Staged neurosurgical approach for giant and progressive neonatal arachnoid cysts: a case series and review of the literature.

OBJECTIVES: Prenatally diagnosed complex arachnoid cysts are very rare. While the true prenatal incidence is still unknown, they account for approximately 1% of intracranial masses in newborns. They rarely exhibit rapid growth or cause obstructive hydrocephalus, but if they increase to such a dimension during pregnancy, the ideal management is not well established. We present our detailed perinatal experience, covering prenatal diagnosis, a compassionate delivery process, and neonatal stabilization. Finally, a thorough postnatal neurosurgical intervention was performed. Initially, our focus was on the gradual reduction of cyst size as a primary effort, followed by subsequent definitive surgical treatment. METHODS: This case series shows the treatment course of three fetuses with antenatally diagnosed large arachnoid cysts. We present pre- and postnatal management and imaging, as well as the surgical treatment plan and the available clinical course during follow-up. RESULTS: Two girls and one boy were included in the current review. All three cases presented with prenatally diagnosed complex arachnoid cysts that increased in size during pregnancy. The mean gestational age at delivery was 35 weeks (range 32 to 37 weeks), and all patients were delivered by a caesarian section. Increasing head circumference and compression of brain structures were indications for delivery, as they are associated with a high risk of excess intracranial pressures and CSF diapedesis, as well as traumatic delivery and maternal complications. All cysts were supratentorial in location; one expanded into the posterior fossa, and one was a multicompartment cyst. All children underwent an initial surgical procedure within the first days of life. To relieve cyst pressure and achieve a reduction in head circumference, an ultrasound-guided or endoscopic-assisted internal shunt with drainage of the cyst to the ventricles or subdural/subarachnoid space was inserted. Definite surgical therapy consisted of cyst marsupialization and/or cysto-peritoneal shunt implantation. All children survived without severe neurodevelopmental impairments. CONCLUSION: With the cases presented, we demonstrate that the slow reduction of immense cyst size as an initial procedure until optimal requirements for final surgical treatment were achieved has proven to be optimal for neurological outcome. Special emphasis has to be taken on the delicate nature of premature newborn babies, and surgical steps have to be thoroughly considered within the interdisciplinary team.

The Potential Role of the Extracellular Matrix Glycoprotein Reelin in Glioblastoma Biology.

Glioblastoma, the most common and lethal primary adult brain tumor, cannot be successfully removed surgically due to its highly invasive nature. Therapeutically, approaches must be aimed at a systemic brain disease and not merely at a tumor located within the brain, unless a successful containment strategy can be found. Reelin, an extracellular matrix glycoprotein, plays an important role in neuronal migration and serves here as a natural stop signal. Interestingly, the expression of reelin is negatively associated with tumor grade and, within glioblastoma, correlates with increased overall survival. To further elucidate a potential biological reason for these findings, we looked at the cellular behavior of glioblastoma cell lines grown on a pure fibronectin matrix or a matrix with reelin inserts. While reelin had no significant effects on cellular metabolism, proliferation, or resistance to chemotherapeutic agents, it did significantly affect the cells' interaction with fibronectin. Both matrix attachment and detachment were modulated by reelin, and thus, the invasion and motility of cells interacting with a reelin-containing matrix were altered. The data presented in this work strongly suggest that reelin might be a potential modulator of underlying molecular mechanisms that contribute to glioblastoma invasion.

Controversies in the Treatment of Arachnoid Cysts with Special Emphasis on Temporal Arachnoid Cysts.

Intracranial arachnoid cysts (ACs) are benign lesions. The incidence in children is 2.6%. ACs are often diagnosed incidentally. Because of the broad use of CT and MR imaging, the frequency of AC diagnosis has increased. In addition, prenatal diagnosis of ACs is becoming more common. This places clinicians in a difficult situation with regard to the optimal treatment, since the presenting symptoms are often vague and operative management includes not negligible risks. It is generally accepted that conservative management is indicated in cases with small and asymptomatic cysts. In contrast, patients with definite signs of raised intracranial pressure should be treated. There are however clinical situations in whom the decision about the preferred treatment is difficult to make. Unspecific symptoms such as headaches and neurocognitive or attention deficits can be challenging to evaluate, whether they are related to the presence of the AC or not. The treatment techniques intent to establish a communication between the cyst and the normal cerebrospinal spaces or consist of a diversion of the cyst fluid by a shunt system. Which surgical method (open craniotomy for cyst fenestration, endoscopic fenestration, or shunting) is preferred differs between neurosurgical centers or the pediatric neurosurgeon in charge. Each treatment option has a unique profile of advantages and disadvantages which should be considered when discussing treatment with the patients or their caregivers.

Bcl-XL but Not Bcl-2 Is a Potential Target in Medulloblastoma Therapy.

Medulloblastoma (MB) is the most common solid tumour in children and, despite current treatment with a rather aggressive combination therapy, accounts for 10% of all deaths associated with paediatric cancer. Breaking the tumour cells' intrinsic resistance to therapy-induced cell death should lead to less aggressive and more effective treatment options. In other tumour entities, this has been achieved by modulating the balance between the various pro- and anti-apoptotic members of the Bcl-2 family with small molecule inhibitors. To evaluate the therapeutic benefits of ABT-199 (Venetoclax), a Bcl-2 inhibitor, and ABT-263 (Navitoclax), a dual Bcl-XL/Bcl-2 inhibitor, increasingly more relevant model systems were investigated. Starting from established MB cell lines, progressing to primary patient-derived material and finally an experimental tumour system imbedded in an organic environment were chosen. Assessment of the metabolic activity (a surrogate readout for population viability), the induction of DNA fragmentation (apoptosis) and changes in cell number (the combined effect of alterations in proliferation and cell death induction) revealed that ABT-263, but not ABT-199, is a promising candidate for combination therapy, synergizing with cell death-inducing stimuli. Interestingly, in the experimental tumour setting, the sensitizing effect of ABT-263 seems to be predominantly mediated via an anti-proliferative and not a pro-apoptotic effect, opening a future line of investigation. Our data show that modulation of specific members of the Bcl-2 family might be a promising therapeutic addition for the treatment of MB.

ONC201/TIC10 Is Empowered by 2-Deoxyglucose and Causes Metabolic Reprogramming in Medulloblastoma Cells in Vitro Independent of C-Myc Expression.

The purpose of this study was to examine whether the imipridone ONC201/TIC10 affects the metabolic and proliferative activity of medulloblastoma cells in vitro. Preclinical drug testing including extracellular flux analyses (agilent seahorse), MTT assays and Western blot analyses were performed in high and low c-myc-expressing medulloblastoma cells. Our data show that treatment with the imipridone ONC201/TIC10 leads to a significant inihibitory effect on the cellular viability of different medulloblastoma cells independent of c-myc expression. This effect is enhanced by glucose starvation. While ONC201/TIC10 decreases the oxidative consumption rates in D458 (c-myc high) and DAOY (c-myc low) cells extracellular acidification rates experienced an increase in D458 and a decrease in DAOY cells. Combined treatment with ONC201/TIC10 and the glycolysis inhibitor 2-Deoxyglucose led to a synergistic inhibitory effect on the cellular viability of medulloblastoma cells including spheroid models. In conclusion, our data suggest that ONC201/TIC10 has a profound anti-proliferative activity against medulloblastoma cells independent of c-myc expression. Metabolic targeting of medulloblastoma cells by ONC201/TIC10 can be significantly enhanced by an additional treatment with the glycolysis inhibitor 2-Deoxyglucose. Further investigations are warranted.

Congruence and Discrepancy of Interictal and Ictal EEG With MRI Lesions in Pediatric Epilepsies.

Purpose. To evaluate the congruence or discrepancy of the localization of magnetic resonance imaging (MRI) lesions with interictal epileptiform discharges (IEDs) or epileptic seizure patterns (ESPs) in surface EEG in lesional pediatric epilepsy patients. Methods. We retrospectively analyzed presurgical MRI and video-EEG monitoring findings of patients up to age 18 years. Localization of MRI lesions were compared with ictal and interictal noninvasive EEG findings of patients with frontal, temporal, parietal, or occipital lesions. Results. A total of 71 patients were included. Localization of ESPs showed better congruence with MRI in patients with frontal lesions (n = 21, 77.5%) than in patients with temporal lesions (n = 24; 40.7%) (P = .009). No significant IED distribution differences between MRI localizations could be found. Conclusions. MRI lesions and EEG findings are rarely fully congruent. Congruence of MRI lesions and ESPs was highest in children with frontal lesions. This is in contrast to adults, in whom temporal lesions showed the highest congruency with the EEG localization of ESP. Lesional pediatric patients should be acknowledged as surgical candidates despite incongruent findings of interictal and ictal surface EEG.

Compare and contrast: pediatric cancer versus adult malignancies.

Cancer is a leading cause of death in both adults and children, but in terms of absolute numbers, pediatric cancer is a relatively rare disease. The rarity of pediatric cancer is consistent with our current understanding of how adult malignancies form, emphasizing the view of cancer as a genetic disease caused by the accumulation and selection of unrepaired mutations over time. However, considering those children who develop cancer merely as stochastically "unlucky" does not fully explain the underlying aetiology, which is distinct from that observed in adults. Here, we discuss the differences in cancer genetics, distribution, and microenvironment between adult and pediatric cancers and argue that pediatric tumours need to be seen as a distinct subset with their own distinct therapeutic challenges. While in adults, the benefit of any treatment should outweigh mostly short-term complications, potential long-term effects have a much stronger impact in children. In addition, clinical trials must cope with low participant numbers when evaluating novel treatment strategies, which need to address the specific requirements of children.

Childhood haemorrhagic stroke: a 7-year single-centre experience.

BACKGROUND: In recent years, there has been increasing research interest in improving diagnostic and management protocols in childhood arterial ischaemic stroke (AIS). However, childhood stroke comprises, in approximately equal parts, both arterial ischaemic and haemorrhagic stroke (HS). OBJECTIVE: The aim of this study was to focus on the aetiology, clinical presentation, treatment and short-term outcome of children with spontaneous intracranial bleeding in a university hospital and elucidate differences to childhood AIS. DESIGN: We performed a retrospective analysis of electronic medical records of children (28 days-18 years) diagnosed with HS between 2010 and 2016. RESULTS: We included 25 children (male child, n=11) with a median age of 8 years 1 month. The most common clinical presentations were vomiting (48%), headache (40%) and altered level of consciousness (32%). In more than half of the patients, HS was caused by vascular malformations. Other risk factors were brain tumour, coagulopathy and miscellaneous severe underlying diseases. Aetiology remained unclear in one child. Therapy was neurosurgical in most children (68%). Two patients died, 5 patients needed further (rehabilitation) treatment and 18 children could be discharged home. CONCLUSIONS: HS differs from AIS in aetiology (vascular malformations as number one risk factor), number of risk factors ('mono-risk' disease), clinical presentation (vomiting, headache and altered level of consciousness) and (emergency) therapy.

Outcome after individualized stereoelectroencephalography (sEEG) implantation and navigated resection in patients with lesional and non-lesional focal epilepsy.

BACKGROUND: Refined localization of the epileptogenic zone (EZ) in patients with pharmacoresistant focal epilepsy proceeding to resective surgery might improve postoperative outcome. We here report seizure outcome after stereo EEG (sEEG) evaluation with individually planned stereotactically implanted depth electrodes and subsequent tailored resection. METHODS: A cohort of consecutive patients with pharmacoresistant focal epilepsy, evaluated with a non-invasive evaluation protocol and invasive monitoring with personalized, stereotactically implanted depth electrodes for sEEG was analyzed. Co-registration of post-implantation CT scan to presurgical MRI data was used for 3D reconstructions of the patients' brain surface and mapping of neurophysiology data. Individual multimodal 3D maps of the EZ were used to guide subsequent tailored resections. The outcome was rated according to the Engel classification. RESULTS: Out of 914 patients who underwent non-invasive presurgical evaluation, 85 underwent sEEG, and 70 were included in the outcome analysis. Median follow-up was 31.5 months. Seizure-free outcome (Engel class I A-C, ILAE class 1-2) was achieved in 83% of the study cohort. Patients exhibiting lesional and non-lesional (n = 42, 86% vs. n = 28, 79%), temporal and extratemporal (n = 45, 80% vs. n = 25, 84%), and right- and left-hemispheric epilepsy (n = 44, 82% vs. n = 26, 85%) did similarly well. This remains also true for those with an EZ adjacent to or distant from eloquent cortex (n = 21, 86% vs. n = 49, 82%). Surgical outcome was independent of resected tissue volume. CONCLUSION: Favourable post-surgical outcome can be achieved in patients with resistant focal epilepsy, using individualized sEEG evaluation and tailored navigated resection, even in patients with non-lesional or extratemporal focal epilepsy.

Epilepsy surgery in the first months of life: a large type IIb focal cortical dysplasia causing neonatal drug-resistant epilepsy.

Focal cortical dysplasia is a common cause of medically refractory epilepsy in infancy and childhood. We report a neonate with seizures occurring within the first day of life. Continuous video-EEG monitoring led to detection of left motor seizures and a right frontal EEG seizure pattern. Brain MRI revealed a lesion within the right frontal lobe without contrast enhancement. The patient was referred for epilepsy surgery due to drug resistance to vitamin B6 and four antiepileptic drugs. Lesionectomy was performed at the age of two and a half months, and histopathological evaluation confirmed the diagnosis of focal cortical dysplasia type IIb (FCD IIb). The patient is free of unprovoked seizures without medication (Engel Class I) and is normally developed at 36 months after surgery. The case study demonstrates that FCD IIb may cause seizures within the first day of life and that epilepsy surgery can be successfully performed in medically intractable patients with a clearly identifiable seizure onset zone within the first three months of life. Although radical surgery such as hemispherectomy and multi-lobar resections are over-represented in early infancy, this case also illustrates a favourable outcome with a more limited resection in this age group.

Multimodal Imaging in Extratemporal Epilepsy Surgery.

Neuroimaging is crucial for the evaluation of patients considered for resective epilepsy surgery. Multimodal image fusion is a new tool to integrate all available localizing information on the individual epileptogenic network in a three-dimensional (3D) manner to plan invasive EEG recordings and delineate the epileptogenic zone from the eloquent cortex for the neurosurgical planning of a tailored resection. Here, we illustrate the multimodal fusion of images from different modalities in a patient with medically intractable non-lesional frontal lobe epilepsy who underwent partial frontal lobe resection, rendering him seizure-free.

Decompression in Chiari Malformation: Clinical, Ocular Motor, Cerebellar, and Vestibular Outcome.

BACKGROUND: Treatment of Chiari malformation can include suboccipital decompression with resection of one cerebellar tonsil. Its effects on ocular motor and cerebellar function have not yet been systematically examined. OBJECTIVE: To investigate whether decompression, including resection of one cerebellar tonsil, leads to ocular motor, vestibular, or cerebellar deficits. PATIENTS AND METHODS: Ten patients with Chiari malformation type 1 were systematically examined before and after (1 week and 3 months) suboccipital decompression with unilateral tonsillectomy. The work-up included a neurological and neuro-ophthalmological examination, vestibular function, posturography, and subjective scales. Cerebellar function was evaluated by ataxia rating scales. RESULTS: Decompression led to a major subjective improvement 3 months after surgery, especially regarding headache (5/5 patients), hyp-/dysesthesia (5/5 patients), ataxia of the upper limbs (4/5 patients), and paresis of the triceps and interosseal muscles (2/2 patients). Ocular motor disturbances before decompression were detected in 50% of the patients. These symptoms improved after surgery, but five patients had new persisting mild ocular motor deficits 3 months after decompression with unilateral tonsillectomy (i.e., smooth pursuit deficits, horizontally gaze-evoked nystagmus, rebound, and downbeat nystagmus) without any subjective complaints. Impaired vestibular (horizontal canal, saccular, and utricular) function improved in five of seven patients with impaired function before surgery. Posturographic measurements after surgery did not change significantly. CONCLUSION: Decompression, including resection of one cerebellar tonsil, leads to an effective relief of patients' preoperative complaints. It is a safe procedure when performed with the help of intraoperative electrophysiological monitoring, although mild ocular motor dysfunctions were seen in half of the patients, which were fortunately asymptomatic.

Falsely low values of oxygen saturation measured by pulse oximetry in a boy treated with Chinese herb tea.

An 8-year-old boy suffering from progressive glioblastoma was scheduled for neurosurgery. Prior to induction of anaesthesia pulse oximetry measured 64 % saturation of oxygen (SpO2). Arterial blood gas analysis revealed normal oxygen saturation and normal oxygen partial pressure. After having ruled out technical problems of pulse oximetry the neurosurgical procedure was halted. Meticulous examination of the child's history and medication did not explain a possible interaction of drugs with pulse oximetry. A Chinese herb tea had been given to the child, but was then stopped on the day of admission. The surgical procedure took place the next day without any complications. During the subsequent inpatient stay, repeated blood gas analyses showed normal oxygenation, but pulse oximetry measured initially SpO2 values of 64 %, gradually increasing over 7 days up to 91 % by the time of discharge from hospital. Blood samples were taken and analysed. Absorption spectroscopy from the patient's blood showed an uncommon absorption maximum at 684 nm besides the normal maxima. The normalisation of SpO2 values after stopping Chinese herb tea administration leads to the conclusion that one of its ingredients caused the distorted pulse oximetry measurement.

Lateralization of cortical negative motor areas.

OBJECTIVE: The lateral and mesial aspects of the central and frontal cortex were studied by direct electrical stimulation of the cortex in epilepsy surgery candidates in order to determine the localization of unilateral and bilateral negative motor responses. METHODS: Results of electrical cortical stimulation were examined in epilepsy surgery candidates in whom invasive electrodes were implanted. The exact localization of subdural electrodes was defined by fusion of 3-dimensional reconstructed MRI and CT images in 13 patients and by analysis of plane skull X-rays and intraoperative visual localization of the electrodes in another 7 patients. RESULTS: Results of electrical stimulation of the cortex were evaluated in a total of 128 patients in whom invasive electrodes were implanted for planning resective epilepsy surgery. Twenty patients, in whom negative motor responses were obtained, were included in the study. Bilateral upper limb negative motor responses were more often elicited from stimulation of the mesial frontal cortex whereas stimulation of the lateral central cortex leads to contralateral upper limb negative motor responses (p<0.0001). Bilateral negative motor responses were exclusively found in the superior frontal gyrus whereas contralateral negative motor responses localized predominantly in the anterior part of the precentral gyrus (p<0.0001). CONCLUSIONS: Exact localization using 3-D fusion methods revealed that negative motor areas are widely distributed throughout the precentral gyrus and the mesial fronto-central cortex showing functional differences with regard to unilateral and bilateral upper limb representation. SIGNIFICANCE: The lateral fronto-central negative motor area serves predominantly contralateral upper limb motor control whereas the mesial frontal negative motor area represents bilateral upper limb movement control.

Early treatment of complex located pediatric low-grade gliomas using iodine-125 brachytherapy alone or in combination with microsurgery.

To analyze efficacy, functional outcome, and treatment toxicity of low-dose rate I-125 brachytherapy (SBT) alone or in combination with best safe resection (in case of larger tumor volumes) as first-line treatment for pediatric low-grade gliomas (PLGGs) not suitable for complete resection. Consecutively treated (2000-2014) complex located circumscribed WHO grade I/II PLGGs were included. For small tumors (≤4 cm in diameter) SBT alone was performed; for larger tumors best safe resection and subsequent SBT was chosen. Temporary Iodine-125 seeds were used (median reference dose: 54 Gy). Treatment response was estimated with the modified MacDonald criteria. Analysis of functional outcome included ophthalmological, endocrinological and neurological evaluation. Survival was analyzed with the Kaplan-Meier method. Prognostic factors were obtained from proportional hazards models. Toxicity was categorized according to the Common Terminology Criteria for Adverse Events. Fifty-eight patients were included treated either with SBT alone (n = 39) or with SBT plus microsurgery (n = 19). Five-year progression-free survival was 87%. Two patients had died due to tumor progression. Among survivors, improvement/stabilization/deterioration of functional deficits was seen in 20/14/5 patients, respectively. Complete/partial response had beneficial impact on functional scores (P = 0.02). The 5-year estimated risk to receive adjuvant radiotherapy/chemotherapy was 5.2%. The overall early (delayed) toxicity rate was 8.6% (10.3%), respectively. No permanent morbidity occurred. In complex located PLGGs, early SBT alone or combined with best safe resection preserves/improves functional scores and results in tumor control rates usually achieved with complete resection. Long-term analysis is necessary for confirmation of these results.

Anomia produced by direct cortical stimulation of the pre-supplementary motor area in a patient undergoing preoperative language mapping.

There is sparse data on the analysis of supplementary motor area in language function using direct cortical stimulation of the supplementary motor area. Here, we report a patient who experienced isolated anomia during stimulation of the anterior supplementary motor area and discuss the role of the supplementary motor area in speech production. The role of the pre-supplementary motor· area in word selection, observed in fMRI studies, can be confirmed by direct cortical stimulation.

Predicting the "usefulness" of 5-ALA-derived tumor fluorescence for fluorescence-guided resections in pediatric brain tumors: a European survey.

BACKGROUND: Five-aminolevulinic acid (Gliolan, medac, Wedel, Germany, 5-ALA) is approved for fluorescence-guided resections of adult malignant gliomas. Case reports indicate that 5-ALA can be used for children, yet no prospective study has been conducted as of yet. As a basis for a study, we conducted a survey among certified European Gliolan users to collect data on their experiences with children. METHODS: Information on patient characteristics, MRI characteristics of tumors, histology, fluorescence qualities, and outcomes were requested. Surgeons were further asked to indicate whether fluorescence was "useful", i.e., leading to changes in surgical strategy or identification of residual tumor. Recursive partitioning analysis (RPA) was used for defining cohorts with high or low likelihoods for useful fluorescence. RESULTS: Data on 78 patients <18 years of age were submitted by 20 centers. Fluorescence was found useful in 12 of 14 glioblastomas (85 %), four of five anaplastic astrocytomas (60 %), and eight of ten ependymomas grades II and III (80 %). Fluorescence was found inconsistently useful in PNETs (three of seven; 43 %), gangliogliomas (two of five; 40 %), medulloblastomas (two of eight, 25 %) and pilocytic astrocytomas (two of 13; 15 %). RPA of pre-operative factors showed tumors with supratentorial location, strong contrast enhancement and first operation to have a likelihood of useful fluorescence of 64.3 %, as opposed to infratentorial tumors with first surgery (23.1 %). CONCLUSIONS: Our survey demonstrates 5-ALA as being used in pediatric brain tumors. 5-ALA may be especially useful for contrast-enhancing supratentorial tumors. These data indicate controlled studies to be necessary and also provide a basis for planning such a study.

Use of intrathecal baclofen in children and adolescents: interdisciplinary consensus table 2013.

In recent years, intrathecal baclofen (ITB) has attained an important role in the treatment of severe spasticity and dystonia in children. There are principal differences between the use of ITB in children and its use in neurology and oncology in adults. Here, we present a consensus report on best practice for the treatment of severe spastic and dystonic movement disorders with ITB. Using a problem-orientated approach to integrate theories and methods, the consensus was developed by an interdisciplinary group of experienced ITB users and experts in the field of movement disorders involving 14 German centers. On the basis of the data pooled from more than 400 patients, the authors have summarized their experience and supporting evidence in tabular form to provide a concise, but still a comprehensive information base that represents our current understanding regarding ITB treatment options in children and adolescents.

Neurodevelopmental and esthetic results in children after surgical correction of metopic suture synostosis: a single institutional experience.

INTRODUCTION: Metopic suture synostosis leading to trigonocephaly is considered the second most frequent type of craniosynostosis. Besides esthetic results, we present 25 consecutive pediatric cases operated upon metopic suture synostosis with a focus on the child's motor, speech, and neurocognitive development. METHODS: Twenty-five children (aged 6 to 33 months; median 9.2 months) with trigonocephaly were operated upon between 2002 and 2012 with fronto-orbital advancement including frontal bone cranioplasty and fronto-orbital bandeau remodeling. Neurodevelopmental deficits were evaluated by a standardized questionnaire including gross motor function, manual coordination, speech, and cognitive function performed by independent pediatric/developmental neurologists before surgery and at 6 and 12 months of time interval postoperatively. RESULTS: Twenty-one (84 %) boys and four (16 %) girls were included in this study. Mean follow-up period was 33 ± 28 months. Outcome analysis for esthetic results showed a high degree of satisfaction by the parents and treating physicians in 23 cases (92 %). Preoperative evaluation revealed neurodevelopmental deficits in 10 children (40 %; six mild, four moderate degree). Twelve children (48 %) were proven to have a normal preoperative neuropediatric development. Mild or moderate developmental restraints were no longer apparent in 6/13, improved but still apparent in 3/13, and stable in 4/13, 6 months after cranial vault reconstruction. At 12 months of follow-up, deficits were no longer present in 9/13 and improved in 4/13. Apart from this cohort, two children were diagnosed with a syndromic form, and one child had a fetal valproate syndrome. In these three children, neurodevelopmental deficits were more pronounced. Neurocognitive progress was obvious, but was comparably slower, and major deficits were still apparent at last follow-up. All children with proven mild/moderate/severe deficits received intensive physiotherapy, logopedic, or neurobehavioral support. CONCLUSIONS: As shown in a single-center observation, surgical correction of metopic suture synostosis not only refines esthetic appearance but also might improve neurodevelopmental outcome if deficits are apparent, even in syndromic forms of the deformity under additional physiotherapy, logopedic, or neurobehavioral support.