BRIEF COMMUNICATION

Gelastic seizures: Incidence, clinical and EEG features in adult patients undergoing video-EEG telemetry *†Stjepana Kovac, *†Beate Diehl, *†Tim Wehner, *‡Chiara Fois, †Nathan Toms, *Matthew C. Walker, and *John S. Duncan Epilepsia, **(*):1–5, 2014 doi: 10.1111/epi.12868

SUMMARY

Dr. Stjepana Kovac has a special interest in clinical and experimental epilepsy.

This study aimed to determine clinical features of adult patients with gelastic seizures recorded on video –electroencephalography (EEG) over a 5-year period. We screened video-EEG telemetry reports for the occurrence of the term “gelastic” seizures, and assessed the semiology, EEG features, and duration of those seizures. Gelastic seizures were identified in 19 (0.8%) of 2,446 admissions. The presumed epileptogenic zone was in the hypothalamus in one third of the cases, temporal lobe epilepsy was diagnosed in another third, and the remainder of the cases presenting with gelastic seizures were classified as frontal, parietal lobe epilepsy or remained undetermined or were multifocal. Gelastic seizures were embedded in a semiology, with part of the seizure showing features of automotor seizures. A small proportion of patients underwent epilepsy surgery. Outcome of epilepsy surgery was related to the underlying pathology; two patients with hippocampal sclerosis had good outcomes following temporal lobe resection and one of four patients with hypothalamic hamartomas undergoing gamma knife surgery had a good outcome. KEY WORDS: Gelastic seizures, Hypothalamic hamartoma, Temporal lobe epilepsy, Epilepsy surgery.

Gelastic seizures are the hallmark of seizures arising from the hypothalamus, with hypothalamic hamartoma being the most frequent underlying pathology.1 Such seizure types are rare and are more likely to be diagnosed in childhood. Gelastic seizures in the setting of hypothalamic hamartomas are associated with childhood onset, intractable seizures, precocious puberty and, commonly, cognitive impairment.1 Functional imaging studies and intracranial electroencephalography (EEG) recordings have shown that seizures originate in the hamartomas.2,3 Recent reports have indicated that there is secondary independent epileptogenesis, 4 which is facilitated by the

plethora of connections between the hypothalamus and other brain areas, particularly the temporal lobe. The hypothalamus is unlikely to be the symptomatogenic zone of gelastic seizures, as laughter and mirth involves a complex brain network involving the cingulate and basal temporal cortex.5 This contention is supported by the fact that gelastic seizures are seen not only with hypothalamic hamartomas, but also with seizures arising from the temporal and frontal lobes.6–8 Most of these cases, with gelastic seizures arising from brain structures other than the hypothalamus, have been reported in adults. Case series of gelastic seizures in an adult cohort are lacking, and it remains to be determined whether hypothalamic hamartomas are the leading underlying pathology, and whether adults with gelastic seizures and hypothalamic hamartomas have secondary epileptogenic zones. Such information would be important, since it would prompt (1) more careful evaluation in adults with gelastic seizures and hypothalamic hamartomas and (2) would lead to a better understanding of brain areas involved in gelastic seizures.

Accepted October 13, 2014. *Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, United Kingdom; †Department of Clinical Neurophysiology, National Hospital for Neurology and Neurosurgery, London, United Kingdom; and ‡Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy Address correspondence to Stjepana Kovac, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, WC1N 3BG London, U.K. E-mail: [email protected] Wiley Periodicals, Inc. © 2014 International League Against Epilepsy

1

2 S. Kovac et al. We aimed to quantify the occurrence of gelastic seizures in adult patients admitted for video-EEG telemetry, and to describe the semiologic and EEG features of gelastic seizures.

Methods We retrospectively reviewed all telemetry reports over a 5-year period (03/2008–03/2013) for the occurrence of the term “gelastic” in the text body. The clinical records of patients with gelastic seizures were analyzed to determine magnetic resonance imaging (MRI) findings and whether patients had epilepsy surgery and the outcomes of epilepsy surgery. Classification of the epilepsy type and presumed epileptogenic zone was based on the multidisciplinary team discussion that was held after the patient underwent telemetry and comprehensive neuroimaging including MRI in all, and optional positron emission tomography (PET) and single-photon emission computed tomography (SPECT). Videos of gelastic seizures were reviewed and the duration of the gelastic component within the seizure was analyzed. Statistical analyses were performed with SPSS (IBM SPSS 21.0; Chicago, IL, U.S.A.). We computed MannWhitney U-tests to compare continuous variables. All data are presented as median and range, with a significance level of p < 0.05. This study was part of an audit assessing presurgical evaluation practice in a tertiary referral center.

Results A total of 2,446 admissions to the Jules Thorn telemetry unit were identified in the 5-year study period. In 19 subjects (8 female; 0.8%), the occurrence of gelastic seizures, either as part of the reported video-EEG telemetry or as a historic feature including seizures that have occurred in the patient’s past were noted in the telemetry report. Of those patients, seven had hypothalamic epilepsy (hypothalamic hamartomas), six temporal lobe epilepsy (four mesial TLE, one neocortical TLE, one unspecified TLE), one patient had frontal lobe epilepsy, and one had parietal lobe epilepsy. Seizures in one patient were classified as left hemispheric and in another patient as multifocal. Epilepsy side was classified as left in seven, right in three, hypothalamic in six, and remained undetermined in three patients. Median age at admission was 35 years (range 19–53 years); median age at onset was 12 (range 2–48 years). There was no significant difference between age at admission between patients with hypothalamic epilepsy and patients with other types of epilepsy. Median age at onset of epilepsy was earlier in patients with epilepsy and hypothalamic hamartoma than in patients with other epilepsies (5 vs. 15; p < 0.01). A lesion on MRI was found in 12 patients, with hypothalamic hamartomas (n = 7; Fig. S1B–D) and hippocampal sclerosis (n = 3; Fig. Epilepsia, **(*):1–5, 2014 doi: 10.1111/epi.12868

S1A) as the most frequent lesion types. One patient showed dual pathology on MRI (hypothalamic hamartoma and focal cortical dysplasia [FCD]), and one had a parietal FCD only (Fig. S1E,F). Two patients, one with hippocampal sclerosis and one with nonlesional mesial temporal lobe epilepsy, underwent temporal lobe resections with excellent outcomes (International League Against Epilepsy [ILAE class 1]; Table 1). Four patients with hypothalamic hamartomas underwent gamma knife surgery, with unfavorable outcomes in three patients (ILAE class 5) and a good outcome in one (ILAE class 1; Table 1). In 12 of the 19 patients, at least one gelastic seizure was recorded during video-EEG telemetry. In the remaining seven, gelastic seizures were reported as part of the patients’ past seizure semiology (n = 4) or were ongoing seizure types, but were not recorded during video-EEG telemetry (n = 3). Gelastic seizures were not an isolated seizure type but were embedded in a seizure semiology and were preceded or followed by automotor seizures in half of the cases (6/12) recorded (Table 2). Video analysis showed that the duration of the gelastic phase within the seizure semiology varied from 2 to 40 s (Table 2). Gelastic seizures were the presenting feature of the initial seizure semiology in three patients. In patients with hypothalamic hamartomas, the gelastic phase was first in one of the three cases identified, whereas in patients with pathology other than hypothalamic hamartoma the gelastic phase was leading in two of nine cases (Table 2). Interictal nonepileptiform EEG changes were found in all apart from two cases, and consisted of intermittent slow activity, and in two cases of background slow activity. Interictal epileptiform activity, that is, sharp waves and spikes, was recorded in all 12 cases. Ictal patterns were regional in 7 of 12, lateralized to one hemisphere in 1 of 12, generalized in 2 of 12, and nonlocalizable in 2 of 12 cases. Of note, of the three patients with hypothalamic hamartomas two had nonlocalizable and one had generalized ictal EEG patterns.

Discussion Very little is known about the incidence of gelastic seizures in an adult population. Hypothalamic hamartoma is the core pathology observed in gelastic seizures in pediatric case series, in which gelastic seizures are often combined with precocious puberty, refractory seizures, and cognitive and behavioral impairment.9 Seizure semiology in hypothalamic hamartoma has been studied in detail and gelastic seizures were found to be the dominant seizure type in the pediatric population, whereas in adult patients other seizure types such as auras and behavioral arrest were seen in addition to gelastic seizures,10 highlighting differences in semiologic presentations depending on the age group. In our selected series of individuals referred for video-EEG telemetry, we found a prevalence of gelastic seizures of

3 Gelastic Seizures in Adults Table 1. Clinical characteristics of patients presenting with gelastic seizures Age at onset of epilepsy (years)

Type of epilepsy/ presumed epileptogenic zone

Gelastic seizures ongoing; Y/N

MRI lesion

Side of epilepsy (R/L/H/U)

No

Age (sex)

1 2

38 (M) 40 (M)

30 2

Mesial TLE Hypothalamic

Ya Ya

Right HS HH

R H

3 4

44 (M) 25 (F)

12 15

Mesial TLE Undetermined

Ya N

L U

5 6

35 (M) 23 (F)

11 2

Hypothalamic Hypothalamic

N Ya

Left HS Right temporal FCD; HH HH HH

7 8 9 10

42 (M) 31 (F) 27 (F) 38 (M)

8 2 15 18

Hypothalamic Hypothalamic Neocortical TLE Undetermined

N Y Ya Ya

HH HH No lesion No lesion

H H L L

11

35 (M)

19

Mesial TLE

Ya

No lesion

L

12 13 14

19 (F) 36 (M) b 26 (M) b

11

Hypothalamic Mesial TLE Hypothalamic

Ya N Y

HH L HS HH

U L H

15

38 (M)

14

FLE

Ya

No lesion

L

16

23 (M)

7

Multifocal

Ya

No lesion

U

17

35 (F)

12

Unspecified TLE

Y

No lesion

R

18

53 (F)

48

L hemispheric

Ya

No lesion

L

19

37 (F)

15

PLE

Ya

R FCD

R

H H

Surgery/radiotherapy

Pathology

Outcome ILAE; (follow-up/years)

Patient declined surgery Gamma knife recommended; lost to follow-up L temporal lobectomy No surgery; infrequent seizures

N/A N/A

N/A N/A

HS N/A

1 (5) N/A

Gamma knife Gamma knife recommended; lost to follow-up Gamma knife Gamma knife No surgery; lost to follow up No surgery; no clear focus identified No surgical candidate (drug trials ongoing) Gamma knife Left temporal lobectomy Gamma knife recommended; patient denied Presurgical investigations ongoing No surgery; no clear focus identified No surgery; patient does not want to proceed to intracranial investigations No surgery; no clear focus identified Not yet; on waiting list

N/A N/A

5 (2) N/A

N/A N/A N/A N/A

5 (3) 5 (3) N/A N/A

N/A

N/A

N/A HS N/A

1 (2) 1 (1) N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

TLE, temporal lobe epilepsy; FLE, frontal lobe epilepsy; PLE, parietal lobe epilepsy; HH, hypothalamic hamartoma; HS, hippocampal sclerosis; FCD, focal cortical dysplasia; L, left; R, right; H, hypothalamic; U, undetermined. a Gelastic seizure (SZ) recorded during current admission. b SZ started in infancy.

0.8%; this seizure type therefore represents a rare entity in adult cohorts, similar to dacrystic seizures.11 Hypothalamic hamartomas were seen in approximately one third of our cases, and another third had temporal lobe epilepsy. A recent study has investigated gelastic seizures of cortical origin excluding hypothalamic hamartoma in an adult cohort. Of interest, the prevalence of gelastic seizures parallels our findings.12 Previous studies have suggested that the temporal lobe is involved in the network-generating laughter. This was concluded from cortical stimulation in patients undergoing invasive EEG recordings for pharmacoresistant epilepsy.5 Stimulation of the temporal lobe induced laughter with mirth. In our case series, gelastic seizures in temporal lobe epilepsy were embedded in a seizure semiology of automotor seizures with loss of consciousness, and therefore we were unable to determine whether seizures were mirthful. Frontal lobe epilepsy was found in only one case in this

series. The frontal lobe has been shown to be involved in the motor aspect of laughter, with a nonemotionally driven pathway involving anterior cingulate, premotor frontal, and opercular areas with projections through the motor cortex directly to the ventral brainstem.13 Gelastic seizures in our case series were not related to generalized epilepsy and therefore gelastic seizures as a part of semiology helps to differentiate between generalized and focal or multifocal epilepsy. Epilepsy surgery/gamma knife was performed in six cases, four with hypothalamic hamartoma had gamma knife treatment and two with hippocampal sclerosis had temporal lobe resections. Given the small numbers, it is difficult to comment on outcomes, but both patients with temporal lobe resections had good outcomes (ILAE 1) concordant with previous results published from our group,14 whereas gamma knife surgery in hypothalamic hamartomas was Epilepsia, **(*):1–5, 2014 doi: 10.1111/epi.12868

Epilepsia, **(*):1–5, 2014 doi: 10.1111/epi.12868

Mesial TLE Hypothalamic

Mesial TLE Hypothalamic

Neocortical TLE

Undetermined

Mesial TLE

Hypothalamic

FLE

Multifocal

L hemispheric

PLE

Pt. no.

1 2

3 6

9

10

11

12

15

16

18

19

4

1

4

20

>100

4

1

2

1

3

Cluster

6 1

3 20

Gelastic seizures recorded

10

4

1

3

Cluster

6 7

3 20

Total seizures recorded

2

2

10

20

Automotor SZ > gelastic SZ > dialeptic SZ > L eye versive SZ Automotor SZ > gelastic SZ Automotor SZ > gelastic SZ

Complex motor SZ > gelastic/hyperkinetic SZ 1. Bilateral symmetric tonic SZ > Gelastic SZ 2. Bilateral symmetric tonic SZ > axial clonic SZ > gelastic SZ R face tonic > gelastic seizure > complex motor SZ Complex motor SZ > gelastic SZ

3

Automotor SZ > gelastic SZ

3

14

6

4 7

2 40

Gelastic SZ > Automotor SZ 1. Gelastic SZ > L face somatosensory aura 2. Gelastic SZ > Axial tonic seizure Gelastic SZ > automotor SZ Unclassified SZ > gelastic SZ

Semiology gelastic SZ

Duration gelastic phase (s)

TLE, temporal lobe epilepsy; FLE, frontal lobe epilepsy; PLE, parietal lobe epilepsy; SZ, seizure; SW, sharp wave; L, left; R, right.

Type of epilepsy/ presumed epileptogenic zone

Intermittent slow, regional

Intermittent slow, regional

Intermittent slow, regional Background slow

Intermittent rhythmic slow, regional Intermittent slow, regional

Intermittent slow, regional Intermittent rhythmic slow, regional

None Background slow

None Intermittent slow, generalized and regional

EEG, interictal nonepileptiform

Table 2. Video and EEG analysis of gelastic seizures

L frontotemporal SWs > bi frontal SWs R frontotemporal SWs L frontotemporal SWs

L temporal or frontotemporal SWs > R temporal or frontotemporal SWs L temporal and L frontotemporal spikes and SWs > R temporal spikes L hemisphere spikes and SWs, (max. temporal) R hemisphere spikes and SWs, (max. temporal) L frontotemporal SWs R frontotemporal SWs Generalized spikes and SWs; spikes in multiple regions

L temporal Generalized

Temporal SWs (L > R) Generalized Spike and wave, generalized polyspike and wave > R temporal SWs L temporal SWs

Vertex, R > L

Nonlocalizable L hemispheric

L temporal Nonlocalizable Generalized

Nonlocalizable

L temporal

L mid to posterior temporal

L posterior temporal

R temporal Nonlocalizable

EEG, ictal

Temporal SWs (L > R) R frontotemporal SWs

EEG, interictal epileptiform

4

S. Kovac et al.

5 Gelastic Seizures in Adults associated with a good outcome in one of four patients (Table 1). One of the largest series of gamma knife surgery in hypothalamic hamartomas reported favorable outcomes, with only rare or nondisabling seizures on follow up in ~60%.15

Conclusion Gelastic seizures in adults are associated with pathologies other than hypothalamic hamartomas, and temporal lobe epilepsy is as frequent in adults with gelastic seizures as in adults with hypothalamic hamartomas. Gelastic seizures are often embedded in a semiology of other seizure types, and outcome of epilepsy surgery depends on the underlying pathology.

Acknowledgments This work was undertaken at University College London Hospitals/ University College London who receives a proportion of funding from the Department of Health National Institute for Health Research Biomedical Research Centres’ funding scheme.

Disclosure None of the authors has any conflict of interest to disclose. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

References 1. Striano S, Striano P, Coppola A, et al. The syndrome gelastic seizureshypothalamic hamartoma: severe, potentially reversible encephalopathy. Epilepsia 2009;50 (Suppl. 5):62–65. 2. Munari C, Kahane P, Francione S, et al. Role of the hypothalamic hamartoma in the genesis of gelastic fits (a video-stereo-EEG study). Electroencephalogr Clin Neurophysiol 1995;95:154–160. 3. Leal AJR, Monteiro JP, Secca MF, et al. Functional brain mapping of ictal activity in gelastic epilepsy associated with hypothalamic hamartoma: a case report. Epilepsia 2009;50:1624–1631.

4. Scholly J, Valenti M-P, Staack AM, et al. Hypothalamic hamartoma: is the epileptogenic zone always hypothalamic? Arguments for independent (third stage) secondary epileptogenesis. Epilepsia 2013;54 (Suppl. 9):123–128. 5. Arroyo S, Lesser RP, Gordon B, et al. Mirth, laughter and gelastic seizures. Brain 1993;116:757–780. 6. Dericioglu N, Cataltepe O, Tezel GG, et al. Gelastic seizures due to right temporal cortical dysplasia. Epileptic Disord 2005;7:137–141. 7. Kovac S, Deppe M, Mohammadi S, et al. Gelastic seizures: a case of lateral frontal lobe epilepsy and review of the literature. Epilepsy Behav 2009;15:249–253. 8. Unnwongse K, Wehner T, Bingaman W, et al. Gelastic seizures and the anteromesial frontal lobe: a case report and review of intracranial EEG recording and electrocortical stimulation case studies. Epilepsia 2010;51:2195–2198. 9. Berkovic SF, Arzimanoglou A, Kuzniecky R, et al. Hypothalamic hamartoma and seizures: a treatable epileptic encephalopathy. Epilepsia 2003;44:969–973. 10. Oehl B, Brandt A, Fauser S, et al. Semiologic aspects of epileptic seizures in 31 patients with hypothalamic hamartoma. Epilepsia 2010;51:2116–2123. 11. Blumberg J, Fernandez IS, Vendrame M, et al. Dacrystic seizures: demographic, semiologic, and etiologic insights from a multicenter study in long-term video-EEG monitoring units. Epilepsia 2012;53:1810–1819. 12. Tran TPY, Truong VT, Wilk M, et al. Different localizations underlying cortical gelastic epilepsy: case series and review of literature. Epilepsy Behav 2014;35:34–41. 13. Wild B, Rodden FA, Grodd W, et al. Neural correlates of laughter and humour. Brain 2003;126:2121–2138. 14. De Tisi J, Bell GS, Peacock JL, et al. The long-term outcome of adult epilepsy surgery, patterns of seizure remission, and relapse: a cohort study. Lancet 2011;378:1388–1395. 15. Regis J, Scavarda D, Tamura M, et al. Epilepsy related to hypothalamic hamartomas: surgical management with special reference to gamma knife surgery. Childs Nerv Syst 2006;22:881–895.

Supporting Information Additional Supporting Information may be found in the online version of this article: Figure S1. Imaging findings in patients presenting with gelastic seizures.

Epilepsia, **(*):1–5, 2014 doi: 10.1111/epi.12868

Gelastic seizures: incidence, clinical and EEG features in adult patients undergoing video-EEG telemetry.

This study aimed to determine clinical features of adult patients with gelastic seizures recorded on video -electroencephalography (EEG) over a 5-year...
105KB Sizes 0 Downloads 6 Views