Minimally invasive procedures for hypothalamic hamartoma–related epilepsy: a systematic review and meta-analysis

Arad IranmehrNeurosurgery Department, Imam Khomeini Hospital Complex (IKHC), Tehran University of Medical Sciences, Tehran, Iran;

Search for other papers by Arad Iranmehr in
jns
Google Scholar
PubMed
Close
 MD
,
Mohammad Amin Dabbagh OhadiNeurosurgery Department, Imam Khomeini Hospital Complex (IKHC), Tehran University of Medical Sciences, Tehran, Iran;

Search for other papers by Mohammad Amin Dabbagh Ohadi in
jns
Google Scholar
PubMed
Close
 MD
,
Mohammadreza ChavoshiDepartment of Radiology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran;

Search for other papers by Mohammadreza Chavoshi in
jns
Google Scholar
PubMed
Close
 MD
,
Amin JahanbakhshiStem Cell and Regenerative Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran; and

Search for other papers by Amin Jahanbakhshi in
jns
Google Scholar
PubMed
Close
 MD
, and
Konstantin V. SlavinDepartment of Neurosurgery, University of Illinois at Chicago, Illinois

Search for other papers by Konstantin V. Slavin in
jns
Google Scholar
PubMed
Close
 MD
Free access

OBJECTIVE

Hypothalamic hamartoma (HH) is a rare, nonmalignant, heterotopic developmental malformation that consists of a mixture of normal neurons and glial cells. Resection of HHs has been associated with high rates of mortality and morbidity. Therefore, minimally invasive ablation methods could be the best treatment option for HH. The most frequently used minimally invasive options for HH ablation are radiofrequency thermocoagulation (RFT), laser ablation (LA), and stereotactic radiosurgery.

METHODS

To investigate three minimally invasive procedures in the treatment of refractory seizures related to HH, the authors conducted a systematic search in March 2022 in the MEDLINE, Embase, Scopus, and Web of Science databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seizure freedom was the primary outcome of interest. The authors defined seizure freedom as Engel class I or International League Against Epilepsy class 1 or 2 or as the reported term “seizure freedom.” The secondary outcome was long-term complications reported in studies. Both random- and fixed-effects models were used to calculate the pooled proportion of seizure freedom and complication rate with 95% confidence intervals. A modified version of the Joanna Briggs Institute (JBI) Critical Appraisal to assess the risk of bias was used.

RESULTS

The authors included 15 studies with 422 patients (RFT, n = 190; LA, n = 171; and Gamma Knife Radiosurgery [GKRS], n = 61). Generally, 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 mean incidence of overall seizure freedom after RFT was 69% (95% CI 0.63–0.75), and the mean incidences of overall seizure freedom after LA and GKRS were 87% (95% CI 0.82–0.92) and 44% (95% CI 0.32–0.57), respectively. The total complication rate with minimally invasive procedures was 13% (95% CI 0.01–0.26). The complication rate in each treatment was as follows: 5% (95% CI 0.0–0.12) for RFT, 20% (95% CI 0.0–0.47) for LA, and 22% (95% CI 0–0.65) for GKRS. Meta-regression analysis showed an association between older age and higher complication rates in the LA group.

CONCLUSIONS

In this meta-analysis, LA showed superiority in seizure freedom over the other two methods. The complication rate associated with RFT was less than those in the other two methods; however, this difference was not statistically significant.

ABBREVIATIONS

GKRS = Gamma Knife radiosurgery; HH = hypothalamic hamartoma; ILAE = International League Against Epilepsy; LA = laser ablation; RFT = radiofrequency thermocoagulation.

OBJECTIVE

Hypothalamic hamartoma (HH) is a rare, nonmalignant, heterotopic developmental malformation that consists of a mixture of normal neurons and glial cells. Resection of HHs has been associated with high rates of mortality and morbidity. Therefore, minimally invasive ablation methods could be the best treatment option for HH. The most frequently used minimally invasive options for HH ablation are radiofrequency thermocoagulation (RFT), laser ablation (LA), and stereotactic radiosurgery.

METHODS

To investigate three minimally invasive procedures in the treatment of refractory seizures related to HH, the authors conducted a systematic search in March 2022 in the MEDLINE, Embase, Scopus, and Web of Science databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seizure freedom was the primary outcome of interest. The authors defined seizure freedom as Engel class I or International League Against Epilepsy class 1 or 2 or as the reported term “seizure freedom.” The secondary outcome was long-term complications reported in studies. Both random- and fixed-effects models were used to calculate the pooled proportion of seizure freedom and complication rate with 95% confidence intervals. A modified version of the Joanna Briggs Institute (JBI) Critical Appraisal to assess the risk of bias was used.

RESULTS

The authors included 15 studies with 422 patients (RFT, n = 190; LA, n = 171; and Gamma Knife Radiosurgery [GKRS], n = 61). Generally, 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 mean incidence of overall seizure freedom after RFT was 69% (95% CI 0.63–0.75), and the mean incidences of overall seizure freedom after LA and GKRS were 87% (95% CI 0.82–0.92) and 44% (95% CI 0.32–0.57), respectively. The total complication rate with minimally invasive procedures was 13% (95% CI 0.01–0.26). The complication rate in each treatment was as follows: 5% (95% CI 0.0–0.12) for RFT, 20% (95% CI 0.0–0.47) for LA, and 22% (95% CI 0–0.65) for GKRS. Meta-regression analysis showed an association between older age and higher complication rates in the LA group.

CONCLUSIONS

In this meta-analysis, LA showed superiority in seizure freedom over the other two methods. The complication rate associated with RFT was less than those in the other two methods; however, this difference was not statistically significant.

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.

TABLE 1.

Quality appraisal

Authors & YearQ1Q2Q3Q4Q5Q6Q7Q8
Abla et al., 201027YesYesYesYesYesYesYesYes
Mathieu et al., 201028YesYesYesNoNoNoYesYes
Régis et al., 201716YesYesYesYesYesYesYesYes
Buckley et al., 201610YesYesYesYesNoNoNoYes
Du et al., 201729YesYesYesYesYesYesYesYes
Curry et al., 201817YesYesYesYesNoNoNoYes
Xu et al., 201830YesYesYesYesYesNoNoYes
Gadgil et al., 202031YesYesYesYesYesNoYesYes
Candela-Cantó et al., 202237YesYesYesNoYesNoYesYes
Kuzniecky & Guthrie, 200332YesYesYesYesNoNoYesYes
Tandon et al., 201833YesYesYesNoNoYesYesYes
Wei et al., 201834YesYesYesYesYesYesYesYes
Shirozu et al., 202026YesYesYesYesYesYesYesYes
Wang et al., 202035YesYesYesYesYesNoYesYes
Wang et al., 202036YesYesYesYesYesNoYesYes

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 articles2225 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 studies10,16,17,2637 (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.

FIG. 1.
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.

TABLE 2.

Seizure outcomes

Authors & YearTxNo. of Pts (males)Age at TxPts w/ Prior ProceduresSeizure Frequency & TypeHH Measurement & TypeSeizure OutcomeFU Time
Abla et al., 201027GKRS7 (6)Mean 12.83 yrs3Mean 4.11/day GS, 5 pts; tonic, 1 pt; CPS 3 pts; absence, 1 pt; generalized, 1 ptMean vol, 0.50 cm3

Delalande 2, 5 pts; Delalande 3, 2 pts
Seizure free, 4 pts; 50–90% reduction, 1 pt; 0% reduction, 2 ptsMean 31.7 mos
Mathieu et al., 201028GKRS6 (4)Mean 30 yrsNRGS, 5 pts; CPS, 3 pts; SPS, 1 pt; generalized, 1 ptMean vol, 0.55 cm3 Régis 1, 2 pts; Régis 2, 4 pts; Régis 3, 1 ptEngel I, 4 pts; Engel II, 1 pt; Engel IV, 1 ptMean 18.6 mos
Régis et al., 201716GKRS48 (27)Median 16.5 yrs4Median 107.3/mo GS, 48 pts; CPS, 48 pts; generalized, 29 pts; status, 15 ptsMedian 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 ptsEngel I, 19 pts; Engel II, 14 pts; Engel III, 8 pts; Engel IV, 7 ptsMedian 71 mos
Buckley et al., 201610Laser6 (5)Mean 10.9 yrsNRMean 21/wk GS, 6 pts; CPS, 1 pt; generalized, 4 pts; SPS, 1 pt; dialeptic, 1 ptMean vol, 0.48 cm3Engel I, 4 pts; Engel II, 2 ptsMean 9.26 mos
Du et al., 201729Laser7Mean 19.43 yrs23.24/day GS, 3 pts; CPS, 2 pts; generalized, 3 pts; focal, 2 ptsMedian vol, 1.4 cm3 Delalande 1, 2 pts; Delalande 2, 3 pts; Delalande 3, 2 ptsEngel I, 6 pts; 75% seizure reduction, 1 ptMean 19.14 mos
Curry et al., 201817Laser71 (46)Range 5 mos– 20 yrsRange every 2 wks to >75/dayRange 4–30 mm in radius Delalande 1, 6 pts; Delalande 2, 35 pts; Delalande 3, 21 pts; Delalande 4, 9 pts12% seizure free; 93% GS free1 yr
Xu et al., 201830Laser18 (14)Mean 23.7 yrs6GS, 15 pts; CPS, 6 pts; tonic-clonic, 3 ptsDelalande 1, 2 pts; Delalande 2, 9 pts; Delalande 3, 6 pts; Delalande 4, 1 pt12 pts GS free; 6/9 non-GS controlMean 19.2 mos
Gadgil et al., 202031Laser58 (40)Median 5.5 yrs18GS, 58 pts; CPS, 16 pts; generalized, 6 ptsMedian vol, 0.52 cm3 Delalande 1, 4 pts; Delalande 2, 30 pts; Delalande 3, 16 pts; Delalande 4, 8 ptsEngel II, 40 pts; Engel II, 7 pts; Engel III, 11 ptsMedian 1.2 yrs
Candela-Cantó et al., 202237Laser11 (9)Mean 6.4 yrs2GS, 11 pts; focal seizure, 6 ptsDelalande 1, 1 pt; Delalande 2, 1 pt; Delalande 3, 3 pts; Delalande 4, 6 ptsEngel I, 9 pts; Engel II, 1 pt; Engel VI, 1 ptMean 12 mos
Kuzniecky & Guthrie, 200332RFT7Mean 14.85 yrsNRNRSmall, 1 pt; medium, 4 pts; large 2 ptsSeizure free, 1 pt; 90% reduction, 3 pts; 50% reduction, 2 pts; 25% reduction, 1 ptMean 48 mos
Tandon et al., 201833RFT5 (5)Mean 5.4 yrsNRMean 21.4/day

GS, 5 pts
Mean vol, 3.6 cm3

Régis 3, 5 pts
ILAE 1, 4 pts; ILAE 4, 1 ptMean 13.2 mos
Wei et al., 201834RFT9 (5)Mean 14.89 yrs3Mean 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 ptsMean 18.78 mos
Shirozu et al., 202026RFT150 (92)Median 8 yrs41Daily 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 ptsMedian max diameter, 1.5 cm Parahypothalamic, 8 pts; intrahypothalamic, 35 pts; mixed, 107Seizure 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., 202035RFT6 (3)Mean 5.08 yrs1Mean 1.16/day GS, 6 pts; tonic, 1 pt; generalized tonic-clonic, 1 ptMean vol, 19.1 cm3Engel I, 4 pts; Engel II, 2 ptsMean 20.17 mos
Wang et al., 202036RFT13 (8)Mean 11.92 yrs2GS, 13 pts; CPS, 5 pts; SPS, 5 pts; generalized tonic-clonic, 2 ptsMean size 13.45 mmILAE 1, 7 pts; ILAE 2, 2 pts; ILAE 4, 4 ptsMean 50.77 mos

CPS = complex partial seizure; FU = follow-up; GS = gelastic seizure; NR = not reported; pt = patient; SPS = simple partial seizure; Tx = treatment.

TABLE 3.

Long-term complications

Authors & YearTxFU TimeNeurological ProblemsBehavioral ProblemsWeight GainPoikilothermiaEndocrinological Problems
Abla et al., 201027GKRSMean 1.7 mosNRWorsening depression, 1 pt; increased anxiety, 1 pt2 pts1 ptNR
Mathieu et al., 201028GKRSMean 18.6 mosNRNRNRNRNR
Régis et al., 201716GKRSMedian 71 mosNRNRNRNRTSH deficit, 1 pt
Buckley et al., 201610LaserMean 9.26 mosNRNRNRNRNR
Du et al., 201729LaserMean 19.14 mosShort-term memory deficit, 1 ptNRNRNRNR
Curry et al., 201817Laser1 yrShort-term memory deficit, 1 ptNRNRNRDI, 1 pt
Xu et al., 201830LaserMean 19.2 mosShort-term memory deficit, 4 pts; lower-limb weakness, 3 pts; lt Horner’s syndrome, 1 ptNR4 ptsNRHypothyroidism, 3 pts
Gadgil et al., 202031LaserMedian 1.2 yrsShort-term memory deficit, 1 ptNRNRNRPermanent DI, 1 pt
Candela-Cantó et al., 202237Laser22 mosSomnolenceNRNRNRNR
Kuzniecky & Guthrie, 200332RFTMean 33 mosNRNRNRNRNR
Tandon et al., 201833RFTMean 13.2 mosNRNRNRNRNR
Wei et al., 201834RFTMean 18.78 mosNRNR1 ptNRNR
Shirozu et al., 202026RFTAnnual visit up to 5 yrsMemory disturbance, 6 pts; hemiparesis, 1 ptConsciousness disturbance, 3 pts61NRHypopituitarism, 4 pts; DI, 2 pts
Wang et al., 202035RFTMean 20.17 mosNRNRNRNRNR
Wang et al., 202036RFTMean 50.77 mosNRNRNRNRHypothyroidism, 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.

FIG. 2.
FIG. 2.

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.

FIG. 3.
FIG. 3.

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).

FIG. 4.
FIG. 4.

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.

References

  • 1

    Kondajji AM, Evans A, Lum M, et al. A systematic review of stereotactic radiofrequency ablation for hypothalamic hamartomas. J Neurol Sci. 2021;424:117428.

  • 2

    Bourdillon P, Ferrand-Sorbet S, Apra C, et al. Surgical treatment of hypothalamic hamartomas. Neurosurg Rev. 2021;44(2):753762.

  • 3

    Cohen M, Bartels U, Branson H, Kulkarni AV, Hamilton J. Trends in treatment and outcomes of pediatric craniopharyngioma, 1975-2011. Neuro Oncol. 2013;15(6):767774.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Chan YM, Fenoglio-Simeone KA, Paraschos S, et al. Central precocious puberty due to hypothalamic hamartomas correlates with anatomic features but not with expression of GnRH, TGFα, or KISS1. Horm Res Paediatr. 2010;73(5):312319.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Parvizi J, Le S, Foster BL, et al. Gelastic epilepsy and hypothalamic hamartomas: neuroanatomical analysis of brain lesions in 100 patients. Brain. 2011;134(Pt 10):29602968.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Wang B, Ma J. The diagnosis and management of hypothalamic hamartomas in children. Chinese Neurosurg J. 2016;2(1):29.

  • 7

    Burghardt T, Basha MM, Fuerst D, Mittal S. Crying with sorrow evoked by electrocortical stimulation. Epileptic Disord. 2013;15(1):7275.

  • 8

    Freeman JL, Coleman LT, Wellard RM, et al. MR imaging and spectroscopic study of epileptogenic hypothalamic hamartomas: analysis of 72 cases. AJNR Am J Neuroradiol. 2004;25(3):450462.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Iranmehr A, Esmaeilnia M, Afshari K, et al. Surgical outcomes of endoscopic endonasal surgery in 29 patients with craniopharyngioma. J Neurol Surg B Skull Base. 2020;82(4):401409.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Buckley RT, Wang AC, Miller JW, Novotny EJ, Ojemann JG. Stereotactic laser ablation for hypothalamic and deep intraventricular lesions. Neurosurg Focus. 2016;41(4):E10.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Delalande O, Fohlen M. Disconnecting surgical treatment of hypothalamic hamartoma in children and adults with refractory epilepsy and proposal of a new classification. Neurol Med Chir (Tokyo). 2003;43(2):6168.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12

    Régis 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(8):881895.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13

    Moola S, Munn Z, Tufanaru C, et al. Chapter 7: Systematic reviews of etiology and risk. In: Aromataris E, Munn Z, eds. JBI Manual for Evidence Synthesis. JBI; 2020.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14

    Régis J, Bartolomei F, de Toffol B, et al. Gamma knife surgery for epilepsy related to hypothalamic hamartomas. Neurosurgery. 2000;47(6):13431352.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15

    Régis J, Hayashi M, Eupierre LP, et al. Gamma knife surgery for epilepsy related to hypothalamic hamartomas. Acta Neurochir Suppl. 2004;91:3350.

    • Search Google Scholar
    • Export Citation
  • 16

    Régis J, Lagmari M, Carron R, et al. Safety and efficacy of Gamma Knife radiosurgery in hypothalamic hamartomas with severe epilepsies: a prospective trial in 48 patients and review of the literature. Epilepsia. 2017;58(suppl 2):6071.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17

    Curry DJ, Raskin J, Ali I, Wilfong AA. MR-guided laser ablation for the treatment of hypothalamic hamartomas. Epilepsy Res. 2018;142:131134.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18

    Boerwinkle VL, Foldes ST, Torrisi SJ, et al. Subcentimeter epilepsy surgery targets by resting state functional magnetic resonance imaging can improve outcomes in hypothalamic hamartoma. Epilepsia. 2018;59(12):22842295.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19

    Wilfong AA, Curry DJ. Hypothalamic hamartomas: optimal approach to clinical evaluation and diagnosis. Epilepsia. 2013;54(suppl 9):109114.

  • 20

    Sonoda M, Masuda H, Shirozu H, et al. Predictors of cognitive function in patients with hypothalamic hamartoma following stereotactic radiofrequency thermocoagulation surgery. Epilepsia. 2017;58(9):15561565.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21

    Hamdi H, Albader F, Spatola G, et al. Long-term cognitive outcome after radiosurgery in epileptic hypothalamic hamartomas and review of the literature. Epilepsia. 2021;62(6)(suppl 1):13691381.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22

    Shirozu H, Masuda H, Ito Y, Sonoda M, Kameyama S. Stereotactic radiofrequency thermocoagulation for giant hypothalamic hamartoma. J Neurosurg. 2016;125(4):812821.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23

    Shirozu H, Masuda H, Kameyama S. Significance of the electrophysiological border between hypothalamic hamartomas and the hypothalamus for the target of ablation surgery identified by intraoperative semimicrorecording. Epilepsia. 2020;61(12):27392747.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24

    Kameyama S, Shirozu H, Masuda H, Ito Y, Sonoda M, Akazawa K. MRI-guided stereotactic radiofrequency thermocoagulation for 100 hypothalamic hamartomas. J Neurosurg. 2016;124(5):15031512.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25

    Homma J, Kameyama S, Masuda H, et al. Stereotactic radiofrequency thermocoagulation for hypothalamic hamartoma with intractable gelastic seizures. Epilepsy Res. 2007;76(1):1521.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26

    Shirozu H, Masuda H, Kameyama S. Repeat stereotactic radiofrequency thermocoagulation in patients with hypothalamic hamartoma and seizure recurrence. Epilepsia Open. 2020;5(1):107120.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27

    Abla AA, Shetter AG, Chang SW, et al. Gamma Knife surgery for hypothalamic hamartomas and epilepsy: patient selection and outcomes. J Neurosurg. 2010;113(suppl):207214.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28

    Mathieu D, Deacon C, Pinard CA, Kenny B, Duval J. Gamma Knife surgery for hypothalamic hamartomas causing refractory epilepsy: preliminary results from a prospective observational study. J Neurosurg. 2010;113(suppl):215221.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29

    Du VX, Gandhi SV, Rekate HL, Mehta AD. Laser interstitial thermal therapy: a first line treatment for seizures due to hypothalamic hamartoma? Epilepsia. 2017;58(suppl 2):7784.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30

    Xu DS, Chen T, Hlubek RJ, et al. Magnetic resonance imaging-guided laser interstitial thermal therapy for the treatment of hypothalamic hamartomas: a retrospective review. Neurosurgery. 2018;83(6):11831192.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31

    Gadgil N, Lam S, Pan IW, et al. Staged magnetic resonance-guided laser interstitial thermal therapy for hypothalamic hamartoma: analysis of ablation volumes and morphological considerations. Neurosurgery. 2020;86(6):808816.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32

    Kuzniecky RI, Guthrie BL. Stereotactic surgical approach to hypothalamic hamartomas. Epileptic Disord. 2003;5(4):275280.

  • 33

    Tandon V, Chandra PS, Doddamani RS, et al. Stereotactic radiofrequency thermocoagulation of hypothalamic hamartoma using Robotic Guidance (ROSA) coregistered with O-arm guidance—preliminary technical note. World Neurosurg. 2018;112:267274.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34

    Wei PH, An Y, Fan XT, et al. Stereoelectroencephalography-guided radiofrequency thermocoagulation for hypothalamic hamartomas: preliminary evidence. World Neurosurg. 2018;114:e1073e1078.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35

    Wang M, Zhou Y, Zhang Y, et al. One-stage high-density focal stereo-array SEEG-guided radiofrequency thermocoagulation for the treatment of pediatric giant hypothalamic hamartomas. Front Neurol. 2020;11:965.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36

    Wang S, Zhao M, Li T, et al. Stereotactic radiofrequency thermocoagulation and resective surgery for patients with hypothalamic hamartoma. J Neurosurg. 2020;134(3):10191026.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37

    Candela-Cantó S, Muchart J, Ramírez-Camacho A, et al. Robot-assisted, real-time, MRI-guided laser interstitial thermal therapy for pediatric patients with hypothalamic hamartoma: surgical technique, pitfalls, and initial results. J Neurosurg Pediatr. 2022;29(6):681692.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38

    Grewal SS, Alvi MA, Lu VM, et al. Magnetic resonance-guided laser interstitial thermal therapy versus stereotactic radiosurgery for medically intractable temporal lobe epilepsy: a systematic review and meta-analysis of seizure outcomes and complications. World Neurosurg. 2019;122:e32e47.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 39

    Drees C, Chapman K, Prenger E, et al. Seizure outcome and complications following hypothalamic hamartoma treatment in adults: endoscopic, open, and Gamma Knife procedures. J Neurosurg. 2012;117(2):255261.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 40

    Wang Y, Xu J, Liu T, et al. Magnetic resonance-guided laser interstitial thermal therapy versus stereoelectroencephalography-guided radiofrequency thermocoagulation for drug-resistant epilepsy: a systematic review and meta-analysis. Epilepsy Res. 2020;166:106397.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 41

    Barbaro NM, Quigg M, Broshek DK, et al. A multicenter, prospective pilot study of gamma knife radiosurgery for mesial temporal lobe epilepsy: seizure response, adverse events, and verbal memory. Ann Neurol. 2009;65(2):167175.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 42

    Romanelli P. CyberKnife® radiosurgery as first-line treatment for catastrophic epilepsy caused by hypothalamic hamartoma. Cureus. 2018;10(7):e2968.

    • Search Google Scholar
    • Export Citation
  • Collapse
  • Expand
  • View in gallery
    FIG. 1.

    PRISMA flow diagram. One article was excluded for two reasons.

  • View in gallery
    FIG. 2.

    Mean seizure-free ratio (A) and complication rate after RFT (B). IV = inverse variance.

  • View in gallery
    FIG. 3.

    Mean seizure-free ratio (A) and complication rate after LA (B).

  • View in gallery
    FIG. 4.

    Mean seizure-free ratio (A) and complication rate after GKRS (B).

  • 1

    Kondajji AM, Evans A, Lum M, et al. A systematic review of stereotactic radiofrequency ablation for hypothalamic hamartomas. J Neurol Sci. 2021;424:117428.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2

    Bourdillon P, Ferrand-Sorbet S, Apra C, et al. Surgical treatment of hypothalamic hamartomas. Neurosurg Rev. 2021;44(2):753762.

  • 3

    Cohen M, Bartels U, Branson H, Kulkarni AV, Hamilton J. Trends in treatment and outcomes of pediatric craniopharyngioma, 1975-2011. Neuro Oncol. 2013;15(6):767774.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4

    Chan YM, Fenoglio-Simeone KA, Paraschos S, et al. Central precocious puberty due to hypothalamic hamartomas correlates with anatomic features but not with expression of GnRH, TGFα, or KISS1. Horm Res Paediatr. 2010;73(5):312319.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5

    Parvizi J, Le S, Foster BL, et al. Gelastic epilepsy and hypothalamic hamartomas: neuroanatomical analysis of brain lesions in 100 patients. Brain. 2011;134(Pt 10):29602968.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6

    Wang B, Ma J. The diagnosis and management of hypothalamic hamartomas in children. Chinese Neurosurg J. 2016;2(1):29.

  • 7

    Burghardt T, Basha MM, Fuerst D, Mittal S. Crying with sorrow evoked by electrocortical stimulation. Epileptic Disord. 2013;15(1):7275.

  • 8

    Freeman JL, Coleman LT, Wellard RM, et al. MR imaging and spectroscopic study of epileptogenic hypothalamic hamartomas: analysis of 72 cases. AJNR Am J Neuroradiol. 2004;25(3):450462.

    • Search Google Scholar
    • Export Citation
  • 9

    Iranmehr A, Esmaeilnia M, Afshari K, et al. Surgical outcomes of endoscopic endonasal surgery in 29 patients with craniopharyngioma. J Neurol Surg B Skull Base. 2020;82(4):401409.

    • Search Google Scholar
    • Export Citation
  • 10

    Buckley RT, Wang AC, Miller JW, Novotny EJ, Ojemann JG. Stereotactic laser ablation for hypothalamic and deep intraventricular lesions. Neurosurg Focus. 2016;41(4):E10.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11

    Delalande O, Fohlen M. Disconnecting surgical treatment of hypothalamic hamartoma in children and adults with refractory epilepsy and proposal of a new classification. Neurol Med Chir (Tokyo). 2003;43(2):6168.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12

    Régis 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(8):881895.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13

    Moola S, Munn Z, Tufanaru C, et al. Chapter 7: Systematic reviews of etiology and risk. In: Aromataris E, Munn Z, eds. JBI Manual for Evidence Synthesis. JBI; 2020.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14

    Régis J, Bartolomei F, de Toffol B, et al. Gamma knife surgery for epilepsy related to hypothalamic hamartomas. Neurosurgery. 2000;47(6):13431352.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15

    Régis J, Hayashi M, Eupierre LP, et al. Gamma knife surgery for epilepsy related to hypothalamic hamartomas. Acta Neurochir Suppl. 2004;91:3350.

    • Search Google Scholar
    • Export Citation
  • 16

    Régis J, Lagmari M, Carron R, et al. Safety and efficacy of Gamma Knife radiosurgery in hypothalamic hamartomas with severe epilepsies: a prospective trial in 48 patients and review of the literature. Epilepsia. 2017;58(suppl 2):6071.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17

    Curry DJ, Raskin J, Ali I, Wilfong AA. MR-guided laser ablation for the treatment of hypothalamic hamartomas. Epilepsy Res. 2018;142:131134.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18

    Boerwinkle VL, Foldes ST, Torrisi SJ, et al. Subcentimeter epilepsy surgery targets by resting state functional magnetic resonance imaging can improve outcomes in hypothalamic hamartoma. Epilepsia. 2018;59(12):22842295.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19

    Wilfong AA, Curry DJ. Hypothalamic hamartomas: optimal approach to clinical evaluation and diagnosis. Epilepsia. 2013;54(suppl 9):109114.

  • 20

    Sonoda M, Masuda H, Shirozu H, et al. Predictors of cognitive function in patients with hypothalamic hamartoma following stereotactic radiofrequency thermocoagulation surgery. Epilepsia. 2017;58(9):15561565.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21

    Hamdi H, Albader F, Spatola G, et al. Long-term cognitive outcome after radiosurgery in epileptic hypothalamic hamartomas and review of the literature. Epilepsia. 2021;62(6)(suppl 1):13691381.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22

    Shirozu H, Masuda H, Ito Y, Sonoda M, Kameyama S. Stereotactic radiofrequency thermocoagulation for giant hypothalamic hamartoma. J Neurosurg. 2016;125(4):812821.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23

    Shirozu H, Masuda H, Kameyama S. Significance of the electrophysiological border between hypothalamic hamartomas and the hypothalamus for the target of ablation surgery identified by intraoperative semimicrorecording. Epilepsia. 2020;61(12):27392747.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24

    Kameyama S, Shirozu H, Masuda H, Ito Y, Sonoda M, Akazawa K. MRI-guided stereotactic radiofrequency thermocoagulation for 100 hypothalamic hamartomas. J Neurosurg. 2016;124(5):15031512.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25

    Homma J, Kameyama S, Masuda H, et al. Stereotactic radiofrequency thermocoagulation for hypothalamic hamartoma with intractable gelastic seizures. Epilepsy Res. 2007;76(1):1521.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26

    Shirozu H, Masuda H, Kameyama S. Repeat stereotactic radiofrequency thermocoagulation in patients with hypothalamic hamartoma and seizure recurrence. Epilepsia Open. 2020;5(1):107120.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27

    Abla AA, Shetter AG, Chang SW, et al. Gamma Knife surgery for hypothalamic hamartomas and epilepsy: patient selection and outcomes. J Neurosurg. 2010;113(suppl):207214.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28

    Mathieu D, Deacon C, Pinard CA, Kenny B, Duval J. Gamma Knife surgery for hypothalamic hamartomas causing refractory epilepsy: preliminary results from a prospective observational study. J Neurosurg. 2010;113(suppl):215221.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29

    Du VX, Gandhi SV, Rekate HL, Mehta AD. Laser interstitial thermal therapy: a first line treatment for seizures due to hypothalamic hamartoma? Epilepsia. 2017;58(suppl 2):7784.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30

    Xu DS, Chen T, Hlubek RJ, et al. Magnetic resonance imaging-guided laser interstitial thermal therapy for the treatment of hypothalamic hamartomas: a retrospective review. Neurosurgery. 2018;83(6):11831192.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31

    Gadgil N, Lam S, Pan IW, et al. Staged magnetic resonance-guided laser interstitial thermal therapy for hypothalamic hamartoma: analysis of ablation volumes and morphological considerations. Neurosurgery. 2020;86(6):808816.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32

    Kuzniecky RI, Guthrie BL. Stereotactic surgical approach to hypothalamic hamartomas. Epileptic Disord. 2003;5(4):275280.

  • 33

    Tandon V, Chandra PS, Doddamani RS, et al. Stereotactic radiofrequency thermocoagulation of hypothalamic hamartoma using Robotic Guidance (ROSA) coregistered with O-arm guidance—preliminary technical note. World Neurosurg. 2018;112:267274.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34

    Wei PH, An Y, Fan XT, et al. Stereoelectroencephalography-guided radiofrequency thermocoagulation for hypothalamic hamartomas: preliminary evidence. World Neurosurg. 2018;114:e1073e1078.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35

    Wang M, Zhou Y, Zhang Y, et al. One-stage high-density focal stereo-array SEEG-guided radiofrequency thermocoagulation for the treatment of pediatric giant hypothalamic hamartomas. Front Neurol. 2020;11:965.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36

    Wang S, Zhao M, Li T, et al. Stereotactic radiofrequency thermocoagulation and resective surgery for patients with hypothalamic hamartoma. J Neurosurg. 2020;134(3):10191026.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37

    Candela-Cantó S, Muchart J, Ramírez-Camacho A, et al. Robot-assisted, real-time, MRI-guided laser interstitial thermal therapy for pediatric patients with hypothalamic hamartoma: surgical technique, pitfalls, and initial results. J Neurosurg Pediatr. 2022;29(6):681692.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38

    Grewal SS, Alvi MA, Lu VM, et al. Magnetic resonance-guided laser interstitial thermal therapy versus stereotactic radiosurgery for medically intractable temporal lobe epilepsy: a systematic review and meta-analysis of seizure outcomes and complications. World Neurosurg. 2019;122:e32e47.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 39

    Drees C, Chapman K, Prenger E, et al. Seizure outcome and complications following hypothalamic hamartoma treatment in adults: endoscopic, open, and Gamma Knife procedures. J Neurosurg. 2012;117(2):255261.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 40

    Wang Y, Xu J, Liu T, et al. Magnetic resonance-guided laser interstitial thermal therapy versus stereoelectroencephalography-guided radiofrequency thermocoagulation for drug-resistant epilepsy: a systematic review and meta-analysis. Epilepsy Res. 2020;166:106397.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 41

    Barbaro NM, Quigg M, Broshek DK, et al. A multicenter, prospective pilot study of gamma knife radiosurgery for mesial temporal lobe epilepsy: seizure response, adverse events, and verbal memory. Ann Neurol. 2009;65(2):167175.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 42

    Romanelli P. CyberKnife® radiosurgery as first-line treatment for catastrophic epilepsy caused by hypothalamic hamartoma. Cureus. 2018;10(7):e2968.

    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 498 498 59
PDF Downloads 490 490 75
EPUB Downloads 0 0 0