Discordant electroencephalogram epileptiform activity and hemispherectomy in children with refractory epilepsy and encephaloclastic lesions: a case series.

This is a case series of six children with unilateral cerebral palsy and hemispheric encephaloclastic lesions who were evaluated for epilepsy surgery. Seizure onset was in the neonatal period in three children, at 17 months in two, and at 5 years in one. Their ictal and interictal electroencephalogram (EEG) abnormalities showed paradoxical lateralization to the incorrect/'normal' hemisphere or showed bilateral abnormalities. After cautious discussion regarding the discordant electroclinical profile and implications for outcome, they proceeded to a functional hemispherectomy (between ages 4-11y) with good outcomes (at 1-10y follow-up). Their clinical details, EEG findings, electrocorticography, neuroimaging, and histology are reported. Possible surgical candidacy should be evaluated early in children with refractory epilepsy, even those with complex profiles and discordant data from the different investigations. Contralateral or bilateral EEG abnormalities should not preclude consideration of hemispherectomy in children with refractory epilepsy, hemiparesis, and uniclastic lesions.

Identification of fibronectin 1 as a candidate genetic modifier in a Col4a1 mutant mouse model of Gould syndrome.

Collagen type IV alpha 1 and alpha 2 (COL4A1 and COL4A2) are major components of almost all basement membranes. COL4A1 and COL4A2 mutations cause a multisystem disorder that can affect any organ but typically involves the cerebral vasculature, eyes, kidneys and skeletal muscles. In recent years, patient advocacy and family support groups have united under the name of Gould syndrome. The manifestations of Gould syndrome are highly variable, and animal studies suggest that allelic heterogeneity and genetic context contribute to the clinical variability. We previously characterized a mouse model of Gould syndrome caused by a Col4a1 mutation in which the severities of ocular anterior segment dysgenesis (ASD), myopathy and intracerebral hemorrhage (ICH) were dependent on genetic background. Here, we performed a genetic modifier screen to provide insight into the mechanisms contributing to Gould syndrome pathogenesis and identified a single locus [modifier of Gould syndrome 1 (MoGS1)] on Chromosome 1 that suppressed ASD. A separate screen showed that the same locus ameliorated myopathy. Interestingly, MoGS1 had no effect on ICH, suggesting that this phenotype could be mechanistically distinct. We refined the MoGS1 locus to a 4.3 Mb interval containing 18 protein-coding genes, including Fn1, which encodes the extracellular matrix component fibronectin 1. Molecular analysis showed that the MoGS1 locus increased Fn1 expression, raising the possibility that suppression is achieved through a compensatory extracellular mechanism. Furthermore, we found evidence of increased integrin-linked kinase levels and focal adhesion kinase phosphorylation in Col4a1 mutant mice that is partially restored by the MoGS1 locus, implicating the involvement of integrin signaling. Taken together, our results suggest that tissue-specific mechanistic heterogeneity contributes to the variable expressivity of Gould syndrome and that perturbations in integrin signaling may play a role in ocular and muscular manifestations.

Neuropsychological presentation of colpocephaly and porencephaly with symptom onset in adulthood.

Colpocephaly is a form of congenital ventriculomegaly while porencephaly describes any full-thickness defect within the brain which usually presents as a cystic structure. Postulated aetologies include intrauterine/perinatal injuries, genetic disorders, and morphogenesis error. Colopocephaly and porencephaly is typically diagnosed in infancy while diagnosis in adulthood is exceptionally rare. We report a case of co-existence of colpocephaly with porencephaly diagnosed incidentally in a 54-year-old male presenting with subtle cognitive and neurologic abnormalities. Neuropsychological assessment revealed weaknesses in executive functions, processing speed, and language.To our knowledge, this is the only reported case of dual incidental findings of porencephaly and colpocephaly in an adult.

Porencephaly in an Italian neonate with foetal alcohol spectrum disorder: A case report.

INTRODUCTION: Foetal alcohol spectrum disorder (FASD) is a complex malformative disease caused by the teratogenic effect of alcohol consumed during pregnancy. Mothers are frequently reluctant to admit alcohol consumption during pregnancy. During infancy and particularly during neonatal period, differential diagnosis is difficult. PATIENT CONCERNS: This case is represented by an Italian neonate boy small for gestational age, born by caesarean section at a gestational age of 37 weeks + 6 days by neglect and single-parent pregnancy. On physical examination, he presented particular facial features: microcephaly, epicanthal folds, flat midface, low nasal bridge, indistinct philtrum, and thin upper lip; moreover, examination revealed a macro-penis and recurvation without evidence of glans. DIAGNOSIS: Echocardiogram showed an inter-ventricular defect of medium-muscular type and brain magnetic resonance imaging showed asymmetry of the cerebral hemispheres with hypoplasia of the left cerebral hemisphere, dilatation of the left ventricle, cerebrospinal fluid cavity, and porencephaly. INTERVENTIONS: We investigated the ethylglucuronide (EtG) concentration in the neonate's hair by liquid chromatography-tandem mass spectrometry and we detected EtG in the infant's hair (normal value, 30 pg/mg), demonstrating prenatal alcohol exposure. OUTCOMES: In this neonate, EtG measure in hairs permitted the diagnosis of FASD, so allowing to exclude genetic diseases associated with similar clinical findings. After this result the mother admitted that she drunk alcohol during pregnancy (she declared 3 glasses of wine every day). At the age of 6 months, the child showed a moderate neurodevelopmental delay. CONCLUSION: This case shows that FAD should be considered in neonates with rare neurological diseases as porencephaly. In neonates and infants born to a mother who did not report alcohol use, EtG measure in hairs can significantly improve diagnosis of FASD, so allowing to exclude genetic diseases associated with similar clinical findings.

Vasospasm Following Hemispherectomy: A Case Report of a Novel Complication.

BACKGROUND: Hemispherectomy has been shown to be successful in treating medically intractable epilepsy, with favorable seizure-free outcomes. However, the procedure is technically challenging with high rates of in-hospital complications. We present a unique case of functional hemispherectomy complicated by diffuse cerebral vasospasm and subsequent death in a patient with COL4A1 gene mutation. CASE DESCRIPTION: A 17-year-old boy presented with right hemispheric epilepsy and a previously diagnosed autosomal dominant heterozygous COL4A1 gene mutation (c.4380T>G;p.Cys1460Trp). Functional hemispherectomy was performed without complications. On postoperative day 8, he developed an acute decline in neurologic status requiring urgent intubation for airway protection. Magnetic resonance imaging revealed areas of restricted diffusion throughout bilateral hemispheres that was explained by severe vasospasm and minimal cerebral blood flow seen on cerebral angiography. Intra-arterial calcium channel blocker infusion and balloon angioplasty were attempted without improvement in perfusion. With a worsening clinical picture, he was transitioned to comfort care and died. CONCLUSIONS: This is the first report in the literature describing global vasospasm and delayed cerebral ischemia following hemispherectomy in a patient carrying COL4A1 gene mutation. We postulate that his COL4A1 gene mutation might have resulted in this exaggerated vasospasm despite minimal residual postoperative subarachnoid hemorrhage burden. This hypothesis needs to be studied in animal models of this genetic disorder.

A porencephalic cyst formation in a 6-year-old female with a functioning ventriculoperitoneal shunt: a case-based review.

INTRODUCTION: Porencephalic cysts and cerebrospinal fluid (CSF) edema around the intracranial shuntcatheter are rare complications of ventriculoperitoneal shunt (VPS) surgery. Possible mechanisms leading to a porencephalic cyst formation in a patient with a VPS include taut ventricle, dysfunction of distalcatheters, and irreversible damage to the brain parenchyma caused by shunt insertion, chemotherapy, or radiation. Most of the previous reports were due to shunt malfunction and treatment consisted of shunt revision or removal. CASE REPORT: We present a case of porencephalic cyst formation in a 6-year-old female as a result ofcerebrospinal fluid under-drainage that was promptly improved with shunt valve adjustment. COCLUSIONS: A heightened index of suspicion is required to prevent misdiagnosis of porencephalic cysts astumors or abscesses that may lead to unnecessary surgical explorations. Further research is needed toelucidate the pathophysiological mechanism that causes a porencephalic cyst formation.

Novel COL4A2 variant in a large pedigree: Consequences and dilemmas.

Pathogenic COL4A2 variants cause abnormalities in collagen production and can have serious implications for a range of organ systems, most notably the brain. Herein, we describe a large family of first-degree relatives affected by a novel heterozygous variant in COL4A2 (c.3490G.A). A wide disease spectrum is described, from asymptomatic to symptomatic, including 2 children with porencephaly and co-existing juvenile idiopathic polyarthritis. During a subsequent pregnancy, antenatal testing identified a positive fetus. In view of the literature, we review management and genetic counselling dilemmas.

MEG May Reveal Hidden Population of Spikes in Epilepsy With Porencephalic Cyst/Encephalomalacia.

Porencephalic cyst/encephalomalacia is often associated with intractable epilepsy. A limited number of studies reported magnetoencephalography's (MEG's) potential to help construct treatment strategy for epilepsies associated with porencephalic cyst/encephalomalacia. The authors present here simultaneous electroencephalography (EEG) and MEG findings in three adult patients with pediatric-onset epilepsy due to porencephalic cyst/encephalomalacia. There were two types of spikes: one type was detected by MEG only (EEG-/MEG+), and the other detected by both EEG and MEG (EEG+/MEG+). Both types were seen in all three cases. The EEG-/MEG+ spikes all formed tight clusters; in contrast, the majority of EEG+/MEG+ spikes formed loose clusters. These data suggest that MEG may be helpful to better identify spike populations in epilepsy patients with porencephalic cyst/encephalomalacia. If hidden spike populations were to be found by MEG, this information would affect the interpretation of patient's pathophysiology and planning of intracranial electrode placement.

Porencefalia y plasticidad cerebral: a proposito de un caso clínico / Porencephaly and brain plasticity: a case report

La porencefalia es una entidad poco común caracterizada por la presencia de cavidades o excavaciones profundas en la corteza cerebral. Se debe principalmente a la destruc- ción del tejido cerebral previamente for- mado, por traumatismos hemorrágicos o infartos vasculares cerebrales, y que llevan a la formación de quistes intraparenquimato- sos. Está demostrado que un cerebro inmadu- ro puede compensar una lesión neuronal mediante una reorganización cortical, siempre y cuando la lesión ocurra muy temprano en la infancia o en la vida prenatal. Este fenómeno es conocido como plasticidad cerebral. Se presenta una paciente de siete meses de edad con hipomotilidad de hemicuerpo dere- cho. Tiene el antecedente de que durante el periodo prenatal los ultrasonidos reportaban hidrocefalia, pero nació vía vaginal, con un crecimiento y desarrollo normal para su edad y ha tenido un perímetro cefálico adecuado. Se le realizó IRM cerebral que mostró un quiste porencefálico izquierdo gigante con ausencia total de hemisferio cerebral izquierdo. Llama la atención que la paciente, a pesar de tan grande injuria cerebral, presenta un desa- rrollo y crecimiento adecuado para su edad, exceptuando por la hipomotilidad. Esto indica que se está efectuando la reorganización cortical compensatoria....(AU)