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 Table of Contents  
Year : 2017  |  Volume : 2  |  Issue : 2  |  Page : 32-36

Chronic electric stimulation in a preschool-aged girl with hypothalamic hamartoma and epilepsy

1 Department of Neurosurgery, First Affiliated Hospital of PLA General Hospital, Beijing, China
2 Department of Pediatrics, First Affiliated Hospital of PLA General Hospital, Beijing, China

Date of Submission05-Dec-2016
Date of Acceptance15-Mar-2017
Date of Web Publication22-Jun-2017

Correspondence Address:
Shuli Liang
Department of Neurosurgery, First Affiliated Hospital of PLA General Hospital, Beijing 100048
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ts.ts_35_16

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Aim: This study aimed to report the first case of deep brain stimulation (DBS) in a preschool-aged child with hypothalamic hamartoma (HH) and discuss the rationale and outcome of this treatment. Methods: A 5.5-year-old girl was diagnosed with HH and intractable epilepsy, including laughing seizures, tonic seizures, and atypical absence seizures, using magnetic resonance imaging and electroencephalograph examination, quality of life (QOL), intelligence quotient (IQ), and memory quotient (MQ) tests. A right trans-temporal lobe approach HH stimulation was performed with a quadripolar electrode along the axial plane of the lesion. The initial stimulation parameters were a wave width of 90 μs, a stimulating frequency of 130 Hz, a voltage of 0.5 V, and a maintenance stimulation voltage of 2.0 V. Results: The girl achieved freedom from tonic seizure after 4 months of stimulation (1.5 V), freedom from laughing seizure after 7 months of stimulation (1.8 V), and a reduction by more than 80% of atypical absence seizure after implantation of the stimulation electrode. At the 18-month follow-up visit, the postoperative QOL, IQ, and MQ scores of the girl had improved more than 10% compared with the preoperative scores. There were no surgical- or stimulation-related complications. Conclusion: DBS is a safe and efficient approach in older preschool-aged patients with HH, and it provided freedom from tonic and laughing seizures, as well as a significant reduction of atypical absence seizure and improvement of IQ, MQ. and QOL.

Keywords: Deep brain stimulation, hypothalamic hamartoma, preschool-aged child

How to cite this article:
Cui J, Liang S, Zhang S, Hu X, Yu X, Yuan L. Chronic electric stimulation in a preschool-aged girl with hypothalamic hamartoma and epilepsy. Transl Surg 2017;2:32-6

How to cite this URL:
Cui J, Liang S, Zhang S, Hu X, Yu X, Yuan L. Chronic electric stimulation in a preschool-aged girl with hypothalamic hamartoma and epilepsy. Transl Surg [serial online] 2017 [cited 2021 Dec 6];2:32-6. Available from: http://www.translsurg.com/text.asp?2017/2/2/32/208868

  Introduction Top

Hypothalamic hamartoma (HH) is an uncommon lesion that may be discovered incidentally, with precocious puberty and stereotactic laughing (gelastic) seizures being its typical clinical presentations. Epilepsy with HH usually responds poorly to anti-epilepsy drugs (AEDs).[1] Early onset of laughing seizures is often recognized during the neonatal period, and the appearance of this condition is followed a few years later by the development of seizures with focal motor features and autonomic manifestations such as flushing and cardiorespiratory changes. Later, during the first decade of life, generalized spike-and-wave, tonic attacks, and drop attacks occur, suggesting the presence of a secondary, generalized epileptic process. This focus has emerged as a major feature associated with, and probably responsible for, the observed cognitive and behavioral deterioration, which are important features of catastrophic epilepsy with HH.[2]

Deep brain stimulation (DBS) is a minimally-invasive, reversible, adjustable epilepsy treatment characterized by the stimulation of the vital hub of the epileptic network or epileptogenic zone.[3],[4],[5] Stimulation of the anterior nucleus of the thalamus and hippocampus provides promising seizure control without apparent complications.[6],[7],[8] Here, we stimulated HH in a preschool aged girl with intractable epilepsy.

  Methods Top


A right-handed girl was born in 2009 after an uneventful full-term pregnancy. Her first seizure was discovered at 19 months of age. The seizure commenced with causeless and uncontrollable paroxysmal laughing. The frequent laughing seizures were subsequently recorded 5–10 times per day, with each attack lasting several seconds. The scalp electroencephalogram (EEG) did not reveal epileptiform discharge, and no AEDs were administered. At 37 months of age, she experienced her first convulsive seizure, which presented as staring for seconds, left deviation of the head, and then bilateral arm tonic-clonic convulsions, complex partial seizure, and secondary generalized seizure. Epilepsy was diagnosed, and valproate was administered. She still experienced daily laughing seizure and monthly complex partial seizures with secondary generalized seizures with 500 mg valproate per day. One year later, she presented with atypical absence seizure and tonic seizure subsequent to laughing seizure or alone. Magnetic resonance imaging (MRI) examination indicated HH, and she was diagnosed with HH and secondary epilepsy. Since then, topamax, lamotrigine, and levetiracetam were administered alone or combined, and the complex partial seizure and secondary generalized seizure disappeared. However, laughing seizure, atypical absence seizure, and tonic seizure showed a poor response to those AEDs. In the 6 months prior to surgery, she suffered approximately 220 laughing seizures, 30 atypical absence seizures, and 7 tonic seizures per month.

Preoperative assessments

The preoperative evaluations included a neurological assessment, long-term scalp video-EEG recording, Magnetic Resonance Imaging (MRI), intracranial EEG, and neuropsychological tests. The neurological assessment did not reveal any positive signs, such as precocious puberty or hypophyseal hormone abnormalities. She had a head circumference of 51.6 cm, weighed 30 kg, and was 1.21 m tall. The scalp video-EEG was recorded for 44 h using a 64–channel recorder after gradual AED withdrawal over 3 days. Eight laughing seizures, three atypical absence seizures, and one tonic seizure were recorded by video-EEG, and the EEG showed slow wave background, paroxysmal bursts of fast rhythm during sleeping, and generalized or right temporal area 1.5–2.5Hz spike-slow wave discharge during the interictal period. The ictal EEG of the tonic seizure revealed a low-voltage fast rhythm for 2–3 s followed by an electromyographic artifact [Figure 1]. The MRI scan included axial T1, T2, fluid attenuation inverse recovery (FLAIR) and diffusion-weighted imaging, sagittal T1-weighted imaging, and coronal hippocampal FLAIR imaging, and the MRI showed a 25 mm × 17 mm × 16 mm oval lesion with equal T1, slightly higher T2, and no enhancement signal in the suprasellar area [Figure 2]. HH was diagnosed. The Wechsler Child Intelligence Quotient Scale (Chinese version) was used for the intelligence quotient (IQ) tests. The girl's verbal IQ was 83, performance IQ was 73, and full-scale IQ was 75. The overall quality of life (QOL) subscale on the epilepsy inventory-31 was 60. The total memory quotient (MQ) in the Wechsler Child Memory Quotient Scale (Chinese version) was 71.
Figure 1: The preoperative ictal electroencephalogram of a typical absence seizure ( first line left) and laughing seizure ( first line right) and poststimulation electroencephalogram of the patient (second and third lines). Middle line: Postoperative interictal electroencephalogram with hypothalamic hamartoma stimulation at 0.5 V (left) and 1.0 V (right). Third line: Postoperative interictal electroencephalogram with hypothalamic hamartoma stimulation at 1.5 V (left) and 2.0 V (right)

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Figure 2: The preoperative T1 axial image (a) and enhanced T1 sagittal image (b) revealed an oval lesion with equal T1, slightly higher T2, and no enhancement signal in the suprasellar area. Postoperative T1 axial image (c), and postoperative coronal fluid attenuation inverse recovery image (d) shows the quadripolar electrode inserted along the axial plane of the lesion. The head of first contact rested in the left boundary of hypothalamic hamartoma, and all of four contacts lay in the hypothalamic hamartoma

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Treatment procedure

The parents of the girl refused to perform resection surgery for fear of the potential complication of hypothalamic injury, and they did not accept radiosurgery because of possible effects on pituitary hormones. A right transtemporal lobe approach to HH stimulation was performed. Under general anesthesia, a stereotaxic head frame was used to insert a quadripolar electrode with a length of 1.5 mm per contact and an inter-contact distance of 1.5 mm (PINZ-L302, Pinz Inc., Beijing, China) along the axial plane of the lesion. The head of the first contact rested in the left boundary of the HH, and all the four contacts were positioned in the HH [Figure 2].

  Results Top

The girl returned to the hospital 1, 4, 7, 10, 12, and 18 months after surgery. The stimulator was switched on with initial contact as the positive electrode; the third contact was the negative electrode on day 14 postsurgery, and the initial stimulation parameters were a wave width of 90 μs, a wave frequency of 130 Hz, and a stimulating voltage of 0.5 V. The stimulating voltage was adjusted to 1.0 V at 1-month visit, 1.5 V at the 4-month visit, 1.8 V at the 7-month visit, and 2.0 V at the 10-month visit. Seizure reduction, which was evaluated every visit, was determined by comparing the mean seizure frequency per month between follow-up visits with the average seizure frequency during the 6 months before surgery. Tonic seizures stopped after surgery either before or 4 months after switching on the stimulator. Laughing seizures were continuous after surgery, but they stopped when the stimulating voltage reached 1.8 V. In addition, reductions of atypical absence seizures exceeded 80% at all visits with valproate and lamotrigine [Figure 3]. Changes in IQ, MQ, and QOL scores were evaluated 18 months after surgery, and the results showed that postoperative scores improved by more than 10% compared with the preoperative scores [Figure 4]. 18 months after surgery, the girl weighed 44 kg and was 1.46 m tall with normal hypophyseal hormones.
Figure 3: The changes in seizure frequency before the operation, 0–1 month (no stimulation), 1–3 months (stimulation voltage 1.0 V), 4–6 months (stimulation voltage 1.5 V), 7–9 months (stimulation voltage 1.8 V), 10–11 (stimulation voltage 2.0 V), 12–18 months after hypothalamic hamartoma-deep brain stimulation. The laughing seizure were continuous after the operation, but the seizures stopped when the stimulating voltage reached 2 V, and reductions of atypical absence seizures were over 80% at all visit

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Figure 4: The changes in the intelligence quotient, memory quotient and quality of live scores from preoperative values to those at 18 months after surgery. Postoperative scores improved more than 10% over preoperative scores in intelligence quotient, memory quotient and quality of live

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  Discussion Top

HH is a rare cause of intractable epilepsy. During the early stage of this condition, laughing seizures are typically ignored until the appearance of convulsive seizures. Therefore, the laughing seizures are always underestimated. The parietal seizures and limited ictal EEG discharges can lead to the misdiagnosis of HH as temporal lobe or frontal lobe epilepsy.[9],[10] HH is also a cause of intractable epileptic encephalopathy, and more than 40% of patients present moderate-to-severe mental retardation, in which frequent epileptic seizures and epileptiform discharges play an important role. Furthermore, Scholly et al.[11] have reported that independent secondary extrahypothalamic epileptogenic zones can occur in patients with laughing seizures with HH. Therefore, seizures with HH should been identified early and controlled.

HH is essentially a type of congenital brain dysplasia, but as a true tumor, it grows very slowly. The goal of treatment for HH is to control the clinical symptoms rather than to remove the lesion. Therefore, candidates for surgery include those with HH with neurological dysfunction of the lesion, precocious puberty unresponsive to medical therapy, and intractable epilepsy.

The different surgical approaches for HH have been developed according to the orientations and initiatives of the different groups.[12],[13] Resective surgery, including the lateral pterional approach and transcallosal approach, rendered 33%–54% patients seizure free but have the disadvantage of serious complications.[12],[13] Disconnective surgery has its own advantages and appears to have a low rate of complications; however, HH with seizures is usually sessile, closely connected to the mammillary body, and not associated with a stalk.[14] The girl did not present neurological dysfunction of the lesion or precocious puberty, but her epilepsy was medicine intractable and secondary mental retardation appeared. Therefore, surgical treatment was taken into consideration. Due to the absence of a stalk, disconnective surgery was excluded by our team, and resective surgery was declined by the girl's parents.

Gamma knife radiosurgery, stereotactic radiofrequency thermocoagulation, and DBS were suitable surgical approaches. Mathieu [15] reported that nine patients with HH and epilepsy underwent gamma knife radiosurgery and 44% of them in whom the entire lesion was treated achieved freedom from seizure. Gamma knife radiosurgery was not a preferred option in the present case because of the large volume of HH and the risk of radiation injury to the optic nerve. Shirozu [16] reported 17 giant HHs treated with 22 stereotactic radiofrequency thermocoagulations and showed that 13 patients (81.3%) achieved freedom from laughing seizures and 58.3% achieved freedom from nonelastic seizures during a follow-up period ranging from 6 to 60 months (mean, 23 months). However, transient complications were experienced in 17 of the 22 procedures, and stereotactic radiofrequency thermocoagulation was also excluded in the present case for fear of the possibility of hypothalamic injury.

Five cases with HH and epilepsy underwent DBS in previous reports. One was seizure free, one with free from laughing seizures, one showed an 80% seizure reduction, and two had no significant seizure reduction.[17] This is the first report of DBS in a preschool-aged patient with HH and epilepsy. The main problems associated with the use of DBS in children are growth of the head and movement of the stimulation electrode. In our case, the head circumference was 51.6 cm, which is approximately 89% of the mean 58cm head circumference of an adult. Thus, movement of the electrode should be <0.3 cm (calculated under the assumption that the head is round). The diameter of the HH was 1.7 cm in axial image, and the working length of the stimulation electrode was 10.5 cm. Therefore, by placing the head of the electrode near the contralateral wall of the HH during surgery, the entire electrode will be positioned in the HH when the patient becomes an adult.

It has been confirmed that HH is the epileptogenic zone of laughing seizures, but whether the other seizures also originate from the HH itself remains controversial.[11],[12],[13],[14],[15],[16],[17],[18] Scholly et al.[11] described two patients with HH who suffered from continuous partial seizures after endoscopic resection of HH. Both patients became seizure free only after temporal lobectomy. The results of the present case showed an elimination of tonic seizure and an 80% reduction of atypical absence seizures after HH stimulation, which indicated that HH itself should be the epileptogenic zone or at least a key hub of the epileptogenic network of tonic and atypical absence seizures. DBS should be performed in more HHs to confirm the role of HH in nonlaughing seizures.

In conclusion, DBS is a safe and efficient approach in older preschool-aged patients with HH, providing freedom from tonic seizures and laughing seizures and a significant reduction of atypical absence seizures, as well as improved IQ, MQ, and QOL.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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


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