ARTICLE
Auteur(s) : Wei Wang1,2,3,4, Weimin
Wang4, Xiaofei Guo4, Yanjun Zeng5, Xiaodan
Jiang1,2,3
1Neurosurgery Institute of Guangdong, Southern
Medical University
2Key Laboratory on Brain Function Repair
and Regeneration of Guangdong
3Department of Neurosurgery, Zhujiang Hospital,
Southern Medical University, Guangzhou
4Department of Neurosurgery, The Military General
Hospital of Guangzhou PLA, Guangzhou
5Biomechanics & Medical Information Institute,
Beijing University of Technology, Beijing, China
Article reçu le 14 Mai 2009, accepté le 24 Septembre 2009
Hypothalamic hamartoma (HH) with gelastic seizures (GSs) is a
rare epilepsy syndrome, affecting approximately 0.5 in
100,000 children (Brandberg et al., 2004). Seizures
caused by hypothalamic hamartoma are always refractory to
antiepileptic drugs (AEDs). The intrinsic epileptogenicity of
hypothalamic hamartoma has been confirmed in the last decade
(Kuzniecky et al., 1997; Munari et al., 1995), and
surgical intervention is required for such lesions. Although
various treatment options for hypothalamic hamartoma with
intractable gelastic seizures have been reported, the optimal
strategies remain controversial. Only a few cases of stereotactic
radiofrequency thermocoagulation have been published, and the
reported seizure-free rates are not consistent (Kuzniecky
et al., 1997; Fukuda et al., 1999; Parrent, 1999; Homma
et al., 2007, Kuzniecky and Guthrie, 2003). Herein, we report
a case of gelastic seizures caused by a small hypothalamic
hamartoma treated with stereotactic radiofrequency
thermocoagulation.
Case report
Clinical presentation
The 22-year-old right-handed man presented with intractable
gelastic seizures and focal seizures refractory to AEDs. He was the
product of a normal pregnancy, and was delivered at term without
complication. At the age of 6 months, he began to experience
seizures characterized by episodes of spontaneous unexplained
laughter without impairment of consciousness and lasting less than
a minute. Despite daily seizures, the patient exhibited no
developmental delay, and treatment was not sought. At the age of
15 years he also experienced focal seizures with a giggling
sensation at onset. Initial magnetic resonance imaging (MRI)
studies failed to reveal any abnormalities. The patient received a
diagnosis of “temporal lobe epilepsy” and was treated with
carbamazepine, valproate, and topiramate. The drugs failed to
control the seizures and he continued to experience one to two
daily seizures. Cognitive and memory functions remained intact but
he frequently exhibited episodes of rage behavior. Repeated MRI
scans (Sonata, 1.5 Tesla, Siemens,Erlangen, Germany) revealed
a 6 mm × 6 mm × 7 mm homogeneously non-enhancing,
soft-tissue intra-third ventricular mass. The mass was attached to
the left mammillary body and mammillothalamic fasciculus, and was
consistent with a hypothalamic hamartoma (figure 1). Continuous
electroencephalography (EEG) monitoring revealed interictal bursts
of 2 to 2.5 Hz spike/polyspike-and-slow wave activity
over the left hemisphere.
Surgical procedure
A stereotactic frame (Leksell G, Elekta, Stockholm,Sweden) was
mounted on the patient’s skull and an MRI scan was performed under
local anesthesia. The MRI protocol included axial T1-weighted and
axial and coronal T2-weighted imaging (3 mm-thickness; no
interslice gap). The target coordinates were determined by
MRI-based software (Leksell SurgiPlan, Elekta, Sweden).
A semi-open cannula (Insertion Cannula kit, Elekta,
Stockholm,Sweden) was introduced to the anterior portion of the
hypothalamic hamartoma with the Leksell Stereotactic System, and a
deep recording electrode (1.3 mm in diameter, 1.5 mm in
length, and 2 mm apart/HKHS, Beijing, China) was implanted in
the same target through the cannula (figure 2). The depth
electrode consisted of six contacts, with contact 1 as the
most ventral contact and contact 3 as the most dorsal. The
depth recording showed spike-slow waves which synchronized with the
scalp EEG. After removing the depth electrode, a radiofrequency
electrode with 1.9 mm diameter and a 2 mm exposed tip
(Radionics Medical Products, Inc., MA, USA) was implanted into the
hypothalamic hamartoma. Lesions were produced using a
radiofrequency (RF) lesion-generator system (model RFG-5; Radionics
Medical Products, Inc., MA, USA). Although various stimulation
indices had been attempted, neither gelastic nor complex partial
seizures could be induced. A test lesion was made (45°C,
40 s) before the final lesions were created (70°C, 70s). After
the first lesion was made, the radiofrequency electrode was
withdrawn 2 mm and the second lesion was created. The third
and the fourth lesions were 2 mm posterior to the first and
the second ones. The patient complained of “palpitations,” and
feeling “hot” and “uncomfortable” during the test and final
lesions; hypertension (up to 160/90 mmHg), tachycardia (up to
110/min), perspiration, and cold limbs were observed during the
procedure.
Results
The post-operative MRI scan, performed just before hospital
discharge, showed that most of the HH was coagulated (figure 3). The
patient experienced mild to moderate fever (37.5-38.4°C) for the
first 3 days postsurgery and discharged on the fifth day.
Gelastic and focal seizures ceased instantly and the patient
remained seizure-free during the 12-month follow-up. We do not
dispose of a MRI control at 12 months from the operation as
the patient could not afford the cost. No hyperphagia, oculomotor
palsy, memory loss, or other permanent surgical complication
occurred.
Discussion
The incidence of hypothalamic hamartoma associated with gelastic
seizures is currently estimated about 0.5 in 100,000 in
children (Brandberg et al., 2004). Although many case reports
have linked gelastic seizures to lesions of the temporal lobe,
frontal lobe, pituitary tumors, and head trauma (Arroyo
et al., 1993; Sartori et al., 1999; McConachie and King,
1997; Cheung et al., 2007), most cases of gelastic seizures
involve the presence of a hypothalamic hamartoma. The diagnosis of
hypothalamic hamartoma can be established in the presence of
gelastic or other types of seizures associated with precocious
puberty and MRI results of a homogeneously non-enhancing
soft-tissue mass located in the hypothalamic region that is
isointense to gray matter on T1-weighted imaging and hyperintense
or isointense on T2-weighted imaging (Freeman et al., 2004)
On the basis of the size of the hamartoma and the patterns of
attachment to the hypothalamus, several classification systems have
been proposed. Delalande’s classification includes four types:
- – type I: the hamartoma is below the third ventricle,
has a horizontal implantation plane, and may be lateralized on one
side;
- – type II: the hamartoma has an intraventricular
location and vertical insertion plane;
- – type III is the combination of type I and type
II;
- – type IV includes all giant hamartomas (Fohlen
et al., 2003).
Although the intrinsic epileptogenicity of hypothalamic
hamartoma had been confirmed by numerous investigators, the
mechanism of seizures associated with HHs is still not completely
understood. Data from intracranial recordings have demonstrated
that the other associated seizure types (i.e., without the laughing
or crying component) do not arise from HHs, but originate in
various cortical areas. These findings suggest that these seizures
may result from secondary epileptogenesis and may explain the
variable scalp EEG results associated with HHs (Kahane et al.,
2003)
Surgical intervention is an effective strategy for hypothalamic
hamartoma with gelastic seizures; surgery may be classified as
lesion resection, disconnection, radiosurgery, or stereotactic
radiofrequency thermocoagulation.
Lesion resection can be achieved through the pterional approach,
lamina terminalis approach, or the transcallosal interforniceal
approach. According to a review by Harvey et al. (2008), the
highest seizure control rate in patients with HH associated with
seizures could be achieved through the transcallosal interforniceal
approach (66% with Engel class I or II outcome). Although most
surgeons believe that the classification system is useful in
selecting the surgical approach, total resection appears to be
dependent on the size and location of HHs. Pedunculated HHs are
generally asymptomatic or associated only with precocious puberty,
and total resection could be achieved easily. Unfortunately, HHs
with gelastic seizures are almost always intraventricular, at least
partially, with significant mammillary body attachment; therefore,
total resection without surgical complication is rarely achieved
(Ng et al., 2006; Shim et al., 2008; Polkey, 2003).
Because the hamartoma is a stable lesion and complete removal
may not by necessary to treat the epilepsy or difficult to achieve,
the disconnection approach using open surgery or endoscopy has been
proposed in the last decade as an alternative. This approach is
primarily used for large pedunculated HHs, and the seizure control
rates have been reported as comparable to the lesion resection
group (Choi et al., 2004).
Radiosurgery (gamma knife) also appears to be an alternative
treatment for HH with epilepsy; its major advantage is its safety.
However, the lesions are benign and not sensitive to radiation,
thus the mechanism of radiosurgery for HH-related seizure control
is not clear. Radiosurgery is typically used for postoperative
residuals and small HHs (i.e., small intraventricular HHs of
Delalande classification type II). A report by Régis
et al. (2006) of the largest series of radiosurgery cases
(27 patients) revealed that complete seizure control or
significant improvement were achieved in 10 (37%) and
6 (22%) patients respectively. These results are less
favorable than the report of largest series of cases of HHs removed
with the transcallosal interforniceal approach, (54% of
26 patients achieved seizure control) (Ng et al., 2006).
Interstitial radiosurgery is another treatment option for HHs
causing gelastic seizures, according to the experience from
Freiburg (Schulze-Bonhage et al., 2008). After a mean 24-month
follow up, 11 of 24 patients were seizure-free or had
seizure reduction of at least 90% (Engel class I and II), although
some patients required repeated treatment.
In 1997, Kuzniecky et al. confirmed the intrinsic
epileptogenicity of hypothalamic hamartoma with a stereotactic deep
recording technique already reported by Munari et al. (1995).
If there is no apparent mass effect from the benign lesion, HHs
associated with seizures may be controlled with stereotactic
radiofrequency thermocoagulation. A literature review suggests
that only a few cases undergoing this treatment have been reported
(Fukuda et al., 1999; Parrent, 1999; Homma et al., 2007;
Kuzniecki and Guthrie, 2003). Fukuda et al. (1999) and Homma
et al. (2007) reported five patients with HH who underwent
stereotactic radiofrequency thermocoagulation for the treatment of
intractable epilepsy; in all cases the hamartoma was
intraventricular and less than 15 mm in diameter. The outcomes
were excellent; three patients became seizure free and the
remaining two patients experienced 90% improvement in seizure
frequency (mean follow-up, 50.6 months) and no permanent
surgical complication occurred (Fukuda et al., 1999). In the
largest series of cases undergoing stereotactic radiofrequency
thermocoagulation (8 patients) reported by Kuzniecky and
Guthrie (2003) seizure control was less favorable (Engel I, n = 3,
Engel II, n = 2, Engel III, n = 2, Engel IV, n = 1 patient);
however, the only complication that occurred was transient
third-nerve palsy (n = 1). In a review of the literature, Harvey
and Freeman (2005) suggested that only 27% of patients with HHs
associated with seizure who undergo stereotactic radiofrequency
ablation could expect to achieve Engel I or II outcomes.
Because a small radiofrequency electrode is unlikely to destroy
a large HH, repeated procedures were needed in some patients after
the first failure. Thus, stereotactic radiofrequency
thermocoagulation may only be suitable for small HHs. As mentioned
above, HHs causing gelastic seizures are always intraventricular,
isointense to the gray matter, and without enhancement on MRI
imaging. For this reason some small HHs, like the present case, may
be difficult to detect unless the hypothalamic region is examined
specifically; a T2 reversed image may improve
interpretation.
Although central hyperthermia and postoperative fever occurred
more frequently compared to using the open approach (Homma
et al., 2007), the disadvantages of stereotactic
radiofrequency thermocoagulation are acceptable. Due to the solid
mass of HHs, there is a small possibility of missing the target by
a few millimeters, even with computer-assisted stereotactic
planning. Some surgeons combine this approach with the endoscopic
technique to improve the accuracy, but the application of endoscopy
is restricted by the width of the third ventricle. For that reason,
we did not use endoscopy to identify the coagulation. The main
limitation of the stereotactic approach is that the seizure-free
rate in patients with large HHs is lower than treatment with open
approaches. However, for small hamartomas, the stereotactic
approach may be appropriate because destruction of the lesion and
seizure control can be achieved with operative risks and
postoperative complication rates that are much lower than any of
the open cranial procedures.
Our patient has been seizure-free for 12 months but the
results need to be evaluated with long-term follow-up. Compared to
radiosurgery, seizure control may be achieved shortly after
stereotactic coagulation. Thus, stereotactic radiofrequency
thermocoagulation appears to be a safe and efficacious treatment
option for select patients with HHs.
Disclosure
This work was supported by the Funds for Medical Research Projects
of Guangdong Province[A2008501] and Key Sci-tech Research Projects
of Guangdong Province [YUE KEJIBAN (2007) 05/06-7005206],
YUECAIJIAO(2008)258-(2008)A030201019], Research Funds of Guangzhou
[SUIKETIAOZI (2008) 3-2008A1-E4011-6, 9B52120112], China.
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