Autonomic function in migraine patients: ictal and interictal pupillometry.

OBJECTIVE AND BACKGROUND: Pupillometric investigations into migraine have suggested that an autonomic disturbance is part of the pathogenesis of that condition. This observation is controversial, however, which may reflect that the putative sympathetic hypofunction is either subtle or transient. In this study, we assessed the sympathetic function of migraine patients and controls during both a symptom-free phase and a migraine attack, and challenged patients with apraclonidine to reveal small changes in autonomic function. METHODS: Infrared pupillometry was used to measure pupillometric parameters in 37 controls and 46 migraine patients in the interictal phase of disease. Fifteen migraine patients were also studied during a migraine attack. In addition, 26 controls and 18 migraine patients were tested interictally both with and without apraclonidine. Of these 18 migraine patients, seven were also tested with and without apraclonidine during a migraine attack. RESULTS: We found no significant differences between migraine patients and controls in the interictal phase. Additionally, no differences in pupil parameters were detected during the migraine attack. However, after administration of apraclonidine, migraine patients had a longer latency of the light reflex compared with controls. This increase in latency was more pronounced ictally (oculus dexter: P = .046, oculus sinister: P = .023) than interictally (oculus dexter: P = .075, oculus sinister: P = .021). CONCLUSIONS: We conclude that there is evidence for a subtle pupillary sympathetic hypofunction in migraine patients, observed as a prolonged latency to light reflex, which is revealed after the administration of apraclonidine.

Apraclonidine and my pupil.

PURPOSE: Used in the diagnosis of Horner's syndrome, apraclonidine 1% dilatates the involved eye due to denervation supersensitivity. Recent literature suggests that in healthy volunteers, apraclonidine provokes a mild miotic effect. Since the comparison of both the pathologic and the non-pathologic eye is important, we wanted to further investigate the effect of apraclonidine on the healthy eye. By measuring the effect on the pupil intermittently over a few hours, we tried to determine the best moment for evaluation after instillation with apraclonidine. Therefore, the effect of apraclonidine on pupillary parameters was investigated in 14 healthy volunteers. METHODS: Infrared pupillography was used to measure the scotopic pupil diameter and the dynamic pupil responses to light. The first measurements were performed prior to instillation of apraclonidine. Measurements were retaken 30, 60, 90, 120, 180, 240, 300 and 360 min after random instillation of one eye with one drop of 1% apraclonidine. RESULTS: The anisocoria after dark adaptation and at minimum pupil diameter differed significantly for the measurements obtained 30 and 60 min after instillation with apraclonidine. The eye with apraclonidine drops showed relative miosis and an increased amplitude of constriction to light. No significant influence was found on the latency, the constriction velocity and redilation velocity. CONCLUSIONS: Instillation of apraclonidine 1% in healthy subjects causes relative miosis, which is most pronounced after 30-60 min. The amplitude of constriction to light also differs significantly. The relative miotic effect of apraclonidine could be explained by the α-2 receptor agonistic effect which is more pronounced than the α-1 agonistic effect in healthy subjects. In patients with Horner's syndrome, the α-1 agonistic effect will dominate because of the supersensitivity of the α-1 receptors, resulting in relative mydriasis. These findings stress the necessity to instill the unaffected eye in diagnosing a suspected Horner's pupil.

Wall-eyed Bilateral Internuclear Ophthalmoplegia (WEBINO) in a Patient With Idiopathic Intracranial Hypertension.

INTRODUCTION: Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) is a variant syndrome of internuclear ophthalmoplegia, consisting of primary gaze exotropia, adduction impairment, nystagmus of the abducting eye, and vertical gaze-evoked nystagmus. It seems to be most frequently associated with multiple sclerosis, although other etiologies such as brainstem ischemia or hydrocephalus have also been described. CASE REPORT: We report the case of a 25-year-old woman who presented with subacute progressive oculomotor disturbances, resulting in the development of a WEBINO over a few days. Fundoscopy showed papilledema first in the right and afterwards also in the left eye. Brain magnetic resonance imaging was normal. Lumbar puncture demonstrated an opening pressure of 38 cm H2O, without pleiocytosis and with normal protein. As no other cause of intracranial hypertension could be identified by imaging or extensive biochemical testing, the patient was treated with acetazolamide for idiopathic intracranial hypertension. As there was further progression despite increase of acetazolamide dosing, more aggressive therapy was pursued, and a ventriculoperitoneal shunt was placed by our neurosurgeons. Clinical follow-up showed progressive recovery of normal oculomotor function and disappearance of papilledema over the course of 6 weeks. CONCLUSIONS: To our knowledge this is the first case description of a patient with WEBINO and idiopathic intracranial hypertension. The diagnosis is supported by the very high opening pressure, the absence of neuroimaging abnormalities, the papilledema, and the response to ventriculoperitoneal drainage.

Practical management of medication-overuse headache.

Epidemiological studies suggest that medication-overuse as defined by the International Headache Society is extremely common in patients with chronic daily headache. If all medication-overuse produces medication-overuse headache (MOH) in headache patients, it would be the third most frequent form of headache, after tension-type headache and migraine. Treatment of MOH is hindered by the absence of placebo-controlled, double-blind, randomised clinical trials. Nevertheless, several headache centers worldwide have developed expertise in the treatment of this syndrome, and have been quite successful. Here, we summarize available data on MOH, including clinical features, drugs used in withdrawal, as well as withdrawal strategies that have been described in the literature. We also include a detailed description of an in-patient and out-patient withdrawal procedure, reflecting personal experience and opinion of the authors.

Visuo-spatial processing in Parkinson's disease: evidence for diminished visuo-spatial sketch pad and central executive resources.

A dual-task study compared the visuo-spatial sketch pad and central executive components of working memory as potential cognitive mechanisms of visuo-spatial dysfunction in Parkinson's disease. Mildly to moderately affected Parkinsonian patients (n = 15) and controls (n = 15) performed the Corsi blocks task concurrently with tasks designed to load on the visuo-spatial sketch pad (spatial tapping) or the central executive (random interval repetition). Patients performed more poorly in both concurrent task conditions, implicating a reduction in both visuo-spatial sketch pad and central executive resources. The impact of the concurrent tasks varied with disease severity, with the central executive deficit prominent at disease onset, but the visuo-spatial sketch pad deficit becoming apparent only in the moderate stages of the illness.

Effect of repetitive transcranial magnetic stimulation on saccades in depression: a pilot study.

Therapeutic repetitive transcranial magnetic stimulation (rTMS) in depression is applied over the prefrontal cortex. This brain region is known to play an important role in the control of saccades. We wanted to investigate whether the fast rTMS procedure affected saccadic activity in depression. Reflexive saccades (RS) and voluntary saccades were studied in 11 patients before and after therapeutic rTMS for depression. Two types of voluntary saccade tasks were used: a voluntary prosaccade (VpS) task and an antisaccade (AS) task. Eye movements were registered by infrared oculography. Latency and directional error rate were analyzed. rTMS was applied over the left dorsolateral prefrontal cortex (DLPFC). RS and VpS parameters were unchanged after 10 sessions of rTMS. However, the latency of antisaccades (AS) was significantly shorter after rTMS than before rTMS. It can be concluded that rTMS over the left DLPFC cortex in depression seems to have no important effect on reflexive saccades, while antisaccade activity is clearly favored by shortening of latency. As voluntary prosaccades were not significantly influenced, our findings may indicate that not merely the voluntary triggering of saccades but the inhibition of unwanted reflexive saccades is influenced by fast rTMS delivered over the DLPFC. These results suggest the intriguing possibility that rTMS might differentially affect specific aspects of saccade behavior.

Migraine-related vertigo: towards a distinctive entity.

Both migraine and vertigo are common complaints. Although they may coincide by chance, there is growing evidence for a clinical entity of recurrent vestibular symptoms related to migraine. This syndrome implies a possible causal relationship although the pathophysiology of migraine-related vertigo has not been fully elucidated. A migrainous aseptic inflammation is thought to create a central sensitivity that spreads from the trigeminal to the vestibular system. Diagnostic criteria for migraine-related vertigo are proposed. Treatment is based on anti-vertiginous drugs for acute interventions and prophylactic measures as are taken for migraine headaches. Multicenter, prospective controlled studies are highly warranted.

Magnetic resonance angiography of the circle of Willis in migraine patients.

We analysed records of 244 consecutive adult outpatients who presented at our neurological polyclinic between 1996 and 2001 with migraine and who underwent a MRA of the circle of Willis. In 80 cases, a definitive migraine diagnosis according to the International Headache Society criteria (1988) could be retrieved from the patient records. Of these, 63 patients had migraine without aura and 17 patients had migraine with aura. Two MRA procedures were abrupted because of claustrophobia and another two MRA studies were unreliable because of movement artefacts. In only one patient of the remaining 240, an aneurysm was suspected with MRA. However, a conventional angiography did not confirm any cerebrovascular abnormality. All other exams were considered normal. This retrospective study argues against a systematic screening of migraine patients with MRA.

Effect of intention and visual fixation disengagement on prosaccades in Parkinson's disease patients.

In a previous study, we postulated a divergence in reflexive versus voluntary saccade behavior in Parkinson's disease (PD) patients and hypothesized a fronto-striatal dysfunction. The voluntary saccade tasks included antisaccades (AS) and remembered saccades (RemS). However, multiple cognitive processes are involved in AS and RemS and the procedures lack a visual target. The present study had two main objectives. Firstly, we wanted to extend our previous findings of disturbed AS and RemS to other intentional (endogenous, "voluntary") saccades but now with a visible target. Therefore, an intentional prosaccade (IpS) task was used. Secondly, we investigated whether there is a different saccade behavior in PD patients and controls in conditions where the central fixation stimulus is extinguished shortly before the onset of the peripheral target (the so called gap condition) to assess the role of disengagement of visual fixation. With respect to the first objective, the present study found a clear dissociation between the performances of PD patients on reflexive saccade (RS) versus IpS tasks. Patients did not differ from controls in latency or error rate of RS. However, in the IpS task, latency was longer and error rate was higher in PD patients. Thus, the present study provides evidence that PD patients are deficient in intentional saccade tasks independent from the fact whether a target is visible or not. As to the second objective, saccades of PD patients did show a shorter latency in the gap than in the no gap condition. This suggests that the gap effect is not dominantly dependent on nigro-collicular neuronal circuits that are affected in PD. In the patients, the gap effect was reliable in the RS task, but not in the IpS condition. These discordant gap findings might suggest modulation of selected neuronal circuits involved in early sensorimotor processing. The present findings do not to support the hypothesis that impaired saccade behavior in PD patients is merely dependent on the presence or the absence of visual fixation and suggests a higher order psychomotor dysfunction, presumably of intentional nature. The dorsolateral prefrontal cortex might correspond to the premotor cognitive dysfunction site. However, an additional involvement of the frontal eye field can not be excluded from the present study.

Latanoprost in hemifacial spasm.

An empirical observation that the prostaglandin derivate latanoprost quited facial spasms in patients with glaucoma prompted us to study latanoprost in non-glaucomatous patients with hemifacial spasms [HFS]. This explorative trial followed an open-label, prospective treatment design. At short term, most patients showed no or only mild improvement and subsequently needed therapy with Botulinum toxin A. Although these results are not impressive, latanoprost could be considered as an interesting alternative in the treatment of patients with HFS and with concomitant glaucoma. A role for prostaglandins in the trigeminofacial reflex is hypothesised.

Patients with migraine correctly estimate the visual verticality.

OBJECTIVE: We wanted to study otolith function by measuring the static subjective visual vertical (SVV) in migraine patients and in controls with and without kinetosis (motion sickness). METHODS AND MATERIAL: Forty-seven patients with moderately severe migraine and 96 healthy controls were enrolled. Using a questionnaire, persons with kinetosis were identified. The SVV test was performed in a totally dark room. Subjects wore a stiffneck to stabilize the head in an erect position. They were required to adjust an infrared line to the gravitational vertical with a hand-held infrared remote controlled potentiometer. RESULTS: The deviation of SVV in the group of migraine patients was not significantly different from that of controls, regardless of whether an aura was associated. SVV was not significantly influenced by the presence of dizziness/non specific vertigo or kinetosis. CONCLUSION: Patients with moderately severe migraine under prophylactic medication correctly estimate the visual verticality in the headache-free period. It is suggested that a deviation of SVV in a headache-free migraine patient may not be attributed to his migraine disorder as such regardless whether kinetosis is associated.

Gap effect in reflexive and intentional prosaccades.

The analysis of saccadic eye movements has assumed an important role as a pathophysiological approach in neuropsychiatric diseases. However, before abnormal cognitive saccade behavior can be fully understood, some basic psychophysiological aspects have to be further investigated. Previous studies have demonstrated a shortening of saccade latency when the fixation stimulus was removed prior to the appearance of a peripheral visual target. This gap effect is smaller for antisaccades (AS; away from the target) than for reflexive saccades (RS; towards the target). Apart from the generation of an intentional eye movement, AS rely on different processes including reflex inhibition and spatial reversal of the saccade direction. We wondered whether intentional prosaccades (IpS) that do not rely on these additional processes also show a reduced gap effect. Therefore, we compared the gap effect in a saccade paradigm for RS and IpS in healthy subjects. We found a smaller gap effect in IpS than in RS and suggest that this reduction reflects endogenous strategic processes. Our findings further imply that reflex inhibition is not the unique cause for the smaller gap effect in AS than in RS and suggest that an endogenous component may be involved. We hypothesize that frontal control on the superior colliculus fixation cell activity may continue even after the fixation stimulus has disappeared, thus inhibiting a fixation offset and reducing the gap effect.

Visual extinction for motion.

PURPOSE: To alert clinicians to the heretofore undescribed visual behavioral phenomenon of visual extinction limited to motion. METHODS: Neuro-ophthalmological, neuropsychological and neuroimaging assessment of a 57-year-old man with vague visual complaints. RESULTS: Extinction limited to visual motion perception in the left hemifield was demonstrated. The visual defect was attributed to a lesion involving the right occipito-temporo-parietal region in the presence of a left posterior infarction. CONCLUSION: The importance of clinical examination for detection of this specific higher-order visual defect is stressed. The present observation may be helpful in understanding the effects of attention on visual perception and may have important implications for rehabilitation of patients with visual neglect.

Effect of sleep deprivation on saccades and eyelid blinking.

In this study the effect of sleep deprivation on specific components of eye and eyelid movement was investigated in a group of young and healthy subjects. The duration of sleep deprivation was 20 h. Each subject had to execute different saccade tasks: reflexive saccades, voluntary prosaccades and antisaccades. Saccade latency, number of saccade errors and blink rate during the saccade tasks were evaluated as predictors of performance decrements resulting from sleep deprivation. The present study showed no significant deterioration of latency and number of errors in the different saccade tasks. However, the blink rate was significantly higher after a night without sleep than before. It is concluded that the blink rate appears to be a promising psychophysical measurement and a more sensitive parameter than saccade performance to evaluate the effects of 20 h of sleep deprivation. These results encourage further research on this topic.

Painful isolated Horner's syndrome caused by pontine ischaemia.

PURPOSE: To alert ophthalmologists to the possibility of brainstem ischaemia in patients with isolated Horner's syndrome. DESIGN: Observational case report. METHODS: Neuro-ophthalmological and neuroimaging assessment of a 59-year-old woman presenting with an isolated Horner's syndrome after an episode of headache. RESULTS: Horner's syndrome was pharmacologically localised to a first- or second-order sympathetic neuron on the right. Magnetic resonance imaging (MRI) showed a small ischaemic lesion at the transition between pons and midbrain, lateral to the anterolateral system involving the sympathetic tract on the right side. CONCLUSION: An isolated Horner's syndrome may be the presenting sign of a brainstem infarction. This case report stresses the importance of a rational approach to Horner's syndrome and the need to order accurate MRI.