A CRITICAL REVIEW OF JWARAHARA YOGAS OF AYURVEDIC CLASSICS: A PARADIGM TO REVERSE PHARMACOLOGY

Jwara is the first and foremost among all somatic diseases. Although an independent disease, it is also seen manifested in the form of premonitory symptom, symptom and causative factor of various disorders. 2019-20 has witnessed a new pandemic identified as Corona virus (COVID-19) with adverse health issues. In proportion to the wide variety of diseases, viral vaccines are very few, that too with adverse effects. Hence there is an urgent need of most promising Indigenous drugs with antipyretic and anti-viral activity in the current scenario. A critical analysis is made to explore the Jwarahara Yogas of classics to unfold the Antiviral, Antipyretic, Antioxidant and Immunomodulatory potential of phytochemicals in formulations. An attempt has been made to explore the antiviral and antipyretic potential of Amrutotharam Kashayam, one of the most popular and widely used Jwarahara yoga in classics. The review will definitely give new insights on the synergistic actions of phytochemicals in formulations to revalidate the clinical evidences and will throw lime light on repurposing of the documented novel drugs and combinations in classics to offer unique preventive strategies and therapeutic solutions to the present pandemic and emerging viral infections.

Premonitory symptoms in migraine from China: A multi-clinic study of 4821 patients

Objective To observe the prevalence and characteristics of premonitory symptoms in Chinese migraineurs and explore their associations with migraine-related factors. Method Migraineurs who visited a tertiary headache clinic and one of nine neurology clinics between May 2014 and November 2019 were studied. Result Among the 4821 patients meeting the migraine criteria (International Classification of Headache Disorders, 3rd edition), 1038 (21.5%) patients experienced at least one premonitory symptom. The most common premonitory symptoms were neck stiffness, dizziness, yawning and drowsiness. The logistic regression analysis demonstrated that aura, photophobia, aggravation by routine physical activity, triggers, family history, depression, coffee consumption and physical exercise were associated with an increased probability of experiencing premonitory symptoms ( p ≤ 0.001). The premonitory symptoms of migraine with and without aura differ in prevalence and most common symptoms. The cluster analysis revealed pairwise clustering of the following premonitory symptoms: Photophobia/phonophobia, concentration change/dysesthesia, loquacity/overactivity, yawning/drowsiness, fatigue/dizziness, and mood change/irritability. The correlation analysis of triggers and premonitory symptoms revealed that temperature change, environment change, sleep disorder, activity and stress were related to multiple premonitory symptoms, and that food, light, menstruation, alcohol and odor were related to special premonitory symptoms ( p ≤ 0.001). Conclusion The prevalence of premonitory symptoms among migraineurs in China is 21.5%. Some factors influence the probability of experiencing premonitory symptoms. Paired premonitory symptoms in the clustering analysis may share similar origins. Certain triggers associated with multiple premonitory symptoms may induce brain dysfunction; however, other triggers that overlap with corresponding special premonitory symptoms may be premonitory symptoms or a form of premonitory symptom.

Predicting the response to a triptan in migraine using deep attack phenotyping: A feasibility study

Background Triptans, specific symptomatic medications for migraine, are not effective in a proportion of patients, or in all attacks, hence the importance of identifying predictors of response. Our aim was to investigate the association between the efficacy of oral frovatriptan 2.5 mg and clinical characteristics of migraine attacks. Methods We enrolled 29 consecutive patients affected by migraine without aura at the Headache Center of “Mondino” Institute of Pavia. Each patient was given a diary and asked to record prospectively the features of three consecutive migraine attacks while using frovatriptan. A generalized estimating equations approach was used to determine phenotypic features associated with the pain free response at 2 hours. Results Participants provided complete data for 85 attacks. Thirty of these (34%) patients reported being pain free 2 hours after taking frovatriptan 2.5 mg intake. Unilateral pain, presence of phonophobia, presence of one or more cranial autonomic symptoms and presence of one or more premonitory symptom were each associated with being pain free at 2 hours. Conclusions The response to frovatriptan was associated with particular features of the migraine attack, either before or during the pain phase of attacks. The data support larger studies to explore detailed attack phenotyping, with particular attention to early signs, to enable individualized treatment in migraine.

Headache and non-headache symptoms provoked by nitroglycerin in migraineurs: A human pharmacological triggering study

Background Studying a spontaneous migraine attack is challenging, particularly the earliest components. Nitroglycerin is a potent, reliable and reproducible migraine trigger of the entirety of the migraine attack, making its use experimentally attractive. Methods Fifty-three subjects with migraine with a history of spontaneous premonitory symptoms were exposed to a 0.5 mcg/kg/min nitroglycerin infusion. Eighty-three percent (n = 44) developed typical premonitory and headache symptomatology. Fifty-seven percent (n = 25) were invited back to further study visits, during which they were re-exposed to nitroglycerin or placebo infusion in a double-blind randomised design. The phenotype of premonitory symptoms and headache was captured and compared to spontaneous attacks and between triggered attacks using agreement analysis. Results More premonitory symptoms were triggered with nitroglycerin than placebo (mean symptom difference = 4, t20 = 7.06, p < 0.001). The agreement in triggering for the most commonly reported premonitory symptoms (concentration difficulty and tiredness) was >66%. The retriggering agreement for all but one premonitory symptom was >60%. The agreement in timing to onset of premonitory symptoms was reliable across two triggered attacks. The agreement with spontaneous attacks and between attacks for headache and its associated symptoms, including laterality, was less reliable. Conclusions Nitroglycerin can reliably and reproducibly provoke premonitory symptomatology associated with migraine. This forms an ideal model to study the earliest manifestations of migraine attacks.

The Prevalence of Premonitory Symptoms in Paediatric Migraine: A Questionnaire Study in 103 Children and Adolescents

The prevalence and characterization of premonitory symptoms have not been rigorously studied in children and adolescents. Using a questionnaire, we retrospectively studied the prevalence of 15 predefined premonitory symptoms in a clinic-based population. In 103 children and adolescents fulfilling the International Classification of Headache Disorders, 2nd edn criteria for paediatric migraine, at least one premonitory symptom was reported by 69 (67%). The most frequently reported premonitory symptoms were face changes, fatigue and irritability. The mean number of premonitory symptoms reported per subject was 1.8 (median 2.2). Age, migraine subtype (with or without aura) and mean attack frequency per month had no effect on the mean number of premonitory symptoms reported per subject. In conclusion, premonitory symptoms are frequently reported by children and adolescents with migraine. Face changes seem to be a premonitory symptom peculiar to paediatric migraine.

The Prevalence of Premonitory Symptoms in Migraine: A Questionnaire Study in 461 Patients

Migraine attacks are often preceded by premonitory symptoms. Prevalence rates of migraine patients reporting one or more premonitory symptoms show considerable variability and rates range between 12% and 79%. Sources of variability might be differences in study population or research design. Using a questionnaire, we retrospectively studied the prevalence of 12 predefined premonitory symptoms in a clinic-based population. Of 461 migraine patients, 374 (81%) responded. At least one premonitory symptom was reported by 86.9% and 71.1% reported two or more. The most frequently reported premonitory symptoms were fatigue (46.5%), phonophobia (36.4%) and yawning (35.8%). The mean number of premonitory symptoms per person was 3.2 (± 2.5). Women reported 3.3 premonitory symptoms compared with 2.5 symptoms in men ( P = 0.01). Age, education, migraine subtype (with or without aura) and mean attack frequency had no effect on the mean number of symptoms per individual. In conclusion, premonitory symptoms are frequently reported by migraine patients. Sensitivity and specificity of premonitory symptoms for migraine need to be assessed using prospective methods.