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INVITED REVIEW
Year : 2008  |  Volume : 3  |  Issue : 1  |  Page : 88-93
 

Surgical considerations in the management of gelastic seizures


1 Department of Neurosurgery, Bombay Hospital Institute of Medical Sciences and B.J. Wadia Hospital for Children, Mumbai - 400 012, India
2 Department of Paediatric Neurosurgery, Bombay Hospital Institute of Medical Sciences and B.J. Wadia Hospital for Children, Mumbai - 400 012, India

Correspondence Address:
C E Deopujari
Room No. 126-B, 1st Floor MRC, 12, New Marine Lines, Mumbai - 400 020
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1817-1745.40595

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   Abstract 

Gelastic or laughter seizures have been poorly understood but are a classic seizure entity. Though rare, gelastic seizures have been described most often in association with hypothalamic hamartomas. No effective medical therapy is available to control these gelastic seizures and early individualized surgical management remains the mainstay. Current opinion on the pathophysiology, evaluation and current management of the poorly understood entity of gelastic seizures is reviewed along with various surgical procedures for hypothalamic hamartoma.


Keywords: Epilepsy, gelastic seizures, hypothalamic hamartoma


How to cite this article:
Deopujari C E, Suhas U. Surgical considerations in the management of gelastic seizures. J Pediatr Neurosci 2008;3:88-93

How to cite this URL:
Deopujari C E, Suhas U. Surgical considerations in the management of gelastic seizures. J Pediatr Neurosci [serial online] 2008 [cited 2019 Dec 8];3:88-93. Available from: http://www.pediatricneurosciences.com/text.asp?2008/3/1/88/40595



   Introduction Top


Daly and Mulder coined the term "gelastic epilepsy" from the Greek word gelos, laughter, to emphasize the main character of these seizures. [1] The possibility of sudden emotions as a manifestation of an epileptic seizure had been recognized since the end of the 19 th century. These emotions were usually characterized as unpleasant and emotions of fear were most often described. Laughing seizures were first described by Trousseau (1877). Gowers observed emotions "with a cheerful character" as part of a seizure (1881). Since then, an ictal laughing or gelastic seizure has been described in different epileptic conditions associated with the temporal or frontal lobes [2] and most commonly with hypothalamic hamartomas (48%). [3]


   Clinical Features Top


Gascon and Lombroso suggested the following criteria for the diagnosis of gelastic epilepsy: stereotyped recurrence; absence of external precipitants (mirthless laughter); concomitance of other manifestations generally accepted as epileptic; presence of interictal or ictal EEG epileptiform discharges; and absence of conditions in which pathological laughter might occur. [4] Some patients have experienced both gelastic and crying seizures, termed "dacrystic" or "quiritarian" seizures. [5]

Laughter is usually a short manifestation (about 30 seconds), particularly when it occurs as an isolated event. Although inappropriate, it can be so similar to the patient's natural laughter that it can go without diagnosis for a long period of time. Some patients may have an interior feeling of laughter and may not do it overtly. Gelastic seizures associated with hypothalamic hamartoma (HH) often appear several times daily or even hourly. This differs from the less frequently appearing gelastic seizures associated with other localizations. Although occurring frequently, gelastic seizures with HH appear benign in infancy. Subsequently, during school-age years, the seizures usually become more complicated, other seizure types develop and cognitive deterioration occurs. [6] Severe behavior problems are common and the seizures are usually intractable. [7],[8] Adult onset non HH patients have a milder epilepsy syndrome and less severe cognitive and behavioral disturbance. [9]

Gelastic seizures are known to occur in the following syndromes and diseases: hypothalamic hamartoma, frontal lobe epilepsy, temporal lobe epilepsy, epileptic encephalopathy and autistic spectrum disorders. Though rare (0.1%), gelastic seizures have been described most often in association with HHs [Figure - 1]. They are classically seen with HH as a common manifestation (48%) and usually presenting in infancy; a mean age of onset at 2.8 years is reported. [3] Gelastic seizures have also been described as a seizure manifestation in connection with temporal and frontal lobe lesions (tumours, post infectious foci, atrophy, tuberous sclerosis foci, haemangiomas and dilated temporal horns) as well as other foci.

Pathophysiology

The pathogenic mechanisms of gelastic seizures are not fully understood. Both focal spikes and generalized spike-and-wave discharges can be seen, thus indicating the involvement of frontal and temporal lobes as well as subcortical structures. [10] The interictal and ictal EEGs are nonspecific in gelastic seizures. [11] Recently, increasing evidence has indicated that HHs are intrinsically epileptogenic (intrinsic pacemaker like activity - Wu et al. [12] ) and responsible for both pseudotemporal and generalized seizures. Clearer evidence of the intrinsic epileptogenicity of HH emerged from direct recording from the HHs itself. Ictal discharges during gelastic seizures were confined to the hamartoma [13] and direct stimulation of the inserted depth electrodes generated gelastic seizures. [14] Freeman et al. in an analysis of 72 patients with refractory seizures demonstrated the common feature to the involvement of the mamillary region. [15] There have been reports of demonstration of seizure propagation via mamillothalamic tract to anterior nucleus of thalamus, which than projects to anterior cingulate gyrus leading to generation of gelastic seizures. [10] This notion is supported by the prolonged remission of seizures after surgical resection of these lesions. [16] Postictal SPECT has shown a suggested frontal focus to create hypoperfusion in both frontoparietal regions as well as in both cerebellar hemispheres. [17] Cascino and colleagues retrospectively studied 12 patients with gelastic seizures and HH, in which intracranial ECoG recordings performed in 8 patients indicated focal onset of seizures in the anterior temporal lobe in 7 and frontal lobe in 1. [18] None of the 7 patients that underwent a focal cortical resection experienced a significant reduction in seizure activity. Even though much effort has been put into understanding how gelastic seizures are being generated, the relationship between a presumed epileptogenic focus and gelastic fits still remains mysterious. Only one of our patients showed on ictal SPECT hypermetabolism mainly at the cingulate gyrus.

Classification of gelastic seizure

Although International classification of epileptic seizures (ICES), proposed by ILAE (in 1981) has been universally accepted and has considerable clinical value, gelastic seizures are not included in it as a distinct entity and was included under the broad terminology of unclassified seizures.

As suggested by the name Semiologic seizure classification is based on the semiologic events as reported by an observer, patient or preferably as documented by video EEG monitoring. Semiologic seizure classification includes this classic entity under the category of "complex motor seizures". [19]


   Management Top


Evaluation of gelastic seizures

Imaging in the form of CT and MRI are essential to diagnose structural lesions. Hypothalamic hamartomas being the commonest structural associated, we would describe it in detail here.

CT scan will reveal an isodense suprasellar mass which does not enhance on contrast. CT may be suggestive but cannot give other details. MRI is the diagnostic imaging of choice. T1 weighted sagittal and coronal being most useful. The anatomic location of these hamartomas together with signal intensity similar to grey matter on T1 WI, a higher intensity (93%) than gray matter on PDWI and T2 WI and no enhancement on post-contrast images strongly supports this diagnosis [20] [Figure - 2].

MR spectroscopy has shown increased concentration of myo -inositol and relatively normal N -acetylaspartate and choline levels [21],[22] correlating with mild gliosis. [15]

In the studies of Debeneix et al. , precocious puberty was associated with small and pedunculated hamartoma and sessile ones with seizures. [3]

The Electroencephalography (EEG) may show focal cortical abnormalities, either from spread of the discharges from the central areas or as indicating a focal lesion and can be the only evidence of the origin of the gelastic seizures. [2] Also there is a progression of EEG abnormalities with worsening clinical seizure activity. [16]

When single photon emission computed tomography is used there may be a dramatic ictal uptake in the area of the tumour, with normalization during the interictal phase. [23],[24] Also positron emission tomography can help to show areas of hypometabolism and confirm the spread of the epileptic discharge to the temporal lobe. [25]

Medical management

A spectrum of antiepileptic drugs has been tried with little success in HH. They may have role in secondary seizure manifestation. Vigabatrin and valproate have limited success.

Zaatreh et al. , have suggested that long-acting gonadotropin releasing hormone analogue should be considered as a possible therapy for gelastic seizures in patients with HH when they found that such a patient, whose fits were resistant to conventional anti-epileptic drugs, responded dramatically to this treatment. [26] The patient reported by Gulati et al. , was given a gonadotropin releasing hormone agonist analogue which resulted in regression of pubertal development and subsequently treatment with phenytoin markedly reduced the incidence of gelastic seizures. [27]

Surgical management

No effective medical therapy is available to control the gelastic seizures. [7] Neither focal corticectomy nor a corpus callosotomy controls the gelastic seizures of patients. In terms of controlling gelastic seizures, the best surgical outcomes have been obtained by direct resection in cases of hamartoma. The overall success rate for curing or reducing seizures after resection of HHs causing gelastic seizures is about 52%. [28]

Surgical options in treatment of hypothalamic hamartoma

The following options are available for the surgical management of HHs. Each has its own indications, depending on size and anatomical location of a given HH and the goals of the surgical procedure.

Pterional approach

For very rare lesions such as HHs, a specific approach cannot be identified as the traditional approach. However, most surgery for HHs has involved transsylvian approach utilizing the optico-carotid corridor, with or without opening the lamina terminalis to access the third ventricle. Palmini et al. in a series of 12 patients operated via pterional, achieved seizure freedom in 3 and 6 had greater than 90% reduction. All had improvement in cognition, behavior and development [24] [Figure - 3],[Figure - 4]. We also have had good experience with this approach.

Transcallosal anterior interforniceal approach

Apuzzo et al. , originally described the transcallosal interforniceal approach for the removal of lesions within the third ventricle when no hydrocephalus distended the foramen of Monro. [29] Rosenfeld et al. , [30] began operating on these lesions using a slightly more anterior interforniceal approach than the classical approach described by Apuzzo et al. [29] This variation was an attempt to remain anterior to the body of the fornix to avoid damaging memory. Rosenfeld et al. , [30] in a series of 29 patients achieved seizure freedom in 15 and greater than 90% reduction in 7 with follow up 1 to 6 years (mean 2.5 years). Parallel improvement in cognition and behavior was observed.

Delalande et al. , illustrated the feasibility and relative safety of disconnection surgery for HHs with seizure relief in 53% of patients and dramatic improvement in the others. [31]

Neuroendoscopic approach

These patients rarely have enlarged ventricles. Intraventricular manipulation of the neuroendoscope is therefore difficult. Patients with small masses situated in the lateral wall of the midportion of the third ventricle are ideal candidates for resection using the neuroendoscope [31],[32] [Figure - 5]. Choi reported their experiences treating HHs neuroendoscopically following the principles of Delalande and Fohlen who believe that only the superior aspect of the mass needs to be disconnected from the surrounding hypothalamus. [31] Choi performed endoscopic exploration on four patients and coagulated the surface of the hamartoma using a yttrium-aluminum-garnet laser (YAG) laser. [33] Akai et al. , used a neuroendoscopic approach to obtain a biopsy to verify the diagnosis of HH. [32] Subsequently, they combined transventricular endoscopic resection with a pterional approach to resect the lesion. Only lesions upto 1.5 cm can be satisfactorily excised. Larger lesions may be disconnected. [34]

The philosophy of disconnection in surgical treatment of HH is that this lesion is not a neoplasm and complete removal is not mandatory. The rational of disconnection also appears attractive alternative in larger lesions where total excision may not be safely possible, focusing on breaking the propagation of the seizure activity, along the limbic circuitry, in particular the maxillary body. This increasingly used treatment modality needs to stand the test of time.

Stereotactic radiofrequency ablation

The stereotactic implantation of a radiofrequency source and denaturing of the HH have been reported to eliminate epilepsy in eight patients. [35],[36]

Gamma knife radiosurgery

Gamma knife radiosurgery has been used to treat intractable seizures in a limited number of patients with HHs. The fact that these lesions are small, well visualized on MR imaging and their surgical removal may be associated with significant morbidity, makes these lesions attractive for gamma knife radiosurgery.

Regis et al. , reported the largest series of HHs treated with Gamma knife radio surgery. [37] This multicenter study evaluated eight patients with drug intractable gelastic, complex partial and generalized seizures. Four patients became seizure free after treatment, the frequency of seizures was reduced markedly in two patients and two patients improved moderately.

Several other centers have reported their experience with fewer patients. Unger et al. , treated four patients with gelastic epilepsy caused by HH; all improved but not seizure free at follow-up intervals ranging from 12 to 68 months. [38] At the University of Pittsburgh, Kondziolka et al. , performed radiosurgery on two patients with intractable epilepsy and small-volume HHs. Seizures had improved in both 18 and 6 months after treatment with margin doses of 16 and 18 Gy, respectively. [39]

Gamma knife radiosurgery results in reduction in frequency and cure in few. The likelihood of becoming seizure free seems greater after open surgical resection of HHs, but the risk of producing new neurologic deficits is considerably lower with radiosurgery. A larger experience is required to arrive at a far reaching conclusion.

At present radiosurgery is a reasonable option for patients willing to try this low risk option, especially if the lesion is small and does not directly contact the optic chiasm. Surgery at a later date can still be an option, if radiosurgery is unsuccessful. Patients who have persistent seizures with residual lesion also may be good candidates for Gamma knife therapy. Regis et al. , recommend GKS as first intention for small/medium-sized HH associated with epilepsy. For large lesions, a two-stage surgery can be proposed with microsurgical disconnection of the lower part followed by radiosurgery of the small upper part. [37]

Regis et al. , [37] achieved a success of 59.2% with a complete seizure freedom in 37% or have rare nondisabling seizures (22.2%).

Interstitial brachytherapy

Interstitial radiosurgery have been proposed recently as an additional possible therapeutic modality. University of Freiberg group reported a series of 7 patients with a relatively short follow up. The rate seizure freedom was 28.5% (2 of 7). No major complications were reported. [39] The advantage was reliable radioactive fall off, the disadvantage being the absence of any possibility of shaping of the field of irradiation.

Vagal nerve stimulation

Vagal nerve stimulation plays no definite role in the current management of gelastic seizures, though unsuccessful attempts have been made. [40],[41]


   Prognosis Top


The prognosis of gelastic seizures originating from frontal, temporal or other regions of the brain is dependent of the underlying pathology; these usually have a better outcome than in connection with a hypothalamic origin. Review of the literature confirms that early diagnosis of gelastic seizures associated with HH is important as it can become catastrophic epilepsy with behavioral and cognitive disturbances if continues unabated. [42] Patients with HH without seizures have normal cognition and behaviour.


   Conclusion Top


Early diagnosis of gelastic seizures is important as it can become catastrophic epilepsy with behavioral and cognitive disturbances if continues unabated. No effective medical therapy is available to control the gelastic seizures. Early individualized surgical management remains the mainstay and the prognosis would depend on the causative lesion and surgical result achieved. Radical excision achieves best results but is not always possible with safety. Philosophy of disconnection has added a new dimension to the surgery of HHs. Alternative approaches like stereotactic radiosurgery, brachytherapy and combination of therapeutic procedures are being increasingly utilized and need further evaluation.

 
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    Figures

  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5]


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