Induction Of Attacks Research Articles

Familial Mediterranean fever: the molecular pathways from stress exposure to attacks.

FMF is an autoinflammatory disease characterized by recurrent attacks and increased IL-1 synthesis owing to activation of the pyrin inflammasome. Although knowledge of the mechanisms leading to the activation of pyrin inflammasome is increasing, it is still unknown why the disease is characterized by attack. The emergence of FMF attacks after emotional stress and the induction of attacks with metaraminol in previous decades suggested that stress-induced sympathoadrenal system activation might play a role in inflammasome activation and triggering attacks. In this review, we will review the possible molecular mechanism of stress mediators on the inflammation pathway and inflammasome activation. Studies on stress mediators and their impact on inflammation pathways will provide a better understanding of stress-related exacerbation mechanisms in both autoinflammatory and autoimmune diseases. This review provides a new perspective on this subject and will contribute to new studies.

The effect of pituitary adenylate cyclase-activating peptide-38 and vasoactive intestinal peptide in cluster headache.

Previously reported increases in serum levels of vasodilating neuropeptides pituitary adenylate cyclase-activating peptide-38 (PACAP38) and vasoactive intestinal peptide (VIP) during attacks of cluster headache could indicate their involvement in cluster headache attack initiation. We investigated the attack-inducing effects of PACAP38 and vasoactive intestinal peptide in cluster headache, hypothesising that PACAP38, but not vasoactive intestinal peptide, would induce cluster-like attacks in episodic active phase and chronic cluster headache patients. In a double-blind crossover study, 14 episodic cluster headache patients in active phase, 15 episodic cluster headache patients in remission phase and 15 chronic cluster headache patients were randomly allocated to receive intravenous infusion of PACAP38 (10 pmol/kg/min) or vasoactive intestinal peptide (8 pmol/kg/min) over 20 min on two study days separated by at least 7 days. We recorded headache intensity, incidence of cluster-like attacks, cranial autonomic symptoms and vital signs using a questionnaire (0-90 min). In episodic cluster headache active phase, PACAP38 induced cluster-like attacks in 6/14 patients and vasoactive intestinal peptide induced cluster-like attacks in 5/14 patients (p = 1.000). In chronic cluster headache, PACAP38 and vasoactive intestinal peptide both induced cluster-like attacks in 7/15 patients (p = 0.765). In episodic cluster headache remission phase, neither PACAP38 nor vasoactive intestinal peptide induced cluster-like attacks. Contrary to our hypothesis, attack induction was lower than expected and roughly equal by PACAP38 and vasoactive intestinal peptide in episodic active phase and chronic cluster headache patients, which contradicts the PAC1-receptor as being solely responsible for attack induction.Trial registration: clinicaltrials.gov (identifier NCT03814226).

Neurochemical characterization of hypothalamic neurons involved in attack behavior: Glutamatergic dominance and co-expression of thyrotropin-releasing hormone in a subset of glutamatergic neurons

The electrical stimulation of a specific hypothalamic area rapidly evokes attacks in rats. Noteworthy, attack-related hypothalamic structures were identified in all species studied so far. The area has been extensively mapped in rats, and its anatomical connections have been studied in detail. However, technical difficulties precluded earlier the precise identification of the neural elements mediating the aggressive effects of stimulation. It now appears that a dense and distinct group of glutamatergic cells expressing vesicular glutamate transporter 2 mRNA extends over the entire hypothalamic attack area. Rostral parts overwhelmingly contained glutamatergic neurons. In more caudal parts, glutamatergic and fewer GABAergic neurons were found. The remarkable similarity in the distribution of hypothalamic attack area and glutamatergic cell groups suggests that these cells mediate the aggressive effects of stimulation. Surprisingly, thyrotropin releasing hormone mRNA was co-localized in a subset of glutamatergic neurons. Such neurons were present at all rostro-caudal levels of the hypothalamic attack area, except for that part of the hypothalamic attack area extending into the ventro-lateral part of the ventromedial hypothalamic nucleus. Earlier data on the projections of hypothalamic thyrotropin releasing hormone neurons suggest that this subpopulation plays a specific role in attack behavior. Thus, we identified three neuronal phenotypes in the hypothalamic structure that is involved in the induction of attacks: glutamatergic neurons co-expressing thyrotropin releasing hormone, glutamatergic neurons without thyrotropin releasing hormone, and GABAergic neurons dispersed among the glutamatergic cells. Assessing the specific roles and connections of these neuron subpopulations would contribute to our understanding of the mechanisms underlying attack behavior and aggression.

The pathogenesis of cluster headache.

Cluster headache is described here as having three distinct and contiguous clinical phases. Evidence of the pathophysiological changes associated with each phase is reviewed. The first phase, the cluster period, is characterized by chronobiological aberrations and impaired sympathetic nervous system activity. These changes may result in impaired autoregulatory chemoreceptor activity and susceptibility to attack provocation. An hypothesis that attempts to explain the second phase, cluster attack induction, is reviewed. Evidence for this model suggests that as a result of chemoreceptor dysfunction, a sustained hypoxemic event, as may result from altitude hypoxia, sleep apnea, or vasodilators, could provoke the cluster attack. Attack symptoms and signs, which constitute the third phase of cluster headache, are likely the result of parasympathetic and trigeminal nerve stimulation. Specifically, cluster headache pain is likely the consequence of neurovascular inflammation, as hypothesized in the trigeminovascular theory.

Changes in plasma renin activity and plasma aldosterone in the induced paralytic attack of thyrotroxic periodic paralysis.

Changes in serum electrolytes, haematocrit, plasma renin activity and plasma aldosterone induced by glucose and insulin (GI) infusion were serially investigated in seven patients with periodic thyrotoxic paralysis. An attack which developed into complete quadriplegia was induced within 90 min after the beginning of the GI infusion in four out of seven patients. Only a slight paralysis of the legs was produced in another two patients and induction of an attack did not materialize in one. In four patients with complete quadriplegia, the mean values of serum sodium and potassium concentrations, haematocrit, plasma renin activity and plasma aldosterone slightly decreased immediately after the beginning of the GI infusion. Induction of a paralytic attack was not accompanied by any significant changes in serum sodium concentration, haematocrit, plasma renin activity and plasma aldosterone either 15 min before or after the onset of attack, while the serum potassium concentration progressively decreased, and an increase in plasma aldosterone associated with an increase of haematocrit and plasma renin activity reached a peak level at the stage of complete quadriplegia. On the other hand, in the three patients in whom an infusion produced slight or no paralysis of the legs, changes in the serum sodium concentration, haematocrit, plasma renin activity and plasma aldosterone were insignificant and the serum potassium concentration was slightly but insignificantly decreased. These results suggest that hyperaldosteronism may not be a trigger for the induced paralytic attack but a phenomenon secondary to volume depletion and a change in potassium homoeostasis induced by GI infusion.