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.

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).

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.

Role of Greater Occipital Nerve Block in Headache Disorders: A Narrative Review.

BACKGROUND: The proximity of sensory neurons in the upper cervical spinal cord to the trigeminal nucleus caudalis (TNC) neurons and the convergence of sensory input to TNC neurons from both cervical and trigeminal fibers underscore the rationale of using greater occipital nerve block (GON-block) for acute and preventive treatment in various headache disorders. OBJECTIVE: The aim of this study was to critically review the existing literature regarding the safety and efficacy of GON-block in various headache disorders. METHODS: We searched the eligible studies in English by searching in PubMed till December 31, 2020 for randomized controlled trials (RCTs), observational studies, open-label studies, case series, and case reports on the efficacy and the safety of GON-block for the treatment of headache disorders using the keywords "greater occipital nerve block", "headache" and "treatment". Studies using combination of GON-block and other peripheral nerve blocks (PNBs) and C2/C3 blocks were excluded. RESULTS: Seventy-two eligible studies were reviewed. Based on RCTs and open-label studies, good evidence of the efficacy of GON-block was found for migraine, cluster headache (CH), post-dural puncture headache (PDPH), cervicogenic headache (CGH), and occipital neuralgia (ON). The analgesic effect of GON-block outlasted its anesthetic effect by days to weeks. Evidence for acute and short-term (transitional) treatment was more robust than for long-term prevention. GON-block was found to be safe and the treatment-emergent adverse effects (TEAEs) were generally mild and transient. CONCLUSION: GON-block is a useful modality of treatment in various headache disorders because of many attractive features such as its early effect in reducing the severity of pain, sustained effect following a single injection, easy technique, minimum invasiveness, minimum TEAE, no drug-to-drug interactions, and negligible cost.

Regularized Particle Filter based algorithm for the state estimation of orphan gamma source in real time using a backpack gamma spectrometry system.

We demonstrate the capability of Regularized Particle Filter (RPF) based algorithm to localise and quantify an orphan gamma-ray source situated in an unknown area using a single radiation detection system. The radiological measurements are made in the form of gamma spectra at multiple locations using an in-house developed backpack gamma spectrometer based on a 2″ x 2″ NaI(Tl) scintillation detector. We developed an Android application based on RPF which processes the gamma spectra received from the backpack over Bluetooth along with location information acquired from the smart phone's GPS in real time to show the source location in latitude, longitude format and source strength. To examine the performance of the algorithm, the radiological source search operation is carried out with 5.74 GBq 137Cs and 2.66 GBq 60Co in two independent experiments. The sources are located within an error of 10 m in location and 10% in source strength during the multiple experiments. The experiments are conducted in an open field where the attenuating medium for gamma rays would appear homogeneous at all the measurement points. Further improvements in the methodology are required for the localisation and quantification of source in an urban environment with a single detector.

Managing Migraine in the Times of COVID-19 Pandemic.

COVID-19 pandemic is an emerging, rapidly evolving situation. Migraine is one of the commonest and highly disabling chronic neurological diseases in the world. During the pandemic and lockdown, migraine patients are facing an enormous problem in getting optimum care because of difficulty in access, forced social isolation, and encountering a health system that is getting rapidly overwhelmed. It is important that they must be protected by minimizing their visits to the clinics and emergency departments. Paradoxically multiple triggers are in operation which is likely to increase their headache frequency. Hence physicians should be made aware of the new rules of the game in treating migraines during this time of the pandemic so that these patients get optimum treatment and care and don't feel left out. This review tries to answer a series of questions related to managing migraines in the times of COVID-19 pandemic.

Numerical simulation of a glucose sensitive composite membrane closed-loop insulin delivery system.

Closed-loop insulin delivery system works on pH modulation by gluconic acid production from glucose, which in turn allows regulation of insulin release across membrane. Typically, the concentration variation of gluconic acid can be numerically modeled by a set of non-linear, non-steady state reaction diffusion equations. Here, we report a simpler numerical approach to time and position dependent diffusivity of species using finite difference and differential quadrature (DQ) method. The results are comparable to that obtained by analytical method. The membrane thickness directly determines the concentrations of the glucose and oxygen in the system, and inversely to the gluconic acid. The advantage with the DQ method is that its parameter values need not be altered throughout the analysis to obtain the concentration profiles of the glucose, oxygen and gluconic acid. Our work would be useful for modeling diabetes and other systems governed by such non-linear and non-steady state reaction diffusion equations.