Trends, outcomes, and complications of surgery for lesional epilepsy in infants and toddlers: A multicenter study.

OBJECTIVE: To assess seizure and developmental outcomes, their predictors, and complications in 160 children who, between 1998 and 2022, underwent surgery for lesional epilepsy with curative intent before the age of 3 years. To compare trends in epilepsy surgery in this age group before and after the year 2014. METHODS: Retrospective multicenter study. Descriptive and univariate analyses, and multivariable models for all outcomes. RESULTS: These 160 patients (76 F; 47.5%) underwent 169 surgeries (age at surgery 20.4 ± 9.4 months). At the last follow-up (77 ± 57.4 months), 121 patients (75.6%) were in Engel class I, 106 (66.2%) of whom were in Engel class Ia. Antiseizure medications were stopped in 84 patients (52.5%). Complications requiring reoperations were observed in 16 patients (10%; 9.5% of surgeries) and unexpected permanent deficits in 12 (7.5%; 7.1% of surgeries). Postoperative cognitive functions remained unchanged in 56 patients (44.4%), improved in 51 (40.5%), and worsened in 19 (15.1%). Multivariable analyses showed that the probability of achieving Engel class Ia was lower when the duration of epilepsy was longer, patients underwent preoperative video-EEG, and unexpected postoperative permanent deficits occurred. Cognitive improvement after surgery was associated with lower preoperative seizure frequency, better preoperative developmental level, and a longer postoperative follow-up. FCDII and tumors were the histopathologies carrying a higher probability of achieving seizure freedom, while polymicrogyria was associated with a lower probability of cognitive improvement. The number of patients operated on after 2014 was higher than before (61.3% vs. 38.7%), with stable outcomes. SIGNIFICANCE: Epilepsy surgery is effective and safe in infants and toddlers, although the complication rate is higher than seen in older patients. Shorter duration of epilepsy, lower seizure frequency, no need for video-EEG, tumors, and some malformations of cortical development are robust predictors of seizure and cognitive outcome that may be exploited to increase earlier referral. PLAIN LANGUAGE SUMMARY: This study analyzed the results of epilepsy surgery in 160 children who had been operated on before the age of 3 years at four Italian centers between 1998 and 2022. At the last follow-up (77 ± 57.4 months), 121 patients (75.6%) were free from disabling seizures, of which 106 (66.2%) were completely seizure-free since surgery. Major surgical complications occurred in 28 patients (17.5%), which is higher than observed with epilepsy surgery in general, but similar to hemispheric/multilobar surgery. Postoperative cognitive function remained unchanged in 56 patients (44.4%), improved in 51 (40.5%), and worsened in 19 (15.1%). Epilepsy surgery is effective and safe in infants and toddlers.

Surgical Management of Chiari Malformation Type I in the Pediatric Population: A Single-Center Experience.

Background: Chiari malformation type 1 (CM-1) involves the cerebellar tonsils' descent below the foramen magnum. In Chiari malformation type 1.5 (CM-1.5), both the cerebellar tonsils and the brainstem are herniated. Common symptoms include headaches and cervical pain, often associated with conditions like syringomyelia and hydrocephalus. Surgical treatment is not performed in asymptomatic patients, while the presence of syringomyelia represents an indication for surgery. Methods: This study retrospectively examined pediatric patients with CM-1 and CM-1.5 at Giannina Gaslini Hospital from 2006 to 2020, analyzing demographics, radiological findings, surgical interventions, and outcomes. Results: Out of 211 patients who underwent surgery, 83.9% were diagnosed with CM-1 and 16.1% with CM-1.5. Headaches were prevalent (69%) and cerebellar signs were noted in 29% of patients. Syringomyelia and hydrocephalus were present in 28.4% and 8% of cases, respectively. Intraoperative ultrasonography guided interventions, with 59.8% requiring bony and ligamentous decompression, and 27.1% undergoing duraplasty. Conclusions: The surgical treatment of CM-1/CM-1.5 involves posterior cranial fossa decompression. Choosing between bony decompression alone and its combination with duraplasty has always been controversial in the pediatric population. If we consider as surgical endpoint the restoration of cerebrospinal fluid (CSF) flux, intraoperative ultrasound may be a real-time helpful tool in orienting the surgical strategy, yet refinement with quantitative measures is needed.

Surgical and radiosurgical treatment of hypothalamic hamartoma: The Italian experience between 2011 and 2021.

OBJECTIVE: To investigate the Italian experience on the surgical and radiosurgical treatment of drug-resistant epilepsy due to hypothalamic hamartoma (HH) in the period 2011-2021 in six Italian epilepsy surgery centers, and to compare safety and efficacy profiles of the different techniques. METHODS: We collected pseudo-anonymized patient's data with at least 12 months of follow-up. Surgical outcome was defined according to Engel classification of seizure outcome. Univariate analysis was performed to assess the risk of post-operative seizures, categorized in dichotomous variable as favorable and unfavorable; explanatory variables were considered. Mann-Whitney or Chi-squared test were used to assess the presence of an association between variables (p < 0.05). RESULTS: Full presurgical and postoperative data about 42 patients from 6 epilepsy surgery centers were gathered. Engel class I was reached in the 65.8% and 66.6% of patients with gelastic and non-gelastic seizures, respectively. Other than daily non-gelastic seizures were associated with seizure freedom (p = 0.01), and the radiological type presented a trend toward significance (p = 0.12). SIGNIFICANCE: Endoscopic disconnection and laser interstitial thermal therapy are effective in the treatment of HH-related epilepsy, with a tolerable safety profile. Both gelastic and non-gelastic seizures can be treated, also in patients with a long history of seizures. PLAIN LANGUAGE SUMMARY: This study collected data about 42 patients with HH-related epilepsies. Endoscopic disconnection and laser therapy are both effective and safe in the treatment of hypothalamic hamartoma-related epilepsies.

Surgical treatment of cavernous malformation-related epilepsy in children: case series, systematic review, and meta-analysis.

OBJECTIVE: Cerebral cavernous malformations (CCMs) are cerebral vascular lesions that occasionally occur with seizures. We present a retrospective case series from IRCCS Gaslini Children's Hospital, a systematic review, and meta-analysis of the literature with the goal of elucidating the post-surgery seizure outcome in children with CCMs. METHODS: a retrospective review of children with cavernous malformation related epilepsy who underwent surgery at Gaslini Children's Hospital from 2005 to 2022 was conducted. We also conducted a comprehensive search on PubMed/MEDLINE and Scopus databases from January 1989 to August 2022. Inclusion criteria were: presence of CCMs-related epilepsy, in under 18 years old subjects with a clear lesion site. Presence of post-surgery seizure outcome and follow-up ≥ 12 months. RESULTS: we identified 30 manuscripts and 223 patients with CCMs-related epilepsy, including 17 patients reported in our series. We identified 85.7% Engel class I subjects. The risk of expected neurological deficits was 3.7%; that of unexpected neurological deficits 2.8%. We found no statistically significant correlations between Engel class and the following factors: site of lesion, type of seizure, drug resistance, duration of disease, type of surgery, presence of multiple CCMs. However, we found some interesting trends: longer disease duration and drug resistance seem to be more frequent in subjects in Engel class II, III and IV; multiple cavernomas would not seem to influence seizure outcome. CONCLUSIONS: epilepsy surgery in children with CCMs is a safe and successful treatment option. Further studies are necessary to define the impact of clinical features on seizure prognosis.

NLP-based tools for localization of the epileptogenic zone in patients with drug-resistant focal epilepsy.

Epilepsy surgery is an option for people with focal onset drug-resistant (DR) seizures but a delayed or incorrect diagnosis of epileptogenic zone (EZ) location limits its efficacy. Seizure semiological manifestations and their chronological appearance contain valuable information on the putative EZ location but their interpretation relies on extensive experience. The aim of our work is to support the localization of EZ in DR patients automatically analyzing the semiological description of seizures contained in video-EEG reports. Our sample is composed of 536 descriptions of seizures extracted from Electronic Medical Records of 122 patients. We devised numerical representations of anamnestic records and seizures descriptions, exploiting Natural Language Processing (NLP) techniques, and used them to feed Machine Learning (ML) models. We performed three binary classification tasks: localizing the EZ in the right or left hemisphere, temporal or extra-temporal, and frontal or posterior regions. Our computational pipeline reached performances above 70% in all tasks. These results show that NLP-based numerical representation combined with ML-based classification models may help in localizing the origin of the seizures relying only on seizures-related semiological text data alone. Accurate early recognition of EZ could enable a more appropriate patient management and a faster access to epilepsy surgery to potential candidates.

Pathogenesis and treatment of a giant occipital bone defect with meningoencephalocele in an NF1 child: case report and review of the literature.

Autosomal dominantly inherited neurofibromatosis type I (NF1) is a systemic disorder caused by a mutation of a gene on chromosome 17q11.2 and characterized by multiple café-au-lait spots, lentiginous macules, Lisch nodules of the iris, and tumors of the nervous system. Bony manifestations such as scoliosis, dysplasia of the greater sphenoidal wing, tibial pseudoarthrosis, short stature, and macrocephaly have been reported in approximately 50% of patients. However, calvarial bone defects are rare. After screening 324 articles, 23 cases (12 adult and 11 pediatric patients) of occipital bone defects in NF1 patients were selected. All patients had a single/multiple bone defect over the lambdoid suture. Adjacent benign plexiform neurofibromas were observed in 14 patients (60.8%, 7 adults and 7 children); one adult patient was diagnosed with neurofibrosarcoma. Meningoencephalocele over the occipital defect was noted in 8 cases (34.78%, all adults). Cranioplasty was performed in only 17.39% of patients. Histologic examination was performed in 7 of the 15 patients with associated neurofibromas/neurofibrosarcomas. Biopsy of the bone margins surrounding the defect was performed in only one case. Pathologic examination of the herniated parieto-occipital or cerebellar tissue was not performed in any of the patients studied. We report the case of a 9-year-old girl with NF1 and a significant occipital bone defect and performed a systematic review of the relevant literature to highlight the challenges in treating this condition and to investigate the underlying mechanisms contributing to bone defects or dysplasia in NF1.

Seizure outcomes and safety profiles of surgical options for epilepsy associated to hypothalamic hamartomas. A systematic review and meta-analysis.

PURPOSE: Several surgical options are available for treating hypothalamic hamartoma-related epilepsy but their respective efficacy and safety profiles are poorly defined. METHODS: A literature search identified English-language articles reporting series of patients (minimum 3 patients with a follow-up ≥12 months) operated on by either microsurgery, endoscopic surgery, radiosurgery, radiofrequency thermocoagulation or laser interstitial thermal therapy for hypothalamic hamartoma-related epilepsy. The unit of analysis was each selected study. Pooled rates of seizure freedom and of neurological and endocrinological complications were analyzed using meta-analysis to calculate both fixed and random effects. The results of meta-analyses were compared. RESULTS: Thirty-nine studies were included. There were 568 and 514 participants for seizure outcome and complication analyses, respectively. The pairwise comparison showed that: i) the proportion of seizure-free cases was significantly lower for radiosurgery as compared to microsurgery, radiofrequency thermocoagulation and laser ablation, and significantly lower for endoscopic surgery as compared to radiofrequency thermocoagulation; ii) the proportion of permanent hypothalamic dysfunction was significantly higher for microsurgery as compared to all other techniques, and significantly lower for endoscopic surgery as compared to radiofrequency thermocoagulation and laser ablation; iii) the incidence of permanent neurological disorders was significantly higher for microsurgery as compared to endoscopic surgery, radiosurgery and radiofrequency thermocoagulation, and significantly lower for radiosurgery as compared to laser ablation. CONCLUSIONS: Minimally invasive surgical techniques, including endoscopic surgery, radiofrequency thermocoagulation and laser ablation, represent an acceptable compromise between efficacy and safety in the treatment of hypothalamic hamartoma-related epilepsy. Microsurgery and radiosurgery should be considered in carefully selected cases.

Intraoperative MRI Assessment of the Tissue Damage during Laser Ablation of Hypothalamic Hamartoma.

Laser ablation for treatment of hypothalamic hamartoma (HH) is a minimally invasive and effective technique used to destroy hamartomatous tissue and disconnect it from the functioning brain. Currently, the gold standard to evaluate the amount of tissue being "burned" is the use of heat maps during the ablation procedure. However, these maps have low spatial resolution and can be misleading in terms of extension of the tissue damage. The aim of this study is to use different MRI sequences immediately after each laser ablation and correlate the extension of signal changes with the volume of malacic changes in a long-term follow-up scan. During the laser ablation procedure, we imaged the hypothalamic region with high-resolution axial diffusion-weighted images (DWI) and T2-weighted images (T2WI) after each ablation. At the end of the procedure, we also added a post-contrast T1-weighted image (T1WI) of the same region. We then correlated the product of the maximum diameters on axial showing signal changes (acute oedema on T2WI, DWI restriction rim, DWI hypointense core and post-contrast T1WI rim) with the product of the maximum diameters on axial T2WI of the malacic changes in the follow-up scan, both as a fraction of the total area of the hamartoma. The area of the hypointense core on DWI acquired immediately after the laser ablation statistically correlated better with the final area of encephalomalacia, while the T2WI, hyperintense oedema, DWI rim and T1WI rim of enhancement tended to overestimate the encephalomalacic damage. In conclusion, the use of intraoperative sequences (in particular DWI) during laser ablation can give surgeons valuable information in real time about the effective heating damage on the hamartomatous tissue, with better spatial resolution in comparison to the thermal maps.

Non-robotized frameless stereotactic magnetic resonance guided laser interstitial thermal therapy for hypothalamic hamartoma.

Various strategies have been proposed for the treatment of gelastic seizures due to hypothalamic hamartomas (HH), advancing from surgical removal techniques toward functional disconnection strategies. One of the most recent procedure is the Magnetic Resonance guided Laser Interstitial Thermal Therapy (MRg-LITT), which has progressively proved to be a safe and effective technique for hamartomas ablation. In this paper, the authors' preliminary experience with the first two patients treated with this technique in Italy is presented, in order to underline the feasibility of a pure non robotized frameless technique (FS MRg-LITT) while confirming the procedure effectiveness on seizure control. Patients undergoing FS MRg-LITT for the treatment of HH related gelastic seizures since January 2020 were included. A two steps procedure was performed by using the neuronavigation system to define the entry point, the trajectories and to assess the accuracy. Visualase Laser Ablation System was then used for the MR guided ablation of the HH. A multidisciplinary (neurosurgeons, epileptologist, neuroradiologist) institutional board evaluated the patients both in the perioperative period and during follow-up. A total number of 2 pediatric patients were described. The mean operative time resulted to be 6 hours while the mean accuracy was 0.4 mm. No perioperative complications were reported. The mean length of stay was 4 days. Lastly, at 1-year follow-up both patients resulted to be seizure free and endocrinological functions were preserved. FS MRg-LITT for the treatment of HH-related epilepsy could represent an effective technique, being able to guarantee adequate level of accuracy and potentially extending the accessibility of MRg-LITT by lowering its costs and simplifying the overall procedure.

Ultrasonography as first line imaging for the diagnosis of positional plagiocephaly.

BACKGROUND: In the last years, numerous studies evaluated different tools for the diagnosis of positional plagiocephaly (PP). The purpose of this study was to evaluate ultrasonography (US) as a first line screening test of lambdoid sutural patency in child with PP and to compare our results with the literature. METHODS: All consecutive patients who referred to our Institute from January 2016 to October 2017 with the suspicion of PP, were included in the study and performed US examination of the lambdoid sutures. A 3-6-month clinical follow-up was performed by a pediatric neurosurgeon or a pediatrician to confirm the diagnosis of PP. RESULTS: Thirty-five children performed US examination and in all cases the diagnosis of PP was confirmed. No cases of anticipated suture fusion were examined during this period. The concordance between US findings and clinical exam follow-up was 100%. CONCLUSIONS: Ultrasonography of the lambdoid sutures represents an ideal first-line screening test and reliable alternative to other diagnostic techniques for lambdoid sutural patency in child with PP, being radiation free, fast and cheap.

Hyaline Protoplasmic Astrocytopathy in the Setting of Epilepsy.

OBJECTIVES: Cerebral hyaline protoplasmic astrocytopathy (HPA) is a clinicopathologic entity characterized by eosinophilic cytoplasmic inclusions within astrocytes. It has been observed in a subset of patients with early-onset epilepsy, brain malformations, and developmental delay. The exact association of this entity with epilepsy is still unknown. This report, with its review of the literature, aims to summarize HPA features to raise awareness regarding this entity. METHODS: We report on 2 HPA cases and critically review the literature. RESULTS: Approximately 42 cases of HPA have been reported, including the 2 cases presented here, consisting of 23 female and 19 male patients. Patient age ranged from 3 to 39 years. All patients had early-onset seizures (3-20 months of age), ranging from partial to generalized, that were refractory despite treatment with antiepileptic drugs. Postoperative follow-up intervals ranged from 2 to 93 months, and the clinical outcome was graded according to the Engel classification, showing variable results. CONCLUSIONS: Clinicians should consider HPA in differential diagnosis in patients with intractable seizures, especially when they are associated with developmental delay and brain malformations. Increasing awareness of this entity among pathologists may promote better understanding of this condition as well as better diagnosis and treatment for these patients.

Sleep Disturbances in Pediatric Craniopharyngioma: A Systematic Review.

Craniopharyngiomas are rare brain tumors of the sellar region and are the most common non-neuroepithelial intracerebral neoplasm in children. Despite a low-grade histologic classification, craniopharyngiomas can have a severe clinical course due to hypothalamic involvement. The hypothalamus plays a crucial role in regulating vital functions, and it is a critical component of the sleep-wake regulatory system. This systematic review aims to provide an overview of the current knowledge on sleep disorders in patients with craniopharyngioma to unravel their underlying mechanisms and identify possible therapeutic strategies. A comprehensive electronic literature search of the PubMed/MEDLINE and Scopus databases was conducted in accordance with the PRISMA® statement. Extensively published, peer-reviewed articles involving patients with childhood craniopharyngioma and focused on this specific topic were considered eligible for inclusion. Thirty-two articles were included; a high prevalence of excessive daytime sleepiness was reported in CP patients, with wide variability (25-100%) depending on the diagnostic method of detection (25-43% by subjective measures, 50-100% by objective investigations). In particular, secondary narcolepsy was reported in 14-35%, sleep-disordered breathing in 4-46%. Moreover, sleep-wake rhythm dysregulation has been notified, although no prevalence data are available. Possible mechanisms underlying these disorders are discussed, including hypothalamic injury, damage to the suprachiasmatic nucleus, low melatonin levels, hypocretin deficiency, and hypothalamic obesity. The diagnosis and management of sleep disorders and associated comorbidities are challenging. This review summarizes the pathophysiology of sleep disorders in childhood-onset CP and the main treatment options. Finally, a possible diagnostic algorithm in order to accurately identify and treat sleep disorders in these patients is proposed.

Imaging characteristics and neurosurgical outcome in subjects with agenesis of the corpus callosum and interhemispheric cysts.

PURPOSE: To explore the relationships between clinical-radiological features and surgical outcomes in subjects with interhemispheric cysts (IHC) and corpus callosum anomalies. METHODS: We reviewed the clinico-radiological and neurosurgical data of 38 patients surgically treated with endoscopic fenestration, shunting, or combined approaches from 2000 to 2018 (24 males, median age 9 years). Pre- and postoperative changes in IHC volume were calculated. Outcome assessment was based on clinico-radiological data. Group comparisons were performed using χ2, Fisher exact, Mann-Whitney U, and Kruskal-Wallis tests. RESULTS: Median age at first surgery was 4 months (mean follow-up 8.3 years). Eighteen individuals (47.3%) required > 1 intervention due to IHC regrowth and/or shunt malfunction. Larger preoperative IHC volume (P = .008) and younger age at surgery (P = .016) were associated with cyst regrowth. At last follow-up, mean cystic volume was 307.8 cm3, with IHC volume reduction > 66% in 19/38 (50%) subjects. The neurological outcome was good in 14/38 subjects (36.8%), fair in 18/38 (47.3%), and poor in 6/38 (15.7%). There were no differences in the postoperative cyst volume with respect to either the type of first surgery or overall surgery type. Higher absolute postoperative IHC reduction was observed in subjects who underwent both IHC fenestration and shunting procedures (P < .0001). No differences in neurological outcome were found according to patient age at surgery or degree of IHC reduction. CONCLUSION: Endoscopic fenestration and shunting approaches are both effective but often require multiple procedures especially in younger patients. Larger IHC are more frequently complicated by cyst regrowth after surgery.

Comparison of Qualitative and Quantitative Analyses of MR-Arterial Spin Labeling Perfusion Data for the Assessment of Pediatric Patients with Focal Epilepsies.

The role of MR Arterial-Spin-Labeling Cerebral Blood Flow maps (ASL-CBF) in the assessment of pediatric focal epilepsy is still debated. We aim to compare the Seizure Onset Zone (SOZ) detection rate of three methods of evaluation of ASL-CBF: 1) qualitative visual (qCBF), 2) z-score voxel-based quantitative analysis of index of asymmetry (AI-CBF), and 3) z-score voxel-based cluster analysis of the quantitative difference of patient's CBF from the normative data of an age-matched healthy population (cCBF). Interictal ASL-CBF were acquired in 65 pediatric patients with focal epilepsy: 26 with focal brain lesions and 39 with a normal MRI. All hypoperfusion areas visible in at least 3 contiguous images of qCBF analysis were identified. In the quantitative evaluations, clusters with a significant z-score AI-CBF ≤ −1.64 and areas with a z-score cCBF ≤ −1.64 were considered potentially related to the SOZ. These areas were compared with the SOZ defined by the anatomo-electro-clinical data. In patients with a positive MRI, SOZ was correctly identified in 27% of patients using qCBF, 73% using AI-CBF, and 77% using cCBF. In negative MRI patients, SOZ was identified in 18% of patients using qCBF, in 46% using AI-CBF, and in 64% using cCBF (p < 0.001). Quantitative analyses of ASL-CBF maps increase the detection rate of SOZ compared to the qualitative method, principally in negative MRI patients.

Knowledge and attitudes of neurologists toward epilepsy surgery: an Italian survey.

The current study, conceived with the contribution of the Commission for Epilepsy Surgery of the Italian League Against Epilepsy (LICE) and the Epilepsy Study Group of the Italian Neurological Society (SIN), aimed to assess potential physician-related barriers to refer subjects for epilepsy surgery. All the members of SIN and LICE were invited by email to complete a 28-item online questionnaire. The survey items included: (1) individual and medical practice characteristics, (2) knowledge of current indications to select candidates for epilepsy surgery, (3) factors potentially affecting the attitude toward epilepsy surgery. Overall, 210 physicians completed the survey. More than half (63.3%) of the participants showed proper knowledge of the ILAE drug-resistance. Definition and almost two-thirds of them (71.9%) considered themselves adequately informed about indications, risks, and benefits of epilepsy surgery. Surgery was regarded as a valid option to be used as early as possible by 84.8% of the interviewees, and 71% of them estimated its complication rate to be low. However, more than half (63%) of the respondents reportedly referred patients for surgery only after the failure of 3-5 antiseizure medications. Overestimation of risks/complications of surgery and inadequate healthcare resources were identified as the main factor contrasting the patient referral for surgery by 43% and 40.5% of the participants, respectively. In conclusion, this survey confirms the existence of knowledge gap within both physicians and the healthcare system, as well as an educational need regarding epilepsy surgery. Further researches are warranted to define learning outcomes and optimize educational tools.

On the role of REM sleep microstructure in suppressing interictal spikes in Electrical Status Epilepticus during Sleep.

OBJECTIVE: Non-Rapid Eye Movement (NREM) sleep promotes the spread and propagation of Interictal Epileptiform Discharges (IEDs), while IEDs are suppressed during REM. Recently, it has been shown that the inhibitory effect on epileptic activity is mostly exerted by the phasic REM (PREM) microstate. This study aims at assessing if this holds true even in the extreme condition of IEDs activation during sleep represented by Electrical Status Epilepticus during Sleep (ESES). METHODS: eight patients affected by ESES, who underwent long-term EEG were included. REM was subdivided into phasic and tonic microstates along with the sleep scoring. IEDs count was carried out using a semi-automatic method and a Spike Index (SI) was calculated. RESULTS: The SI was significantly higher in NREM sleep than in REM. Within REM, the SI was significantly lower in PREM than in tonic REM (TREM). The SI was reduced by 84% in TREM with respect to NREM and by 97% in PREM with respect to NREM. Moreover, the SI was reduced by 87% in PREM with respect to TREM. CONCLUSIONS: PREM has a greater suppressive effect on epileptic activity even in the extreme IEDs activation during sleep typical of ESES. SIGNIFICANCE: Understanding the protective effect of PREM sleep on epileptic activity might be relevant for future therapeutic approaches.