La lissencéphalie : à propos de deux cas

Introduction : La lissencéphalie est une malformation grave du cortex cérébral, définie par une absence totale ou partielle de circonvolutions à la surface du cerveau. C'est une pathologie rare et handicapante. Non connue dans les pays en développement, sa prise en charge est lourde et difficile. Observations : Nous rapportons 2 patients suivis dans le service de pédiatrie du Centre Hospitalier Universitaire Joseph Raseta de Befelatanana (CHUJRB),Antananarivo, admis pour crise convulsive évoluant depuis l'âge de 6 mois, un retard de développement psychomoteur et une microcé¬phalie, chez qui le diagnostic de lissencéphalie a été porté ultérieurement après la réalisation de l'IRM cérébrale. Sans incident pendant la grossesse, le premier est né à terme avec une bonne adaptation néonatale. On notait un faciès particulier avec un diamètre bitemporal étroit et un hypotélo-risme, une microcéphalie et des crises hypertoniques. Le second est né asphyxié, il présentait des crises sous forme de spasme en flexion confirmant le syndrome de West à l'EEG. A noter l'absence d'antécédent familial particulier chez les 2 patients. Conclusion : Bien que rare, la lissencéphalie existe bien dans les pays en développement. Il faut y penser devant une épilepsie de l'enfant associée à une microcephalie et un retard de dévelop¬pement psychomoteur. Son diagnostic reste iconographique. Sa prise en charge est lourde et difficile par son coût. Donc la prévention est impor¬tante. Mais la consultation génétique n'est pas encore accessible dans les pays en développement

Trastornos de la migración neuronal: un caso de lisencefalia / Neuronal migration disorders: a lissencephaly case

Las malformaciones del desarrollo cortical originan un grupo de patologías, que cursan con diversas manifestaciones las cuales marcan un grado de minusvalía significativo en quienes las padecen. La Lisencefalia es una de las alteraciones de la migración neuronal caracterizada por una corteza cerebral de superficie lisa o con pocas circunvoluciones. Este trastorno está frecuentemente asociado a epilepsias de difícil manejo. Se presenta el caso de un paciente masculino de 18 meses de edad con diagnóstico de Lisencefalia quien cursa con convulsiones tónicas generalizadas desde los 8 meses de edad. Se le realizó TAC de cráneo simple y resonancia magnética de cerebro para confirmar el diagnóstico y se dio manejo farmacológico a las convulsiones.

Malformations of cortical development originate a group of pathologies that involve diverse manifestations that mark a significant degree of disability in those who suffer from. The Lissencephaly is one of alterations in neuronal migration characterized by a smooth surface or with few convolutions in the cerebral cortex. This disorder is often associated with difficult management Epilepsies. We report the case of a male patient from 18 months of age with a diagnosis of Lissencephaly, who presents generalized tonic seizures from 8 months of age. Was performed a simple skull CT and brain magnetic resonance to confirm the diagnosis and the pharmacological management was given to seizures.

A Forensic Autopsy Case of Lissencephaly for Evaluating the Possibility of Child Abuse / 대한법의학회지

A 9-year-old Korean boy with lissencephaly was found dead at home. He had previously been diagnosed with lissencephaly that presented with infantile spasm on the basis of magnetic resonance imaging and electroencephalogram results. Antemortem chromosomal banding revealed a normal karyotype. A legal autopsy was requested to eliminate the possibility of neglect or abuse by his parents. The autopsy findings revealed type I lissencephaly with the associated microcephaly. No external wounds or decubitus ulcers were noted. Postmortem fluorescence in situ hybridization for the LIS1 locus and nucleotide sequence analysis of the whole coding regions of the LIS1 gene did not reveal any deletions. The antemortem and postmortem findings revealed that lissencephaly syndrome was associated with isolated lissencephaly sequence. External causes of death were excluded by the full autopsy and toxicology test results. Because patients with mental retardation are frequently victimized and suffer neglect or abuse, thorough external and internal examinations should be conducted at the time of autopsy.

A Collodion Baby with Facial Dysmorphism, Limb Anomalies, Pachygyria and Genital Hypoplasia: A Mild Form of Neu-Laxova Syndrome or a New Entity?

Neu-Laxova syndrome is a rare, lethal, autosomal recessive disorder characterized by intrauterine growth retardation, central nervous system anomalies, skin findings, such as ichthyosis, edema, collodion baby and harlequin fetus, facial dysmorphic features, limb anomalies and genital hypoplasia. Although it is generally a lethal condition, cases of such patients who lived beyond 6 months and 10 months of age have been reported. Here, we describe an 8-year-old boy who was born with collodion membrane, facial dysmorphic features, limb anomalies, genital hypoplasia and pachygyria. He had no major health problems over the course of 8 years of follow-up, except for mild mental/motor retardation, ichthyosis, facial dysmorphic features and limb anomalies. Based on these features, we suggest that because Neu-Laxova syndrome represents a heterogeneous phenotype, our case may be a milder variant of this syndrome or a new genetic entity.

A Case of Cecal Volvulus Presenting with Chronic Constipation in Lissencephaly / 대한소아소화기영양학회지

Cecal volvulus is uncommon in pediatric patients and there are few reports of cecal volvulus with cerebral palsy. Here, we report the case of a 19-year-old male patient who presented with abdominal distension, a history of cerebral palsy, refractory epilepsy due to lissencephaly, and chronic constipation. An abdominal x-ray and computed tomography without contrast enhancement showed fixed dilated bowel intensity in the right lower abdomen. Despite decompression with gastric and rectal tube insertion, symptoms did not improve. The patient underwent an exploratory laparotomy that revealed cecal volvulus. Cecal volvulus usually occurs following intestinal malrotation or previous surgery. In this patient, however, intestinal distension accompanying mental disability and chronic constipation resulted in the development of cecal volvulus. We suggest that cecal and proximal large bowel volvulus should be considered in patients presenting with progressive abdominal distension combined with a history of neuro-developmental delay and constipation.

Avaliação de linguagem em um caso de associação entre surdez e paquigiria / Language evaluation in a case of association between deafness and pachygyria

Para que ocorra a aquisição e o desenvolvimento da linguagem é necessária a associação de uma série de fatores, cujo funcionamento harmonioso determina o sucesso desse processo. O comprometimento auditivo pode ser um obstáculo, mas, mesmo assim, a criança surda será capaz de adquirir linguagem por meio de uma língua de sinais. Porém, quando a criança apresenta alterações neurológicas, o acompanhamento fonoaudiológico se faz necessário. Esta pesquisa é um estudo de caso sobre uma criança surda, com idade de 5 anos e 10 meses, em processo de aquisição da língua de sinais, com comprometimento neurológico. Tem como objetivo avaliar, analisar e aprofundar conhecimentos sobre uma doença rara (paquigiria), associada com surdez, mostrando os impactos que isso pode acarretar à criança, em relação à comunicação. A coleta de dados foi efetuada por meio de avaliações formais e observacionais sobre habilidade e modalidade de comunicação utilizada, desenvolvimento linguístico, fonologia e conhecimento lexical na Língua Brasileira de Sinais (LIBRAS), além da aplicação de um questionário. Os resultados apontaram atraso no processo de aquisição de linguagem, mesmo considerando-se a defasagem entre o nascimento da criança e o início da aquisição da LIBRAS, aspectos que podem estar relacionados com o diagnóstico de paquigiria. É importante que o fonoaudiólogo conheça a LIBRAS e saiba avaliar a linguagem da criança utente dessa língua, pois casos como estes revelam a complexidade da associação entre surdez e quadros neurológicos variados.

In order for the acquisition and development of language to occur, it is necessary to associate a number of factors, whose harmonious functioning determines the success of this process. The hearing loss may be an obstacle, but even so, the deaf child will be able to acquire language through a sign language. However, when the child shows neurological changes, the speech monitoring becomes necessary. This research is a case study of a deaf child, aged 5 years and 10 months, in the acquisition of sign language, who presents neurological impairment. It aims to assess, analyze, and deepen the knowledge on a rare disease (pachygyria) associated with deafness, showing the impact that this can pose to the child regarding communication. Data collection was done through formal evaluations and observational regarding the ability and modality used for communication, language development, phonological and lexical knowledge in Brazilian Sign Language (LIBRAS); in addition to a questionnaire. The results showed delay in language acquisition, even considering the gap between the child’s birth and the early acquisition of LIBRAS, aspects that may be related to the diagnosis of pachygyria. It is important that the audiologist know LIBRAS and know to assess the language of the child who uses this language, because cases like these reveal the complexity of the association between deafness and various neurological disorders.

Neuronal stem cells in the central nervous system and in human diseases

The process of cortical expansion in the central nervous system is a key step of mammalian brain development to ensure its physiological function. Radial glial (RG) cells are a glial cell type contributing to this progress as intermediate neural progenitor cells responsible for an increase in the number of cortical neurons. In this review, we discuss the current understanding of RG cells during neurogenesis and provide further information on the mechanisms of neurodevelopmental diseases and stem cell-related brain tumorigenesis. Knowledge of neuronal stem cell and relative diseases will bridge benchmark research through translational studies to clinical therapeutic treatments of these diseases.

Mutational screening of ARX gene in Iranian families with X-linked intellectual disability

Mutations in the human aristaless-related homeobox [ARX] gene are amongst the major causes of developmental and neurological disorders. They are responsible for a wide spectrum of phenotypes, including nonsyndromic X-linked intellectual disability [NS-XLID], and syndromic [XLIDS] forms such as X-linked lissencephaly with abnormal genitalia [XLAG], Partington syndrome [PRTS], and X-linked infantile spasm syndrome [ISSX]. The recurrent 24 bp duplication mutation, c.428_451dup[24 bp], is the most frequent ARX mutation, which accounts for 40% of all cases reported to date. We have screened the entire coding sequences of the ARX gene in 65 Iranian families with intellectual disabilities in order to obtain the relative prevalence of ARX mutations. At first these families were screened for the most recurrent mutation, the c.428_451dup[24 bp]. For samples with negative results, single strand conformation polymorphism [SSCP] analysis was performed. We identified one family with the c.428_451dup[24 bp] duplication. Three shifts [one shift in exon 5 and two shifts in exon 4] were also identified among the total families. According to the results of the sequencing analysis, two shifts were not associated with any mutation and the other one was a c.1347C>T [p.G449G] substitution in exon 4. Hence, we suggest that molecular analysis of ARX mutations as a second cause of XLID should be considered as routine diagnostic procedure in any male who presents with either NS-XLID or XLIDS

Analysis of the clinical manifestations and magnetic resonance imaging features of 11 patients with lissencephaly / 南方医科大学学报

<p><b>OBJECTIVE</b>To analyze the clinical manifestations and magnetic resonance imaging (MRI) features of lissencephaly of various types and provide clinical and imaging evidences for the clinical diagnosis of the disease.</p><p><b>METHODS</b>The clinical symptoms and signs and the findings in neurobehavioral evaluation, laboratory examination and magnetic resonance imaging (MRI) of 11 cases of lissencephaly were investigated retrospectively.</p><p><b>RESULTS</b>The 11 patients consisted of 4 with isolated lissencephaly sequence, 3 with Miller-Dieker syndrome, 3 with cobblestone lissencephaly, and 1 with lissencephaly with cerebellar hypoplasia. The main clinical manifestations included mental retardation, developmental delay, microcephaly, epilepsy, hearing abnormality and facial malformation. Cobblestone lissencephaly presented with congenital muscular dystrophy and eye malformation, and lissencephaly with cerebellar hypoplasia showed ataxia manifestations. In terms of MRI features, classical lissencephaly displayed absent or broad cerebral gyri, thickened cortex and reduced white matter, smooth border between the gray and white matter, and thin white matter. Cobblestone lissencephaly displayed thick cortex and gyri deficiency with cobblestone surface. Lissencephaly with cerebellar hypoplasia presented with pachygyria, cerebellar hypoplasia and hippocampal dysplasia.</p><p><b>CONCLUSION</b>Lissencephaly is a developmental malformation of the brain with obvious heterogeneity, and the clinical manifestations and MRI features can be the evidences for a clinical diagnosis and classification of the disease.</p>

A Case of Walker-Warburg Syndrome Presented with Seizures / 대한소아신경학회지

Walker-Warburg syndrome (WWS) is a rare autosomal recessive disorder characterized by congenital muscular dystrophy, brain (lissencephaly, hydrocephalus, cerebellar malformations) and retinal abnormalities, and is associated with mental retardation and seizures. In 1942, Walker was the first to report a case of WWS. As Fukuyama congenital muscular dystrophy or muscle-eye-brain disorder, it has been demonstrated that the glycosylation defects of alpha-dystroglycan which take a great role in muscle and neuron regeneration are at the root of these disorders. We report a five months old male patient who was presented with seizures as the chief complaint and was diagnosed with WWS, based on clinical criteria, MRI, muscular biopsy, ocular examination, and laboratory findings.

Three-Dimensional Brain Surface Rendering Imaging of Cortical Dysplasia

PURPOSE: The study was to evaluate the localization of the abnormal gyral and sulcal patterns obtained by means of brain surface rendering imaging. MATERIALS AND METHODS: Nineteen patients with cortical dysplasia who underwent brain surface rendering MR imaging were included in this study. We acquired MP-RAGE sequence and created the 3-D surface rendering MR images by using VoxelPlus(R). Anatomical locations and configurations of abnormal gyri and sulci were reviewed. RESULTS: Abnormal gyral and sulcal patterns were seen 18 in 19 patients. The configuration and orientation of affected gyri and sulci were clearly evaluated in the brain surface rendering images. In a lissencephaly, the a cortex was not delineated and showed markedly thick and smooth gyral pattern. In a schizencephaly, there were wheel shaped broad gyral pattern around the cleft. In a hemimegalencephaly, an affected hemisphere were enlarged and displayed thick and wide gyral pattern. In CBPS, the insular cortex was exposed and the gyri of the lesion were thickened. In focal cortical dysplasia, there were irregular serrated or thick and enlarged gyri. CONCLUSION: Brain surface rendering MR imaging is useful for the evaluation of a detailed gyral pattern and accurate involvement site of abnormal gyri.

A Child With Muscle-eye-brain Disease

PURPOSE: To describe a child with muscle-eye-brain disease as the first case report in Korea. CASE SUMMARY: A 35-month-old girl presented with esotropia and nystagmus since birth. She was born with a birth weight of 3.45 Kg at the gestational age of 39 weeks. She had a history of developmental delay and developmental dislocation of the hip. Her elder sister also had generalized weakness and mental retardation. The patient's creatinine kinase and lactate dehydrogenase serum levels were high. Cycloplegic refraction showed a significant myopic astigmatism in both eyes. She showed nystagmus and 20 prism diopters of esotropia in the primary position with the alternative prism cover test. Slit lamp examination revealed a mild posterior subcapsular cataract and lower lid epiblepharon in both eyes. Funduscopic examination showed diffuse retinal degeneration with remnant hyaloids membranes in both eyes. Both optic nerves were dysplastic with abnormal vascular branching pattern. Flash visual evoked potential was normal and standard electroretinography showed decreased amplitude in both eyes. Brain magnetic resonance imaging (MRI) revealed diffuse T2 high signal lesions of the cerebral white matter, diffuse pachygyria of the cerebral cortices, pontine hypoplasia, and multiple small cerebellar cysts. CONCLUSIONS: When a child with developmental delay has ophthalmologic problems including severe myopia, cataract, strabismus and retinal degeneration, the systemic condition should be examined. In this case, in addition to the ophthalmologic findings, blood test and brain MRI were helpful for the diagnosis of muscle-eye-brain disease.

A Case of Diffuse Cerebral Cortical Dysplasia and Partial Agenesis of Corpus Callosum in Seckel Syndrome / 대한소아신경학회지

Seckel syndrome is a rare autosomal recessive disorder characterized by low birth weight, short but proportionate stature, microcephaly, moderate to severe mental retardation and typical facial features mimicking bird including receding forehead and chin, a prominent beaked nose and large eyes. A number of CNS anomalies have been reported in literature that are mental retardation, seizures, pachygyria, arachnoid cysts, large basal ganglia, agenesis of corpus callosum, hypoplasia of cerebellar vermis and cerebral aneurysms. Our patient had seizures, microcephaly, mental retardation and CNS anomalies, including diffuse cerebral dysgenesis, pachygyria and partial agenesis of corpus callosum. We report a case of Seckel syndrome with CNS anomalies and a follow up visit at 5 years later

Pattern of childhood neuronal migrational disorders in Oman

To record the pattern of different neuronal migrational disorders [NMD] and their associated neurological conditions. The data were collected at the Child Neurology Services of Sultan Qaboos University Hospital, Oman, from January 1993 to September 2006 from all children with psychomotor delay and epilepsy, who underwent brain imaging [mostly MRI]. The MR imaging was used for the diagnosis of a neuronal migration anomaly. There were 86 cases of NMD. Corpus callosum agenesis and lissencephaly/pachygyria formed the major group. There were 48 cases of corpus callosum agenesis, and 16 cases of lissencephaly/pachygyria. Other disorders were 10 cases of heterotopias, 5 schizencephaly, 3 holoprosencephaly, 2 polymicrogyria, and one each of hemimegalencephaly, and hydranencephaly. Developmental delay was the most common associated finding noted in 80 [93%] cases. Sixty-seven [77.9%] cases had motor deficit. Forty out of 86 [46.5%] cases had epilepsy. Partial/partial complex seizures were the most common at 13 out of 40 [32.5%]. Syndromic seizures were seen in 11 out of 40 [27.5%] cases. The seizures were controlled in only 3/40 [7.5%] cases. The NMD constitute a significant number of child neurology patients with psychomotor delay and intractable epilepsy. Exogenic and genetic factors affecting the early embryonic and fetal development from sixth to twenty-sixth weeks of gestation result in NMD. Recent genetic studies are defining the underlying mechanism and these studies will help in early diagnosis and possible prevention of NMD

Cytomegalovirus infection with lissencephaly.

Lissencephaly is a malformation of the brain in which the brain surface is smooth, rather than convoluted. Among the various causes of lissencephaly, infection by a virus during pregnancy plays an important role. Cytomegalovirus (CMV) is an important pathogen causing this anomaly. We present this case of a young female with 24-week-gestation diagnosed on ultrasound as carrying an anomalous fetus with lissencephalic features. At autopsy, there were multiple intra-nuclear CMV inclusions in the brain and the kidneys. This case is presented for its rarity and for the documentation of the tissue localization of CMV inclusions at autopsy.

A Case of Miller-Dieker Syndrome with Infantile Spasm and Lennox-Gastaut Syndrome / 대한소아신경학회지

Miller-Dieker syndrome is a contiguous gene deletion syndrome involving chromosome 17p13.3, which is characterized by type 1(classical) lissencephaly and typical craniofacial abnormalities. Children with Miller-Dieker syndrome have profound psychomotor retardation, seizures that often are intractable, chronic feeding problems that lead to recurrent pneumonia, and shortened lifespan. We have experienced a Miller-Dieker syndrome female who has lived to 8years, showing severe mental and motor retardation and intractable epilepsy. She was diagnosed as Miller-Dieker syndrome in the neonatal period, showing typical facial features, type 1 lissencephaly, and chromosome 17p13.3 microdeletion in fluorescence in situ hybridization. Infantile spasm occurred at 4 months of age and progressed to Lennox-Gastaut syndrome at 3 years and 6 months, both of which were not controlled by antiepileptic drugs.

Images in clinical medicine congenital neural malformations related to their embryological background

Congenital neural malformations are complex anomalies, which stem from an abnormality in the embryological development of the nervous system. The development of the nervous system begins by the formation of the neural tube and its subsequent closure. The failure of closure results in neural tube defects [NTD]. Defect in the formation of prosencephalon or rhornbencephalon will result in holoprosencephaly or Dandy walker complex respectively. The formation of neuroblasts and their migration to cerebral cortex may be altered by many neuronal migration disorders, Lissencephaly, schizencephaly, and heterotopic gray matter are the most prominent. The objective of the study is relating congenital neural malformations to their corresponding embryological background, and so helping in better understanding the time and the way of the occurrence of such anomalies

Lissencephaly, abnormal genitalia and refractory epilepsy: case report of XLAG syndrome / Lisencefalia, genitália ambígua e epilepsia refratária: relato de caso da síndrome XLAG

INTRODUCTION: X-linked lissencephaly with ambiguous genitalia (XLAG) is a recently described genetic disorder caused by mutation in the aristaless-related homeobox (ARX) gene (Xp22.13). Patients present with lissencephaly, agenesis of the corpus callosum, refractory epilepsy of neonatal onset, acquired microcephaly and male genotype with ambiguous genitalia. CASE REPORT: Second child born to healthy nonconsanguineous parents, presented with seizures within the first hour of life that remained refractory to phenobarbital, phenytoin and midazolam. Examination identified microcephaly, axial hypotonia, pyramidal signs and ambiguous genitalia. EEG showed disorganized background activity and seizures starting at the right midtemporal, central and occipital regions. MRI showed diffuse pachygyria, moderate thickening of the cortex, enlarged ventricles, agenesis of the corpus callosum and septum pellucidum. Karyotype showed a 46,XY genotype. Additional findings were hypercalciuria, vesicoureteral reflux, patent ductus arteriosus and chronic diarrhea.

INTRODUÇÃO: Lisencefalia com genitália ambígua ligada ao X (XLAG) é doença genética recentemente descrita, causada por mutação no gene aristaless-related homeobox (ARX) (Xp22.13). Os pacientes apresentam lisencefalia, agenesia de corpo caloso, epilepsia refratária com início no período neonatal, microcefalia adquirida e genótipo masculino com genitália ambígua. RELATO DE CASO: Segundo filho de pais não-consangüíneos, apresentou crises na primeira hora de vida que permaneceram refratárias a fenobarbital, fenitoína e midazolam. Apresentava microcefalia, hipotonia axial, sinais de liberação piramidal e genitália ambígua. EEG demonstrou atividade de base desorganizada, crises convulsivas com início nas regiões temporal-média, central e occipital direitas. RNM demonstrou paquigiria difusa, moderado espessamento do córtex, ventrículos aumentados, agenesia de corpo caloso e septo pelúcido. Cariótipo evidenciou genótipo 46,XY. Achados adicionais foram: hipercalciúria, refluxo vésico-ureteral, ducto arterioso persistente e diarréia crônica.

Epilepsia e desordens de malformação do desenvolvimento cortical / Epilepsy and malformations of cortical development disorders

OBJETIVOS: As desordens do desenvolvimento cortical (DDC) constituem a segunda causa de epilepsia refratária. Diversas patologias estão incluídas nas DDC. Seu diagnóstico foi facilitado com o desenvolvimento na neuroimagem. MÉTODOS: No presente artigo, apresentamos sete casos divididos em três grupos, de acordo com o mecanismo de produção das DDC: 1) anormalidades da proliferação e diferenciação de neurônios da glia; 2) anormalidades de migração neuronal; 3) anormalidades na organização neuronal. A investigação consistiu em história mais exame neurológico, avaliação neuropsicológica, ressonância magnética e eletrencefalograma. RESULTADOS E CONCLUSÕES: Três pacientes apresentaram displasia cortical focal, dois apresentaram heterotopia em banda, um paciente apresentava lisencefalia e uma apresentava esquizencefalia. Todos os pacientes apresentavam epilepsia de difícil controle. Malformações corticais constituem um grupo heterogêneo de causas de epilepsia de difícil controle. É importante para o manejo médico que as diversas formas de malformações corticais sejam conhecidas e diagnosticadas, o que foi facilitado pelo advento da ressonância magnética.

OBJECTIVES: Cortical development disorders (CDD) are the second cause of refratary epilepsy. Various patologies are included in the CDD. The diagnosis was easy with the continuous development of the neuroimaging. METHODS: In the present paper we show seven cases divided in three groups, accourding with the mecanism of production of the CDD: 1) proliferation and diferentiation abnormalities of the glial cells; 2) abnormalities of the neuronal migration; 3) abnormalities of the neuronal organization. The investigation consisted in story and neurological examination, neuropsicological avaliation, magnetic ressonance imaging and eletroencephalogram. RESULTS AND CONCLUSION: Three patients had focal cortical dysplasia; two had heterotopic band, one patient had lissecephaly and another had schizencephaly. All the patients had refractory epilepsy. Cortical malformations are a heterogeneous group of refractory epilepsy. Knowing and diagnosing these different types of cortical malformations are important steps for their treatment, and were facilitated by de advent of magnetic resonance imaging.