Hypothalamic hamartoma (HH) is a rare, nonmalignant, heterotopic developmental malformation that consists of a mixture of normal neurons and glial cells. The incidence of these lesions has been reported in approximately 1–2 cases in 100,000.1 HHs originate from the ventral hypothalamus. They may be found as sporadic masses or accompany other developmental malformations.2 HHs may have various clinical manifestations, categorized into three main groups as endocrine, psychiatric, and neurological.2,3 Endocrine problems may be present when the tumor is close to the infundibulum and tuber cinereum. Precocious puberty is the most common manifestation in the endocrine group.4 Mammillary body involvement tends to be associated with psychiatric and neurological manifestations.5 Cognitive disorders, including intellectual disability, mood disorders, and behavioral problems, can be related to HHs. Epilepsy is the primary and probably most important clinical problem in these patients. HHs are associated with several seizures, including gelastic, complex partial, tonic-clonic, and secondarily generalized seizures.6 Among the seizure types, gelastic attacks are the most common and associate explicitly with HH; these seizures are defined by inappropriate laughing and are often resistant to antiepileptic agents.1 Gelastic and dacrystic (associated with a crying sound and less common than gelastic) seizures7 are the primary seizure types in patients with an HH, and their onset usually occurs in the 1st year of life. Still, these seizures are not diagnosed until the patient develops other seizure types, which are probably a consequence of secondary epileptogenesis involving temporal and frontal structures.2,8 There are many surgical techniques for managing these patients; open surgical techniques include resection of the lesion and disconnection procedures. Because of the deep anatomical location, surgical management of any lesion in this region could be complicated and catastrophic.9 Resection of HHs has been associated with high rates of mortality and morbidity, but since gross-total resection is not the primary goal (based on their noncancerous histology), minimally invasive ablation methods could be the best treatment option for HH.2,10 Considering the rarity of HH, the main limitation that narrows available data for comparing alternative treatment modalities, a meta-analysis of available and commonly used treatments could provide comprehensive and more objective insight of the issue.
The most frequently used minimally invasive options for HH ablation are radiofrequency thermocoagulation (RFT), laser ablation (LA), and stereotactic radiosurgery. In this systematic review and meta-analysis, we aimed to compare different minimally invasive procedures in the treatment of HHs.
Methods
Search Strategy and Selection Criteria
The search strategy was designed around the population, intervention, and outcome question format. To investigate three minimally invasive procedures in the treatment of refractory seizures associated with HH, we conducted a systematic search in March 2022 of the MEDLINE, Embase, Scopus, and Web of Science databases based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using the search string format provided in the Appendix. All identified articles were then systematically assessed against inclusion and exclusion criteria by two independent reviewers (A.I. and M.A.D.O.), and discrepancies were resolved by a third reviewer (M.C.). Inclusion criteria were articles written in the English language reporting on human participants with HH leading to medically refractory epilepsy who underwent RFT, LA, or Gamma Knife radiosurgery (GKRS). Articles with fewer than 5 cases or less than 6 months of mean follow-up time were excluded. To demonstrate precise results, all studies of patients (if the study reported) undergoing secondary interventions during the follow-up in addition to the one of interest were excluded. A strict review was done to identify and exclude the articles with potential duplicated patient data from the same institutions; for this reason, when institutions published duplicate studies with increasing case numbers or increased follow-up time, only the most complete reports were included. Finally, a forward citation search was done before the analysis to find the possible recently published articles and double-check the search.
Primary and Secondary Outcomes
Seizure freedom was the primary outcome of interest. It was defined as Engel class I or International League Against Epilepsy (ILAE) class 1 or 2 or as the reported term “seizure freedom.” The secondary outcome was long-term complications; for this purpose, we did not assess transient complications that had resolved at the last follow-up. The total number of patients experiencing complications was analyzed. The reported complications in studies varied as memory problems, endocrine disturbances, and cognitive complications. Although we agree that there is a wide range of complications regarding the severity, this classification and analysis only focused on this critical aspect of treatment, which makes the findings as objective as possible.
Data Extraction
The following variables were extracted: patient demographics such as age and sex, mean follow-up time, seizure characteristics (categorized as two groups: pure gelastic and other), and anatomical description of the lesion (classified by Delalande et al.11 and Régis et al.12). Volume means were reported in articles; if not, we calculated them using the individual data.
Quality Appraisal
A modified version of the Joanna Briggs Institute (JBI) Critical Appraisal tool13 was assessed by two examiners (M.A.D.O. and A.I.) for quality appraisal. The questions were as follows. Question 1: “Were there clear criteria for inclusion in the case series?” Question 2: “Was the condition measured in a standard, reliable way for all participants included in the case series?” Question 3: “Were valid methods used for identification of the condition for all participants included in the case series?” Question 4: “Does the study include all the target patients of the center?” Question 5: “Was there clear reporting of the demographics of the participants in the study?” Question 6: “Was there clear reporting of clinical information of the participants?” Question 7: “Does the study have more than 1 year follow-up and used a specific criteria?” Question 8: “Was statistical analysis appropriate?”
The first, second, and third questions were evaluated based on the appropriate inclusion criteria with sufficient diagnostic tools such as imaging data fulfilled by all studies. We combined the fourth and fifth questions of the original questionnaire as a single question which explains if the study includes all the target patients of the center. The fifth question assesses demographic data, including the prior treatment report. We criticized the clinical assessment of the studies, including tumor characteristics (size and classification) and seizure characteristics (frequency and type) through the sixth question. In the seventh question, studies are categorized as “yes” if they have more than 1 year of follow-up and use specific criteria or enough explanation for the seizure outcome. The ninth question of the original questionnaire explains demographic data, which was stated in our fifth question, and the final question shows the statistical method that was accomplished by all of the studies. Quality appraisal data are shown in Table 1.
Quality appraisal
| Authors & Year | Q1 | Q2 | Q3 | Q4 | Q5 | Q6 | Q7 | Q8 |
|---|---|---|---|---|---|---|---|---|
| Abla et al., 201027 | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
| Mathieu et al., 201028 | Yes | Yes | Yes | No | No | No | Yes | Yes |
| Régis et al., 201716 | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
| Buckley et al., 201610 | Yes | Yes | Yes | Yes | No | No | No | Yes |
| Du et al., 201729 | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
| Curry et al., 201817 | Yes | Yes | Yes | Yes | No | No | No | Yes |
| Xu et al., 201830 | Yes | Yes | Yes | Yes | Yes | No | No | Yes |
| Gadgil et al., 202031 | Yes | Yes | Yes | Yes | Yes | No | Yes | Yes |
| Candela-Cantó et al., 202237 | Yes | Yes | Yes | No | Yes | No | Yes | Yes |
| Kuzniecky & Guthrie, 200332 | Yes | Yes | Yes | Yes | No | No | Yes | Yes |
| Tandon et al., 201833 | Yes | Yes | Yes | No | No | Yes | Yes | Yes |
| Wei et al., 201834 | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
| Shirozu et al., 202026 | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
| Wang et al., 202035 | Yes | Yes | Yes | Yes | Yes | No | Yes | Yes |
| Wang et al., 202036 | Yes | Yes | Yes | Yes | Yes | No | Yes | Yes |
Q = question.
Statistical Analysis
The proportion of seizure freedom was calculated for each study. Both random- and fixed-effects models were used to calculate the pooled proportion of seizure freedom and complication rate with 95% CI. Higgins’ I2 statistics and Cochran’s Q test were used for heterogeneity analysis. Egger’s regression test was used for publication bias analysis. Considering the available covariates, a meta-regression analysis was performed to find the source of heterogeneity or important factors. All analyses were conducted in R statistical analysis software (version 4.1.2, R Foundation for Statistical Computing) using “metafor” and “meta” packages.
Results
After removing duplicates, 367 articles were screened by title and abstract, and retrieved articles went through full-text review. There were 3 articles from Timone University Hospital12,14,15 by Régis et al. using the same cohort data from the same institution covered by Régis et al.16 These articles were excluded from the study. Articles from the same institution as Curry et al.17 that included patients in a similar period were also excluded.18,19 Studies by Sonoda et al.20 and Hamdi et al.21 were also excluded since they reported cognitive results rather than epilepsy outcomes after HH treatment. Four articles22–25 were excluded because of duplicated data with the study by Shirozu et al.26 Only 7 patients from Abla et al.27 and 6 from Mathieu et al.28 were included because other procedures were performed during the follow-up period. A patient from the study by Du et al.29 was excluded because of the absence of seizures at HH presentation. Finally, 15 studies10,16,17,26–37 (422 patients in total: 190 RFT, n = 190; LA, n = 171; and GKRS, n = 61) were considered eligible to enter the study. The study selection flowchart is presented in Fig. 1.
PRISMA flow diagram. One article was excluded for two reasons.
Quality Assessment
Some of the included studies lacked basic demographic information. Four studies did not report the mean patient age. Two studies did not report the sex composition of their patients. Some of the studies did not report the prior surgical treatment. Tables 2 and 3 demonstrate the detailed characteristics of the included studies.
Seizure outcomes
| Authors & Year | Tx | No. of Pts (males) | Age at Tx | Pts w/ Prior Procedures | Seizure Frequency & Type | HH Measurement & Type | Seizure Outcome | FU Time |
|---|---|---|---|---|---|---|---|---|
| Abla et al., 201027 | GKRS | 7 (6) | Mean 12.83 yrs | 3 | Mean 4.11/day GS, 5 pts; tonic, 1 pt; CPS 3 pts; absence, 1 pt; generalized, 1 pt | Mean vol, 0.50 cm3 Delalande 2, 5 pts; Delalande 3, 2 pts | Seizure free, 4 pts; 50–90% reduction, 1 pt; 0% reduction, 2 pts | Mean 31.7 mos |
| Mathieu et al., 201028 | GKRS | 6 (4) | Mean 30 yrs | NR | GS, 5 pts; CPS, 3 pts; SPS, 1 pt; generalized, 1 pt | Mean vol, 0.55 cm3 Régis 1, 2 pts; Régis 2, 4 pts; Régis 3, 1 pt | Engel I, 4 pts; Engel II, 1 pt; Engel IV, 1 pt | Mean 18.6 mos |
| Régis et al., 201716 | GKRS | 48 (27) | Median 16.5 yrs | 4 | Median 107.3/mo GS, 48 pts; CPS, 48 pts; generalized, 29 pts; status, 15 pts | Median vol, 0.4 cm3 Régis 1, 11 pts; Régis 2, 15 pts; Régis 3, 17 pts; Régis 4, 1 pt; Régis 5, 1 pt; Régis 6, 1 pt; Régis mixed, 2 pts | Engel I, 19 pts; Engel II, 14 pts; Engel III, 8 pts; Engel IV, 7 pts | Median 71 mos |
| Buckley et al., 201610 | Laser | 6 (5) | Mean 10.9 yrs | NR | Mean 21/wk GS, 6 pts; CPS, 1 pt; generalized, 4 pts; SPS, 1 pt; dialeptic, 1 pt | Mean vol, 0.48 cm3 | Engel I, 4 pts; Engel II, 2 pts | Mean 9.26 mos |
| Du et al., 201729 | Laser | 7 | Mean 19.43 yrs | 2 | 3.24/day GS, 3 pts; CPS, 2 pts; generalized, 3 pts; focal, 2 pts | Median vol, 1.4 cm3 Delalande 1, 2 pts; Delalande 2, 3 pts; Delalande 3, 2 pts | Engel I, 6 pts; 75% seizure reduction, 1 pt | Mean 19.14 mos |
| Curry et al., 201817 | Laser | 71 (46) | Range 5 mos– 20 yrs | Range every 2 wks to >75/day | Range 4–30 mm in radius Delalande 1, 6 pts; Delalande 2, 35 pts; Delalande 3, 21 pts; Delalande 4, 9 pts | 12% seizure free; 93% GS free | 1 yr | |
| Xu et al., 201830 | Laser | 18 (14) | Mean 23.7 yrs | 6 | GS, 15 pts; CPS, 6 pts; tonic-clonic, 3 pts | Delalande 1, 2 pts; Delalande 2, 9 pts; Delalande 3, 6 pts; Delalande 4, 1 pt | 12 pts GS free; 6/9 non-GS control | Mean 19.2 mos |
| Gadgil et al., 202031 | Laser | 58 (40) | Median 5.5 yrs | 18 | GS, 58 pts; CPS, 16 pts; generalized, 6 pts | Median vol, 0.52 cm3 Delalande 1, 4 pts; Delalande 2, 30 pts; Delalande 3, 16 pts; Delalande 4, 8 pts | Engel II, 40 pts; Engel II, 7 pts; Engel III, 11 pts | Median 1.2 yrs |
| Candela-Cantó et al., 202237 | Laser | 11 (9) | Mean 6.4 yrs | 2 | GS, 11 pts; focal seizure, 6 pts | Delalande 1, 1 pt; Delalande 2, 1 pt; Delalande 3, 3 pts; Delalande 4, 6 pts | Engel I, 9 pts; Engel II, 1 pt; Engel VI, 1 pt | Mean 12 mos |
| Kuzniecky & Guthrie, 200332 | RFT | 7 | Mean 14.85 yrs | NR | NR | Small, 1 pt; medium, 4 pts; large 2 pts | Seizure free, 1 pt; 90% reduction, 3 pts; 50% reduction, 2 pts; 25% reduction, 1 pt | Mean 48 mos |
| Tandon et al., 201833 | RFT | 5 (5) | Mean 5.4 yrs | NR | Mean 21.4/day GS, 5 pts | Mean vol, 3.6 cm3 Régis 3, 5 pts | ILAE 1, 4 pts; ILAE 4, 1 pt | Mean 13.2 mos |
| Wei et al., 201834 | RFT | 9 (5) | Mean 14.89 yrs | 3 | Mean 3.1/day GS, 7 pts; dialeptic, 2 pts; generalized, 4 pts | Mean vol, 2.4 cm3 Delalande 1, 2 pts; Delalande 2, 3 pts; Delalande 3, 3 pts; Delalande 4, 1 pt | Engel I, 5 pts; Engel II, 4 pts | Mean 18.78 mos |
| Shirozu et al., 202026 | RFT | 150 (92) | Median 8 yrs | 41 | Daily GS, 134 pts, daily non-GS, 44 pts; GS, 150 pts; preceding non-GS, 6 pts; CPS, 76 pts; generalized tonic-clonic, 61 pts; tonic, 50 pts; atonic, 15 pts; myoclonic, 5 pts | Median max diameter, 1.5 cm Parahypothalamic, 8 pts; intrahypothalamic, 35 pts; mixed, 107 | Seizure freedom, 110 pts; 135 pts GS free: by 1st RFT, 103 pts; by 2nd RFT, 30 pts; by 3rd RFT, 3 pts; by 4th RFT, 2 pts; 90 pts non–GS free (89 at 1st RFT) | Annual visit up to 5 yrs |
| Wang et al., 202035 | RFT | 6 (3) | Mean 5.08 yrs | 1 | Mean 1.16/day GS, 6 pts; tonic, 1 pt; generalized tonic-clonic, 1 pt | Mean vol, 19.1 cm3 | Engel I, 4 pts; Engel II, 2 pts | Mean 20.17 mos |
| Wang et al., 202036 | RFT | 13 (8) | Mean 11.92 yrs | 2 | GS, 13 pts; CPS, 5 pts; SPS, 5 pts; generalized tonic-clonic, 2 pts | Mean size 13.45 mm | ILAE 1, 7 pts; ILAE 2, 2 pts; ILAE 4, 4 pts | Mean 50.77 mos |
CPS = complex partial seizure; FU = follow-up; GS = gelastic seizure; NR = not reported; pt = patient; SPS = simple partial seizure; Tx = treatment.
Long-term complications
| Authors & Year | Tx | FU Time | Neurological Problems | Behavioral Problems | Weight Gain | Poikilothermia | Endocrinological Problems |
|---|---|---|---|---|---|---|---|
| Abla et al., 201027 | GKRS | Mean 1.7 mos | NR | Worsening depression, 1 pt; increased anxiety, 1 pt | 2 pts | 1 pt | NR |
| Mathieu et al., 201028 | GKRS | Mean 18.6 mos | NR | NR | NR | NR | NR |
| Régis et al., 201716 | GKRS | Median 71 mos | NR | NR | NR | NR | TSH deficit, 1 pt |
| Buckley et al., 201610 | Laser | Mean 9.26 mos | NR | NR | NR | NR | NR |
| Du et al., 201729 | Laser | Mean 19.14 mos | Short-term memory deficit, 1 pt | NR | NR | NR | NR |
| Curry et al., 201817 | Laser | 1 yr | Short-term memory deficit, 1 pt | NR | NR | NR | DI, 1 pt |
| Xu et al., 201830 | Laser | Mean 19.2 mos | Short-term memory deficit, 4 pts; lower-limb weakness, 3 pts; lt Horner’s syndrome, 1 pt | NR | 4 pts | NR | Hypothyroidism, 3 pts |
| Gadgil et al., 202031 | Laser | Median 1.2 yrs | Short-term memory deficit, 1 pt | NR | NR | NR | Permanent DI, 1 pt |
| Candela-Cantó et al., 202237 | Laser | 22 mos | Somnolence | NR | NR | NR | NR |
| Kuzniecky & Guthrie, 200332 | RFT | Mean 33 mos | NR | NR | NR | NR | NR |
| Tandon et al., 201833 | RFT | Mean 13.2 mos | NR | NR | NR | NR | NR |
| Wei et al., 201834 | RFT | Mean 18.78 mos | NR | NR | 1 pt | NR | NR |
| Shirozu et al., 202026 | RFT | Annual visit up to 5 yrs | Memory disturbance, 6 pts; hemiparesis, 1 pt | Consciousness disturbance, 3 pts | 61 | NR | Hypopituitarism, 4 pts; DI, 2 pts |
| Wang et al., 202035 | RFT | Mean 20.17 mos | NR | NR | NR | NR | NR |
| Wang et al., 202036 | RFT | Mean 50.77 mos | NR | NR | NR | NR | Hypothyroidism, 2 pts |
DI = diabetes insipidus; TSH = thyroid-stimulating hormone.
General Results for Minimally Invasive Procedures
The combined analysis of all 15 included studies showed that the mean incidences of overall seizure freedom after minimally invasive procedures were 77% (95% CI 0.74–0.81) and 68% (95% CI 0.57–0.79) using fixed- and random-effects models, respectively. The heterogeneity analysis showed high interstudy heterogeneity (tau2 = 0.03, I2 = 84%, χ2 = 86.17, df = 14, p < 0.01). The value of 84% for I2 means that 84% of the observed variance is probably due to real differences between studies and can be potentially explained by study-level covariates.
The meta-regression analysis was conducted considering the type of treatment as an independent variable and the results showed that 45.24% of the heterogeneity was due to the type of treatment with a significant effect on the results (p = 0.02). Therefore, subgroup analysis based on type of the treatment was done.
Although 22.95% of the heterogeneity was found to be related to Delalande type11 (type 1 vs others), the effect on the results was not significant (p = 0.13).
The type of seizure (pure gelastic vs nonpure gelastic), sex, and tumor volume were not sources of heterogeneity.
The total complication rate with minimally invasive procedures was 13% (95% CI 0.01–0.26) with high heterogeneity (tau2 = 0.053, I2 = 87.4%, χ2 = 111.2, df = 14, p < 0.0001). None of the available covariates were found as a source of heterogeneity.
Radiofrequency Thermocoagulation
Six studies used RFT. The mean incidences of overall seizure freedom were 69% (95% CI 0.63–0.75) and 60% (95% CI 0.40–0.80) using fixed- and random-effects models, respectively (Fig. 2A). The plot also revealed that more recent studies had better results. The heterogeneity analysis showed moderate interstudy heterogeneity (tau2 = 0.04, I2 = 74%, χ2 = 19.61, df = 5, p < 0.01); therefore, the random-effects result seems more realistic.
Mean seizure-free ratio (A) and complication rate after RFT (B). IV = inverse variance.
The meta-regression analysis was conducted to evaluate the effect of sex, age, and type of seizure (pure gelastic vs nonpure gelastic). The analysis revealed that 39.9% of the heterogeneity was due to age. However, the effect of age on the results was not significant (p = 0.18). This means that other unaccounted, more important heterogeneity factors exist. On the other hand, neither sex nor type of seizure significantly affected the results.
The mean complication rate was 5% (95% CI 0.0–0.12) with mild heterogeneity (tau2 = 0.0018, I2 = 14%, χ2 = 5.79, df = 5, p = 0.33) (Fig. 2B). The meta-regression analysis was not reliable since only 2 studies had nonzero reports.
Publication bias was also assessed with a funnel plot and Egger’s regression test, and the results showed no significant bias (p = 0.34). Considering the small sample size, the results are not very reliable.
Laser Ablation
LA was used in 6 studies. The mean incidences of overall seizure freedom were 87% (95% CI 0.82–0.92) and 82% (95% CI 0.72–0.92) using fixed- and random-effects models, respectively (Fig. 3A). The heterogeneity analysis showed moderate between-study heterogeneity (tau2 = 0.0079, I2 = 65%, χ2 = 14.16, df = 5, p = 0.01). Available covariates for meta-regression were age, sex, tumor volume, and type of seizure (pure gelastic vs nonpure gelastic). However, none of the mentioned covariates significantly affected the results, which means that the sources of heterogeneity are other potential unaccounted covariates.
Mean seizure-free ratio (A) and complication rate after LA (B).
The mean complication rate was 20% (95% CI 0.0–0.47) with high heterogeneity (tau2 = 0.0989, I2 = 94%, χ2 = 86.28, df = 5, p < 0.01) (Fig. 3B). The meta-regression analysis showed that age had a major role in this heterogeneity (R2 = 70.86%) and a significant effect on the results (p = 0.0092), meaning that 70.86% of the heterogeneity accounts for the difference in mean ages of the patients between studies, with older age resulting in a higher rate of complication.
Although Egger’s regression test for publication bias showed no significant bias (p = 0.21), considering the small sample size, the results are not very reliable.
Gamma Knife Radiosurgery
Three studies evaluated the outcome of GKRS.16,27,28 The mean incidence of overall seizure freedom was 44% (95% CI 0.32–0.57) for fixed-effects and 48% (95% CI 0.30–0.65) for random-effects models (Fig. 4A). The heterogeneity was also mild (tau2 = 0.007, I2 = 12%, χ2 = 2.27, df = 2, p = 0.32). The analysis of long-term complications was significantly heterogeneous (tau2 = 0.135, I2 = 8%, χ2 = 16.35, df = 2, p < 0.01), most probably due to variation in complication definition in each study. However, the results showed a 22% (95% CI 0–0.65) complication rate for this treatment option (Fig. 4B).
Mean seizure-free ratio (A) and complication rate after GKRS (B).
The low sample size prohibited meta-regression analysis and publication bias tests.
Discussion
This systematic review aimed to compare the surgical outcomes of three minimally invasive techniques that have emerged as successful techniques for epilepsy control in patients with HH. Previous studies of surgery for mesial temporal lobe sclerosis revealed that LA and stereotactic radiosurgery are very efficient minimally invasive techniques for seizure freedom, compared with open surgical procedures.38 In the case of HH, the condition is different, as open surgical approaches are associated with high complications because of the anatomical site, and minimally invasive methods have gained superiority compared with open resection.39 Considering the limitations of the presented data in previously published literature and the limited numbers of studies, the level of evidence obtained from this review is low. In our meta-analysis, LA showed superiority in seizure freedom compared with two other methods, and RFT was superior to GKRS. This is consistent with findings of prior meta-analyses for the application of LA, RFT, and GKRS in the surgical treatment of epilepsy.40 One of the main disadvantages of GKRS is the long period between treatment and symptomatic improvement,41 which may be an essential factor associated with HH epilepsy cases. All stereotactic radiosurgery studies analyzed here used GKRS; CyberKnife stereotactic radiosurgery may be an alternative option in HH surgery,42 but sufficient data in the literature are lacking for the analysis of this alternative. According to our forest plot in the RFT group, this technique showed an improvement in efficacy in terms of seizure freedom over time, which could be related to advancement in device technology used in this procedure. Stereo-electroencephalography–guided RFT is an emerging technique that gained popularity for its accurate epileptogenic zone localization.40 Still, in most patients with HH, the localization of the epileptogenic zone is not a challenging task. Despite differences in the seizure freedom between the three groups, all showed a significant improvement rate. This is essential in developing countries with limited sources for a proper setting for these procedures.
We categorized seizure types associated with HH into two groups: pure gelastic and others. The rationale for this categorization was the predominance of gelastic seizures in the clinical history of these patients. Still, our analysis of three treatment modalities showed that seizure type did not influence postsurgical seizure freedom. We classified anatomical subtypes into two groups: Delalande type 1 and other types of Delalande classification. This was done for proper homogenization of the studies because some reported other classification methods, and we attempted to convert them into the Delalande classification. The anatomical subtype did not influence seizure freedom in our research. Age and sex also did not affect the seizure freedom.
Although the complication rate was different among the three subgroups, it was not statistically significant. Also, there was an association between older age and higher complication rates in the LA group.
There were some limitations in this study. The rarity of the disease was the main reason for the small sample sizes, which reduced the power of analysis. Notable variation in reporting methods of studies led to missing data or discrepancies that limited our analysis. Even some basic demographic information such as sex and mean patient age was not mentioned in some studies. It would be important for future articles about such rare conditions to report all available data so the subsequent analyses could provide more comprehensive understanding of the disease and treatment options.
Conclusions
In this meta-analysis, LA showed superiority in seizure freedom over the other two methods (RFT and GKRS). The complication rate associated with RFT was less than those for the other two methods; however, this difference was not statistically significant.
Appendix
Search Terms
Title/Abstract aura* or hamartoma* or epilep* or seizure*
AND
Title/Abstract hypothalam*
AND
Title/Abstract (“Gamma Knife” or “Gamma Knifes” or “Gamma Knive” or “Gamma Knives” or GammaKnife or GammaKnifes or GammaKnive or GammaKnives or “GK RS” or GKRS or “GK-RS” or “interstitial Laser thermal therap*” or “inter-stitial Laser thermal therap*” or “interstitial laser thermotherap*” or “interstitial laser thermo-therap*” or “inter-stitial laser thermotherap*” or “inter stitial laser thermo-therap*” or “laser ablat*” or “Laser interstitial thermal therap*” or “Laser inter-stitial thermal therap*” or “laser interstitial thermotherap*” or “laser interstitial thermo-therap*” or “laser inter-stitial thermotherap*” or “laser inter-stitial thermo-therap*” or “laser knife” or “laser knifes” or “laser knive” or “laser knives” or “laser photoablat*” or “laser photo-ablat*” or “laser scalpel*” or “laser surg*” or “laser therap*” or “laser thermotherap*” or “laser thermo-therap*” or “laser tissue ablat*” or “laser vaporiz*” or “Leksell Perfexion” or LITT or “MR-g-LITT” or Perfexion)
Disclosures
The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.
Author Contributions
Conception and design: all authors. Acquisition of data: Iranmehr, Dabbagh Ohadi, Chavoshi. Analysis and interpretation of data: Iranmehr, Chavoshi. Drafting the article: Iranmehr, Dabbagh Ohadi, Chavoshi, Jahanbakhshi. Critically revising the article: Slavin, Iranmehr, Jahanbakhshi. Reviewed submitted version of manuscript: Slavin, Iranmehr, Chavoshi, Jahanbakhshi. Approved the final version of the manuscript on behalf of all authors: Slavin. Statistical analysis: Iranmehr, Chavoshi. Administrative/technical/material support: Iranmehr, Chavoshi. Study supervision: Slavin.
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