Migraine: is it related to hormonal disturbances or stress?

BACKGROUND: Common neurological syndrome (migraine without aura) is more common among women than men. Migraine is among the top 20 causes of disability. Menstruation is known to be a powerful trigger for migraine, and so is stress, but the presentation of headache is similar in both. Also, women are more vulnerable to stress as well as migraine, and this makes a complex relationship of menstruation, stress, and migraine. OBJECTIVE: This study was done to understand the association of hormonal fluctuation in menstruation and stress with common migraine. MATERIALS AND METHODS: A cross-sectional comparative study was conducted in 40 young adult females, of whom 20 participants were cases of migraine without aura (18-35 years old), and the remaining 20 participants were age-matched controls. The study was done in Maulana Azad Medical College, New Delhi. Study participants were selected on the basis of International Headache Society (ICHD-IIA1.1) (2004) classification. Study participants with neurological disorders, chronic diseases, and disease suggestive of any hormonal disturbances were excluded. Clinically diagnosed migraine cases were asked to maintain a headache diary and to fill in the Depression Anxiety Stress Scales questionnaire. Biochemical assessment of hormonal status for thyroid-stimulating hormone, triiodothyronine, thyroxine, estrogen, follicle-stimulating hormone, luteinizing hormone, and prolactin was also done on the second day of their menstrual cycle. We used the Mann-Whitney U test to compare hormonal levels and the χ (2) test to compare anxiety- or depression-related stress among the migraine and nonmigraine groups. RESULTS: Significantly higher values of prolactin were observed in cases (mean ± standard deviation, 152.7 mIU/L±30.5) compared to controls (76.1 mIU/L±8.7), with a P-value <0.001. There was no statistically significant difference observed in levels of thyroid-stimulating hormone (P=0.081), estrogen (P=0.086), luteinizing hormone (P=0.091), or follicle-stimulating hormone (P=0.478). Also, anxiety with stress or depression with stress was significantly higher among the migraine group than the controls (P=0.002). Odds of any stress in migraine were higher in the migraine group than in the nonmigraine group (odds ratio 12, 95% confidence interval 2.7-53.33). CONCLUSION: Migraine, particularly without aura, in women is mainly associated with stress-related anxiety or depression, and are more susceptible to stress in the premenstrual period.

Nitric oxide and prostaglandin as mediators in the pathogenesis of hyperkinetic circulatory state in a model of endotoxemia-induced portal hypertension.

AIMS: To evaluate the participation of nitric oxide (NO) and prostaglandin (PGI2) on hyperdynamic state in endotoxemia-induced portal hypertension (EIP) induced by chronic endotoxemia. METHODS: The portal pressure (PP) and mean arterial pressure (MAP) were recorded, in vivo before and after administration of L-NAME (NOS inhibitor) and indomethacin (specific blocker of COX). The vasoactive responses to acetylcholine of thoracic rat aortic rings were studied in vitro before and after nitric oxide and cyclooxygenase blockade using multichannel organ bath. The mRNA expression for isoforms of (cyclooxygenase) COX and nitric oxide synthase (NOS) were analyzed using RT-PCR. RESULTS: Administration of both L-NAME and indomethacin in EIP rabbits significantly reduced (p < 0.05) the PP and reversed the MAP to normal as compared to sham-operated (SO) rabbits. There was impaired vasodilatory response to acetylcholine in EIP rabbits. L-NAME caused a significant reduction in acetylcholine-induced vasorelaxation in SO rabbits than EIP due to preexisting hyperemia in EIP. Indomethacin partially restored vasoresponsiveness to acetylcholine in EIP group. The mRNA expression of eNOS (endothelial NOS) and COX-1 (constitutive COX) were significantly higher in SO than EIP rabbits. iNOS (inducible NOS) and COX-2 (inducible COX) mRNA expression was seen only in EIP rabbits. CONCLUSIONS: A significant component of acetylcholine-mediated vasorelaxation in EIP model is modulated by eNOS. There was increased production of contractile prostaglandin in EIP rabbits. iNOS and COX-2 play an important role in the hemodynamic abnormalities of PHT. This novel model of PHT produced by chronic splanchnic endotoxemia in rabbit, mimics impaired vasodilation and vasoreactivity akin to other models of PHT.

Effect of body mass index on physical self concept, cognition & academic performance of first year medical students.

BACKGROUND & OBJECTIVES: The relationship between obesity and self perception, particularly in children and young adults has important implications for physical and psychosocial health and well-being. A better understanding of this relationship could help target psychology services and public health strategies more effectively. The aim of the present study was to assess the effect of body mass index (BMI) on physical self concept and cognition of the first year medical undergraduate students in a medical college in north India. The relationship between physical self concept and academic performance and presence of any gender differences were also examined. METHODS: The study was carried out on 18-21 yr old first year M.B.B.S. students of Maulana Azad Medical College, New Delhi, India. Physical self concept was assessed using short version of Physical Self Description Questionnaire (PSDQ-S) which is a psychometrically strong instrument for measuring multiple dimensions of physical self-concept. Cognition was assessed by P300 evoked potentials and academic performance was evaluated on the basis of marks obtained in anatomy, physiology and biochemistry subjects. RESULTS: There was no association between BMI and physical self-concept or between BMI and cognition. Gender differences on physical self-concept were also insignificant. No correlation was seen between physical self-concept and academic performance. INTERPRETATION & CONCLUSION: The present results suggest that negative consequences of high body mass index on physical self-concept and cognition are not seen in young adults. It may be that academic achievement nullifies the effect on physical self-concept and the effect on cognition accumulates as the age progresses, therefore, appears later in life.

A study of autonomic nervous system status in children of asthmatic parents.

Asthmatic patients are known to have autonomic abnormalities. This study evaluated the status of autonomic nervous system in children of asthmatic parents for any occurrences of autonomic abnormalities that are known to occur in asthma. In this study autonomic function tests were conducted in children (5 to 10 years of age) divided into two groups: Group A had children from non-asthmatic parents as Control Group and Group B had children from asthmatic parents as Test Group. Both the groups had healthy children showing no clinical signs and symptoms of asthma, allergy or any illness known to affect autonomic nervous system. In response to various parasympathetic function tests (S/L ratio, 30:15 ratio, valsalva ratio and tachycardia ratio) and sympathetic function tests (handgrip test and cold pressor test) done, the two groups did not show any statistically significant dissimilarity for any of the parameters. The results of our study showed that there were no autonomic abnormalities found in the children of asthmatic parents. Thus this study indicates that the autonomic defects seen in asthmatics could be secondary to asthma and not because of autonomic aberrations inheritance in asthmatics as shown by earlier few studies supporting the possible role of inherited automatic reactivity in the pathogenesis and progression of asthma.

Terminalia arjuna enhances baroreflex sensitivity and myocardial function in isoproterenol-induced chronic heart failure rats.

Chronic heart failure (CHF) is characterized by left ventricular (LV) dysfunction along with impaired autonomic control functions. Herbal drugs are increasingly being used in the treatment of cardiovascular disorders. The present study was designed to examine the protective effect of Terminalia arjuna (T arjuna) bark extract on LV and baroreflex function in CHF and to elucidate the possible mechanistic clues in its cardioprotective action. The baroreflex was evaluated by measuring the changes in heart rate (HR) with changes in arterial blood pressure induced by bolus injections of phenylephrine (vasoconstrictor) and sodium nitroprusside (vasodilator). T arjuna bark extract and fluvastatin were tested/administered therapeutically and prophylactically in isoproterenol-induced rat model of CHF. Fifteen days after isoproterenol administration, rats exhibited cardiac dysfunction, hypertrophy, and LV remodeling along with reduced baroreflex sensitivity. Prophylactic and therapeutic treatment with T arjuna improved cardiac functions and baroreflex sensitivity. It also attenuated hypertrophy and fibrosis of the LV. Fluvastatin treatment exerted a similar protective effect against myocardial remodeling and heart failure. Further, T arjuna and fluvastatin significantly reduced oxidative stress and inflammatory cytokine level in CHF rats. In conclusion, T arjuna exerts beneficial effect on LV functions, myocardial remodeling, and autonomic control in CHF possibly through maintaining endogenous antioxidant enzyme activities, inhibiting lipid peroxidation and cytokine levels.

Brainstem auditory evoked responses in different phases of menstrual cycle.

BACKGROUND AND OBJECTIVES: Brainstem Auditory Evoked Potentials (BAEP) show variations with age, sex and other physiological factors. The gonadal steroids may also alter the neuronal functioning, but an electrophysiological evidence is sparse. This study was undertaken to analyze the auditory evoked response in females of the reproductive age group during four different hormonal states of the menstrual cycle. METHODS: This was a prospective, single centered, longitudinal study. The waves of BAEP were recorded in 50 young females (of the ages of 19-36 years, who used no hormonal therapy) during four different phases of the same menstrual cycle. The peak latencies of the waves, I, II, III, IV and V, IPL I-III, I-V and III-V and the amplitude ratio, V/I were recorded and statistically analyzed. RESULTS: A significant increase in the peak latencies of the waves, I-V in the oestrogen peak mid cycle was observed, while a significant decrease in the progesterone peak mid-luteal phase was observed. However, IPL did not show any statistically significant change in the above two phases. All the parameters did not show significant changes in the menstrual and the pre-menstrual phases. INTERPRETATION AND CONCLUSION: The results indicated the BAEP changes in the mid follicular and the mid luteal phases of the menstrual cycle, thus suggesting the changes which were attributable to oestrogen and progesterone.

Correlation between cognitive functions and nitric oxide levels in patients with dementia.

Dementia is defined as a clinical syndrome characterized by acquired loss of cognitive and emotional abilities, severe enough to interfere with daily functioning and quality of life. Event related potentials (ERP) are sensitive to task variables that relate to cognitive behavior. They might be altered in patients with disorders of cognition such as dementia. Application of the P300 ERP component to the study of cognitive disorders provides a means of quantifying the level of mental impairment. At high levels, nitric oxide (NO), which is produced by microglia due to induction of nitric oxide synthase (NOS), is neurotoxic and may play a role in neurodegeneration. In our study an attempt has been made to record ERP in patients of mild and moderate dementia and to correlate their findings with nitric oxide levels in CSF and serum. Twenty patients with dementia were selected as cases and 20 subjects as controls, which were further subdivided according to the age groups. Both dementia cases and controls were assessed by minimental state examination (MMSE) and clinical dementia rating scale (CDRS) for evaluating the degree of dementia. It was observed that the MMSE score was reduced in demented cases. P300 latency was significantly delayed in mild and moderate cases of dementia. However, no change was seen in NO levels of cerebrospinal fluid (CSF) and serum in dementia cases and controls. A negative correlation was found between MMSE and P300 latency. Hence we conclude that cognitive impairment in demented patients is reflected in P300 latency but not in NO levels in CSF and serum.

Mechanistic clues in the cardioprotective effect of Terminalia arjuna bark extract in isoproterenol-induced chronic heart failure in rats.

The present study demonstrated prophylactic and therapeutic potential of Terminalia arjuna bark extract in isoproterenol (ISO)-induced chronic heart failure (CHF). Fifteen days after injection of ISO (85 mg/kg twice at an interval of 24 h, s.c), rats showed decline in maximal rate of rise and fall of left ventricular pressure (LV (dP/dt)(max) and LV (dP/dt)(min)), cardiac contractility index (LV (dP/dt)(max)/LVP), cardiac output and rise in LV end-diastolic pressure. CHF rats showed a significant increase in serum creatine kinase isoenzyme-MB (CK-MB) and malondialdehyde levels, as well as fall in the activities of superoxide dismutase, reduced glutathione. Altered lipid profile and increased level of cytokine tumour necrosis factor-α (TNF-α) along with histological changes in heart were also observed in CHF rats. T. arjuna bark extract (500 mg/kg, p.o) treatment prior and 15 days after ISO injection significantly attenuated cardiac dysfunction and myocardial injury in CHF rats. Cardioprotective action of T. arjuna was comparable to fluvastatin, a synthetic drug. The results suggest that T. arjuna bark extract has a significant prophylactic and therapeutic beneficial effect on protection of heart against ISO-induced CHF possibly through maintaining endogenous antioxidant enzyme activities, inhibiting lipid peroxidation and cytokine levels.

Sensory nerve conduction velocity is greater in left handed persons.

Dependence of nerve conduction velocity on factors like age, sex and temperature is well known. Effect of handedness on nerve conduction velocity has not been studied adequately. In this study correlation between handedness and motor as well as sensory conduction velocity of right as well as left median nerve was studied in 84 medical students in the age group between 17-21 years out of which 72 were right handed and 12 were left handed. In addition auditory and visual reaction times were also studied. Sensory conduction velocity in both right and left median nerve was significantly higher in left handers as compared with right handers whereas, the motor conduction velocity in right handers and left handers was not different. The auditory and visual reaction times were also not different in these groups. Because of greater sensory conduction velocity in left handers there is a requirement of different set of normal reference values for left handers in clinical diagnosis.

Effect of ramipril therapy on cognitive functions in cases of mild to moderate essential hypertension.

Several studies have questioned the effect of hypertension on cognitive functions. Event related potentials (P300) have been used as a reliable and reproducible indicator of cognitive functions. In this non-randomized, open label study we investigated cognitive functions using event related potentials in newly diagnosed mild to moderate essential hypertensive patients and whether or not there was any effect of antihypertensive treatment with angiotensin converting enzyme inhibitor ramipril on the event related potentials. We selected twenty male patients of newly diagnosed mild to moderate essential hypertension by using ambulatory blood pressure monitoring who were previously untreated and compared their event related potentials with 10 normotensive controls. At the beginning of the study, the hypertensive group showed increased P300 and N2 wave latency as compared to the normotensive control subjects. After three months of Ramipril therapy at a dose of 5mg per day, there was a significant decrease in all the ambulatory blood pressure parameters and the mean P300 latency from the pretreatment values. But no significant change in the N2 latency was observed. Thus, treatment with Ramipril 5 mg daily for a period of three months can reverse some aspects of cognitive dysfunction associated with hypertension.

Antihypertensive and antioxidant action of amlodipine and vitamin C in patients of essential hypertension.

The etiology of essential hypertension includes increased oxidative stress. The role of antihypertensive drug amlodipine as an antioxidant and the benefit of addition of vitamin C, an antioxidant to antihypertensive therapy were studied. Forty male patients of essential hypertension were randomly divided into two groups and treated with 5 mg amlodipine. In addition one group also received 1000 mg vitamin C (as two 500 mg tablets) once daily for three months. Although blood pressure decreased in both groups, the systolic blood pressure in patients given vitamin C was less (126.4 +/- 7.47) compared to the other group (130.9 +/- 7.27). A decrease in malondialdehyde, an increase in erythrocyte sodium-potassium adenosine triphosphatase (Na(+) K(+) ATPase) and an increase in the superoxide dismutase levels were observed in both groups. The increase in SOD was statistically more in the patients given vitamin C in addition to amlodipine (0.1717 +/- 0.0150 compared to 0.152 +/- 0.0219 units/100 ml assay). In spite of the known antihypertensive, antioxidant activity, similarity in correcting endothelial dysfunction independently, giving the two drugs together and early introduction of vitamin C perhaps decreases oxidative stress and augments the antioxidant status. This may prevent further vascular damage due to oxidative stress, leading to a better prognosis in essential hypertension patients.

Spinal motoneuron excitability in iron deficiency anaemia.

Decreased tissue oxygenation resulting from iron deficiency anaemia produces generalized weakness and fatigue. The precise physiological mechanism underlying this weakness is unknown and studies in this regard have been scarce. One possible underlying mechanism has been suggested to be reduction of spinal motoneuron excitability. F waves are low amplitude motor responses to nerve stimulation, produced by antidromic activation of the peripheral motor fibers, resulting in recurrent discharge of motoneurons. F waves have been established as an efficient tool to assess spinal motoneuron excitability. 15 patients of iron deficiency anaemia using inclusion criteria of hemoglobin level < 9 g/dL and serum ferritin < 15 microg/L were studied. 8 controls with hemoglobin levels > 12 g/ dL were also included. Bilateral median and common peroneal F wave studies were performed. F wave mean latency, chronodispersion, persistence and mean amplitude were studied. They were within the normal range and no significant differences between the patients and the controls were found. We conclude that spinal motoneuron excitability is not reduced in iron deficiency anaemia. A decreased tissue oxygenation leading to a change in the brain neurotransmitters may have a role to play.

Effect of ionophore monensin on anaesthetized dogs in hemorrhagic hypotension.

AIM: Progressive decompensation and irreversible cellular injury from the severe hemorrhagic shock can be reversed therapeutically with aggressive and timely resuscitation by administering volume expanding fluids. The possibility of the use of rapidly acting pressor agents which can effectively maintain the blood pressure and peripheral perfusion (without volume resuscitation) and prevent the progression of shock and providing in regular time interval for volume replacement has not been looked into. In the present investigation, two pressor agents, dopamine and a long acting carboxylic ionophore monensin, were examined for their potential role in hemorrhagic hypotension produced experimentally in dogs. METHODS: Two groups of animals were studied: (a) In the first group (n=10) 20% of the total blood volume i.e. moderate hemorrhage was induced. (b) In the second group (n=10) 35% of the total blood volume i.e. severe hemorrhage was induced. After 30 min of induction of hemorrhage both the groups were given intravenous infusion of dopamine (20 microgm/kg/min) for 10 min. Then after 30 min of stopping dopamine infusion, both the groups were given intravenously a single bolus dose (50 microgm/kg) of monensin. RESULTS: In both moderate and severe hemorrhage monensin injection produced significant increases in systolic arterial blood pressure, mean arterial blood pressure, cardiac output and stroke volume. The effects persisted for 1 h of administration. In severe hemorrhage dopamine infusion produced significant decrease in mean arterial blood pressure, diastolic blood pressure and pH. Dopamine produced a significant rise in heart rate also while monensin did not have such an effect. CONCLUSION: Monensin produced a rapid and sustained recovery of the arterial blood pressure without requiring adequate preload. Dopamine failed to produce such an effect because it requires adequate circulating blood volume for its pressor action. Thus monensin has the potential to prevent progression of shock and improving the prognosis in management of hemorrhagic hypotension.

Effect of sodium citrate ingestion on oxygen debt & exercise endurance during supramaximal exercise.

BACKGROUND & OBJECTIVES: Administration of alkalinizing agents has been shown to improve performance in high intensity exercise. The present investigation was undertaken to determine whether sodium citrate ingestion enhances supramaximal endurance performance on a cycle ergometer and to assess its effect on oxygen debt incurred for the same supramaximal energy output. METHODS: Ten untrained, healthy, males performed acute intense bicycle ergometry exercise in two sessions viz., without (control) and with sodium citrate ingestion (experimental) in a dose of 0.5 g/kg body weight. Pre-exercise O2 consumption, pulse rate (PR) and respiratory rate (RR)/minute were recorded before both sessions. Exhaustion time (ET) was noted and work done calculated in the control session. Post-exercise PR and RR/min were also recorded in both sessions of study. Venous blood samples were drawn post-exercise and analysed for pH and lactate. O2 debt incurred was calculated in both sessions. RESULTS: Work output in supramaximal exercise averaged 69.40 +/- 15.31 Watts in the control session. None of the subjects in the experimental session complained of fatigue even when the exhaustion time noted in the control session was reached. Post-exercise tachycardia and tachypnoea were both significantly less (P<0.05 and P<0.001 respectively) in subjects after the experimental session as compared to the control. O2 debt incurred and lowering of blood pH were also significantly less (P<0.001) in the post-citrate phase. However, serum lactate increased significantly (P<0.05) in subjects after the experimental session. INTERPRETATION & CONCLUSION: Ingestion of sodium citrate prior to supramaximal exercise resulted in a reduction in post exercise O2 debt incurred. Blood pH was almost normal despite a higher serum lactate concentration. This probably led to an enhancement in exercise performance.