EPILEPSY AND VESTIBULAR SYSTEM

Vertiginous Epilepsy: Documentation of Clinical and Electrophysiological Findings of Nine Patients

Reyhan Surmeli, Ayse Destina Yalcin, Mehmet Surmeli, Gozde Gunay

ABSTRACT

Aim: Epileptic vertigo is often a diagnostic problem. We aimed to present the clinical and electrophysiological features of patients with epileptic vertigo and attempted to explain the pathophysiology of this rare aura symptom.

Patients and Methods: Nine epileptic vertigo patients were included in the study. All patients were subjected to neuro-otologic examination, interictal electroencephalogram (EEG), audiogram, cervical vestibular evoked myogenic potential test (cVEMP), video head impulse test (vHIT) and brain magnetic resonance imaging (MRI).

Results: Eight patients were describing their aura as epileptic vertigo and one as dizziness. In three patients auditory hallucinations preceded epileptic vertigo. Semiology of epileptic vertigo was true vertigo in five patients, vertigo with nausea in two patients and vertigo with hearing loss in one patient. Two patients were suffering from focal seizures, in seven patients the seizures evaluated to focal to bilateral tonic-clonic seizures. MRI was normal in all patients. EEG was abnormal in all cases, showed high voltage spike or spike-slow wave complexes or both located more frequently in temporal region and more left than right. In vHIT examination abnormal responses were recorded bilateral or unilateral in five patients. Similarly, cVEMP revealed no response bilateral or unilateral in five patients. In three patients the side of none response of cVEMP was in line with the side of epileptiform pathology in EEG. Two patients with bilateral abnormalities in EEG showed bilateral abnormalities either in cVEMP or in vHIT or in both of them.

All of these findings support the involvement of the brainstem connections of the peripheral vestibular system in patients with vertiginous epilepsy.

Conclusion: The pathological results of vestibular tests in the majority of our patient combined with EEG abnormalities can be interpreted as a supporting data on the hypothesis of system epilepsies which is based on the dysfunction of specific neural systems.

INTRODUCTION

Vertigo is defined as a sense of self-movement when no self-movement occurs, or otherwise a distorted sense of self-movement during a normal head movement. Non-vertiginous dizziness is described as the sensation of disturbed or impaired spatial orientation feeling without a false or distorted sense of motion (Bisdorff et al., 2009).

Epileptic vertigo is a rare form of focal seizures, frequently presenting as an aura symptom. The episodes usually last for a few seconds to minutes; unconsciousness may follow when the seizure spreads (Kluge et al., 2000). Epileptic vertigo is thought to result from abnormal stimulation of central vestibular cortical structures such as the parietal, temporal and frontal cortex. These specific cortical areas include the superior lip of the intraparietal sulcus, the posterior superior temporal lobe, the posterior medial parietal lobe, the temporal parietal border regions, and frontal cortex -- left middle frontal gyrus (Kluge et al., 2000; Wiest et al., 2004; Blanke et al., 2000; Kahane et al., 2003). In addition, it was stated that vestibular sensations developed by stimulating in the occipital, frontal and insular cortex (Kahane et al., 2003).

Epileptic vertigo is often a diagnostic problem when vestibular symptoms are not accompanied by symptoms and signs associated with classic focal or generalized seizures. Epileptic vertigo is easily recognized in the presence of classic seizure-related symptoms and signs such as automatism, twitching or convulsion accompanying vestibular symptoms. Epileptic vertigo with isolated vestibular symptoms was already reported (Kluge et al., 2000; Wiest et al., 2004), however, there is limited information on the prevalence, clinical and electrophysiological features of this rare aura symptom. Useful diagnostic tests for epileptic vertigo are electroencephalography (EEG) and brain magnetic resonance imaging (MRI).

In this study, we aimed to present the clinical and electrophysiological findings of nine patients with epileptic vertigo and attempted to explore the pathophysiology of epileptic vertigo analyzing the EEG findings together with the results of vestibular tests.

MATERIALS and METHODS

Until January 2012, we had diagnosed four patients with vertiginous epilepsy in our epilepsy clinic of a tertiary center (University of Health Sciences, Umraniye Training and Research Hospital, Department of Neurology, Epilepsy Section Istanbul, Turkey) and then we started a prospective study for these patients in order to detect their clinical and electrophysiological features. Aura and ictal symptomatology were assessed from the patients’ own description and their first grade relatives who had observed their seizures. In all cases, a thorough neuro-ophthalmologic and neuro-otologic clinical examination was performed by two of the authors (ADY or RS, and MS), including description of nystagmus, and positive or negative video head impulse test (vHIT), presence of a typically biphasic shape in cervical vestibular evoked myogenic potential test (cVEMP). In addition, all patients underwent neuroimaging and periodically repeating EEG examination.

After the patients gave their informed consent, they underwent video-EEG investigation with a 32 channel device (Micromed, Italy) for routine EEG recording during interictal period. The electrodes were placed according to the international 10-20 system, and both bipolar and referential montages were used. EEG tests were performed for at least 30 minutes in an environment with favorable conditions. All patients underwent intermittent photic stimulation, hyperventilation for 5 minutes and eye opening and closing reactions were examined. EEG interpretation was performed in longitudinal, transverse and other appropriate montages.

Brain imaging of all patients was performed with 1.5T MRI scanner (Siemens Healthcare, Erlangen, Germany).

v-HIT recordings were performed with the EyeSeeCam system (Interacoustics a/s, Middelfart, Denmark). For the recording, a light and tightly fitting glasses were used, on which a small video camera and a half-silver mirror reflecting the eye image (left side) were mounted. Patients were asked to pin to the target, which was placed on the wall at a distance of 1.2 meters. Calibration was performed prior to each recording. For the test, head impulse at the velocity of 1500 - 2000/s was applied to 15-20 degrees lateral side of the midline along both lateral semicircular canal axles in an unpredictable manner. Fifteen records were held separately on each side. VOR Gains at 40-60 and 80 ms were recorded. Mean VOR Gain at 60 ms was taken for evaluation. Normal values for VOR Gain were considered 0.8-1.2.

c-VEMP recordings were performed with an evoked potentials machine (Eclipse EP- 25/VEMP; Interacoustics, Denmark). The active electrode is placed in the middle of the same sternocleidomastoid (SCM) muscle, the upper 2/3 of the reference electrode SCM, and the centering electrode in the middle of the forehead. The test was performed once in a silent environment and sitting position with each patient awake. Warning was obtained from the right and left ear, and ipsilateral records were obtained. Electrode impedance was <5 kΩ. The acoustic was 100dB for 0.1 ms and was delivered to each ear separately at 5 Hz. The EMG signal was filtered in the range of 10 to 500 Hz and averaged over a 100 ms interval. Average of a total of 200 results. P13 and N23 positive / negative polarity were measured as peak waves. P13 and N23 peak latencies and P13-N23 inter- peak amplitudes were calculated.

vHIT and cVEMP recordings were evaluated in interictal period in all patients.

Case 1 (39 years old, male)

He visited our epilepsy outpatient department after his second generalized seizure and was suffering from focal seizures since he was 15 years old which started with a rotatory sensation of the environment in horizontal plane, lasting approximately for 10-20 seconds, followed by hyper-salivation causing drip of saliva from the right edge of his mouth and deviation of his eyes and head to the right side. He had more than 10 seizures in the previous month before his application and two of them were focal to bilateral tonic-clonic seizures. He was also describing some episodes lasting longer than one hour, characterized by his aura symptoms which were interpreted as non-convulsive status epilepticus episodes. His repeated EEGs showed sharp-slow wave activity located in both posterior temporal regions which were more prominent on the left side. In the follow-up period lasting 24 years, he was seizure free first under carbamazepine (CBZ) and later levetiracetam (LEV) monotherapy but had a relapse as we attempted to reduce his CBZ dosage. vHIT and cVEMP responses were evaluated as bilaterally normal (Table 3).

Case 2 (42 years old, male)

He was referred to our epilepsy outpatient department because of his pathological EEG findings. When he was twenty years old he began to complain about a strange sound like a running machine in his right ear, rising in intensity, and then heard it on the left side, followed by rotation of the environment in vertical plane up and down, and nausea. The whole episode was lasting for approximately one minute. Also he had focal to bilateral tonic-clonic seizures frequently during Ramadan when he was fasting. In the follow-up period lasting twenty years, he had one convulsive status epilepticus in Ramadan probably because of long lasting starvation and impaired sleep rhythm. He had spike-wave complexes in the left temporal region in line with his ictal symptoms in the right ear. Under 800 mg per day CBZ treatment he has no seizure. vHIT and cVEMP responses were evaluated as bilaterally normal (Table 3).

Case 3 (36 years old, male)

He was suffering from a strange sound in his right ear describing it like the sound when one dives deep under the water. The sound was becoming louder, passing over to the left side accompanied by rotatory sensation of the environment. The duration was a few seconds. These attacks began when he was 24 years old and repeated one or two times weekly. He was examined by many otologists, took different medications but his complaints continued. After a head trauma caused by an attack, he was examined by our team in the emergency department and diagnosed with epilepsy. His repeated EEG’s revealed spike-wave activity in the left temporal region in accordance with the initial auditory ictal symptoms in the right ear. Under 1250 mg LEV treatment he is seizure free for 9 years. vHIT response was evaluated as bilaterally normal. However, there was no cVEMP response on the left side. (Table 3).

Case 4 (36 years old, female)

She was referred to our epilepsy outpatient department by an otologist for consultation. She was describing a strange motion sensation inside her head like swinging on a ship in stormy weather, repeating many times daily for six months, and lasting for 10-20 seconds. Her EEG showed high voltage sharp wave activity on the left temporal region which was enhanced during hyperventilation. She did not have any generalized convulsion and is seizure free under 1000 mg LEV treatment for five years. vHIT was evaluated as bilaterally abnormal. Additionally, there was no cVEMP response on the left side. (Table 3).

Case 5 (30 years old, male)

He sought medical advice when he was 17 years old because of repeated focal to bilateral tonic-clonic seizures during the last two years. He described nausea, a rotatory sensation of the environment from right to left, deviation of his eyes and head to the left side and drawing a half circle with his trunk to the left side. After these symptoms, he was losing consciousness. His repeated EEG’s delineated high voltage sharp-slow wave activity in both temporal regions extending to parietal. Under 1000 mg LEV treatment his seizures did not repeat during follow-up period lasting 15 years. vHIT was evaluated as bilaterally abnormal. Additionally, cVEMP test, there was no response bilaterally (Table 3).

Case 6 (28 years old, female)

She described three episodes in the last year which started with urgency sensation waking her in the middle of the night, followed by sliding of the objects seen in horizontal plane from left to right and loss of consciousness. On the last episode she fell down and got injured. Her subsequent EEG’s in the follow-up period lasting 8 years, showed sharp-slow wave complexes in both temporal region appearing independently from each other. Under oxcarbazepine treatment (900 mg/day) she is seizure free. vHIT was evaluated as bilaterally abnormal. However, cVEMP response was evaluated as bilaterally normal (Table 3).

Case 7 (53 years old, female)

She was complaining of episodes characterized by rotatory sensation inside her head, followed by total loss of hearing. Some of these attacks were associated with loss of consciousness and injured her. She was suffering from these attacks since she was 28 years old and was sent to psychiatrists because her episodes were interpreted as psychological. She was referred to our epilepsy outpatient department after she fell down from the ladder and got injured during an attack. Her EEGs showed high voltage sharp-slow wave activity on the left temporal region which was increased during hyperventilation. She is seizure free under valproate (1000 mg/day) treatment for five years. vHIT was evaluated on the right side as abnormal. cVEMP test, there was no response bilaterally (Table 3).

Case 8 (45 years old, female)

She was seen in our emergency department after her third focal to bilateral tonic-clonic seizures. Her medical history included nearly identical episodes which started in her childhood and were characterized by dizziness sensation, unsteadiness, nausea, vomiting, excessive sweating lasting a few minutes and ending with falling asleep. Her seizure frequency was a few per year and she had three focal to bilateral tonic-clonic seizures each starting with her aura symptoms appearing in her focal seizures. She did not go to any doctor for these attacks. Her EEG’s showed sharp-slow wave complexes in the right temporal region. Under LEV treatment (1000 mg/day) she is seizure free for 15 years. vHIT was evaluated on the right side as abnormal. Additionally, cVEMP test, there was no response on the right side (Table 3).

Case 9 (25 years old, female)

She was suffering from a crackling sound in her right ear, increasing in intensity, accompanied with rotatory sensation inside her head lasting almost one minute for two years. The frequency of the attacks was two or three times per month. She explained these complaints with tiredness. In the last two attacks, she lost consciousness and was referred to our epilepsy department with possible diagnosis of epilepsy when she was twenty years old. Her repeated EEG’s showed high voltage sharp waves in the left temporal region and generalized spike-wave discharges during hyperventilation. She is seizure free under LEV treatment for five years. vHIT and cVEMP responses were evaluated as bilaterally normal (Table 3).

RESULTS

We included 4 male and 5 female patients with a diagnosis of epileptic vertigo in the study. The age of onset ranged between 15 - 31 years and the age on the last examination between 25-53 years. None of our patients had febrile seizure, head trauma, family history of epilepsy or consanguinity.

Eight patients were describing their aura as epileptic vertigo and one as dizziness. In three patients, auditory hallucinations preceded epileptic vertigo. Semiology of epileptic vertigo was true vertigo in 5, vertigo with nausea in 2 and vertigo with hearing loss in one patient. Two patients were suffering from focal seizures and in seven patients the seizures were evaluated as focal bilateral tonic-clonic seizures (Table 1).

EEG was abnormal in all cases, showed high voltage spike or spike-slow wave complexes or both located in left temporal region in 4 (44%), %), bitemporal in 2 (22%), right temporal in 1 (11%), left temporal with secondary generalization in 1 (11%), bitemporoparietal in 1 (11%) (Table 2) (Figure1).

In vHIT examination abnormal responses were recorded in 5 (55.5%), bilateral in 3 (case 4,5,6) and unilateral in 2 (case 7,8) patients. Similarly, cVEMP revealed no response in 5 (55.5%), bilateral in 2 (case 5,7) and unilateral in 3 (case 3,4,8) patients (Table 3). In three patients the side of none response of cVEMP was in line with the side of epileptiform pathology in EEG (cases 3,4,8). Two patients with bilateral abnormalities in EEG located in temporal and temporoparietal regions (cases 5,6) showed bilateral abnormalities either in cVEMP or in vHIT or in both of them (Table 3).

MRI of brain was normal in all patients.

DISCUSSION

Vertigo as a manifestation of epilepsy was first described by Hughlings Jackson (Kogeorgos et al., 1981). Today it is well known that the possibility of brief episodes of vertigo may be due to epilepsy and that 19% of temporal lobe epilepsy presents by vertigo only (Pedersen and Epson, 1956; Erbayat Altay et al., 2005).

There is no valid information supporting the genetic transition in epileptic vertigo. In limited patient series and in a small number of cases, the presence of epilepsy in the family has been reported (Saad et al., 2011). None of our cases had a family history of epilepsy.

Vertigo alone may be an aura. Also, epileptic vertigo is sometimes preceded by other aura symptoms as described by 3 of our patients (33%) as sounds of running machine, diving deep under the water and crackling. These findings are compatible with previous studies (Kluge et al., 2000; Hughes and Drachman, 1977).

Isolated epileptic vertigo is less common than non-isolated epileptic vertigo. There is no diagnostic parameter specific to epileptic vertigo. Therefore, it takes a long time to establish the correct diagnosis like some of our patients. Two of our cases were evaluated as isolated epileptic vertigo, which is also correlated with other studies (Ransohoff and Feinstein, 1978; Tarnutzer et al., 2015).

In all patients, vertigo occurred in brief episodes, each lasting for a few seconds to a few minutes. In two cases with isolated epileptic vertigo, episodes are most often very brief (lasting seconds) than non-isolated epileptic vertigo.

There is no consensus about the exact location of epileptogenic focus causing epileptic vertigo. In most of the studies temporal lobe was found to be affected. (Saad et al., 2011; Hughes and Drachman, 1977; Ransohoff and Feinstein, 1978; Tarnutzer et al., 2015). In our study, EEG was abnormal in all cases, in the form of focal high voltage spike or spike-slow wave activity, reported mainly in left temporal region (55%). In one study right hemisphere dominance was suggested for epileptic vertigo (Hewett et al., 2011). In another study, no statistically significant differences were found but left hemisphere has been reported to be more common (Tarnutzer et al., 2015). In attempting to identify the accurate cortical area responsible for epileptic vertigo, cortical stimulation was used. As known, it may induce dysfunction rather than a functional activation of the stimulation region. For this reason, the area of vertigo defined by cortical stimulation would not be in line with the symptomatogenic area of the epileptic vertigo. Studies of patients with epileptic vertigo and concurrent EEG monitoring are scarce in the literature. One comprehensive study including 40 patients experienced epileptic vertigo or dizziness as aura revealed five different regions as seizure onset site, even mesial temporal lobe. An intracranial EEG with cortical stimulation was performed in 7 of these 40 patients but in only one patient the area of stimulation induced vertigo overlapped with ictal onset area (Kim et al.,2016).

We found good response rates to antiepileptic drug treatment in all patients with epileptic vertigo. Antiepileptic drugs include carbamazepine, valproate, levetiracetam and oxcarbazepine. In a previous study, antiepileptic drugs response rate in epileptic vertigo was reported to be 90% (Tarnutzer et al., 2015).

Although temporal lobe lesions were reported as underlying causes of epileptic vertigo (Saad et al., 2011), no demonstrable pathology was detected in brain imaging performed in any of our patients.

Further clinical tests that may help to evaluate peripheral vestibular system and central connections are the cVEMP and vHIT. These are useful bedside tests in acute vestibular syndrome patients as they are quick and easy to perform. cVEMP evaluates the vestibulo-collic reflex and is mostly used in peripheral diseases such as acoustic neurinoma, Meniere's disease, but also provides information about the brainstem. vHIT evaluates the gain of vestibulo-ocular reflex (VOR), and the abnormal vHIT is suggested to be the most reliable single tool for prospectively differentiating between central and peripheral causes of acute vestibular syndrome (Newman-Toker et al., 2008). In 55.5% of our cases, unilateral or bilateral abnormalities were observed in vHIT responses. Similarly, cVEMP responses could not be obtained unilateral or bilaterally in 55.5 % of the cases. These findings may support the involvement of the brainstem connections of the peripheral vestibular system in patients with vertiginous epilepsy. Furthermore, in three patients the side of none response of cVEMP was in line with the side of epileptiform pathology in EEG, and two patients with bilateral abnormalities in EEG located in temporal and temporoparietal regions showed bilateral abnormalities either in cVEMP or in vHIT or in both of them. To our opinion, this overlap of EEG abnormalities with pathological cVEMP and vHIT results confirms the dysfunction of vestibular network in patients with epileptic vertigo.

Study limitations: Firstly, it includes only nine patients and we made only video scalp EEG recordings of our patients. Invasive intracranial EEG monitoring is necessary for ictal onset area of epileptic vertigo. Although vertigo was first described in 1981 as a manifestation of epilepsy today there is no consensus about the exact location of epileptogenic focus causing epileptic vertigo. Another important point is to differentiate epileptic and nonepileptic vertigo or dizziness. We believe that a very crucial step for this is to obtain a detailed medical history of the patient as we have done in our cases.

System epilepsies is a new concept proposing novel pathophysiological hypothesis of epilepsy based on an enduring tendency of functionally characterized brain systems to generate seizures. Data supporting this new hypothesis have shown that some types of epilepsy depend on dysfunction of specific neural systems (Avanzini et al., 2012). The pathological results of both vestibular tests in the majority of our patients combined with EEG abnormalities in all of them suggest that epileptic vertigo is a good example of system epilepsies.

There are limited number of studies that investigate pathogenesis in vertiginous epilepsy. Our study is the first study with further vestibular tests in vertiginous epilepsy. Therefore, we believe that it will be a good starting point for discussions on this topic. It may also shed light for future works.

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