Clinical Phenotype of Cerebral Palsy Depends on the Cause: Is It Really Cerebral Palsy? A Retrospective Study

Cerebral palsy is the most common motor disability in childhood. Still, the precise definition in terms of causes and timing of the brain damage remains controversial. Several studies examine the clinical phenotype of cerebral palsy types. The aim of our study was to determine to what extent the clinical phenotype of cerebral palsy patients depends on the underlying cause. We retrospectively evaluated the clinical phenotype, abnormalities during pregnancy, and cerebral palsy cause of 384 patients, treated at Charité-Medicine University, between 2015 and 2017. The cause of cerebral palsy was identified in 79.9% of cases. Causes prior to the perinatal period were, compared to perinatal brain damage, associated significantly with different comorbidities. The term cerebral palsy does not describe a single disease but is an umbrella term covering many different diseases. Depending on the cause, a varying clinical phenotype can be found, which offers great potential in terms of individual treatment and preventing comorbidities.

Evaluation of outcome probability of perinatal brain damage using immunological parameters of blood

Актуальность. Риск развития тяжёлых патологических состояний у детей раннего возраста с последствиями в виде перинатальных поражений (ПП) ЦНС определяет необходимость разработки прогностических моделей, позволяющих оценить вероятность благоприятного/неблагоприятного исхода этих состояний. Принимая во внимание вовлечённость иммунных механизмов в патогенез ПП ЦНС, решение этой задачи возможно на основе использования иммунологических показателей крови, отражающих особенности клинического состояния пациентов. Цель исследования. Сопоставление уровня иммунологических маркёров, выявляемых на первом году жизни у детей с последствиями ПП ЦНС, с динамикой их клинического состояния через год, а также построение математической модели для вероятностной оценки исхода этих патологических состояний. Материал и методы. 114 детей с последствиями ПП ЦНС гипоксического генеза обследованы в динамике методом клинического наблюдения. Первое обследование детей проведено в возрасте от 6 до 12 месяцев (средний возраст 8,6 ± 2,7 месяца), повторное - через 9-12 месяцев (средний возраст 18,5 ± 3,5 месяцев). Группу контроля составили 73 здоровых ребенка соответствующего возраста без признаков ПП ЦНС. Иммунологические показатели крови - активность лейкоцитарной эластазы (ЛЭ), α1-протеиназного ингибитора (α1-ПИ) и уровень антител к белкам нервной ткани (S100B, ГФКП, ОБМ, ФРН) - определяли однократно при первом обследовании детей. Результаты. На первом году жизни в общей группе пациентов выявлена активация воспалительных, а в 25% случаев - и аутоиммунных реакций в сыворотке крови по сравнению с контролем (p < 0,05). Показано, что степень активации иммунной системы, выявляемой у обследованных детей при первичном клиническом исследовании, сопряжена с разной динамикой их нервно-психического развития в последующий год жизни. На основе полученных результатов построена модель бинарной логистической регрессии, позволяющая оценить вероятность дальнейшего исхода по индивидуальным иммунологическим показателям крови и возрасту ребёнка с последствиями ПП ЦНС. Диагностическая эффективность полученной регрессионной модели составила 79,8%, что указывает на её высокую прогностическую возможность. Заключение. Полученные результаты подтверждают значимость таких иммунологических маркёров, как активность ЛЭ и уровень антител к белкам нервной ткани в качестве предикторов исхода перенесенных ПП ЦНС у детей первых лет жизни, и позволяют рекомендовать эти показатели для объективизации состояния пациентов на ранних доклинических этапах развития заболевания. Background. The risk of developing severe pathological conditions in young children with the consequences of perinatal brain damage (PBD) determines the need to create a prognostic model to assess the probability of a favorable/unfavorable outcome. Taking into account the involvement of immune mechanisms in the pathogenesis of PBD, the solution of this problem is possible based on the use of immunological blood indicators associated with the peculiarities of the clinical state of the patients. Aim. To compare the level of immunological markers identified in the first year of life in PBD children with the dynamics of their clinical condition a year later, and to create a mathematical model for the prediction of the outcome of these pathological conditions. Material and methods. 114 children with consequences of perinatal hypoxic-ischemic brain damage were examined in dynamics by the clinical observation. The first examination was carried out in children aged 6 to 12 mos (mean age 8.6 ± 2.7 mos), and the second examination after 9 - 12 mos (18.5 ± 3.5 mos). The control group consisted of 73 age-matched healthy children without signs of PBD. Immunological blood parameters, the activities of leukocyte elastase (LE) and a1-proteinase inhibitor (a1-PI), as well as the levels of antibodies to nervous tissue proteins (S100B, GFAP, MBP, NGF) were determined during the first examination. Results. The activation of inflammatory, and in 25% of cases, of autoimmune reactions was evident in blood of children with PBD in the first year of life as compared with control children (p<0.05). The degree of immune system activation during the first clinical examination was associated with different dynamics of their mental development during the next year. Based on these findings, a binary logistic regression model was constructed. This model makes it possible to assess the PBD outcome based on the child’s immunological blood parameters and age. The diagnostic efficiency of the regression model was 79.8%, which demonstrates its high predictive value. Conclusion. The results confirm the importance of immunological markers of LE activity and the level of antibodies to nervous tissue proteins as predictors of PBD consequences in children during the first year of life. The results allow us to recommend these indicators for objectifying the condition of patients at the early preclinical stages of PBD development.

Early predictors of perinatal brain damage: the role of neurobiomarkers

The early detection of perinatal brain damage in preterm and term newborns (i.e. intraventricular hemorrhage, periventricular leukomalacia and perinatal asphyxia) still constitute an unsolved issue. To date, despite technological improvement in standard perinatal monitoring procedures, decreasing the incidence of perinatal mortality, the perinatal morbidity pattern has a flat trend. Against this background, the measurement of brain constituents could be particularly useful in the early detection of cases at risk for short-/long-term brain injury. On this scenario, the main European and US international health-care institutions promoted perinatal clinical and experimental neuroprotection research projects aimed at validating and including a panel of biomarkers in the clinical guidelines. Although this is a promising attempt, there are several limitations that do not allow biomarkers to be included in standard monitoring procedures. The main limitations are: (i) the heterogeneity of neurological complications in the perinatal period, (ii) the small cohort sizes, (iii) the lack of multicenter investigations, (iv) the different techniques for neurobiomarkers assessment, (iv) the lack of consensus for the validation of assays in biological fluids such as urine and saliva, and (v), the lack of reference curves according to measurement technique and biological fluid. In the present review we offer an up-to-date overview of the most promising developments in the use of biomarkers in the perinatal period such as calcium binding proteins (S100B protein), vasoactive agents (adrenomedullin), brain biomarkers (activin A, neuron specific enolase, glial fibrillary acidic protein, ubiquitin carboxyl-terminal hydrolase-L1) and oxidative stress markers.

Diffic ulties of diagnostics of epilepsy due to mol ybdenum cofactor deficienc y: a case report

The article presents a clinical study of an infant with rare inherited metabolism disorder – molybdenum cofactor deficiency, for the first time in Russian literature. The onset of disorder – in early neonatal period with a suppression syndrome and myoclonic seizures combined with a burstsuppression electroencephalographic patterns, followed by a reveal of psychomotor delay. Сraniofacial dystrophies were present, including craniostenosis and microcephaly. Somatic status was characterized by hepatolienomegaly, dysmetabolic changes of kidneys’ parenchyma (suggested by ultrasound) and crystalluria. Neuroimaging data were contradictory. Neurosonography results allowed diagnosing concomitant inborn brain development defect: true porencephalia of large hemispheres. However, brain magnetic resonance imaging revealed a picture of diffuse leukomalacia with pseudocyst formation, which were considered a consequence of perinatal brain damage. Magnetic resonance imaging revealed a picture of diffuse leukomalacia with pseudocyst formation, which were considered a consequence of perinatal brain damage. Differential diagnosis was held between the early infantile epileptic encephalopathy (Ohtahara syndrome) and early myoclonic encephalopathy (Aicardi syndrome). However, etiology of the disease remained unclear. To eliminate inherited metabolic disease accompanied by epilepsy, Inherited Epilepsy Panel DNA sequencing was used. The results showed a homozygotic mutation on the exon 6 of MOCS2 gene, leading to deletion of amino acid in position 158 of the protein, which was described before in patients with molybdenum cofactor deficiency (OMIM: 252160).