ABSTRACT
BACKGROUND: The nosological assignment of congenital ocular motor apraxia type Cogan (COMA) is still controversial. While regarded as a distinct entity by some authorities including the Online Mendelian Inheritance in Man catalog of genetic disorders, others consider COMA merely a clinical symptom. METHODS: We performed a retrospective multicenter data collection study with re-evaluation of clinical and neuroimaging data of 21 previously unreported patients (8 female, 13 male, ages ranging from 2 to 24 years) diagnosed as having COMA. RESULTS: Ocular motor apraxia (OMA) was recognized during the first year of life and confined to horizontal pursuit in all patients. OMA attenuated over the years in most cases, regressed completely in two siblings, and persisted unimproved in one individual. Accompanying clinical features included early onset ataxia in most patients and cognitive impairment with learning disability (n = 6) or intellectual disability (n = 4). Re-evaluation of MRI data sets revealed a hitherto unrecognized molar tooth sign diagnostic for Joubert syndrome in 11 patients, neuroimaging features of Poretti-Boltshauser syndrome in one case and cerebral malformation suspicious of a tubulinopathy in another subject. In the remainder, MRI showed vermian hypo-/dysplasia in 4 and no abnormalities in another 4 patients. There was a strong trend to more severe cognitive impairment in patients with Joubert syndrome compared to those with inconclusive MRI, but otherwise no significant difference in clinical phenotypes between these two groups. CONCLUSIONS: Systematical renewed analysis of neuroimaging data resulted in a diagnostic reappraisal in the majority of patients with early-onset OMA in the cohort reported here. This finding poses a further challenge to the notion of COMA constituting a separate entity and underlines the need for an expert assessment of neuroimaging in children with COMA, especially if they show cognitive impairment.
Subject(s)
Apraxias/congenital , Cogan Syndrome/diagnosis , Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/pathology , Adolescent , Adult , Apraxias/diagnosis , Apraxias/pathology , Cerebellum/abnormalities , Cerebellum/pathology , Child , Child, Preschool , Cogan Syndrome/pathology , Eye Abnormalities/diagnosis , Eye Abnormalities/pathology , Female , Humans , Kidney Diseases, Cystic/diagnosis , Kidney Diseases, Cystic/pathology , Magnetic Resonance Imaging , Male , Neuroimaging , Retina/abnormalities , Retina/pathology , Retrospective Studies , Young AdultABSTRACT
UNLABELLED: Surfactant therapy does not lead to a uniform, optimal and sustained effect on gas exchange in neonatal respiratory distress syndrome (RDS) and acute respiratory distress syndrome (ARDS). The aim of the present study therefore was to compare the effects of a lipid-enriched and protein-modified natural surfactant preparations with a licensed, clinically used bovine surfactant preparation - SF-Ril (Alveofact). METHODS: SF-Ril was enriched with phosphatidylglycerol, sphingomyeline, phosphatidylethanolamine plasmalogen, phosphatidylethanolamine. Furthermore, SF-Ril was modified with increased surfactant protein B (SP-B)/surfactant protein C (SP-C) content and finally a mercaptoethanol (ME) treated preparation for breaking the sulfhydril bondage of SP-B/SP-C by chemical reduction in methylene chloride using ME was developed. Finally ME was removed by vacuum extraction. These modified surfactants were tested at a dosage of 100 mg/ kg each in a model of respiratory failure induced by lung lavage in male adult rats and compared with SF-Ril at an identical dosage. Mechanical ventilation was standardised with fraction of inspiratory oxygen (FiO2) 1.0 and time-cycled pressure limited ventilation 16/0.8 cmH2O before and 26/6 cmH2O (peak inspiratory pressure/positive endexpiratory pressure) after lung lavage (target arterial oxygen pressure [pa02] < 100 mmHg), respiratory rate 36/min, inspiration/expiration time ratio 1:2. RESULTS: During the observation period of 120 min, the sphingomyeline substituted and protein-modified (ME reduced) surfactant preparations exerted improved and sustained oxygenation compared with SF-Ril. Similar effects were observed for tidal volumes. All other preparations were equal or inferior to SF-Ril in our model. CONCLUSION: For the development of surfactant preparations less prone for inactivation the above mentioned data may provide useful information, provided they can be confirmed in further investigations employing other alternative models.
