Milena De Marinis

Decreased habituation of the R2 component of the blink reflex in migraine patients

OBJECTIVE Activation of the trigemino-vascular system as well as of brainstem trigeminal nuclei are thought to play an important role in migraine. The aim of this study was to investigate the habituation phenomenon of the blink reflex in 30 headache-free migraine patients and 30 control subjects. METHODS An electromyographic device with a specific habituation test program was used to elicit and record blink reflex responses on both the right and left sides, and to randomly repeat the stimulations at different time intervals in order to induce habituation. RESULTS Whereas the R1 and R2 latencies, amplitudes and areas in the basal assessment were similar in patients and control subjects, the blink reflex habituation responses were markedly reduced in migraine patients who had a migraine attack within 72 h after testing (group A). In these patients, the differences between the R2 areas, obtained when stimuli were delivered at subsequent time intervals ranging between 10-5, 5-4, 4-3 and 3-2 s, were statistically different (P<0.001) from those of the patients who had a migraine attack after a longer time interval (group B) and control subjects. CONCLUSIONS Our data suggest that the brainstem pathways involved in the blink reflex may be activated in the premonitory phase of migraine attacks, probably through mechanisms that involve dopaminergic function.

Optic neuropathy after treatment with anti-tuberculous drugs in a subject with Leber's hereditary optic neuropathy mutation

Sirs: In February 1997, a 54-yearold man came to our attention because of a sudden and significant loss of vision. He had been hospitalized for lung tuberculosis from February 1996 to August 1996 and treated with isoniazid (5 mg/kg daily), ethambutol (20 mg/kg daily) and rifampicin (8 mg/kg daily) for 11 months. When visited by us he was no longer taking rifampicin but was still on ethambutol (1500 mg/day) and isoniazid (400 mg/day). His visual acuity was 5/10 in the right eye and 2/50 in the left eye, intraocular pressure was normal and funduscopy showed only slight vascular tortuosities. Computerized central visual field assessment revealed a small central scotoma in the right eye and a large central scotoma in the left eye. Ishihara’s test for dyschromatopsia (21 plates) showed deficit for colour in all plates. Pattern reversal visualevoked potentials were bilaterally extinct. Renal function was normal during hospitalization for lung tuberculosis and during our subsequent observation. All other routine laboratory data were normal. Fluorescein angiography and cerebral MRI were negative. A preliminary diagnosis of optic neuropathy induced by ethambutol and isoniazid was made [1]. The antituberculous drugs were discontinued and the patient was given vitamins (B and A) and zinc [1]. Subsequently, the fact that the patient remembered that one of his maternal uncles had suffered from “blindness” from an early age led to further investigations being performed. Interestingly, the analysis for the mitochondrial DNA mutation of Leber’s hereditary optic neuropathy (LHON) at position 11 778 was positive in this patient [2]. He was heteroplasmic, with at least 55 % mutant mitochondrial DNA in his peripheral blood. The patient was followed by us for two years and ophthalmological examinations were repeated every 2–3 months during the follow-up. After discontinuation of the antituberculous drugs, no improvement in visual function (visual acuity, visual field, colour vision and visual-evoked potentials) was observed for about 4 months. A slight improvement in visual perception was subsequently reported by the patient over a period of 2 months. This improvement, however, did not correspond to any substantial change in the objective findings and was followed by a subjective worsening. All the findings remained unchanged for a total of 11 months after the first observation. A slow and progressive recovery occurred only subsequently (from the 12th to the 21st month after the first observation). At the 2 examinations, performed 21 and 24 months after our first observation, visual acuity was 10/10 in the right eye and 7/10 in the left eye. Computerized central visual field assessment revealed that the central scotomas had bilaterally regressed. Testing showed a bilateral recovery of colour vision (right eye all plates and left eye 16/21 plates). Pattern reversal visual-evoked potentials revealed only a delayed P100 latency (right eye 120 ms and left eye 128 ms). At a further examination, performed 3 years after the first observation, visual function was unchanged. Renal function was normal in all the last three assessments. Ethambutol and isoniazid are specifically toxic for visual function [1]. In our patient, the absence of visual symptoms before the antituberculous treatment, the temporal relationship between long-term treatment and visual loss, and the reversibility of the visual alterations after discontinuation of antituberculous drugs indicate that these drugs played an important role in the development of the visual symptoms and suggest the diagnosis of ethambutol optic neuropathy in a LHON carrier. Optic neuropathy is a rare complication of ethambutol treatment that generally resolves when the drug is discontinued [3, 4]. Renal function was normal in our patient and the risk of developing ocular toxicity was not very high [5]. Moreover, the time evolution of the recovery and the marked visual function asymmetry between the eyes were also unusual [6]. In this subject, the presence of the mitochondrial DNA mutation may suggest a diagnosis of LHON and challenge the diagnosis of ethambuthol optic neuropathy. If so ethambutol would have acted as a trigger factor for LHON. Several features, however, particularly the degree and type of recovery were not consistent with LHON due to 11 778 mutation that commonly induces a severe and irreversible optic neuropathy with dyschromatopsia [2, 7]. In addition, heteroplasmy with mutant DN levels of less than 60 % is not commonly associated with visual loss [8]. Both ethambutol and Leber’s mutation affect oxidative phosphorylation through impairment of mitochondrial function each in its own way. LETTER TO THE EDITORS

Impairment in Color Perception in Migraine With and Without Aura

Objective.—To assess visual perception in 40 patients suffering from migraine with aura (MA), 40 patients suffering from migraine without aura (MO), and 40 controls.

Pupillary abnormalities due to sympathetic dysfunction in different forms of idiopathic headache

Idiopathic vascular-type headache is frequently associated with pupillary alteration, which is often presumed to be due to malfunction of the sympathetic nervous system. In this review the anatomical and neurotransmitter basis of oculosympathetic function is briefly discussed along with some of the common pharmacological and physiological pupillary tests used in its assessment. The clinical and subclinical features of the pupil abnormalities are analysed in idiopathic headache, which includes migraine, tension headache, cluster headache, and chronic paroxysmal hemicrania. Possible mechanisms underlying these alterations are suggested. Among secondary headaches, carotid dissection and aneurysm have to be excluded when unilateral headache is associated with a persistent ipsilateral oculosympathetic deficit. From the literature, specific responses to pupillary tests apparently are present in idiopathic headache. Pupillary tests may differentiate between the subtypes of idiopathic headache. The investigation of pupillary dysfunction may provide information on the physiopathological basis of headache.

Headache associated with non‐cephalic infections: classification and mechanisms

A classification of headache associated with non-cephalic infections is proposed. The classification is supported by published case series and reports. The head pain can be explained by direct activation of pain producing mechanisms by microorganisms or can be secondary to fever or to a combination of both.

Evaluation of vesico-urethral and sweating function in disorders presenting with parkinsonism

Investigation of vesico-urethral and sweating function was performed in twelve patients with classical idiopathic Parkinsons disease and ten patients with parkinsonism associated with features suggestive of more extensive involvement of the nervous system, as in the Shy—Drager syndrome. The urodynamic studies revealed detrusor hyperreflexia with reduction of maximal cystometric capacity in only one patient with Parkinsons disease (8%), but in nine patients with parkinsonism associated with other features (90%). Urethral sphincter electromyography did not indicate denervation in any patient of either group. Delayed or incomplete relaxation of the urethral sphincter during micturition was observed in seven patients with Parkinsons disease (58%) and in two patients of the other group (20%). Decreased sweating responses were found in both groups of patients when compared with control subjects. Hypohidrosis was more pronounced in parkinsonism associated with other features than in Parkinsons disease. Differences in sweating between the two sides of the body were observed in both groups of patients. Although there are differences in vesico-urethral and sweating function, they do not precisely differentiate between patients with classical Parkinsons disease and those with parkinsonism associated with features suggestive of more extensive involvement of the nervous system.

Alterations in cardiovascular autonomic function tests in idiopathic hyperhidrosis

We performed cardiovascular autonomic function tests to assess sympathetic and parasympathetic functions in patients with idiopathic hyperhidrosis. We studied 35 patients with idiopathic hyperhidrosis and 35 age- and sex-matched controls. A thermoregulatory sweat test (TST) was performed in all subjects. Sweating was qualitatively (Minors test at 22°C) and quantitatively (skin conductance) evaluated. Orthostatism, tilt to 65°, cold pressor test, deep breathing, Valsalva maneuver and hyperventilation were performed in patients and controls. A greater fall in blood pressure values was observed in patients than in controls in the upright tests (p<0.05). In particular, postural hypotension was present in a subgroup of patients (34%), in whom changes in lying-to-standing blood pressure and heart rate were greater (p<0.001) than those of the remaining patients. The TST revealed that the total body sweat rate (ml/cm(2)/min) was more pronounced in patients with postural hypotension (p<0.001) than in the other patients and controls. The skin conductance values of patients with postural hypotension were higher (p<0.001) than those of the remaining patients. A positive correlation was found between skin conductance values and postural hypotension. Dehydration and poor water intake may play a role in postural hypotension in patients with severe hyperhidrosis and pronounced thermoregulatory sweating. A significantly marked increase in parasympathetic function was observed in patients. Responses to deep breathing, Valsalva maneuver and hyperventilation were significantly greater in patients (p<0.001) than in controls. Idiopathic hyperhidrosis seems to be a complex dysfunction that involves autonomic pathways other than those related to sweating.

Vascular headaches and cerebral circulation: an overview.

complex network of neurotransmission systems underlies the control of the cerebral circulation. Classical neurotransmitters, vasoactive peptides and receptors have been found in cerebral arteries. Central and peripheral structures are also probably involved in the neurogenic control of the cerebral circulation. Vascular and neurotransmission changes reported in vascular headaches suggest that an alteration of the neurogenic control of the brain circulation may be implicated in vascular headaches. In particular, locus coeruleus, which may control the intracerebral adrenergic pathway, can induce vascular changes similar to those of migraine. Moreover, the trigeminal ganglion, which may induce the release of substance P, can change the extracranial and intracranial vasodilator activity. The vascular theory of migraine, proposed by Wolff, is re-evaluated on the grounds of a possible mediation of the vascular responses by neurotransmitters. It is hypothesized that a deficient modulation by enkephalins may cause alterations of locus coeruleus and/or trigeminal ganglion. The problem of pain in vascular headaches is also considered: whether it is of vascular origin or whether it is due to a dysfunction of the central nociceptive pathway. Knowledge of the neurogenic control of the cerebral circulation may be useful in understanding some pathogenetic mechanisms of vascular headaches.

Trigeminal Control of Cranio-Facial Vasomotor Response: I. Histamine Test in Patients with Unilateral Gasserian Ganglion Lesions

It has been hypothesized that the trigeminal system may control vasomotor changes and pain in vascular headaches. In this study, headache was induced by an intravenous injection of histamine in 37 patients with trigeminal rhizotomy and in 12 controls. The vasomotor response to histamine was studied with facial telethermography. The headache in patients with trigeminal lesions differed, in a prevalence of unilateral localization contralaterally to the operated side (21 patients), from that in controls. No relationship was found between the hypoesthesia caused by the operation and the prevalence of unilateral headache. A statistically significant correlation (p < 0.001) was found between unilateral absence of headache and decreased vasomotor response on the operated side. These reactions occurred more in patients who underwent thermocoagulation than in patients who underwent retro-gasserian rhizotomy. Thus the gasserian ganglion seems to control the cranio-facial vasomotor response and the headache through a vascular pathway, acting on cerebral arteries, which differs from the sensory pathway.

Oculosympathetic hyperactivity in idiopathic hyperhidrosis.

We describe a patient suffering from idiopathic hyperhidrosis, more pronounced on the right side, who presented with intermittent oculosympathetic hyperactivity (mydriasis, lid retraction and more rapid pupillary dilatation) on the same side. Mydriasis was induced by stress, loss of sleep and cold pressor test. The clinical features in this patient suggest an involvement of the hypothalamic structures.