Regresja zmian torbielowatych w obrazie MR mózgu u dziecka z noworodkową encefalopatią niedotlenieniowo-niedokrwienną, poddanego hipotermii leczniczej

The authors present the first case of regression of cystic lesions on brain MRI in a newborn after therapeutic hypothermia in Poland. Multicystic encephalopathy is the most severe form of hypoxic-ischemic encephalopathy and its regression is described very rarely in the literature. Magnetic resonance imaging is an accepted, optimal method of evaluation of the brain and establishing prognosis in children with HIE. After normal pregnancy an emergency cesarean section was performed at 37 weeks gestation due to the markers of intrauterine hypoxia on CTG. The condition of the newborn was serious: 3 ,5, 7, 8 points according to Apgar score in 1st, 3nd, 5th and 10th minute of life, respectively. The infant required resuscitation. The cooling procedure lasted 72 hours. The first MRI study was performed at the age of 3 weeks and revealed cavities in the frontal and parietal lobed. The Evans index was 0.33. The second MRI investigation was carried out at the age of 5 weeks. The cavitary appearance did not change, the Evans index decreased to 0.32. The child underwent third MRI at the age of 2 years 4 months. No cystic lesions were found. There were signs of gliosis in their place and focal corticalsubcortical atrophy. The Evans index was 0.28 (within the normal limits). The neuropsychological status of the child at the age of 2.5 years is normal and brain MRI reveals strikingly mild lesions as compared to cavitary injury reported at the age of 3 and 5 weeks. The presented case shows that severe hypoxic-ischemic lesions such as cavities in an infant after cooling procedure do not necessarily mean poor prognosis, as with time even such lesions may regress. Therefore, even after the MRI diagnosis of multicystic encephalopathy the prognosis should be made with care.Autorki przedstawiają pierwszy w Polsce przypadek regresji zmian torbielowatych w obrazie MR mózgu u noworodka poddanego hipotermii leczniczej. Encefalopatia wielotorbielowata jest najcięższą postacią zmian niedotlenieniowo-niedokrwiennych i ustąpienie zmian jest opisywane niezwykle rzadko. Rezonans magnetyczny jest uznaną, optymalną metodą oceny stanu mózgowia, prognozowania dalszego rozwoju dziecka z ENN i określania rokowania. Noworodek z prawidłowej ciąży I został urodzony cięciem cesarskim w 37 tygodniu ciąży ze wskazań nagłych wobec wykładników kardiotokograficznych niedotlenienia wewnątrzmacicznego. Stan dziecka był ciężki, punktacja wg Apgar 3 ,5, 7, 8 odpowiednio w 1., 3., 5. i 10. minucie życia. Noworodek wymagał resuscytacji. Był poddany procedurze chłodzenia przez 72 godz. Pierwsze badanie MR wykonano w 3. tygodniu życia i uwidoczniono jamy wypełnione płynem w płatach czołowych i ciemieniowych. Wskaźnik Evansa wynosił 0,33. Drugie badanie MR wykonano w wieku 5 tygodni. Obraz jam nie uległ zmianie, wskaźnik Evansa zmniejszył się do 0,32. Trzecie badanie MR wykonano w wieku 2 lat i 4/12 i nie uwidoczniono jam. W ich miejscu widoczna była glioza i odcinkowy zanik korowo-podkorowy. Wskaźnik Evansa wyniósł 0,28 (w granicach normy). Stan neuropsychologiczny dziecka w wieku 2,5 lat nie odbiega od normy, a obraz MR mózgu wykazuje uderzająco niewielkie zmiany w stosunku do stwierdzanych w wieku noworodkowym. Prezentowany przypadek pokazuje, że ciężkie zmiany niedotlenieniowo-niedokrwienne w postaci jam u dziecka po leczeniu hipotermią nie muszą rokować źle, ponieważ z upływem czasu nawet zmiany jamiste mogą ulec regresji. Zatem nawet po stwierdzeniu w obrazie MR cech encefalopatii wielotorbielowatej rokowanie odnośnie przeżycia i dalszego stanu neurorozwojowego dziecka powinno być stawiane ostrożnie

Intrathecal Infusion of Autologous Adipose-Derived Regenerative Cells in Autoimmune Refractory Epilepsy: Evaluation of Safety and Efficacy

Objective/Purpose. Evaluation of efficacy and safety of autologous adipose-derived regenerative cells (ADRCs) treatment in autoimmune refractory epilepsy. Patients. Six patients with proven or probable autoimmune refractory epilepsy (2 with Rasmussen encephalitis, 2 with antineuronal autoantibodies in serum, and 2 with possible FIRES) were included in the project with approval of the Bioethics Committee. Method. Intrathecal injection of autologous ADRC acquired through liposuction followed by enzymatic isolation was performed. The procedure was repeated 3 times every 3 months with each patient. Neurological status, brain MRI, cognitive function, and antiepileptic effect were monitored during 12 months. Results. Immediately after the procedure, all patients were in good condition. In some cases, transient mildly elevated body temperature, pain in regions of liposuction, and slight increasing number of seizures during 24 hours were observed. During the next months, some improvements in school, social functioning, and manual performance were observed in all patients. One patient has been seizure free up to the end of trial. In other patients, frequency of seizures was different: from reduced number to the lack of improvement (3-year follow-up). Conclusion. Autologous ADRC therapy may emerge as a promising option for some patients with autoimmune refractory epilepsy. Based on our trial and other clinical data, the therapy appears to be safe and feasible. Antiepileptic efficacy proved to be various; however, some abilities improved in all children. No signs of psychomotor regression were observed during the first year following the treatment

Exome Sequencing Reveals Novel Variants and Expands the Genetic Landscape for Congenital Microcephaly

Congenital microcephaly causes smaller than average head circumference relative to age, sex and ethnicity and is most usually associated with a variety of neurodevelopmental disorders. The underlying etiology is highly heterogeneous and can be either environmental or genetic. Disruption of any one of multiple biological processes, such as those underlying neurogenesis, cell cycle and division, DNA repair or transcription regulation, can result in microcephaly. This etiological heterogeneity manifests in a clinical variability and presents a major diagnostic and therapeutic challenge, leaving an unacceptably large proportion of over half of microcephaly patients without molecular diagnosis. To elucidate the clinical and genetic landscapes of congenital microcephaly, we sequenced the exomes of 191 clinically diagnosed patients with microcephaly as one of the features. We established a molecular basis for microcephaly in 71 patients (37%), and detected novel variants in five high confidence candidate genes previously unassociated with this condition. We report a large number of patients with mutations in tubulin-related genes in our cohort as well as higher incidence of pathogenic mutations in MCPH genes. Our study expands the phenotypic and genetic landscape of microcephaly, facilitating differential clinical diagnoses for disorders associated with most commonly disrupted genes in our cohort