ArticlePublisher preview availableLiterature Review

Neurosurgical intervention for the Meckel-Gruber Syndrome: A systematic review

March 2024
Child's Nervous System 40(7)

March 2024
40(7)

Authors:

Introduction Meckel-Gruber Syndrome (MKS) is an autosomal recessive genetic disorder, notable for its triad of occipital encephalocele, polycystic renal dysplasia, and postaxial polydactyly. Identified by Johann Friederich Meckel in 1822, MKS is categorized as a ciliopathy due to gene mutations. Diagnosis is confirmed by the presence of at least two key features. The condition is incompatible with life, leading to death in the womb or shortly after birth. Recent studies have largely focused on the genetic aspects of MKS, with limited information regarding the impact of neurosurgical approaches, particularly in treating encephaloceles. Methods A systematic review was performed according to the PRISMA statement. The PubMed, Embase, and Web of Science databases were consulted for data screening and extraction, which was conducted by two independent reviewers. The search strategy aimed to encompass studies documenting cases of MKS with published reports of encephalocele excisions, and the search strings for all databases were: Meckel-Gruber syndrome OR Meckel Gruber syndrome OR Meckel-gruber OR Meckel Gruber. Results The study included 10 newborns with MKS associated with occipital encephalocele or meningocele, all of whom underwent surgical repair of the occipital sac. The mean gestational age at birth was 36 (± 2) weeks. The mean of birth weight was 3.14 (± 0.85) kilograms. The average head circumference at birth was 33.82 cm (± 2.17). The mean diameter of the encephalocele/meningocele was 5.91 (± 1.02) cm. Other common central nervous system abnormalities included hydrocephalus, Dandy-Walker malformation, and agenesis of the corpus callosum. 40% required shunting for hydrocephalus. Surgery to remove the occipital sac occurred at a median age of 2.5 days (1.5–6.5). The most common post-surgical complication was the need for mechanical ventilation. The most common cause of death was pneumonia and the median age at death was 6.66 (0.03–18) months. Conclusion Our findings suggest that neurosurgical intervention, especially for managing encephaloceles, may offer some improvement in survival, albeit within a context of generally poor prognosis. However, these results should be interpreted with caution.

PRISMA framework

…

Figures - available from: Child's Nervous System

This content is subject to copyright. Terms and conditions apply.

A preview of this full-text is provided by Springer Nature.

Learn more

Content available from Child's Nervous System

This content is subject to copyright. Terms and conditions apply.

Vol.:(0123456789)

Child's Nervous System (2024) 40:2161–2168

https://doi.org/10.1007/s00381-024-06346-3

REVIEW

Neurosurgical intervention fortheMeckel‑Gruber Syndrome:

Asystematic review

JeffersonHeberMarquesFontesJunior1· SilvioPortoJunior2· HugoNunesPustilnik3· LeonardodeAlmeidaLeão2·

MatheusGomesda SilvadaPaz4· TaianeBritoAraujo4· FernandaOliveiraGonçalvesdeDeus4·

TancredoAlcântara4· JulesCarlosDourado4· LeonardoMirandadeAvellar4

Received: 15 January 2024 / Accepted: 27 February 2024 / Published online: 9 March 2024

Abstract

Introduction Meckel-Gruber Syndrome (MKS) is an autosomal recessive genetic disorder, notable for its triad of occipital encepha-

locele, polycystic renal dysplasia, and postaxial polydactyly. Identified by Johann Friederich Meckel in 1822, MKS is categorized

as a ciliopathy due to gene mutations. Diagnosis is confirmed by the presence of at least two key features. The condition is incom-

patible with life, leading to death in the womb or shortly after birth. Recent studies have largely focused on the genetic aspects of

MKS, with limited information regarding the impact of neurosurgical approaches, particularly in treating encephaloceles.

Methods A systematic review was performed according to the PRISMA statement. The PubMed, Embase, and Web of Science

databases were consulted for data screening and extraction, which was conducted by two independent reviewers. The search strat-

egy aimed to encompass studies documenting cases of MKS with published reports of encephalocele excisions, and the search

strings for all databases were: Meckel-Gruber syndrome OR Meckel Gruber syndrome OR Meckel-gruber OR Meckel Gruber.

Results The study included 10 newborns with MKS associated with occipital encephalocele or meningocele, all of whom

underwent surgical repair of the occipital sac. The mean gestational age at birth was 36 (± 2) weeks. The mean of birth

weight was 3.14 (± 0.85) kilograms. The average head circumference at birth was 33.82cm (± 2.17). The mean diameter

of the encephalocele/meningocele was 5.91 (± 1.02) cm. Other common central nervous system abnormalities included

hydrocephalus, Dandy-Walker malformation, and agenesis of the corpus callosum. 40% required shunting for hydrocepha-

lus. Surgery to remove the occipital sac occurred at a median age of 2.5days (1.5–6.5). The most common post-surgical

complication was the need for mechanical ventilation. The most common cause of death was pneumonia and the median age

at death was 6.66 (0.03–18)months.

Conclusion Our findings suggest that neurosurgical intervention, especially for managing encephaloceles, may offer some improve-

ment in survival, albeit within a context of generally poor prognosis. However, these results should be interpreted with caution.

Introduction

Meckel-Gruber Syndrome MKS is a rare autosomal

recessive genetic disorder characterized by congenital

malformations that are incompatible with life [1–4].

This pathology is classified as a ciliopathy, caused by a

dysfunction of both cilia and cellular flagella, and is related

to changes in genes on different chromosomes that encode

these structures [5, 6]. MKS was first described by Johann

Friederich Meckel in 1822 after he followed the case of two

siblings who died shortly after birth with typical changes of

the disease such as polycystic kidneys, encephalocele, and

polydactyly. In 1934, some similar cases were also described

by George B. Gruber, naming the condition Dysencephalia

Splanchnocystica. Subsequently, the syndrome was

identified as “Meckel-Gruber” in 1969 by other scholars

who described the disease [7, 8]

The clinical manifestations of MKS have a varied phe-

notype, but its diagnosis requires at least two of the follow-

ing changes: occipital encephalocele/central nervous system

* Jeﬀerson Heber Marques Fontes Junior

jeﬀerson_heber@hotmail.com

1 Metropolitan Union ofEducation andCulture, Salvador,

Brazil

2 Bahiana School ofMedicine andPublic Health, Salvador,

Brazil

3 Salvador University, Salvador, Brazil

4 General Hospital Roberto Santos, Salvador, Brazil

Content courtesy of Springer Nature, terms of use apply. Rights reserved.

Occipital encephalocele: a retrospective analysis and assessment of post-surgical neurodevelopmental outcome

Article

Full-text available

Jun 2024
CHILD NERV SYST

Background Encephalocele represent a group of disorders which is characterised by extracranial herniation of the leptomeninges, brain, and CSF through a structural defect in the cranium. They are usually associated with other intracranial anomalies which may impact the neurological development. Aim This study aimed to assess the predictors of neurological development of patients undergone surgical excision of occipital encephalocele. Methods All patients with occipital encephaloceles operated over the last decade (2012–2022). The sac size, presence of hydrocephalous, and associated anomalies were noted. The biopsy of these patients were reviewed and categorised as those which contains mature neural tissue and those without. The neurological outcomes were assessed by social, language, cognitive, and motor milestone and has been stratified into no delay, mild (1 of 4), moderate (2 or 3 of 4), and severe development delay (4 of 4). Results Total of 35 patients were included with median age of 10 months (IQR = 5–20 months). Fifteen (42.9%) patients had sac size of ≥ 5 cm, and 23 (65.7%) patients had mature neural tissues on biopsy. The median follow-up period was 6.4 years (IQR = 4.38–10.65) years. Seventeen (49.6%) patients had moderate to severe developmental delay. The sac size of ≥ 5 cm (AOR = 33.5; 95%CI = 3.35–334.8) (p = 0.003) and presence of mature neural content in the sac (AOR = 13.32; 95%CI = 1.1–160.36) (p = 0.041) were associated with significant neurodevelopmental delay. Conclusion The presence of a large sac of ≥ 5 cm and the presence of mature neural tissues on histopathological specimen of patients with encephalocele point towards the possibility of poor neurological development.

Craniofacial Encephalocele: Updates on Management

Article

Full-text available

May 2023

Craniofacial encephaloceles are rare, yet highly debilitating neuroanatomical abnormalities that result from herniation of neural tissue through a bony defect and can lead to death, cognitive delay, seizures, and issues integrating socially. The etiology of encephaloceles is still being investigated, with evidence pointing towards the Sonic Hedgehog pathway, Wnt signaling, glioma-associated oncogene (GLI) transcription factors, and G protein-coupled receptors within primary cilia as some of the major genetic regulators that can contribute to improper mesenchymal migration and neural tube closure. Consensus on the proper approach to treating craniofacial encephaloceles is confounded by the abundance of surgical techniques and parameters to consider when determining the optimal timing and course of intervention. Minimally invasive approaches to encephalocele and temporal seizure treatment have increasingly shown evidence of successful intervention. Recent evidence suggests that a single, two-stage operation utilizing neurosurgeons to remove the encephalocele and plastic surgeons to reconstruct the surrounding tissue can be successful in many patients. The HULA procedure (H = hard-tissue sealant, U = undermine and excise encephalocele, L = lower supraorbital bar, A = augment nasal dorsum) and endoscopic endonasal surgery using vascularized nasoseptal flaps have surfaced as less invasive and equally successful approaches to surgical correction, compared to traditional craniotomies. Temporal encephaloceles can be a causative factor in drug-resistant temporal seizures and there has been success in curing patients of these seizures by temporal lobectomy and amygdalohippocampectomy, but magnetic resonance-guided laser interstitial thermal therapy has been introduced as a minimally invasive method that has shown success as well. Some of the major concerns postoperatively include infection, cerebrospinal fluid (CSF) leakage, infringement of craniofacial development, elevated intracranial pressure, wound dehiscence, and developmental delay. Depending on the severity of encephalocele prior to surgery, the surgical approach taken, any postoperative complications, and the age of the patient, rehabilitation approaches may vary.

The outcome of surgical management for the patient with giant occipital encephalocele: a case illustration and systematic review

Article

Full-text available

Apr 2023
CHILD NERV SYST

Purpose Occipital encephalocele (OE) is one of congenital malformation of the central nervous system. However, giant OE, mostly defines as bigger-than-head OE, is extremely rare and carries a worse prognosis. Here, we presented our systematic review of the management of the giant OE and illustrated our case. Method The systematic review was carried out under PRISMA guidelines. Publications were searched under “occipital encephalocele” from 1959 to April 2021. Our primary area of interest was the outcome of patients who have undergone surgery for giant OE. Variables of interest included age, sex, size of the sac, presentations, associated anomalies, management, outcome, and follow-up period were collected. Result We collected 35 articles, consisting of 74 cases (including 1 case from our illustrative case), to perform a systematic review. The mean age at the time of surgery was 3.53 ± 8.22 months. The mean circumference of the sac was 52.41 ± 18.6 cm. The three most common associated anomalies were microcephaly, corpus callosal agenesis/dysgenesis, and Chiari malformation. After the surgery, survival was reported in 64 (90.1%) patients. Postoperative complications were reported in 14 cases (16 events). Age above 1 month at the time of surgery was significantly associated with survival (p = 0.02) but not with complication (p = 0.22). In contrast, the type of surgery was not associated with survival (p = 0.18) or complications (p = 0.41). Conclusion Despite a rare condition with a poor prognosis, our reported case and systematic review revealed promising outcomes of surgery regardless of surgical strategies, especially in patients older than 1 month. Thus, appropriate planning is essential for the treatment of this condition.

Síndrome de Meckel-Gruber en un lactante menor con sobrevida prolongada. Reporte de Caso

Article

Full-text available

Jan 2018

Hydrocephalus in encephalocele

Article

Full-text available

Aug 2022

OBJECTIVE: Encephalocele is a rare congenital neural tube defect (NTD) characterized by herniation of intracranial contents through a defect in the skull. In our study, encephalocele was diagnosed in our clinic and its association with hydrocephalus was evaluated. The effect of this association on the prognosis was discussed. PATIENTS AND METHODS: Patients who underwent surgery and follow-up with the diagnosis of encephalocele in the neurosurgery clinic of our hospital in an 8-year period from 2013 to 2021 were retrospectively examined. RESULTS: Patient records were obtained from the case notes of patients who underwent excision and repair for encephalocele. Of the 78 patients included in the study, 88.4% underwent surgery in the neonatal period. Moreover, 47% of the patients are male, and 31% are female. Encephalocele was present in 62.8% of patients and meningocele in 37.2%. Furthermore, 82.1% of encephalocele sacs were located in the occipital region. Chiari type 3 malformation was present in 57.6% of patients. Hydrocephalus developed in 56.4% of patients. There was an additional syndrome in 10.3% of the cases. The most common additional syndromes were corpus callosum dysgenesis with 39.7% and colpocephaly with 29.5%. The additional disease was present in 43.6% of patients. Preoperative and postoperative examination findings of more than half of patients were normal, but 33.3% were apathetic. Furthermore, 67.9% of patients, who underwent complete repair, survived, and 32.1% died. Hydrocephalus was present in 73.5% of patients with encephalocele (p

Hydrocephalus and occipital encephaloceles: presentation of a series and review of the literature

Article

Full-text available

Nov 2021
CHILD NERV SYST

Introduction: Encephaloceles are rare congenital malformations of the central nervous system in which brain tissue is extruded from a defect in the skull. Hydrocephalus can occur in 60 to 90% of patients with posterior encephaloceles when compared to other types of this malformation. This article aims to present a series of posterior encephaloceles and its association with hydrocephalus as well as promote a review of the pertinent literature. Material and methods: A retrospective study of our series based on hospital charts of 50 patients with posterior encephaloceles was performed. Data on sex, location of encephalocele, presence of associated malformations, presence of neural tissue within the malformation, presence of hydrocephalus and microcephaly were recorded. Results: There were 29 females and 21 males. There were 25 (50%) supratorcular, 8 (16%) torcular, and 17 (34%) infratorcular lesions. Mean age of encephalocele primary repair was 8 days (range 2-120 days). Hydrocephalus was diagnosed in 25 (50%) of the cases. Ventriculoperitoneal shunt was inserted in 24 patients. The mean age at VP shunt insertion was 1.3 months (range 0.3-9 months). Endoscopic third ventriculostomy was successfully performed in one patient. Dandy-Walker malformation and ventriculomegaly prior to encephalocele surgical correction were positively associated with hydrocephalus (p values 0.05 and 0.01, respectively). Chiari III malformation was found in 2 cases, both requiring CSF shunt for treatment of hydrocephalus and are stable in follow-up. Microcephaly was present in 9 cases. The known mortality rate was 8%. Conclusions: Hydrocephalus is common in patients with posterior encephaloceles, being more frequent in the supratorcular type, especially when associated to Dandy-Walker, Chiari III malformation, and pre-existing ventriculomegaly. The severity of giant encephaloceles, when associated to torcular types and microcephaly, is a limiting factor for development of hydrocephalus, due both to the rapid evolution of natural history and the structural changes in microcephaly.

Occipital Encephalocele: Cause, Incidence, Neuroimaging and Surgical Management

Article

Full-text available

Oct 2019
Curr Pediatr Rev

Aims: To review and present the current knowledge of incidence, signs and symptoms, diagnosis and treatment of the occipital encephalocele. Background: Encephalocele (E) is a defect of the neural tube that refers to congenital malformations featured by skull defect and dura with extracranial spread of intracranial structures. Occipital encephalocele (OE) are the most common form of this congenital disorder and are manifested as a swelling of different sizes over the occipital bone in the midline. Proper diagnosis and treatment is highly important in the management of this congenital malformation of brain. Objective: To review and present the current knowledge of incidence, signs and symptoms, diagnosis and treatment of the occipital encephalocele. Methods: We conducted a search of case reports or case-series of patients by the use of electronic databases: Pub Med, Medline, Index Medicus, Scorpus. The key words were: encephalocele, occipital encephalocele, neural tube defect, congenital malformation. The search was updated to December 31, 2018. Papers published in English were the only source of information. Results: Occipital encephalocelle are more frequent in females than in males. The incidence is between 1 in 3000 to 1 in 10,000 live births; approximately 90% of them involve the midline. Magnetic resonance imaging is the method of choice in diagnosis and surgery is the best option for the treatment of OE. Overall morbidity and mortality is still high in spite of advenced surgical management, but have been significantly improved in recent years thanks to sophisticated highresolution imaging, adequate and proper surgical treatment and decent post-operative care. Conclusion: Occipital encephalocele is the most common form of encephalocele. The diagnosis is mostly based by the use of neuroimaging techniques. Operation is the best option for treatment. Overall morbidity and mortality is still high, but have been significantly improved in recent years thanks to sophisticated high-resolution imaging, adequate and proper surgical treatment and decent post-operative care.

Giant Encephalocoele: A Rare Case Report and Review of Literature

Article

Full-text available

Jan 2019

Giant encephalocoeles are rare entities with only one case series and few case reports reported in medical literature. Encephalocoeles, which reach a size larger than the head size, are be called Giant encephalocoeles. We report a case of a 6 month old child who had giant encephalocoele with delayed motor milestones in the form of inability to hold neck. Anesthetic implications include difficulty in securing air way due without undue pressure on the sac. She underwent VP shunt followed by excision of the encephalocele sac. Patient is doing well at 1 year of follow up. Preoperative neurological status and amount of brain tissue herniating into the sac are the most important factors determining the long term prognosis.

A Brief Review of Giant Occipital Encephalocele

Article

Full-text available

Oct 2018

RajendraKumar Ghritlaharey

Meckel-Gruber Syndrome: Pathologic Manifestations, Minimal Diagnostic Criteria, and Differential Diagnosis

Article

Aug 2006

This article provides an overview of the major pathologic manifestations of Meckel-Gruber syndrome, current knowledge about its pathogenesis, minimal diagnostic criteria, and differential diagnosis. Typical sonographic findings (occipital encephalocele, postaxial polydactyly, and cystic enlargement of the kidneys) allow for diagnosis of most cases before the 14th week of gestation, but the pathologist may encounter clinically unsuspected or atypical cases that require morphologic confirmation. In these cases, a meticulous autopsy is necessary to establish the diagnosis of Meckel-Gruber syndrome.

Meckel-Gruber Syndrome: A Case Who Lived for 5 Months

Article

Jul 2019

The Meckel-Gruber syndrome is a rare, congenital, and lethal malformation characterized by typical manifestations such as encephalocele, polycystic kidneys, and polydactyly. Herein, we present a case of a patient with the typical triad as well as facial, ocular, liver, and genital abnormalities who lived for almost 5 months.