with increased adverse events.

Sumatriptan (intranasal route of administration) for acute migraine attacks in adults.

BACKGROUND: Migraine is a highly disabling condition for the individual and also has wide-reaching implications for society, healthcare services, and the economy. Sumatriptan is an abortive medication for migraine attacks, belonging to the triptan family. Intranasal administration may be preferable to oral for individuals experiencing nausea and/or vomiting, although it is primarily absorbed in the gut, not the nasal mucosa. OBJECTIVES: To determine the efficacy and tolerability of intranasal sumatriptan compared to placebo and other active interventions in the treatment of acute migraine attacks in adults. SEARCH METHODS: We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, online databases, and reference lists for studies through 13 October 2011. SELECTION CRITERIA: We included randomised, double-blind, placebo- and/or active-controlled studies using intranasal sumatriptan to treat a migraine headache episode, with at least 10 participants per treatment arm. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. We used numbers of participants achieving each outcome to calculate relative risk (or 'risk ratio') and numbers needed to treat to benefit (NNT) or harm (NNH) compared to placebo or a different active treatment. MAIN RESULTS: Twelve studies (4755 participants) compared intranasal sumatriptan with placebo or an active comparator. Most of the data were for the 10 mg and 20 mg doses. Sumatriptan surpassed placebo for all efficacy outcomes. For sumatriptan 10 mg versus placebo the NNTs were 7.3, 7.4, and 5.5 for pain-free at two hours, and headache relief at one and two hours, respectively. For sumatriptan 20 mg versus placebo the NNTs were 4.7, 4.9, and 3.5, respectively, for the same outcomes. The 20 mg dose was significantly better than the 10 mg dose for each of these three primary efficacy outcomes.Relief of headache-associated symptoms, including nausea, photophobia, and phonophobia, was greater with sumatriptan than with placebo, and use of rescue medication was lower with sumatriptan than placebo. For the most part, adverse events were transient and mild and were more common with sumatriptan than placebo.Direct comparison of sumatriptan with active treatments was limited to two studies, one comparing sumatriptan 20 mg and dihydroergotamine (DHE) 1 mg, and one comparing sumatriptan 20 mg with rizatriptan 10 mg. AUTHORS' CONCLUSIONS: Intranasal sumatriptan is effective as an abortive treatment for acute migraine attacks, relieving pain, nausea, photophobia, phonophobia, and functional disability, but is associated with increased adverse events compared with placebo.

Sumatriptan (rectal route of administration) for acute migraine attacks in adults.

BACKGROUND: Migraine is a highly disabling condition for the individual and also has wide-reaching implications for society, healthcare services, and the economy. Sumatriptan is an abortive medication for migraine attacks, belonging to the triptan family. Rectal administration may be preferable to oral for individuals experiencing nausea and/or vomiting. OBJECTIVES: To determine the efficacy and tolerability of rectal sumatriptan compared to placebo and other active interventions in the treatment of acute migraine attacks in adults. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, online databases, and reference lists for studies through 13 October 2011. SELECTION CRITERIA: We included randomised, double-blind, placebo- and/or active-controlled studies using rectally administered sumatriptan to treat a migraine headache episode, with at least 10 participants per treatment arm. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. We used numbers of participants achieving each outcome to calculate relative risk (or 'risk ratio') and numbers needed to treat to benefit (NNT) or harm (NNH) compared to placebo or a different active treatment. MAIN RESULTS: Three studies (866 participants) compared rectally administered sumatriptan with placebo or an active comparator. Most of the data were for the 12.5 mg and 25 mg doses. For the majority of efficacy outcomes, sumatriptan surpassed placebo. For sumatriptan 12.5 mg versus placebo the NNTs were 5.2 and 3.2 for headache relief at one and two hours, respectively. Results for the 25 mg dose were similar to the 12.5 mg dose, and there were no significant differences between the two doses for any of the outcomes analysed. The NNTs for sumatriptan 25 mg versus placebo were 4.2, 3.2, and 2.4 for pain-free at two hours, headache relief at one hour, and headache relief at two hours, respectively.Relief of functional disability was greater with sumatriptan than with placebo, with NNTs of 8.0 and 4.0 for the 12.5 mg and 25 mg doses, respectively. For the most part, adverse events were transient and mild and were more common with sumatriptan than with placebo, but there were insufficient data to perform any analyses.Direct comparison of sumatriptan with active treatments was limited to one study comparing sumatriptan 25 mg with ergotamine tartrate 2 mg + caffeine 100 mg. AUTHORS' CONCLUSIONS: Based on limited amounts of data, sumatriptan 25 mg, administered rectally, is an effective treatment for acute migraine attacks, with participants in these studies experiencing a significant reduction in headache pain and functional disability within two hours of treatment. The lack of data on relief of headache-associated symptoms or incidence of adverse events limits any conclusions that can be drawn.

Sumatriptan (subcutaneous route of administration) for acute migraine attacks in adults.

BACKGROUND: Migraine is a highly disabling condition for the individual and also has wide-reaching implications for society, healthcare services, and the economy. Sumatriptan is an abortive medication for migraine attacks, belonging to the triptan family. Subcutaneous administration may be preferable to oral for individuals experiencing nausea and/or vomiting OBJECTIVES: To determine the efficacy and tolerability of subcutaneous sumatriptan compared to placebo and other active interventions in the treatment of acute migraine attacks in adults. SEARCH METHODS: We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, online databases, and reference lists for studies through 13 October 2011. SELECTION CRITERIA: We included randomised, double-blind, placebo- and/or active-controlled studies using subcutaneous sumatriptan to treat a migraine headache episode, with at least 10 participants per treatment arm. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. We used numbers of participants achieving each outcome to calculate relative risk (or 'risk ratio') and numbers needed to treat to benefit (NNT) or harm (NNH) compared to placebo or a different active treatment. MAIN RESULTS: Thirty-five studies (9365 participants) compared subcutaneous sumatriptan with placebo or an active comparator. Most of the data were for the 6 mg dose. Sumatriptan surpassed placebo for all efficacy outcomes. For sumatriptan 6 mg versus placebo the NNTs were 2.9, 2.3, 2.2, and 2.1 for pain-free at one and two hours, and headache relief at one and two hours, respectively, and 6.1 for sustained pain-free at 24 hours. Results for the 4 mg and 8 mg doses were similar to the 6 mg dose, with 6 mg significantly better than 4 mg only for pain-free at one hour, and 8 mg significantly better than 6 mg only for headache relief at one hour. There was no evidence of increased migraine relief if a second dose of sumatriptan 6 mg was given after an inadequate response to the first.Relief of headache-associated symptoms, including nausea, photophobia, and phonophobia, was greater with sumatriptan than with placebo, and use of rescue medication was lower with sumatriptan than placebo. For the most part, adverse events were transient and mild and were more common with sumatriptan than placebo.Sumatriptan was compared directly with a number of active treatments, including other triptans, acetylsalicylic acid plus metoclopramide, and dihydroergotamine, but there were insufficient data for any pooled analyses. AUTHORS' CONCLUSIONS: Subcutaneous sumatriptan is effective as an abortive treatment for acute migraine attacks, quickly relieving pain, nausea, photophobia, phonophobia, and functional disability, but is associated with increased adverse events.

Nocturnal Frontal Lobe Epilepsy vs Parasomnias.

OPINION STATEMENT: The diagnosis and treatment of nocturnal events can present significant challenges to the clinician. Correct diagnosis is the first step towards appropriate treatment, but may not be straightforward. In particular, non-rapid eye movement (NREM) arousal parasomnias, such as sleepwalking, sleep terrors, and confusional arousal can present in a similar fashion to nocturnal frontal lobe epilepsy (NFLE); dramatic and often bizarre behaviors from sleep are features of both conditions, and may result in diagnostic confusion. A careful clinical history, however, often enables accurate diagnosis, and the frontal lobe epilepsy and parasomnia (FLEP) scale, a validated questionnaire for the diagnosis of nocturnal events, can add diagnostic confidence. Recording of events on video-EEG-polysomnography is required if diagnostic doubt remains although is not always achievable, particularly if events are occurring infrequently. Treatments for NFLE and parasomnias are different, but lifestyle modification and treatment of coexisting sleep disorders (such as obstructive sleep apnoea) may have a role in both. In NFLE, medical treatment with antiepileptic drugs, particularly carbamazepine and topiramate, forms the mainstay of treatment; a small proportion of individuals with treatment-resistant seizures may benefit from epilepsy surgery. For parasomnias, reassurance and the removal of priming and precipitating factors is often sufficient. A minority of individuals will, however, need medical treatment, usually with benzodiazepines or tricyclic antidepressants. Unfortunately, there are few data on which to base treatment decisions in this area, with the evidence comprising predominantly case reports and case series. Well-designed studies, including randomised control trials, are needed and may require a multicentre approach.

NREM Sleep Parasomnias Commencing in Childhood: Trauma and Atopy as Perpetuating Factors.

Objective/Background: Phenotyping of non-rapid-eye-movement (NREM) parasomnias is currently poorly undertaken. This study aimed to determine whether there are differences phenotypically among childhood-, adolescent-, and adult-onset NREM parasomnias continuing into and presenting in adulthood. Patients/Methods: A retrospective, cohort study of patients presenting with NREM parasomnia between 2008 and 2019 (n = 307) was conducted. Disorders included sleepwalking (n = 231), night terrors (n = 150), sexualised behaviour in sleep (n = 50), and sleep-related eating disorder (n = 28). Results: Compared to the adult-onset NREM behaviours group, the childhood- and adolescent-onset groups were more likely to have a family history of NREM behaviours (p < 0.001), experience a greater spectrum of NREM disorders (p = 0.001), and report a history of sleep-talking significantly more frequently (p = 0.014). Atopy was most prevalent in the childhood-onset group (p = 0.001). Those with childhood-onset NREM parasomnias were significantly more likely to arouse from N3 sleep on video polysomnography (p = 0.0003). Psychiatric disorders were more likely to be comorbid in the adult-onset group (p = 0.012). A history of trauma coinciding with onset of NREM behaviours was significantly more common in the childhood- and adolescent-onset groups (p < 0.001). Conclusions: Significant differences exist across childhood-, adolescent-, and adult-onset NREM parasomnia presenting in adulthood. This study suggests that adult-onset slow-wave sleep disorders may be confounded by psychiatric disorders resulting in nocturnal sleep disruption and that unresolved traumatic life experiences perpetuate NREM disorders arising in childhood and comprise one of the strongest external risk factors for triggering and perpetuating these disorders in adolescence.

The sleep manifestations of frontal lobe epilepsy.

Frontal lobe seizures have a tendency to occur from sleep, and in some cases occur exclusively (or almost exclusively) from sleep; these individuals are said to have nocturnal frontal lobe epilepsy (NFLE). NFLE can be difficult to distinguish clinically from various other sleep disorders, particularly parasomnias, which also present with paroxysmal motor activity in sleep. Here, the manifestations of frontal lobe epilepsy are reviewed in detail, with particular reference to the influence of sleep and the characteristics of NFLE. Key aspects of differential diagnosis are also considered, and the underlying mechanisms involved in NFLE discussed.

Autoimmune limbic encephalitis.

Autoimmune limbic encephalitis is an increasingly recognised cause of cognitive decline and confusion. The typical presentation is with subacute cognitive decline, behavioural disturbance and seizures. Magnetic resonance imaging may show characteristic changes in the medial temporal regions. The diagnosis is confirmed by identification of elevated voltage-gated potassium channel antibody (VGKC-Ab) titres. It is a highly treatable condition, often responding well to intravenous immunoglobulin or steroids. Recognition of autoimmune limbic encephalitis is sometimes delayed--usually because the diagnosis has not been considered--which can result in long-term neurological consequences.

NREM arousal parasomnias and their distinction from nocturnal frontal lobe epilepsy: a video EEG analysis.

STUDY OBJECTIVES: To describe the semiological features of NREM arousal parasomnias in detail and identify features that can be used to reliably distinguish parasomnias from nocturnal frontal lobe epilepsy (NFLE). DESIGN: Systematic semiologial evaluation of parasomnias and NFLE seizures recorded on video-EEG monitoring. PATIENTS: 120 events (57 parasomnias, 63 NFLE seizures) from 44 subjects (14 males). Interventions. The presence or absence of 68 elemental clinical features was determined in parasomnias and NFLE seizures. Qualitative analysis of behavior patterns and ictal EEG was undertaken. Statistical analysis was undertaken using established techniques. RESULTS: Elemental clinical features strongly favoring parasomnias included: interactive behavior, failure to wake after event, and indistinct offset (all P < 0.001). Cluster analysis confirmed differences in both the frequency and combination of elemental features in parasomnias and NFLE. A diagnostic decision tree generated from these data correctly classified 94% of events. While sleep stage at onset was discriminatory (82% of seizures occurred during stage 1 or 2 sleep, with 100% of parasomnias occurring from stage 3 or 4 sleep), ictal EEG features were less useful. Video analysis of parasomnias identified three principal behavioral patterns: arousal behavior (92% of events); non-agitated motor behavior (72%); distressed emotional behavior (51%). CONCLUSIONS: Our results broadly support the concept of confusion arousals, somnambulism and night terrors as prototypical behavior patterns of NREM parasomnias, but as a hierarchical continuum rather than distinct entities. Our observations provide an evidence base to assist in the clinical diagnosis of NREM parasomnias, and their distinction from NFLE seizures, on semiological grounds.