Silvia Colnaghi

Vestibular evoked myogenic potentials in multiple sclerosis patients

OBJECTIVES Vestibular evoked myogenic potentials (VEMPs) are saccular responses to loud acoustic stimuli and are recordable from the sterno-cleido-mastoid muscle ipsilaterally to the stimulated ear. This study aimed to investigate VEMPs in patients suffering from multiple sclerosis (MS), and to compare these findings with both clinical and instrumental data. METHODS We recorded VEMPs from 70 MS patients, whose clinical data were retrospectively evaluated for the possible occurrence of: past and current (with respect to VEMP recording) brainstem and/or cerebellar symptoms; current brainstem and/or cerebellar signs. Sixty-five patients underwent brainstem auditory evoked potentials (BAEPs) recording; 63 of the same patients underwent saccadic eye movement recording and subjective visual vertical (SVV) evaluation. RESULTS VEMPs were abnormal in 31%, BAEPs in 38% and SVV in 21% of the patients. Saccadic eye movements showed a possible brainstem dysfunction in 44.4% of the patients. There was no correlation between the occurrence of abnormalities and the technical means of detection. The same held true for correlations with clinical data, with the exception of the BAEPs; these proved to be more frequently abnormal in patients presenting at neurological examination with brainstem and/or cerebellar signs that were possibly related to the complaint of dizziness. CONCLUSIONS VEMPs should be considered a useful complementary neurophysiological tool for the evaluation of brainstem dysfunction.

ICHD‐II diagnostic criteria for Tolosa–Hunt syndrome in idiopathic inflammatory syndromes of the orbit and/or the cavernous sinus

A bibliographical search was conducted for papers published between 1999 and 2007 to verify the validity of International Classification of Headache Disorders (ICHD)-II criteria for the Tolosa-Hunt syndrome (THS) in terms of (i) the role of magnetic resonance imaging (MRI); (ii) which steroid treatment should be considered as adequate; and (iii) the response to treatment. Of 536 articles, 48, reporting on 62 patients, met the inclusion criteria. MRI was positive in 92.1% of the cases and it normalized after clinical resolution. There was no evidence of which steroid schedule should be considered as adequate; high-dose steroids are likely to be more effective both to induce resolution and to avoid recurrences. Pain subsided within the time limit required by the ICHD-II criteria, but signs did not. We conclude that THS diagnostic criteria can be improved on the basis of currently available data. MRI should play a pivotal role both to diagnose and to follow-up THS.

Ocular neuromyotonia with both tonic and paroxysmal components due to vascular compression

Sirs: Ocular neuromyotonia (ONM) is characterized by brief spells of diplopia occurring spontaneously or after eccentric gaze holding due to tonic involuntary ocular muscle contraction [9]. ONM is a rare disorder, described in only 41 patients according to a recent review paper [10]. In most cases ocular neuromyotonia follows months or years after radiotherapy to the sellar or parasellar region [1, 2, 5, 8, 11, 13, 15], but it may be idiopathic [5, 6, 12, 13] or it may be secondary to differing pathological conditions [3–5, 7, 13, 15] including vascular compression [14]. We describe a patient in whom the neuromyotonic phenomenon was associated with a subclinical tonic component between the spells of diplopia, and was attributable to a vascular compression. It subsided with carbamazepine, but not with gabapentin administration. The patient was a 45-year-old healthy woman who suddenly had the onset of brief spells of vertical diplopia in all positions of gaze. The spells lasted about 30 seconds and consisted of left eye depression with pure vertical diplopia and without a clinically evident torsional component, pupil size modification or lid or horizontal eye movement involvement. The spells could be triggered by asking the patient to look down for about 20 seconds or by a prolonged hyperventilation. Between the spells she only showed a slight right hyperphoria. Cranial MRI disclosed a vascular compression between the left III cranial nerve and the P1 tract of the posterior cerebral artery (Fig. 1). Vertical saccades were recorded monocularly by means of the scleral magnetic search coil technique before (both between and during the spells) and after carbamazepine (CBZ) treatment. The patient had to make 10 and 20 degrees up and down saccades starting from and getting back to the primary position. The analyses focused on the phoria (right eye minus left eye position) and on the velocity-velocity ratio (vvr: the ratio of right to left eye peak velocity). The patient data were compared with those obtained from three normal subjects and from a 51 year-old patient presenting with a left superior rectus paresis. Between the spells, eye movement recording confirmed the vertical heterophoria slightly greater during upgaze (Fig. 2). This finding suggested a possible left superior rectus paresis, but this was incompatible with other data. The vvr was significantly greater than one (the peak velocity was greater in the right than in the left eye) for downward (both centrifugal and centripetal) rather than for upward saccade. These two findings were at variance both with those detectable in normal subjects and with those shown by the patient with the left superior rectus paresis (Fig. 2). The spells modified both left eye position and peak velocity, and increased both the phoria and and the vvr mainly below primary position within the lower ocular motor hemifield (Fig. 2). The patient was initially treated with gabapentin 400 mg t. i. d. unsuccessfully, and the spells subsided only after a few days of carbamazepine therapy (200 mg b. i. d.). Fourteen days later eye movement recording still showed a vertical misalignment, but consisted in a small left hyperphoria and the vvr pattern was similar to pre-treatment between spell recording. We hypothesize that vascular compression was likely to be the cause of ONM. Accordingly, all the ocular motor signs and symptoms were attributable to ephaptic transmission and axonal hyperexcitability that in our patient showed both a tonic and a paroxysmal component. The tonic component, already reported in ONM [14, 15], consisted of a small and slightly incomitant vertical misalignment explainable by a left inferior rectus spasm on the basis of the larger vvr LETTER TO THE EDITORS

A New Tool for Investigating the Functional Testing of the VOR

Peripheral vestibular function may be tested quantitatively, by measuring the gain of the angular vestibulo-ocular reflex (aVOR), or functionally, by assessing how well the aVOR performs with respect to its goal of stabilizing gaze in space and thus allow to acquire visual information during the head movement. In recent years, several groups have developed clinical and quantitative approaches to functional testing of the vestibular system based on the ability to identify an optotype briefly displayed on screen during head rotations. Although the proposed techniques differ in terms of the parameters controlling the testing paradigm, no study has thus far dealt with understanding the role of such choices in determining the effectiveness and reliability of the testing approach. Moreover, recent work has shown that peripheral vestibular patients may produce corrective saccades during the head movement (covert saccades), yet the role of these eye movements toward reading ability during head rotations is not yet understood. Finally, no study has thus far dealt with measuring the true performance of their experimental setups, which is nonetheless likely to be crucial information for understanding the effectiveness of functional testing approaches. Thus we propose a new software and hardware research tool allowing the combined measurement of eye and head movements, together with the timing of the optotype on screen, during functional testing of the vestibulo-ocular reflex (VOR) based on the Head Impulse Test. The goal of such tool is therefore that of allowing functional testing of the VOR while collecting the experimental data necessary to understand, for instance, (a) the effectiveness of the covert saccades strategy toward image stabilization, (b) which experimental parameters are crucial for optimizing the diagnostic power of the functional testing approach, and (c) which conditions lead to a successful reading or an error trial.

Seizure frequency and sex steroids in women with partial epilepsy on antiepileptic therapy

Purpose:  Neuroactive sex steroids influence neuron excitability, which is enhanced by estradiol (E2) and decreased by progesterone (Pg). In epilepsy, the production, metabolism, biologic availability, and activity of sex hormones may be affected by seizures themselves or by antiepileptic drugs (AEDs). This cross‐sectional observational study was aimed at evaluating the relationships between sex steroids, seizure frequency, and other clinical parameters in women with partial epilepsy (PE) on AED treatments.

Theta-Burst Stimulation of the Cerebellum Interferes with Internal Representations of Sensory-Motor Information Related to Eye Movements in Humans

Continuous theta-burst stimulation (cTBS) applied over the cerebellum exerts long-lasting effects by modulating long-term synaptic plasticity, which is thought to be the basis of learning and behavioral adaptation. To investigate the impact of cTBS over the cerebellum on short-term sensory-motor memory, we recorded in two groups of eight healthy subject each the visually guided saccades (VGSs), the memory-guided saccades (MGSs), and the multiple memory-guided saccades (MMGSs), before and after cTBS (cTBS group) or simulated cTBS (control group). In the cTBS group, cTBS determined hypometria of contralateral centrifugal VGSs and worsened the accuracy of MMGS bilaterally. In the control group, no significant differences were found between the two recording sessions. These results indicate that cTBS over the cerebellum causes eye movement effects that last longer than the stimulus duration. The VGS contralateral hypometria suggested that we eventually inhibited the fastigial nucleus on the stimulated side. MMGSs in normal subjects have a better final accuracy with respect to MGSs. Such improvement is due to the availability in MMGSs of the efference copy of the initial reflexive saccade directed toward the same peripheral target, which provides a sensory-motor information that is memorized and then used to improve the accuracy of the subsequent volitional memory-guided saccade. Thus, we hypothesize that cTBS disrupted the capability of the cerebellum to make an internal representation of the memorized sensory-motor information to be used after a short interval for forward control of saccades.

A device for the functional evaluation of the VOR in clinical settings

We developed the head impulse testing device (HITD) based on an inertial sensing system allowing to investigate the functional performance of the rotational vestibulo-ocular reflex (VOR) by testing its gaze stabilization ability, independently from the subject’s visual acuity, in response to head impulses at different head angular accelerations ranging from 2000 to 7000 deg/s2. HITD was initially tested on 22 normal subjects, and a method to compare the results from a single subject (patient) with those from controls was set up. As a pilot study, we tested the HITD in 39 dizzy patients suffering, non-acutely, from different kinds of vestibular disorders. The results obtained with the HITD were comparable with those from the clinical head impulse test (HIT), but an higher number of abnormalities was detectable by HITD in the central vestibular disorders group. The HITD appears to be a promising tool for detecting abnormal VOR performance while providing information on the functional performance of the rotational VOR, and can provide a valuable assistance to the clinical evaluation of patients with vestibular disorders.

SPIR MRI usefulness for steroid treatment management in Tolosa-Hunt syndrome

A 40-year-old man underwent surgery for a right middle ear cholesteatoma. One month later, he presented with a subacute ocular pain that was followed one day later by the appearance of vertical diplopia attributable to a right superior rectus paresis, lid ptosis and hypoaesthesia in the territory of the I and the II right trigeminal branches. A fatsuppressed (selective partial inversion recovery, SPIR) gadolinium-enhanced MRI favours the detection of inflammatory pathological tissue inside the right cavernous sinus, and in this patient it suggested a diagnosis of Tolosa-Hunt syndrome. The pain disappeared quickly after steroid treatment was started whereas the ocular nerve involvement improved only slightly during the first week of treatment. After two months, the patient only complained of diplopia on up-gaze, but the therapy was discontinued two months later on the basis of both clinical signs and MRI findings. SPIR MRI may be useful not only to support a diagnosis of Tolosa-Hunt syndrome, but also to follow-up the disease course and to manage steroid treatment.

A prospective multicentre study to evaluate the consistency of the IHS diagnostic criteria, the usefulness of brain MRI for the diagnosis, follow-up and treatment management, and the outcome after high dosage 6-methylprednisolone therapy, in subjects with Tolosa-Hunt syndrome.

As discussed in a previous review [1], several reasons suggest the need for a revision of diagnostic criteria of the International Headache Classification (IHS) [2] for Tolosa–Hunt syndrome (THS). First of all evidence is lacking on the most appropriate steroid treatment, secondly several reports suggest that neurological signs persist beyond the time limit defined by the IHS criteria. Furthermore, specific MRI techniques are necessary for detecting the inflammatory tissue, which can extend beyond the cavernous sinus and the orbit. Since data available from the literature mostly derive from case reports which differ in terms of treatment schedules, MRI techniques, and follow-up strategies, IHS diagnostic criteria cannot be improved by adopting an evidence-based methodology. Thus, we are promoting a non-profit multicentre study aimed at revising THS diagnostic criteria, considering (1) the clinical and MRI characteristics of the disease at presentation, after a standardized steroid treatment, and during an 8-month followup from the time symptoms, signs and MRI normalize, (2) the occurrence of relapses after treatment discontinuation, and (3) the effect of the lesion site on the outcome. Any participating centre will be asked to follow a simple management protocol based on serial MRI evaluations. All data will be recorded in case report forms provided by the Coordinator Centre, and no migration of investigators or patients is needed. The study has received approval from the Ethical Committee of the Coordinator Centre IRCCS ‘‘National Neurological Institute C. Mondino’’ Foundation. All contributors will appear as co-authors of every presentation and/or scientific publication of partial or complete results of the study. The readers of The Journal of Headache and Pain who are willing to participate can download the Study Summary, a Schematic Diagram and a Time and Event Schedule (available online as supplementary material), and can ask the corresponding author for complete documentation of the study.

Binocular control of saccades in idiopathic Parkinson's disease

Abstract: We focused on the saccade disconjugate control in idiopathic Parkinsons disease patients. Our data showed that in IPD patients the saccade precision was differently impaired in the two eyes—namely, the disconjugate component was larger than in controls—more for the remembered than for the reflexive task.