Long-term outcome of ten children with opsoclonus-myoclonus syndrome

Opsoclonus-myoclonus syndrome (OMS) in children is a rare neurological condition with opsoclonus, myoclonus, ataxia and irritability in the first 2 years of life. It can be idiopathic, parainfectious, or paraneoplastic with tumours of the neural crest. Few studies of long-term follow-up after OMS have been published. We investigated the motor, cognitive and behavioural outcome of ten patients (eight girls and two boys) seen between 1987 and 2002. We reviewed the records and reassessed the patients. A ganglioneuroma was found in one patient and a neuroblastoma in another. Tumour resection did not influence the OMS. The age at diagnosis was 10-24months and the follow-up period 1-17years (average 6.5years). The interval between the first signs and symptoms and starting treatment was 2-12weeks: treatment consisted of different immunosupressants. Remission was achieved within 5months in seven, and relapses were present in seven of ten. At follow-up, only one child had mild ataxia. IQ testing was performed in nine with scores below 75 in four and above 85 in four. Attention deficit and visuomotor difficulties led to school problems with special needs, also in those three children with normal IQs. Only two children were attending regular schools. Behavioural problems were reported in seven, and speech difficulties were present in five. In conclusion, the long-term outcome in our patients with OMS was dominated by cognitive and behavioural problems and not by ataxia. Compared with previous reports, our patients were treated earlier. Larger studies and uniform treatment protocols are needed to demonstrate whether early and prolonged immunosupressant therapy has a favourable influence on outcom

Severe neurological impairment in hereditary methaemoglobinaemia type 2

Recessive congenital methaemoglobinaemia (RCM) due to NADH-cytochrome b5 reductase (cytb5r) deficiency is a very rare disorder. We report on two unrelated patients (4 and 2.5 years old) with RCM type 2. Developmental delay was obvious at the age of 4 months. On follow-up, both children showed severe tetraspastic cerebral palsy, profound cognitive impairment, strabismus, impressive secondary microcephaly and failure to thrive. One novel mutation in the DIA1gene was identified. Prenatal diagnosis was successfully done in both families by mutation analysis in chorionic villi or measurement of cytb5r in fetal amniotic cells. Conclusion:due to the severity of this disease and its 25% recurrence risk, prenatal diagnosis should be made available to all affected familie

Pituitary duplication and nasopharyngeal teratoma in a newborn: CT, MRI, US and correlative histopathological findings

The computed tomography and MRI imaging findings in a case of pituitary duplication and epipharyngeal teratoma are described in a newborn baby girl with respiratory difficulties. Associated skull base and central nervous system malformations are presented. Teratoma diagnosis was confirmed by histology. The embryological pathogenesis is discusse

Magnetic toys: forbidden for pediatric patients with certain programmable shunt valves?

Background: Inadvertent adjustments and malfunctions of programmable valves have been reported in cases in which patients have encountered powerful electromagnetic fields such as those involved in magnetic resonance imaging, but the potential effects of magnetic toys on programmable valves are not well known. Materials and methods: The magnetic properties of nine toy magnets were examined. To calculate the effect of a single magnet over a distance, the magnetic flux density was directly measured using a calibrated Hall probe at seven different positions between 0 and 120mm from the magnet. Strata II small (Medtronic Inc.), Codman Hakim (Codman & Shurtleff), and Polaris (Sophysa) programmable valves were then tested to determine the effects of the toy magnets on each valve type. Results: The maximal flux density of different magnetic toys differed between 17 and 540mT, inversely proportional to the distance between toy and measurement instrument. Alterations to Strata and Codman valve settings could be effected with all the magnetic toys. The distances that still led to an alteration of the valve settings differed from 10 to 50mm (Strata), compared with 5 to 30mm (Codman). Valve settings of Polaris could not be altered by any toy at any distance due to its architecture with two magnets adjusted in opposite directions. Conclusion: This is the first report describing changes in the pressure setting of some adjustable valves caused by magnetic toys in close contact. Parents, surgeons, neurologists, pediatric oncologists, and paramedics should be informed about the potential dangers of magnetic toys to prevent unwanted changes to pressure setting

Facial nerve palsy—an unusual complication after evacuation of a subdural haematoma or hygroma in children

Objective: This paper reports and discusses on the possible etiology of postoperative contralateral facial nerve palsy after uneventful evacuation of a subdural haematoma or hygroma after mild head trauma in two children with pre-existing middle cranial fossa subarachnoid cysts. Results: Two 14- and 15-year-old boys had prolonged headaches after mild head injuries. CT showed a right-sided middle cranial fossa arachnoid cyst in each patient. In one patient, an ipsilateral subdural haematoma was identified, and in the other, bilateral hygromas were identified. Exacerbation of symptoms required emergency evacuation of the subdural haematoma in the first child, and bilateral external drainage of the hygroma in the other child. In both children the late postoperative period was complicated by peripheral facial nerve palsies contralateral to the arachnoid cyst. Conclusion: Facial nerve palsy may be a complication of hygroma or haematoma drainage. The etiology is not clear; traction of the facial nerve due to displacement of the brainstem may be the most likely explanatio

Does diagnostic delay result in decreased survival in paediatric brain tumours?

To study the hypothesis that a delay in the diagnosis of paediatric brain tumours results in decreased survival outcome probability, we compared the prediagnostic period of 315 brain tumour patients (median age 6.7years, range, 0 to 16years) with progression-free and overall survival. The median prediagnostic symptomatic interval was 60days (range, 0 to 3,480days), with a median parental delay of 14days (range, 0 to 1,835days) and a median doctor's delay of 14days (range, 0 to 3,480days). The prediagnostic symptomatic interval correlated significantly with the patient age, tumour histology, tumour location and year of diagnosis, but not with gender. We then grouped the patients according to histology (low-grade glioma [n=77], medulloblastoma [n=57], high-grade glioma [n=40], craniopharyngioma [n=27], ependymoma [n=20] and germ cell tumours [n=18]). Contrary to common belief, long prediagnostic symptomatic interval or long doctor's delay did not result in decreased survival outcome probability in any of these groups. The effect of tumour biology on survival seems to be dominant and overwhelms any possible opposing effect on survival of a delay in diagnosi

Long-term outcome of ten children with opsoclonus-myoclonus syndrome

Opsoclonus-myoclonus syndrome (OMS) in children is a rare neurological condition with opsoclonus, myoclonus, ataxia and irritability in the first 2 years of life. It can be idiopathic, parainfectious, or paraneoplastic with tumours of the neural crest. Few studies of long-term follow-up after OMS have been published. We investigated the motor, cognitive and behavioural outcome of ten patients (eight girls and two boys) seen between 1987 and 2002. We reviewed the records and reassessed the patients. A ganglioneuroma was found in one patient and a neuroblastoma in another. Tumour resection did not influence the OMS. The age at diagnosis was 10-24months and the follow-up period 1-17years (average 6.5years). The interval between the first signs and symptoms and starting treatment was 2-12weeks: treatment consisted of different immunosupressants. Remission was achieved within 5months in seven, and relapses were present in seven of ten. At follow-up, only one child had mild ataxia. IQ testing was performed in nine with scores below 75 in four and above 85 in four. Attention deficit and visuomotor difficulties led to school problems with special needs, also in those three children with normal IQs. Only two children were attending regular schools. Behavioural problems were reported in seven, and speech difficulties were present in five. In conclusion, the long-term outcome in our patients with OMS was dominated by cognitive and behavioural problems and not by ataxia. Compared with previous reports, our patients were treated earlier. Larger studies and uniform treatment protocols are needed to demonstrate whether early and prolonged immunosupressant therapy has a favourable influence on outcom

Gómez-López-Hernández syndrome: reappraisal of the diagnostic criteria

Gómez-López-Hernández syndrome (GLHS) is a rare and possibly underdiagnosed condition. So far, 21 patients have been reported and all of them were sporadic observations. We report six additional patients. The hallmark triad of GLHS, also named cerebellotrigeminal dermal dysplasia, consists of rhombencephalosynapsis, trigeminal anesthesia (often giving rise to corneal opacities), and bilateral parietal or parieto-occipital alopecia. Our patients had rhombencephalosynapsis and alopecia, but none had trigeminal dysfunction. In this respect, the term cerebellotrigeminal dermal dysplasia is potentially misleading. In conclusion, only rhombencephalosynapsis and alopecia are consistently present in GLHS and are required diagnostic criteria, while trigeminal anesthesia, dysmorphic features, and ataxia are inconsistent findings. A high index of suspicion is required to diagnose GLHS, particularly as alopecia tends to be hidden by surrounding scalp hai

Ketogenic Diet Treatment of Defects in the Mitochondrial Malate Aspartate Shuttle and Pyruvate Carrier

The mitochondrial malate aspartate shuttle system (MAS) maintains the cytosolic NAD+/NADH redox balance, thereby sustaining cytosolic redox-dependent pathways, such as glycolysis and serine biosynthesis. Human disease has been associated with defects in four MAS-proteins (encoded by MDH1, MDH2, GOT2, SLC25A12) sharing a neurological/epileptic phenotype, as well as citrin deficiency (SLC25A13) with a complex hepatopathic-neuropsychiatric phenotype. Ketogenic diets (KD) are high-fat/low-carbohydrate diets, which decrease glycolysis thus bypassing the mentioned defects. The same holds for mitochondrial pyruvate carrier (MPC) 1 deficiency, which also presents neurological deficits. We here describe 40 (18 previously unreported) subjects with MAS-/MPC1-defects (32 neurological phenotypes, eight citrin deficiency), describe and discuss their phenotypes and genotypes (presenting 12 novel variants), and the efficacy of KD. Of 13 MAS/MPC1-individuals with a neurological phenotype treated with KD, 11 experienced benefits—mainly a striking effect against seizures. Two individuals with citrin deficiency deceased before the correct diagnosis was established, presumably due to high-carbohydrate treatment. Six citrin-deficient individuals received a carbohydrate-restricted/fat-enriched diet and showed normalisation of laboratory values/hepatopathy as well as age-adequate thriving. We conclude that patients with MAS-/MPC1-defects are amenable to dietary intervention and that early (genetic) diagnosis is key for initiation of proper treatment and can even be lifesaving. Keywords: mitochondrial disease; epilepsy; hepatopathy; aspartate glutamate carrier 1 deficiency; AGC1; citrin deficiency; Citrullinemia; treatment; modified Atkins diet; serin