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Biomedical subjects

M Fanciullacci

Publications and source records attributed to M Fanciullacci.

At least 55 records · Page 3Linked to original sources

Pupillary and vascular effects of calcium antagonists in migraine.

In migraine patients the effect of calcium antagonists (flunarizine, verapamil and nifedipine) on both venous and pupillary neuromuscular functions, as well as on blood pressure have been evaluated. A single oral dose of flunarizine (10 mg) and verapamil infusion (50 micrograms/ml/min) increased venous compliance. Verapamil also counteracted dose-dependent dopamine induced venoconstriction. Nifedipine (10 mg orally) reduced mean arterial pressure in upright position in migraineurs but not in controls. In addition, chronic treatment with flunarizine (10 mg for 2 weeks) induced a transient miotic effect and a reduction of tyramine induced mydriasis. These findings demonstrated that calcium antagonists affect vascular and extravascular structures. It is postulated that, in migraine, calcium entry blockers may prevent exaggerated responses to catecholaminergic stimulation.

Blood Pressure↗

Morphine eye-drops reduce homatropine induced mydriasis in man.

In 7 healthy volunteers 4% morphine eye-drops, when administered to one eye, caused a miosis limited to that eye. In 7 other healthy volunteers morphine was administered into one eye after bilateral instillation of 0.5% homatropine ophthalmic drops; the eye treated with morphine and homatropine showed a mydriasis less intense than the other eye treated only with homatropine. It is suggested that topical morphine locally affects sympathetic function by inhibiting noradrenaline release into the iris neuromuscular junction.

Female↗

Coexistence of pupillary and heart sympathergic asymmetries in cluster headache.

Ten cluster headache patients and 10 healthy controls were subjected to electrocardiographic and pupillometric procedures in a search for cardiac and pupillary sympathergic asymmetry. Sympathergic stimulation was provoked by hyperventilation and by instilling tyramine into both eyes. In the control group, hyperventilation changed neither the T-wave form and polarity nor the QTc. Tyramine provoked an equal mydriasis on the two sides. In cluster headache sufferers, hyperventilation produced changes in the T-wave form and polarity as well as an increase of the QTc due to a disproportionate shortening of the R-R and Q-T intervals. An unequal mydriasis was noted after tyramine instillation due to less marked response on the symptomatic side. The observed electrocardiographic abnormalities are considered an expression of an asynchronous repolarization attributed to a sympathergic asymmetry. It is postulated that both the cardiac and pupillary sympathetic imbalance associated with cluster headache are central in origin.

Adolescent↗

Asymmetric mydriatic response to topical tyramine in cluster headache relatives.

A pupillometric study was performed to evaluate the mydriatic response to tyramine, a noradrenaline releaser. There were three groups of subjects: (a) 10 cluster headache patients, in an asymptomatic period; (b) 20 of their close relatives, exempt from this disease; (c) 10 healthy controls. The tyramine was instilled into both eyes of each subject. The controls displayed an isocoric tyramine-induced mydriasis but the cluster headache sufferers and their relatives showed an anisocoric mydriasis. This anisocoric mydriasis was caused by a deficient mydriatic response on one side, which in the cluster patients corresponded to the symptomatic side. The sympathetic abnormality of the iris may be the expression of a functional asymmetry in the hypothalamus. Central sympathetic asymmetry could thus represent a dysgenetic family predisposition to lateralized headache attacks.

Administration, Topical↗

Does lithium balance the neuronal bilateral asymmetries in cluster headache?

Pupil size was measured using a pupillograph, and an asymmetric responsiveness to tyramine, instilled bilaterally, was observed in asymptomatic cluster headache patients. Relatives of cluster headache patients showed an anisocoric mydriasis to tyramine, too. This asymmetry was caused by a less marked mydriatic response of one side which, in the cluster headache sufferers, corresponds to the symptomatic side. After three months of treatment with lithium carbonate (900 mg/die), a bilateral decrease of pupil size was noted, possibly due to a reduced sympathergic tone. After six months of continued treatment an unknown mechanism, likely adaptive in nature, attenuated the effect of lithium on pupil size. Lithium also induced a symmetric response to tyramine by increasing tyramine mydriasis on the symptomatic pupil while reducing it on the asymptomatic pupil. It is postulated that lithium improves cluster headache by correcting abnormal bilateral asymmetries in central neuronal systems which regulate autonomic function and pain sensitivity of the structures involved in the cluster attack.

Cluster Headache↗

Latent dysautonomic pupillary lateralization in cluster headache. A pupillometric study.

Forty-five patients with cluster headache in the asymptomatic phase were studied by electronic pupillography, testing autonomic function of both pupils pharmacologically. Topical sympathetically-acting mydriatics, tyramine and cocaine and the cholinoceptor blocker, homatropine, induced defective mydriatic responses on the symptomatic side, indicating latent impairment of sympathetic function. The abnormality was found in interattack intervals of the cluster period or during intercluster phases. The tyramine test can be proposed for objective diagnosis of cluster headache. We postulate that cluster attacks are triggered and lateralized by a permanent latent unilateral sympathetic dysfunction. Lithium reduced the mydriatic response to tyramine of the pupil contralateral to the pain, thus restoring the equilibrium between both pupils; this therapy may correct the asymmetric sympathetic function by attenuating the activity in the asymptomatic side.

Adolescent↗

Disruption of iris adrenergic transmission as an index of poor endorphin modulation in headache.

Pupillometry was used to evaluate the effect of oral or topically applied adrenomimetic drugs and of local morphine on pupillary size in headache patients and controls. In headache sufferers, a disruption of adrenergic transmission is suggested since the iris adrenergic nerve terminal is apparently poor in NE; this neuron also exhibits a reduced capacity of neurotransmitter synthesis and an adrenoceptor hypersensitivity. The spontaneous reduction of pupillary size detected in headache sufferers also suggests a decreased sympathetic input. The miosis, registered after conjunctival instillation of morphine, demonstrates that iris is a possible example of an opioid-dependent adrenergic neuron in man. A poor modulation of the iris adrenergic transmission induces, in headache sufferers, a neuronal incontinence and therefore a chronic intrasynaptic leakage of NE, resulting in an exhausted empty neuron on the one hand and a compensatory hyperactivity of the effector muscular cell on the other. Since indirect evidence suggests a morphine modulation of the iris adrenergic neuron, a deficiency of endorphin modulation could be the mechanism of disruption of iris adrenergic transmission. Apart from the theoretical aspects, the exploration of iris neuroeffector junction represents a noninvasive an simple diagnostic tool in headache.

Endorphins↗

Possible lateralization of the cardiac sympathetic function in cluster headache.

In cluster headache an adrenergic dysfunction of the pupillary sympathetic system can be demonstrated even during pain-free periods by instillation of tyramine in the conjunctival sac. In this study 10 patients with typical cluster headache syndrome exhibited a positive tyramine conjunctival test (minor mydriatic response in the pain side). As the adrenergic dysfunction may also involve the heart, possible neurogenic changes in ventricular repolarization were investigated in a group of patients with cluster headache by means of a hyperventilation test. When compared to controls, an increase of the QTc interval, a faster heart rate and a minor shortening of the QT interval, were observed. In all cases except one the T waves became bifid or inverted, sometimes showing a pseudoischemic aspect. Since the positive response to hyperventilation seems to depend on an asynchronous repolarization which can, in turn, be related to asymmetric sympathetic function, the present results seem to suggest the presence of a possible lateralization of the cardiac sympathetic function, in cluster headache patients.

Adolescent↗

A new nonvascular interpretation of syncopal migraine.

Migraine suffers who experience spontaneous syncopes (syncopal migraine) during attacks exhibit a dramatic intolerance to bromocriptine, a dopamine agonist. An oral dose of this drug renders these patients unable to stand, even for some hours, because of precipitously falling of arterial blood pressure. Treatment with domperidone, a specific dopamine receptor antagonist, abolishes the syncopal effect of bromocriptine. This evidence is compatible with a supersensitivity of those dopamine receptors, which exert an inhibiting activity and are located on blood pressure regulating centers as well as on cardiovascular sympathergic neurons.

Adolescent↗

A putative 5-HT central feedback in migraine and cluster headache attacks.

5-HT is considered to play a role in the migraine mechanism; its decrease in the midbrain during migraine attacks has been postulated. CSF TP and plasma and platelet 5-HT levels in migraine and cluster headache sufferers have been evaluated; the values registered were compared to those of neurological and carcinoid patients, respectively. The following results were obtained: (a) no significant difference in the time course of free and total TP after l-TP intravenous loading, (b) increased levels of CSF TP during migraine and cluster headache attacks, (c) impressively increased levels of plasma 5-HT only in carcinoid patients. These findings suggest the existence of a positive 5-HT central feedback mechanism during attacks of migraine and cluster headache and thus exclude peripheral 5-HT effects in the generation of pain.

Adolescent↗