Headache prevalence and demographic associations in the Delhi and National Capital Region of India: estimates from a cross-sectional nationwide population-based study.

BACKGROUND: India is a large and populous country where reliable data on headache disorders are relatively scarce. This study in northern India (Delhi and National Capital Territory Region [NCR], including surrounding districts in the States of Haryana, Uttar Pradesh and Rajasthan) continues the series of population-based studies within the Global Campaign against Headache and follows an earlier study, using the same protocol and questionnaire, in the southern State of Karnataka. METHODS: This cross-sectional study used the Global Campaign's established methodology. Biologically unrelated Indian nationals aged 18-65 years were included through multistage random sampling in both urban and rural areas of NCR. Interviews at unannounced household visits followed the structured Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire in its original English version or in the validated Hindi version. Demographic enquiry was followed by a neutral headache screening question and diagnostic questions based on the International Classification of Headache Disorders edition 3 (ICHD-3), which focused on each respondent's most bothersome headache. Questions about headache yesterday (HY) enabled estimation of 1-day prevalence. A diagnostic algorithm first identified participants reporting headache on ≥ 15 days/month (H15+), diagnosing probable medication-overuse headache (pMOH) in those also reporting acute medication use on ≥ 15 days/month, and "other H15+" in those not. To all others, the algorithm applied ICHD-3 criteria in the order definite migraine, definite tension-type headache (TTH), probable migraine, probable TTH. Definite and probable diagnoses were combined. RESULTS: Adjusted for age, gender and habitation, 1-year prevalences were 26.3% for migraine, 34.1% for TTH, 3.0% for pMOH and 4.5% for other H15+. Female preponderance was seen in all headache types except TTH: migraine 35.7% vs. 15.1% (aOR = 3.3; p < 0.001); pMOH 4.3% vs. 0.7% (aOR = 5.1; p < 0.001); other H15 + 5.9% vs. 2.3% (aOR = 2.5; p = 0.08). One-day prevalence of (any) headache was 12.0%, based on reported HY. One-day prevalence predicted from 1-year prevalence and mean recalled headache frequency over 3 months was slightly lower (10.5%). CONCLUSIONS: The prevalences of migraine and TTH in Delhi and NCR substantially exceed global means. They closely match those in the Karnataka study: migraine 25.2%, TTH 35.1%. We argue that these estimates can reasonably be extrapolated to all India.

The burden of headache disorders in North India: methodology, and validation of a Hindi version of the HARDSHIP questionnaire, for a community-based survey in Delhi and national capital territory region.

BACKGROUND: Knowledge of the prevalence and attributable burden of headache disorders in India is sparse, with only two recent population-based studies from South and East India. These produced conflicting results. A study in North India is needed. We report the methodology of such a study using, and validating, a Hindi translation of the Headache-Attributed Restriction, Disability, Social Handicap, and Impaired Participation (HARDSHIP) questionnaire developed by Lifting The Burden (LTB). Almost half of the Indian population speak Hindi or one of its dialects. METHODS: The study adopted LTB's standardized protocol for population-based studies in a cross-sectional survey using multistage random sampling conducted in urban Delhi and a surrounding rural area. Trained interviewers visited households unannounced, randomly selected one adult member from each and applied the Hindi version of HARDSHIP in face-to-face interviews. The most bothersome headache reported by participants was classified algorithmically into headache on ≥ 15 days/month (H15 +), migraine (including definite and probable) or tension-type headache (including definite and probable). These diagnoses were mutually exclusive. All participants diagnosed with H15 + and a 10% subsample of all others were additionally assessed by headache specialists and classified as above. We estimated the sensitivity and specificity of HARDSHIP diagnoses by comparison with the specialists' diagnoses. RESULTS: From 3,040 eligible households, 2,066 participants were interviewed. The participating proportions were 98.3% in rural areas but 52.9% in urban Delhi. In the validation subsample of 291 participants (149 rural, 142 urban), 61 did not report any headache (seven of those assessed by HARDSHIP, eight by headache specialists and 46 by both) [kappa = 0.83; 95% CI: 0.74-0.91]. In the remaining 230 participants who reported headache in the preceding year, sensitivity, specificity and kappa with (95% CI) were 0.73 (0.65-0.79), 0.80 (0.67-0.90) and 0.43 (0.34-0.58) for migraine; 0.71 (0.56-0.83), 0.80 (0.730.85) and 0.43 (0.37-0.62) for TTH and 0.75 (0.47-0.94), 0.93 (0.89-0.96) and 0.46 (0.34-0.58) for H15 + respectively. CONCLUSION: This study validates the Hindi version of HARDSHIP, finding its performance similar to those of other versions. It can be used to conduct population surveys in other Hindi-speaking regions of India.

Greater occipital nerve blockade for the preventive treatment of chronic migraine: A randomized double-blind placebo-controlled study.

BACKGROUND: Greater occipital nerve blockade for the prevention of chronic migraine has a limited evidence base. A robust randomized double-blind, placebo-controlled trial is needed. METHODS: This double-blind, placebo-controlled, parallel-group trial, following a baseline period of four weeks, randomly assigned patients of chronic migraine 1:1 to receive four-weekly bilateral greater occipital nerve blockade with either 2 ml of 2% (40 mg) lidocaine (active group) or 2 ml of 0.9% saline (placebo) injections for 12 weeks. The primary and key secondary efficacy endpoints were a change from the baseline in the mean number of headache and migraine days and the achievement of ≥50% reduction in headache days from baseline across the weeks 9-12 respectively. Safety evaluations included the documentation and reporting of serious and other adverse events. RESULTS: Twenty-two patients each were randomly allocated to the active and placebo group. Baseline demography and clinical characteristics were similar between the two groups. Mean headache and migraine days at baseline (±SD) were 23.4 ± 4.4 and 15.6 ± 5.7 days in the active group and 22.6 ± 5.0 and 14.6 ± 4.6 days in the placebo group respectively. The active group compared to the placebo had a significantly greater least-squares mean reduction in the number of headache and migraine days (-4.2 days [95% CI: -7.5 to -0.8; p = 0.018] and -4.7 days [95%CI: -7.7 to -1.7; p = 0.003] respectively). 40.9% of patients in the active group achieved ≥50% reduction in headache days as compared with 9.1% of patients receiving a placebo (p = 0.024). Overall, 64 mild and transient adverse events were reported by 16 patients in the active group and 15 in the placebo. No death or serious adverse events were reported. CONCLUSION: Four-weekly greater occipital nerve blockade with 2% lidocaine for 12 weeks was superior to placebo in decreasing the average number of headache and migraine days in patients with chronic migraine with a good tolerability profile.Clinical trial.gov no. CTRI 2020/07/026709.

Galcanezumab in patients with episodic migraine: results from the open-label period of the phase 3 PERSIST study.

BACKGROUND: The phase 3 randomized PERSIST study demonstrated the efficacy and tolerability of galcanezumab, a humanized anti-calcitonin gene-related peptide (CGRP) monoclonal antibody for prevention of episodic migraines. We present findings from the open-label extension (OLE) of PERSIST, which evaluated the long-term efficacy and safety of galcanezumab in patients from China, India, and Russia. METHODS: Patients completing the 3-month double-blind period of PERSIST were eligible for the 3-month OLE. Patients previously randomized to galcanezumab (GMB/GMB group) continued to receive galcanezumab 120 mg at all three visits during the OLE whereas patients randomized to placebo received a 240 mg loading dose of galcanezumab and then two 120 mg doses (PBO/GMB group). The primary outcome was the mean change (from double-blind baseline) in the number of monthly migraine headache days (MHDs) to month 6. Other endpoints included percent reduction in monthly MHDs from double-blind baseline to month 6, functional outcomes, safety and tolerability. RESULTS: Overall, 99% of patients completing the double-blind period entered the OLE, and 96% completed through month 6. Patients in the GMB/GMB group achieved continued improvements in efficacy, with the reduction from baseline in the mean number of monthly MHDs, and slightly increasing from 4.01 days at the end of the double-blind period to 4.62 at the end of the OLE. Of patients who were ≥ 50% responders to galcanezumab at month 3, 66% maintained this response through to month 6. Patients in the PBO/GMB group experienced a rapid reduction in the number of monthly MHDs after initiation of galcanezumab, with a mean reduction from baseline of 4.56 days by month 6. The long-term benefits of galcanezumab were also supported by improvements in other efficacy and functional endpoints. All safety findings were consistent with the known long-term safety profile of galcanezumab; no patients experienced a treatment-related serious adverse event. CONCLUSIONS: Galcanezumab was efficacious and well-tolerated in patients with episodic migraine from China, India and Russia, for up to 6 months. TRIAL REGISTRATION: ClinicalTrisABSTRACT_pals.gov NCT03963232, registered May 24, 2019.

Comparison of Serum Holotranscobalamin with Serum Vitamin B12 in Population Prone to Megaloblastic Anemia and their Correlation with Nerve Conduction Study.

Early detection of megaloblastic anemia and associated neurological complications is crucial for management. This study was conducted to compare serum holotranscobalamin level with serum vitamin B12 level as early biomarker in people prone to megaloblastic anemia and to evaluate co-relation between these biomarkers and nerve conduction study in study patients. 83 adult patients (Hb > 12 gm/dl) prone to megaloblastic anemia were studied for basic haematological investigations, random blood sugar, thyroid function test, liver function test, kidney function test, serum vitamin B12, serum holotranscobalamin and serum folic acid levels. 45 patients among them underwent nerve conduction studies. All study patients were classified in 6 groups on the basis of risk factors for megaloblastic anemia. 29 patients (34.9%) were on antiepileptic drugs, 26 (31.3%) were chronic alcoholic, 10 patients (12%) each, had malabsorption and ileal tuberculosis, 6 (7.22%) had chronic pancreatitis and 2 (2.4%) had ileal resection. 30 patients (36.14%) had low serum holotranscobalamin, including 7 patients (8.43%) with low serum vitamin B12 level also, unmasking vitamin B12 deficiency in 23 patients (27.7%). 7 patients (8.43%) had mean corpuscular volume (MCV) > 100fL and 8 patients (9.63%) had vitamin B12 deficiency related changes on peripheral smear. Serum vitamin B12 and holotranscobalamin levels were significantly low in patients with peripheral smear changes, with p value 0.039 and 0.041 respectively, while no such association seen with MCV. Subclinical peripheral neuropathy was detected in 18 (40%) out of 45 patients on nerve conduction study. Serum holotranscobalamin levels were significantly lower (p = 0.031) than serum vitamin B12 levels (p = 0.2) in patients with neuropathic changes. Rest investigations and serum folic acid levels were normal in all patients. Holotranscobalamin levels can be considered early and reliable marker for vitamin B12 deficiency and deficiency associated peripheral neuropathy, even in patients who are prone to megaloblastic anemia, and not yet anemic or symptomatic for neuropathy.

Efficacy and tolerability of combination treatment of topiramate and greater occipital nerve block versus topiramate monotherapy for the preventive treatment of chronic migraine: A randomized controlled trial.

OBJECTIVE: To compare the efficacy and tolerability of combination treatment of topiramate and greater occipital nerve block to topiramate monotherapy in adult chronic migraine patients. BACKGROUND: Options for the preventive treatment of chronic migraine are limited and costly. Combination treatments do not have an evidence base yet. METHODS: This was a parallel group, 3 arms with 1:1:1 allocation ratio randomized controlled study in consecutive adult chronic migraine patients attending Headache Clinic in a tertiary care hospital. Patients received either topiramate monotherapy 100 mg/day (group A), or topiramate plus greater occipital nerve block with 40 mg lidocaine (2%) and 80mg (2 ml) methylprednisolone as the first injection followed by monthly injections of lidocaine for the next 2 months (group B) or topiramate plus greater occipital nerve block with 40 mg lidocaine (2%) injections monthly for 3 months (group C). The primary endpoint was the mean change in monthly migraine days at Month 3. Multiple secondary endpoints were assessed that included among others, achievement of ≥50% reduction in mean monthly headache days compared to baseline at Month 3 and assessment for any adverse events. RESULTS: One hundred and twenty-five patients were randomized; 41 to group A, 44 to group B, and 40 to group C. Efficacy assessments were done for 121 patients. Patients receiving combination treatment of topiramate and greater occipital nerve block with steroids and lidocaine and greater occipital nerve block with only lidocaine compared to topiramate monotherapy showed greater reductions in monthly migraine days at Month 3 (-9.6 vs -7.3 days; p = 0.003) and (-10.1 vs -7.3 days; p < 0.001) respectively. Greater proportion of patients in both the combination treatment groups (added greater occipital nerve block with and without steroid) achieved ≥50% reduction in mean monthly headache days [71.4% vs 39%; OR (95% CI) 3.9(1.6-9.8); p = 0.004] and [62.4% vs 39%; OR (95% CI) 2.7(1.1-6.7); p = 0.034] respectively, compared to those receiving topiramate monotherapy. Adverse effects between the groups were comparable although patients receiving combination treatment with added greater occipital nerve block reported transient adverse effects like post-injection dizziness, local site swelling, and pain. No serious adverse event was reported. CONCLUSION: Combination treatments of topiramate with monthly injections of greater occipital nerve block were more effective in reducing monthly migraine days in chronic migraine than topiramate monotherapy at Month 3. Combination treatments were well tolerated.

TOP-PRO study: A randomized double-blind controlled trial of topiramate versus propranolol for prevention of chronic migraine.

OBJECTIVE: The aim of the TOP-PRO-study, a double-blind randomized controlled trial, was to assess the efficacy (non-inferiority) and tolerability of propranolol compared to topiramate for the prevention of chronic migraine. BACKGROUND: Except for topiramate, oral preventive treatment for chronic migraine lacks credible evidence. METHODS: Chronic migraine patients aged above 18 years and less than 65 years of age, not on any preventive treatment were randomly allocated to receive topiramate (100 mg/day) or propranolol (160 mg/day). The primary efficacy outcome was the mean change in migraine days per 28 days at the end of 24 weeks from baseline. A mean difference of 1.5 days per four weeks was chosen as the cut-off delta value. Multiple secondary efficacy outcomes and treatment emergent adverse events were also assessed. RESULTS: As against the planned sample size of 244, only 175 patients could be enrolled before the spread of the corona virus disease-2019 pandemic and enforcement of lockdown in India. Of the 175 randomized patients, 95 (topiramate 46 and propranolol 49) completed the trial. The mean change in migraine days was -5.3 ± 1.2 vs -7.3 ± 1.1 days (p = 0.226) for topiramate and propranolol groups respectively. Propranolol was found to be non-inferior and not superior to topiramate (point estimate of -1.99 with a 95% confidence interval of -5.23 to 1.25 days). Multiple secondary outcomes also did not differ between the two groups. Intention to treat analysis of 175 patients and per-protocol analysis of 95 patients yielded concordant results. There was no significant difference in the incidence of adverse events between the two groups. CONCLUSION: Propranolol (160mg/day) was non-inferior, non-superior to topiramate (100mg/day) for the preventive treatment of chronic migraine and had a comparable tolerability profile.Trial Registration: Clinical Trials Registry-India CTRI/2019/05/018997).

Randomised, controlled trial of erenumab for the prevention of episodic migraine in patients from Asia, the Middle East, and Latin America: The EMPOwER study.

OBJECTIVE: EMPOwER, a double-blind, randomised, phase 3 study, evaluated the efficacy and safety of erenumab in adults with episodic migraine from Asia, the Middle East, and Latin America. METHODS: Randomised patients (N = 900) received monthly subcutaneous injections of placebo, erenumab 70 mg, or 140 mg (3:3:2) for 3 months. Primary endpoint was change from baseline in monthly migraine days at Month 3. Other endpoints included achievement of ≥50%, ≥75%, and 100% reduction in monthly migraine days, change in monthly acute migraine-specific medication treatment days, patient-reported outcomes, and safety assessment. RESULTS: At baseline, mean (standard deviation) age was 37.5 (9.9) years, 81.9% were women, and monthly migraine days was 8.2 (2.8). At Month 3, change from baseline in monthly migraine days (primary endpoint) was -3.1, -4.2, and -4.8 days for placebo, erenumab 70 mg, and erenumab 140 mg, respectively, with a statistically significant difference for erenumab versus placebo (P = 0.002 [70 mg], P < 0.001 [140 mg]). Both erenumab doses were also significantly superior to placebo on all secondary endpoints, including the proportion of patients achieving ≥50% reduction from baseline in monthly migraine days, change from baseline in monthly acute migraine-specific medication treatment days and change from baseline in the Headache Impact Test-6™ scores. The safety profile of erenumab was comparable with placebo; no new safety signals were observed. CONCLUSIONS: This study of erenumab in patients with episodic migraine from Asia, the Middle East, and Latin America met all primary and secondary endpoints. A consistent numerical benefit was observed with erenumab 140 mg versus erenumab 70 mg across all efficacy endpoints. These findings extend evidence of erenumab's efficacy and safety to patients under-represented in previous trials.ClinicalTrials.gov identifier: NCT03333109.

An Internet-based study on the impact of COVID-19 pandemic-related lockdown on migraine in India.

OBJECTIVES: To assess the impact of lockdown during the COVID-19 pandemic on migraine patients in India on disease activity, healthcare accessibility, and quality of life (QoL). MATERIALS & METHODS: This internet-based survey study using a structured questionnaire was conducted from 27th April to 31st July 2020. Previous physician-diagnosed migraine patients or those fulfilling any two of three clinical features (limitation of activities for >1 day, associated nausea or vomiting, and photophobia or phonophobia) were diagnosed as migraine patients. QoL was captured using a Likert scale and determinants of poor QoL were identified by logistic regression. RESULTS: A total of 4078 persons completed the full survey out of which 984 (24.1%) had migraine (mean age 35.3 ±11.2). Compared to pre-lockdown, 51.3% of migraineurs reported worsening of their headaches in terms of increased attack frequency (95.6%), increased headache days (95%), increased attack duration (89.9%) and increased headache severity (88.1%). The worsening was attributed to anxiety due to the pandemic (79.7%), inability or difficulty to access healthcare (48.4%) and migraine medicines (48.9%), and financial worries (60.9%). 26.8% of migraineurs reported poor QoL compared to 7.37% of non-migraineurs [p<0.0001]. Migraine affected QoL in 61.4% of migraineurs. The predictors of poor QoL on logistic regression included worsening migraine during the lockdown (AOR 4.150; CI 2.704- 6.369) and difficulty accessing migraine medicines (AOR 4.549; CI 3.041- 6.805). Employment as an essential COVID-19 worker (AOR 0.623; CI 0.409- 0.950) protected against poor QoL. CONCLUSIONS: COVID-19 pandemic-related lockdown greatly impacted migraine patients in India which significantly reduced their QoL.

Structural conditions on complex networks for the Michaelis-Menten input-output response.

The Michaelis-Menten (MM) fundamental formula describes how the rate of enzyme catalysis depends on substrate concentration. The familiar hyperbolic relationship was derived by timescale separation for a network of three reactions. The same formula has subsequently been found to describe steady-state input-output responses in many biological contexts, including single-molecule enzyme kinetics, gene regulation, transcription, translation, and force generation. Previous attempts to explain its ubiquity have been limited to networks with regular structure or simplifying parametric assumptions. Here, we exploit the graph-based linear framework for timescale separation to derive general structural conditions under which the MM formula arises. The conditions require a partition of the graph into two parts, akin to a "coarse graining" into the original MM graph, and constraints on where and how the input variable occurs. Other features of the graph, including the numerical values of parameters, can remain arbitrary, thereby explaining the formula's ubiquity. For systems at thermodynamic equilibrium, we derive a necessary and sufficient condition. For systems away from thermodynamic equilibrium, especially those with irreversible reactions, distinct structural conditions arise and a general characterization remains open. Nevertheless, our results accommodate, in much greater generality, all examples known to us in the literature.

51-year old man with tingling, burning and progressive limb weakness.

Peripheral neuropathy is a common reason for referral to neurology. Chronic acquired demyelinating neuropathies are an important and varied group with overlapping presentations, and may have an immune-mediated cause. Their correct diagnosis is important as they respond to different treatments; timely intervention can prevent irreversible axonal degeneration. We present a case that highlights the approach to an adult presenting with a chronic demyelinating neuropathy.

A Generalized Michaelis-Menten Equation in Protein Synthesis: Effects of Mis-Charged Cognate tRNA and Mis-Reading of Codon.

The sequence of amino acid monomers in the primary structure of a protein is decided by the corresponding sequence of codons (triplets of nucleic acid monomers) on the template messenger RNA (mRNA). The polymerization of a protein, by incorporation of the successive amino acid monomers, is carried out by a molecular machine called ribosome. We develop a stochastic kinetic model that captures the possibilities of mis-reading of mRNA codon and prior mis-charging of a tRNA. By a combination of analytical and numerical methods, we obtain the distribution of the times taken for incorporation of the successive amino acids in the growing protein in this mathematical model. The corresponding exact analytical expression for the average rate of elongation of a nascent protein is a 'biologically motivated' generalization of the Michaelis-Menten formula for the average rate of enzymatic reactions. This generalized Michaelis-Menten-like formula (and the exact analytical expressions for a few other quantities) that we report here display the interplay of four different branched pathways corresponding to selection of four different types of tRNA.

Intensive care unit models: Do you want them to be open or closed? A critical review.

Intensive care is a specialized branch of medicine dealing with the diagnosis, management, and follow up of critically ill or critically injured patients. It requires input from other branches of medicine on various issues. A critical care specialist has expertise in managing such patients round the clock. Based on his freedom to take decisions in the intensive care unit (ICU), different types of ICUs - open, closed, or semi-closed - have been defined. There is no doubt that all critical patients should be evaluated by an intensivist. Therefore, it is argued that a closed ICU model would be the ideal model. However, this may not always be feasible and other models may be more useful in resource-limited countries. In this review, we compare the different formats of ICU functioning and their suitability in different hospitals.

The dilemma of arranged marriages in people with epilepsy. An expert group appraisal.

INTRODUCTION: Matrimony remains a challenging psychosocial problem confronting people with epilepsy (PWE). People with epilepsy are less likely to marry; however, their marital prospects are most seriously compromised in arranged marriages. AIMS: The aim of this study was to document marital prospects and outcomes in PWE going through arranged marriage and to propose optimal practices for counseling PWE contemplating arranged marriage. METHODS: A MEDLINE search and literature review were conducted, followed by a cross-disciplinary meeting of experts to generate consensus. RESULTS: People with epilepsy experience high levels of felt and enacted stigma in arranged marriages, but the repercussions are heavily biased against women. Hiding epilepsy is common during marital negotiations but may be associated with poor medication adherence, reduced physician visits, and poor marital outcome. Although divorce rates are generally insubstantial in PWE, divorce rates appear to be higher in PWE undergoing arranged marriages. In these marriages, hiding epilepsy during marital negotiations is a risk factor for divorce. CONCLUSIONS: In communities in which arranged marriages are common, physicians caring for PWE are best-equipped to counsel them about their marital prospects. Marital plans and aspirations should be discussed with the family of the person with epilepsy in a timely and proactive manner. The benefits of disclosing epilepsy during marital negotiations should be underscored.

Distribution of lifetimes of kinetochore-microtubule attachments: interplay of energy landscape, molecular motors and microtubule (de-)polymerization.

Before a cell divides into two daughter cells, chromosomes are replicated resulting in two sister chromosomes embracing each other. Each sister chromosome is bound to a separate proteinous structure, called kinetochore (kt), that captures the tip of a filamentous protein, called microtubule (MT). Two oppositely oriented MTs pull the two kts attached to two sister chromosomes, thereby pulling the two sisters away from each other. Here we theoretically study an even simpler system, namely an isolated kt coupled to a single MT; this system mimics an in vitro experiment where a single kt-MT attachment is reconstituted using purified extracts from budding yeast. Our models not only account for the experimentally observed 'catch-bond-like' behavior of the kt-MT coupling, but also make new predictions on the probability distribution of the lifetimes of the attachments. In principle, our new predictions can be tested by analyzing the data collected in the in vitro experiments, provided that the experiment is repeated a sufficiently large number of times. Our theory provides a deep insight into the effects of (a) size, (b) energetics, and (c) stochastic kinetics of the kt-MT coupling on the distribution of the lifetimes of these attachments.

Coordination, cooperation, competition, crowding and congestion of molecular motors: Theoretical models and computer simulations.

Cytoskeletal motor proteins are biological nanomachines that convert chemical energy into mechanical work to carry out various functions such as cell division, cell motility, cargo transport, muscle contraction, beating of cilia and flagella, and ciliogenesis. Most of these processes are driven by the collective operation of several motors in the crowded viscous intracellular environment. Imaging and manipulation of the motors with powerful experimental probes have been complemented by mathematical analysis and computer simulations of the corresponding theoretical models. In this article, we illustrate some of the key theoretical approaches used to understand how coordination, cooperation and competition of multiple motors in the crowded intra-cellular environment drive the processes that are essential for biological function of a cell. In spite of the focus on theory, experimentalists will also find this article as an useful summary of the progress made so far in understanding multiple motor systems.

Treatment in the emergency department.

As a common headache disorder, migraine is also a common cause for emergency department (ED) visiting, which leads to tremendous medical and economic burden. The goals of migraine management in ED are resolving headache and migraine-related most bothersome symptoms rapidly, preventing ED revisiting due to headache relapse, and referring patients at risk, e.g., patients with chronic migraine and/or medication-overuse headache, to specialists. In this chapter, we elucidated the algorithm which was particularly adapted to ED settings for the diagnosis and treatment of migraine. We reviewed a plentiful amount of high-quality clinical trials, especially those conducted in populations derived from ED, to provide readers insights into the optimized treatment options for migraine in ED.

Interictal Dysfunctions of Attention, Vigilance, and Executive Functions in Migraine and Their Reversal by Preventive Treatment: A longitudinal Controlled Study.

OBJECTIVE: To assess attention, vigilance, and executive functions in migraine patients during headache-free (interictal) periods and in healthy controls without migraine and to study the impact of migraine preventive treatment on these cognitive functions. METHODS: Preventive drug-naive migraine patients, aged ≥18 years, without a history of medication overuse were studied and compared to non-migraine controls. Psychiatric comorbidity was screened by Patient Health Questionnaire-9, and those who screened positive were evaluated further by specific scales. The Epworth Sleepiness Scale assessed subjective complaints of sleep quality. Cognitive functions were assessed by Mini-Mental State Examination (MMSE), digit span forward and backward (DS-F, DS-B), trail-making tests (TMT-A and B) and Stroop word (SW), Stroop color (SC), and Stroop interference (SI) tests. Cognitive test scores at the end of 6 months following treatment were compared to baseline scores. RESULTS: One hundred and fifty migraine patients and controls each were studied. Compared to controls, migraine patients performed significantly worse in DS-B ( P < 0.0001), TMT-A ( P = 0.00004), TMT-B ( P < 0.0001), SW ( P < 0.0001), SC ( P < 0.0001), and SI ( P = 0.0221). MMSE scores did not differ between patients and the controls ( P = 0.3224). Compared to the patients without psychiatric comorbidity, migraine patients with psychiatric comorbidity showed no significant differences in the cognitive test scores. Significant improvement in all cognitive test scores ( P < 0.001) was observed after 6 months of treatment. CONCLUSION: Migraine patients, compared to non-migraine controls, showed deficits in attention, vigilance, and executive functions during the interictal period, which improved with successful preventive treatment. Psychiatric comorbidities did not have a significant impact on cognitive dysfunctions.