Cerebrospinal Fluid Concentrations of Neurotransmitters in a Greek Pediatric Reference Population.

BACKGROUND: Biogenic amines and pterins analysis in cerebrospinal fluid (CSF) are reliable biomarkers for the diagnosis of inherited disorders of monoamine neurotransmitters. OBJECTIVE: The objectives of this study were the establishment of reference values of CSF biogenic amine metabolites in a cohort of Greek children, the detection of primary defects of biogenic amine metabolism, and the assessment of biogenic amine metabolites in children with different neurological disorders. METHODS: CSF biogenic amine metabolites and pterins (biopterin and neopterin) were analyzed using high-performance liquid chromatography with electrochemical and fluorescence detection. Three hundred sixty-three samples were analyzed: 60 infants and children with no history of neurological disorder, 6 with inherited disorders of monoamine neurotransmitters, and 297 with diverse neurological disorders. RESULTS: Reference values were stratified into six age groups. A strong correlation between homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) levels with age was detected (p < 0.001). Two patients were diagnosed with a defect of the biogenic amine synthetic pathway and three with a defect of tetrahydrobiopterin cofactor production. HVA and 5HIAA abnormalities were detected within different groups of neurological disorders, but none followed a specific pattern of HVA and 5HIAA abnormalities. CONCLUSION: In the current study, Greek reference values of biogenic amines and pterins in CSF are presented. Five new patients with inherited monoamine neurotransmitter disorders are described. Nonspecific secondary biogenic amine disturbances can be seen in patients with different neurological disorders.

Bradykinesia assessment in children with cerebral palsy and periventricular leukomalacia.

OBJECTIVE: To analyse the motor phenotype with a focus on bradykinesia in children with Cerebral Palsy (CP) in the setting of periventricular leukomalacia (PVL). METHODOLOGY: Analysis of a cohort of 25 children with CP and PVL. The Gross Motor Function Classification System (GMFCS) and the Manual Ability Classification System (MACS) were used to classify the severity of motor function. Spasticity was rated using the Modified Ashworth Scale (MAS), dystonia was rated using the Burke-Fahn-Marsden Scale (BFMS), and bradykinesia was rated using the Unified Parkinson's disease rating scale (UPDRS). All patients were video-recorded following a standard protocol. RESULTS: Bradykinesia was observed in 96% of patients. It was noted mainly in the limbs, and it was moderate-to-severe in the legs and mild-to-moderate in the arms. Bradykinesia correlated with functional level, as classified by GMFCS and MACS; also with dystonia, as rated by BFMS but did not correlate with a measure of spasticity (MAS). CONCLUSIONS: This study confirms the existence of bradykinesia in patients with CP in the setting of PVL. Bradykinesia and dystonia appear to be important interrelated factors influencing the level of gross and fine motor skills in patients with PVL.

Dystonia assessment in children with cerebral palsy and periventricular leukomalacia.

OBJECTIVE: To describe the frequency, motor phenotype, clinical patterns and functional consequences of dystonia in patients with cerebral palsy (CP) in the setting of periventricular leukomalacia. METHODS: Retrospective analysis of a cohort of 31 patients with CP and periventricular leukomalacia. Gross Motor Function Classification System (GMFCS) and Manual Ability Classification System (MACS) were used to classify functional ability. Spasticity was rated using the Modified Ashworth Scale. Presence of dystonia was assessed by reviewing video recordings, and its severity by using the Burke-Fahn-Marsden Dystonia Rating Scale. RESULTS: All patients showed evidence of dystonia involving upper and/or lower limbs, neck, trunk, mouth and eyes in order of frequency. In 29% of patients dystonia involved only the limbs and in 71% it was multifocal. Dystonia severity ranged from slight to severe. Severity and distribution of dystonia did not correlate with gender, age, weeks of gestation or duration of neonatal unit stay. GMFCS and MACS correlated with dystonia but not with spasticity. CONCLUSIONS: Severity of dystonia, but not spasticity is associated with the severity of motor functional disability in CP patients with periventricular leukomalacia and demonstrates the key role of dystonia in the motor function of these patients.