Umberto Pietrini

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.

Acute oral captopril inhibits angiotensin converting enzyme activity in human cerebrospinal fluid

Angiotensin converting enzyme (ACE) activity in human plasma and cerebrospinal fluid (CSF), was measured by a fluorimetric method, following an acute oral dose (75 mg) of captopril. A decrease of approximately 60% in enzyme activity was observed in CSF, suggesting that the drug penetrates the blood/brain barrier (BBB) in sufficient amounts to inhibit the ACE in CSF. The activity of CSF enkephalinase, an enzyme present in human brain and inhibited in vitro by an elevated concentration of captopril, was, however, unaffected by the acute drug administration. It is proposed that the antihypertensive effect of captopril in humans may be due, at least in part, to the inhibition of ACE contained within brain structures.

Visceral Pain Threshold is Deeply Lowered Far From the Head in Migraine

SYNOPSIS

Hypertension in headache patients? A clinical study.

Objectives –  The aim of the present study was to assess the prevalence of hypertension in patients with headache, coming to the observation of an Headache Center.

The use of pupillometry in joint and connective tissue diseases.

Abstract: The central and peripheral nervous systems are variably affected in the rheumatic diseases. Automated standardized infrared pupillometry allows the safe, noninvasive assessment of the pupillary innervation. Pupillometry has already been used in studying the autonomic nervous system (ANS) in various rheumatic diseases. In systemic lupus erythematosus, the irideal parasympathetic branch of ANS was more affected then the sympathetic branch. In Sjögrens syndrome, signs of pupillary parasympathetic denervation have been reported. In rheumatoid arthritis, pupil parasympathetic dysfunction has been shown to correlate with ocular dryness. In systemic sclerosis (SSc), both sympathetic and parasympathetic irideal impairment have been demonstrated. Beside providing autonomic innervation, sensory nerves fibers are able to control iris diameter. Exogenous ocular instillation of substance P (SP), a sensory neuropeptide, can determine an omathropine‐resistant, non‐cholinergic myosis, acting on specific receptors present on the iris sphincter muscle. We first studied pupillary SP‐ergic responsiveness in SSc, evaluating substance P (SP)‐stimulated pupillary diameters by pupillometry. A higher basal and SP‐stimulated myosis was found in lSSc versus both dSSc and controls, whereas no differences existed between dSSc and controls. From the literature, the pupillary parasympathetic nervous system seems to be more affected than the sympathetic branch of ANS in the rheumatic diseases characterized by an inflammatory status. However, we found in SSc both sympathetic and parasympathetic pupil control to be equally impaired. From our experience, we conclude that pupillary nervous control is differently affected in the two subsets of SSc, and that the SP‐ergic system seems to be impaired only in lSSc.

Long‐term ergotamine abuse: Effect on adrenergically induced mydriasis

The mydriatic action of sympathomimetic eyedrops after a therapeutic dose of ergotamine was measured in migraine patients with and without histories of long‐term ergotamine abuse. Mydriasis induced by the postsynaptic α1‐agonist phenylephrine was similar in both groups of patients tested, whereas pupillary dilation caused by the release of noradrenaline tyramine was markedly greater in patients with histories of ergotamine abuse. The enhanced response to tyramine disappeared after drug withdrawal. These findings indicate that continuous ergotamine medication causes a reversible alteration in iris sympathetic transmission. This manifestation may reflect a central inhibition of pupillary sympathetic activity.

Does anisocoria by clonidine reflect a central sympathetic dysfunction in cluster headache

Local pharmacological manipulations of both pupils in persons with cluster headache (CH) have shown a reduced pain-side sympathetic activity. It is difficult to determine if this sympathetic defect is localized in the nuclei of the CNS and/or in peripheral neurons that innervate the pupil. This study demonstrates that in a CH group 2% tyramine (an intraneuronal norepinephrine releaser) instillation into both eyes induces an asymmetric and bilateral mydriasis with the onset of anisocoria characterized by a pupillary diameter being less on the pain-side eye. In addition, intravenous administration of 0.10 mg clonidine, an inhibitor of central sympathetic activity, causes a bilateral miotic response, which is more marked on the pain-side eye. In a healthy control group, clonidine induces a symmetric and bilateral miosis but less intense than that observed in both eyes of CH sufferers. In CH patients, pretreatment with clonidine augments the degree of anisocoria induced by tyramine instillation, increasing the mydriatic response only in the pain-free-side pupil. The hypothesis of a permanent sympathetic defect of the pain-side pupil expressing itself as a reduced sympathetic tone of CNS nuclei and peripheral neurons that innervate the pupil is proposed.

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.

A pharmacological approach to the analgesizing mechanism of somatostatin in cluster headache.

SummaryVasodilatation, conjunctival and nasal edema as well as miosis are symptoms associated with cluster headache (CH) attacks. Similar symptomatology is caused by substance P (SP) release from peripheral trigeminal nerve endings. The symptomatic effect of somatostatin (SRIF) during CH attacks was attributed to the inhibition of SP release from trigeminal neurons. This study was designed to evaluate both the vascular effect of SRIF on the dorsal hand vein and SRIF plasma levels prior to and after subcutaneous and intranasal administration in CH patients. A powerful venoconstriction and tachyphylaxis were demonstrated when SRIF was administered both as bolus and infusion. Plasma levels of SRIF in CH sufferers were lower than in control subjects. Subcutaneous and intranasal SRIF administrations induced maximal plasma levels after 5 and 10 min, respectively. These data suggest that SRIF plays an important role during CH attacks; however, its exact mechanism of action is still to be defined.

Substance P in the Human Iris: Possible Involvement in Echothiophate-Induced Miosis in Cluster Headache:

Substance P-like immunoreactivity (SP-LI) was measured by radioimmunoassay in iris, choroid, and retina obtained from men after death. Although present in different amounts, SP-LI, eluting as authentic SP or SP sulfoxide in the high-performance liquid chromatography system, was found in the three ocular structures. The retina contained higher concentrations of SP-LI than the iris and choroid. The possible functional involvement of iris SP was studied in 22 episodic cluster headache (CH) patients by using the anticholinesterase agent echothiophate iodide (EI), which also induces an atropine-resistant miosis, putatively due to release of SP from trigeminal sensory neurons. In CH patients EI eye drops instilled into both eyes provoked a prolonged miosis with a more marked response in the pupil of the symptomatic eye. It is proposed that the hyperfunction of SP-containing neurons may coexist with the previously documented sympathetic hypofunction in the innervation of the symptomatic pupil of CH.