Phosphorylated neurofilament heavy chain in cerebrospinal fluid and plasma as a Nusinersen treatment response marker in childhood-onset SMA individuals from Serbia.

Introduction: Biomarkers capable of reflecting disease onset and short- and long-term therapeutic effects in individuals with spinal muscular atrophy (SMA) are still an unmet need and phosphorylated neurofilament heavy chain (pNF-H) holds significant promise. Methods: We conducted a longitudinal prospective study to evaluate pNF-H levels in the cerebrospinal fluid (CSF) and plasma of 29 individuals with childhood-onset SMA treated with Nuinersen (SMA type 1: n = 6, 2: n = 17, 3: n = 6). pNF-H levels before and during treatment were compared with the levels of controls (n = 22), patients with Duchenne muscular dystrophy (n = 17), myotonic dystrophy type 1 (n = 11), untreated SMA individuals with chronic type 3 disease (n = 8), and children with presymptomatic SMA (n = 3). Results: SMA type 1 showed the highest mean CSF pNF-H levels before treatment initiation. All Nusinersen-treated individuals (types 1, 2, and 3) showed significantly elevated mean baseline CSF pNF-H compared to controls, which inversely correlated with age at disease onset, age at first dose, disease duration and the initial CHOP INTEND result (SMA type 1 and 2). During 22 months of treatment, CSF pNF-H levels declined during loading doses, stabilizing at reduced levels from the initial maintenance dose in all individuals. Baseline plasma pNF-H levels in type 1 and 2 SMA were significantly increased compared to other cohorts and decreased notably in type 1 after 2 months of treatment and type 2 after 14 months. Conversely, SMA type 3, characterized by lower baseline pNF-H levels, did not show significant fluctuations in plasma pNF-H levels after 14 months of treatment. Conclusion: Our findings suggest that CSF pNF-H levels in untreated SMA individuals are significantly higher than in controls and that monitoring of CSF pNF-H levels may serve as an indicator of rapid short-term treatment response in childhood-onset SMA individuals, irrespective of the subtype of the disease, while also suggesting its potential for assessing long-term suppression of neurodegeneration. Plasma pNF-H may serve as an appropriate outcome measure for disease progression and/or response to treatment in types 1 and 2 but not in type 3. Presymptomatic infants with SMA may show elevated pNF-H levels, confirming early neuronal degeneration.

A Review of Current Perspectives on Motoric Insufficiency Rehabilitation following Pediatric Stroke.

Pediatric stroke (PS) is an injury caused by the occlusion or rupture of a blood vessel in the central nervous system (CNS) of children, before or after birth. Hemiparesis is the most common motoric deficit associated with PS in children. Therefore, it is important to emphasize that PS is a significant challenge for rehabilitation, especially since the consequences may also appear during the child's growth and development, reducing functional capacity. The plasticity of the child's CNS is an important predecessor of recovery, but disruption of the neural network, specific to an immature brain, can have harmful and potentially devastating consequences. In this review, we summarize the complexity of the consequences associated with PS and the possibilities and role of modern rehabilitation. An analysis of the current literature reveals that Constraint-Induced Movement Therapy, forced-use therapy, repetitive transcranial magnetic stimulation, functional electrical stimulation and robot-assisted therapy have demonstrated at least partial improvements in motor domains related to hemiparesis or hemiplegia caused by PS, but they are supported with different levels of evidence. Due to the lack of randomized controlled studies, the optimal rehabilitation treatment is still debatable, and therefore, most recommendations are primarily based on expert consensuses, opinions and an insufficient level of evidence.

Cognitive profile, psychopathological symptoms, and quality of life in newly diagnosed pediatric epilepsy: A six-month, naturalistic follow-up study.

Long-term studies indicated changes in aspects of cognition, psychopathology, and quality of life (QOL) in children and adolescents followed up after the diagnosis of epilepsy. However, evidence is limited regarding what happens during the first few months after epilepsy is diagnosed because at this phase is possible to adjust and/or change an AED regimen or add other treatment interventions, if needed. This is a naturalistic, six months follow-up study that evaluated changes in overall cognitive profiles, levels of psychopathological symptoms, and quality of life (QOL) in newly diagnosed, uncomplicated pediatric epilepsy. In total, 61 (35 [57.4%] males) children and adolescents aged 7-18 years were assessed at the time of diagnosis and the initiation of antiepileptic drug (AED) treatment and six months afterward. The Revised Wechsler Intelligence Scale for Children, the Revised Child Anxiety and Depression Scale (RCADS), Nisonger Child Behavior Rating Form for typically developing children and adolescents (NCBRF), KIDSCREEN-10 Quality of Life Measure, and Adverse Event Profile (AEP) were used. The RCADS and NCBRF scores significantly increased over time, while the KIDSCREEN-10 scores significantly decreased. The most significant increases were observed in scores measuring social phobia and depressive symptoms and inattentiveness. Verbal cognitive abilities and full-scale intelligence scores changed slightly, while more changes were found in aspects of non-verbal cognitive abilities. This study showed that six months after epilepsy diagnosis and AED initiation, there were marked increases in anxiety levels, depressive symptoms, and behavioral problems, with deteriorations in QOL, while cognitive changes were relatively minimal. Therefore, monitoring levels of psychopathological symptoms and QOL in newly diagnosed epilepsy is highly recommended.

A 6-month follow-up of disability, quality of life, and depressive and anxiety symptoms in pediatric migraine with magnesium prophylaxis.

Magnesium is frequently used for pediatric migraine prophylaxis. The aim of this study was to evaluate to which extent the disability levels, quality of life (QOL), and anxiety and depressive symptoms change after 6-month magnesium prophylaxis in pediatric migraine. This is a follow-up study of 34 children aged 7-17 years with migraine treated with oral magnesium. Disability due to migraine was assessed by the Pediatric Migraine Disability Assessment tool (PedMIDAS), QOL was assessed by the KIDSCREEN-27, and anxiety and depressive symptoms were assessed by the Revised Child Anxiety and Depression Scale (RCADS). PedMIDAS scores significantly decreased from baseline to end-point (F(df, dferror) = 11.10 (1.63, 50.49), p<0.001), as well as anxiety (F(df, dferror) = 8.95 (1.64, 50.67), p = 0.001) and depressive symptoms (F(df, dferror) = 8.91 (1.59, 49.29), p = 0.001). Considering the KIDSCREEN-27, scores for physical and psychological well-being and social support domain significantly increased from baseline to end-point (p≤0.01). After 6 months of magnesium prophylaxis, disability due to migraine significantly decreased, whereas physical and psychosocial well-being improved. Children also reported fewer anxiety and depressive symptoms. More follow-up and randomized controlled clinical trials are needed to propose clinical recommendations for magnesium prophylaxis in pediatric migraine.