Eleftherios S. Papathanasiou

International guidelines for the clinical application of cervical vestibular evoked myogenic potentials: an expert consensus report.

BACKGROUND Cervical vestibular evoked myogenic potentials (cVEMPs) are electromyogram responses evoked by high-level acoustic stimuli recorded from the tonically contracting sternocleidomastoid (SCM) muscle, and have been accepted as a measure of saccular and inferior vestibular nerve function. As more laboratories are publishing cVEMP data, there is a wider range of recording methods and interpretation, which may be confusing and limit comparisons across laboratories. OBJECTIVE To recommend minimum requirements and guidelines for the recording and interpretation of cVEMPs in the clinic and for diagnostic purposes. MATERIAL AND METHODS We have avoided proposing a single methodology, as clinical use of cVEMPs is evolving and questions still exist about its underlying physiology and its measurement. The development of guidelines by a panel of international experts may provide direction for accurate recording and interpretation. RESULTS cVEMPs can be evoked using air-conducted (AC) sound or bone conducted (BC) vibration. The technical demands of galvanic stimulation have limited its application. For AC stimulation, the most effective frequencies are between 400 and 800 Hz below safe peak intensity levels (e.g. 140 dB peak SPL). The highpass filter should be between 5 and 30 Hz, the lowpass filter between 1000 and 3000 Hz, and the amplifier gain between 2500 and 5000. The number of sweeps averaged should be between 100 and 250 per run. Raw amplitude correction by the level of background SCM activity narrows the range of normal values. There are few publications in children with consistent results. CONCLUSION The present recommendations outline basic terminology and standard methods. Because research is ongoing, new methodologies may be included in future guidelines.

Ocular vestibular evoked myogenic potentials (OVEMPs): Saccule or utricle?

Testing ocular vestibular evoked myogenic potentials (OVEMPs) is a recently discovered way of recording function from the vestibular system (Rosengren et al., 2005; Iwasaki et al., 2007; Todd et al., 2007). Sound or vibration stimuli are used to stimulate the vestibular end organs of the inner ear, and the OVEMP response is recorded from beneath the contralateral eye using surface electrodes. During the test, the patient is asked to look up. This causes contraction of the inferior oblique muscle, with the upward eye movement also bringing the muscle closer to the recording electrodes, and the response is an excitatory one. A negative peak is recorded at around 10 ms after stimulus onset, and represents vestibular function starting from the otolith organs in the inner ear and traveling via the medial longitudinal fasciculus in the rostral brainstem to the extraocular eye muscle nuclei. But which otolith organs? Is it the saccule or the utricle? The vestibular world is divided at the moment between the two, with evidence that seems to favor either the one or the other. Evidence favoring a utricular origin are (1) that both saccular and utricular irregular afferents are activated by bone conducted vibration (Curthoys, 2010), (2) some utricular receptors and afferents respond to air conducted sound (ACS) (Murofushi et al., 1995), and (3) unilateral stimulation of the utricular nerve in cats causes activation of the contralateral inferior oblique muscle (Suzuki et al., 1969). Evidence favoring a saccular origin are (1) sound and bone vibration evoke different ocular movements in human subjects, suggesting that different populations of receptors are stimulated (Todd et al., 2007; Colebatch, 2010), (2) findings from human tuning experiments support projections from both otolith organs to the ocular muscles (Todd et al., 2009; Govender et al., 2011), and (3) bone conducted lateral impulses applied at the mastoids, which have been shown to selectively stimulate the utricles (Todd et al., 2008), produce cervical VEMPs (with recording from the sternocleidomastoid muscles, CVEMPs) and OVEMPs with comparably high interside amplitude asymmetries in a series of patients with vestibular neuritis (Govender et al., 2011). However, all the above studies agree that it is the superior vestibular nerve that is part of the OVEMP pathway and not the inferior vestibular nerve. In this issue, Shin and his group also report the selective involvement of OVEMPs in vestibular neuritis of the superior vestibular nerve (Shin et al., 2012). The findings are similar to those reported in parallel by Govender et al. (2011). In their study (Shin et al., 2012), two groups of patients with vestibular neuritis were examined; one group with superior vestibular nerve involvement and a much smaller group with inferior vestibular nerve involvement. In the former group, all OVEMPs were abnormal with normal CVEMPs, whereas in the latter group all CVEMPs were abnormal and OVEMPs normal. They therefore concluded that with air-conducted sound OVEMPs involve superior vestibular and not inferior vestibular nerve function, and this constructively adds to the above literature on the origin of the OVEMP. However, the authors went one step further to conclude that the OVEMP was utricular in origin, based on the fact that the utricular nerve fibers pass through the superior vestibular nerve. Unfortunately, the authors have not taken into account the fact that the saccule also contributes nerve fibers to the superior vestibular nerve (Lorente de No, 1933). Therefore, their study does not rule out a saccular contribution to the OVEMP response.

A novel PMP22 mutation Ser22Phe in a family with hereditary neuropathy with liability to pressure palsies and CMT1A phenotypes

Abstract.We describe a Cypriot family in which some family members presented with episodes of pressure palsies, while other family members had a slowly progressive chronic polyneuropathy typical of the Charcot-Marie-Tooth type 1 phenotype. All family members were evaluated clinically, with nerve conduction studies, and with genetic testing. In all affected individuals there was clinical and electrophysiological evidence of diffuse demyelinating sensorimotor polyneuropathy and a novel point mutation in the PMP22 gene (Ser22Phe) was identified.

Sleep hypoventilation syndrome and respiratory failure due to multifocal motor neuropathy with conduction block

Sleep hypoventilation syndrome and respiratory failure have been reported in association with a diverse spectrum of neuromuscular disorders. We report a patient with multifocal motor neuropathy with conduction block who presented with sleep hypoventilation, presumably due to bilateral phrenic neuropathy and was initially diagnosed to have obstructive sleep apnea syndrome. Once the correct diagnosis was made the patient was treated successfully with a combination of regular immunoglobulin and bilevel nocturnal ventilation. Delay in the administration of intravenous immunoglobulin resulted in respiratory failure. Muscle Nerve, 2011

Visual cortical plasticity following unilateral sensorimotor cortical lesions in the neonatal rat

Previous work has shown that unilateral sensorimotor cortex (SMC) lesions in newborn rats resulted in an apparent shift of the motor cortex map in the spared hemisphere, particularly of the hindlimb cortex. In view of such findings, the present study was initiated to determine if the visual cortex located both ipsilateral and contralateral to neonatal SMC, or contralateral to occipital cortical (OC) lesions, would show similar remodeling. Visual evoked potentials (VEPs) were used to map the visual cortex electrophysiologically. The results show an expansion of the visual cortex, in both the contralateral and ipsilateral hemisphere, into normally motor cortical areas in adult animals that had sustained unilateral neonatal unilateral SMC lesions. In contrast, similar changes were not seen within the spared visual cortex after unilateral occipital cortical lesions, suggesting that the shift in the visual map was specifically in response to the SMC lesion and was not a generalized response to neonatal cortical damage. Histological analysis showed a functional expansion in the rostral boundary of visual cortex with no corresponding cytoarchitectural alterations.

Vestibular evoked myogenic potentials: the fuzzy picture of different stimulation types is beginning to come into focus.

Vestibular evoked myogenic potentials (VEMPs) are an easy and reliable way of evaluating function of the vestibular nervous system. Using reproducible sound stimuli of short duration and fast rise time, one can record evoked potentials either caudally through the brainstem towards the sternocleidomastoid muscle (cervical VEMPs or cVEMPs) or rostrally through the medial longitudinal fasciculus towards the extraocular muscle nuclei (ocular VEMPs or oVEMPs). Inferior vestibular nerve function is specific to cVEMPs, while superior vestibular nerve function is specific to oVEMPs (Rosengren et al., 2011). Various stimulation methods are currently available to record VEMPs. Originally, air-conducted sound in the form of clicks was used (Colebatch et al., 1994), followed by tendon tap stimulation to the forehead (Halmagyi et al., 1995), and then by short duration electrical (‘‘galvanic’’) stimuli (Watson and Colebatch, 1998). Bone-conducted vibration was then developed (Sheykholeslami et al., 2000), followed almost at the same time by air-conducted tone stimulation (Welgampola and Colebatch, 2001a), and more recently by lateral pulse stimulation at the mastoids (Todd et al., 2008). Air-conducted tone stimulation has been shown to produce responses of higher amplitude with a lower threshold than air-conducted click stimulation, and bone-conducted stimulation is advantageous in cases of conductive hearing loss as it bypasses the outer and middle ear. Forehead taps produce a wave of vibration that bypasses the middle ear as well, and directly activates the vestibular apparatuses on both sides simultaneously (Welgampola and Colebatch, 2001b). The precise afferents activated by skull taps are not known, although based on the appearance of lateral skull taps in normal subjects and in unilateral vestibulopathy, utricular stimulation has been proposed (Brantberg and Tribukait, 2002; Brantberg et al., 2003; Welgampola and Colebatch, 2005). However, bone-conducted sound, compared to the forehead tap, has the advantage of being a calibrated and reproducible stimulus and therefore elicits consistent responses and enables the measurement of stimulus thresholds (Welgampola et al., 2003). Lateral pulse stimulation is a more direction specific form of bone-conduction in the transmastoid plane, and is believed to be specific to utricular stimulation (Todd et al., 2008). The technique of galvanic stimulation may be well suited to investigating central disorders of vestibular function but the technical demands have limited the application of this stimulus to date. The wealth of stimulation types available as a result of intense research in the field may however have created confusion amongst clinicians. A reassessment of this information and a study of how they are all related was therefore needed in the field of vestibular electrophysiology. Several studies have been published in the past that compared the properties of the stimuli and the characteristics of the VEMP responses obtained (Welgampola and Colebatch, 2001b; Murofushi et al., 2002; Bacsi et al., 2003; Welgampola et al., 2003; Cheng et al., 2009). However, the different stimuli were still considered separately. This includes the more recent paper by Rosengren et al. (2011) even though it was detailed in its analysis. There are two aspects with respect to VEMP stimuli that a recent letter by Colebatch and his group has managed to address, and is the subject of this Editorial (Colebatch et al., 2013). One is the clarification with respect to the relationship between the different stimuli listed above. It required a further evaluation of the data published in the paper by Rosengren et al. (2011) to bring everything with regards to stimuli together. In this letter, a reassessment of all stimulus types was made with respect to age. Out of this analysis, it appeared that the stimuli were not something that would be compared to a recipe list after all. It instead revealed that the stimuli were in fact related to each other. Specifically, for both cVEMPs and oVEMPs, AC-clicks, AC tone burst and BC tone burst all decrease in amplitude with age, whereas cVEMPs and oVEMPs obtained with forehead taps and lateral pulse stimulation were all resistant to age effects. The second important piece of information that this reanalysis has provided is related to the otolith organ of origin of cVEMPs and oVEMPs. Although it is accepted by everyone that air-conducted click and tone stimulation stimulates the saccule to produce the cVEMP, this is not so straightforward for the oVEMP (Papathanasiou, 2012). The paper in this issue argues that the similarity in both responses (cVEMPs and oVEMPs) to click and tone (airand bone-conducted) stimuli is due to a common origin and based on earlier publications this would imply the saccule as the main otolith organ stimulated. The difference in the two groups of responses (correlating and not correlating with age) may be related to the frequency content of the stimulus and their ability to stimulate either the utricle or the saccule. An earlier study has shown that 100 Hz air-conducted tone stimulation may be selective for utricular stimulation (Zhang et al., 2011), in contrast to saccule stimulation where it is now known that 500 Hz is the best mode of air-conducted stimulation. Therefore, in relation to their frequency content, air-conducted click, tone and bone-conducted

Levetiracetam in three cases of progressive myoclonus epilepsy

We present three unrelated cases of genetically confirmed progressive myoclonic epilepsy of the Unverricht–Lundborg type who were treated with Levetiracetam as adjunctive therapy for their myoclonus. All cases responded with decrease of their myoclonus and improvement of quality of life. Two were able to return to or continue their employment. Patients tolerated the drug well without side effects reported. Levetiracetam appears to be a useful antimyoclonic agent in cases of progressive myoclonic epilepsy and should be considered for adjunctive therapy.

Radial nerve F-waves: normative values with surface recording from the extensor indicis muscle.

OBJECTIVES In the present study we set out to obtain normative values for radial nerve F-waves, with surface recording from the extensor indicis muscle. METHODS Forty-nine patients with unrelated complaints were tested. Surface recording electrodes were placed on the extensor indicis muscle. This was found by asking the patient to extend the second digit against resistance. The active surface recording electrode was placed over the most distal portion of the muscle, near the radial border of the ulnar bone near the wrist. Stimulation was performed near the lateral epicondyle between the radial and ulnar bones. RESULTS The mean F-wave minimum latency was found to be 20.55 ms, with an upper limit of 24.35 ms. The absolute interside minimum latency difference was found to have a mean of 0.55 ms, with a maximum of 1.7 ms. The mean amplitude of the F-waves was 145.61 microV and the mean mF/M ratio was 0.022. F-waves were unobtainable in 2/62 (3.2%) of limbs. Normative values for the radial nerve motor response were also obtained. Three cases are described to illustrate the usefulness of the above technique. CONCLUSIONS It is technically feasible to record radial nerve F-waves from the extensor indicis muscle.

Brainstem lesions may be important in the development of epilepsy in multiple sclerosis patients: an evoked potential study.

OBJECTIVE Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, with epileptic seizures sometimes observed in the same patients. In this study, we used evoked responses to study the pathogenesis of epilepsy in MS. METHODS Patients with a diagnosis of definite MS and who had EPs performed (visual (VEP), brainstem auditory (BAEP) and short latency somatosensory (upper (USSEP) and lower (LSSEP))) were retrospectively included in this study. They were divided into three groups; Group I: Patients with no epilepsy and who were not taking anti-epileptic drugs (AED); Group II: Patients with epilepsy and taking AEDs; and Group III: Patients with no epilepsy who were taking AEDs for symptoms related to neuropathic pain. RESULTS Three hundred and fifty-five patients were included in this study; Group I: 229 patients (64.5%), Group II: 20 patients (5.6%) and Group III: 106 patients (29.9%). The proportion of patients with abnormal BAEP and USSEP was higher in Group II. CONCLUSIONS A positive association exists between the presence of epilepsy in MS patients and BAEP and USSEP abnormalities. Analysis of Group III ruled out AED use as a factor. SIGNIFICANCE Brainstem lesions may be the cause of epileptogenicity in MS.

Tuberous sclerosis successfully treated with levetiracetam monotherapy: 18 months of follow-up

CaseWe present the case of a boy with tuberous sclerosis who was referred for evaluation and treatment of his intractable epileptic seizures, having failed multiple anti-epileptic drug trials. He was subsequently treated with Levetiracetam that was gradually titrated to an effective dose, achieving full suppression of his seizures. Thereafter, his concomitant anti-epileptic drugs were gradually reduced and eventually discontinued. He remained on monotherapy with Levetiracetam, which continued to fully control his seizures. His EEG tracings before and after treatment are presented and compared, showing normalization of the latter.ConclusionLevetiracetam appears to be effective in treatment-resistant seizures which are symptomatic to tuberous sclerosis when used adjunctively as well as in monotherapy. This is the first report in the English literature regarding its use and efficacy in this condition.