Predictors of outcome in term infants with neonatal seizures subsequent to intrapartum asphyxia

The objective of this study was to define potential clinical prognostic factors for term infants with neonatal seizures subsequent to intrapartum asphyxia. The authors completed a retrospective analysis of 62 term infants with clinical neonatal seizures subsequent to intrapartum asphyxia. Logistic regression analysis was applied to determine the independent prognostic indicators of an adverse outcome. A total of 23 (37%) infants had a normal outcome, 34 (55%) survived with 1 or more neurodevelopmental impairments (23 cerebral palsy, 28 global developmental delay, 15 epilepsy, with 18 combination of two, and 9 all three), and 5 (8%) died. Six variables were associated with an adverse outcome, but only the presence of meconium aspiration, a low (≤ 3) 1-minute Apgar score, seizure type other than focal clonic, and moderately severely abnormal electroencephalography (EEG) background findings were independently associated with an adverse outcome. Signs of acute distress are predictors of adverse outcome, alongside seizure semiology and moderate to severe EEG background abnormalities.     

Mothers' assessments of term and pre-term infants with respiratory distress syndrome: Reliability and predictive validity

Assessments of term and preterm RDS infants were made by mothers on an adaptation of the Brazelton scale. The mothers' assessments were not significantly different from those assessments made by trained clinicians, and both mothers and clinicians assigned less optimal ratings to the preterm infants. These ratings were correlated with Bayley motor scores at eight months. Mothers' assessments of infant temperament were made at four and eight months. These temperament ratings were significantly correlated with each other and with clinicians' ratings on the Brazelton neonatal and eight-month Bayley Scales. These findings suggest that mothers' assessments are reliable and have some predictive validity during early infancy.This research has been supported by grants from the Massachusetts Department of Public Health and the National Foundation March of Dimes.     

Post-transplant seizures in infants with hypoplastic left heart syndrome

Seizures are common in infants undergoing cardiac transplant and are usually attributed to a non-specific “post-pump” phenomenon. In this study, we determined which variables were associated with the occurrence of post-transplant seizures in infants with hypoplastic left heart syndrome and the need for continued treatment with antiepileptic medication. Of 127 infants studied over an 11-year period, 27 (21%), ages 9 to 90 days, had post-transplant seizures. These patients were compared to 27 age-matched transplanted infants without seizures. We compared multiple variables before, during, and after transplant including growth parameters, time of diagnosis, cyclosporine levels, maternal variables, circulatory and bypass parameters, laboratory data, neuroimaging and electroencephalographic studies, neurologic examination findings, and peri-operative complications. Post-transplant seizures were associated with total cardiopulmonary bypass time and the presence of post-transplant complications. Deep hypothermic circulatory arrest time was inversely correlated with seizure severity. Pre-transplant electroencephalographic abnormalities and total bypass time were associated with seizures requiring continued use of antiepileptic therapy. Post-transplant electroencephalograms were not associated with the need for continued treatment. Identification of variables associated with the development of post-transplant seizures is essential for early intervention to reduce long-term morbidity and mortality. Future studies to reduce risk of post-transplant seizures are warranted.     

Outcome of infants with unilateral Sturge-Weber syndrome and early onset seizures

Patients with Sturge-Weber syndrome often present with seizures during the first year of life. Currently, only patients with clinically significant seizures who do not respond to medical treatment are candidates for early epileptic surgery. However, a delay of surgical treatment may result in cognitive deterioration. We studied the correlation between parameters and outcome of seizures to re-examine the criteria for early epilepsy surgery. We performed a retrospective chart review combined with telephone interviews of parents of all Israeli infants with unilateral Sturge-Weber syndrome and early onset seizures, and we examined whether age of seizure onset and seizure intensity were correlated with cognitive level and the degree of hemiparesis at follow-up. We recruited a total of 15 patients with unilateral Sturge-Weber syndrome and early onset seizures, five of whom underwent epilepsy surgery. The mean follow-up period of all the patients was 15 years: six patients had normal intelligence, four had borderline cognitive level, three had mild mental retardation and two had moderate mental retardation. Eight of the ten non-operated patients still experience seizures at follow-up. Cognitive delay was significantly correlated with seizure intensity in the early period, but not with the age of seizures onset, the degree of hemiparesis, or the presence of ongoing seizures. We conclude that high seizure intensity in young patients with Sturge-Weber syndrome is a prognostic marker for mental deterioration.     

Acute respiratory distress syndrome in children with severe motor and intellectual disabilities

We report 13 severely disabled children with acute respiratory distress syndrome, who were treated at the Department of Pediatrics, Niigata City General Hospital between 1995 and 2002. The children ranged in age from 1 year to 16 years. All were non-ambulant. Chronic aspiration and gastro-esophageal reflux were recognized in 12 patients. Patients had the rapid onset of dyspnea refractory to oxygen therapy. Diffuse bilateral lung infiltrates were present on chest X-ray. Predisposing events included sepsis (3 patients), pneumomia (7 patients), pancreatitis (1 patient) and two children with other infections. All required mechanical ventilation for periods of 3-26 days and received oxygen for 5-64 days. Steroid therapy and surfactant therapy were given to eight and three patients, respectively. Only one patient developed an air leak complication. Despite intensive care, three children died, one underwent tracheostomy and nine recovered completely. Acute respiratory distress syndrome is a commonly recognized cause of acute respiratory failure following a variety of insults. It is characterized by the acute onset of dyspnea refractory to oxygen therapy, and diffuse lung infiltrates. Children with severe motor and intellectual disabilities had various complications. In this study, chronic aspiration and gastro-esophageal reflux are considered to be one of predisposing factors triggering acute respiratory distress syndrome in children with severe motor and intellectual disabilities. Although acute respiratory distress syndrome was considered to be a not infrequent occurrence, its mortality rate might be low despite the severity of the disease in children with severe motor and intellectual disabilities. Acute respiratory distress syndrome can be a complication seen in severely disabled children.     

Neuromuscular function in survivors of the acute respiratory distress syndrome

BACKGROUND: Survivors of acute respiratory distress syndrome (ARDS) report generalized weakness and reduced exercise tolerance up to two years following discharge from the intensive care unit (ICU). Persistent neuromuscular complications of ARDS may contribute to the functional disability observed in these patients. METHODS: Sixteen ARDS survivors underwent comprehensive neurological evaluation and standardized electrodiagnostic testing 6 to 24 months after ICU discharge. Four of these patients agreed to open muscle biopsy. RESULTS: Seven of sixteen patients had clinically significant focal compressive mononeuropathies. Electrodiagnostic testing failed to reveal any changes attributable to critical illness polyneuropathy or myopathy. All four muscle biopsies were abnormal, and although the pathological features were structurally non-specific, the presence of an acquired myopathy remains possible. Four patients had persistent mixed sensory complaints but had normal electrodiagnostic evaluation. CONCLUSIONS: The high frequency of mononeuropathies highlights the need for vigilance in daily ICU care. The findings also suggest that complaints of weakness and reduced exercise capacity in ARDS survivors may be related to combined effects of compressive neuropathies and generalized longstanding structural changes in muscle and may support an organic basis for long-term functional disability.     

Effect of topiramate on seizures and respiratory dysrhythmia in Rett syndrome

Rett syndrome, a neurodevelopmental disorder, manifests in the first few years of life with developmental arrest, stereotyped behaviors, and respiratory abnormalities. Seizures occur in 70 to 80% of patients. Clinical drug trials have not demonstrated the superiority of any specific antiepilepsy drug. We report our experience with topiramate in eight patients with Rett syndrome. Topiramate was initiated as monotherapy in two patients and as adjunctive therapy in six patients. Seven patients had improved seizure control. Respiratory abnormalities improved by 50 to 75% in two patients and by 20 to 50% in two others. In our cohort, seven of eight patients showed improvement in seizure control and/or respiratory abnormalities on topiramate. Topiramate was well tolerated. The effect of topiramate, a broad-spectrum drug, could be due to its gamma-aminobutyric acid (GABA)ergic and glutaminergic effects, both systems thought to be disordered in Rett syndrome.     

Postnatal delay of myelin formation in brains from Down syndrome infants and children

Myelination up to the age of 6 years was studied in two groups consisting of 129 Down syndrome (DS) 17/129 fetuses and 112/129 postnatal) and 73 non-DS cases (10/73 fetuses and 63/73 postnatal). In both groups studied a similar number of congenital heart disease (CHD), gastrointestinal (GI) malformations and infections were diagnosed. Paraffin or celloidin brain sections were stained with Klüver-Barrera, Heidenhain or Loyez method. The myelination was found to be delayed in 29/129 (22.5%) DS and only in 5/73 (6.8%) non-DS cases. Myelination in fetuses and newborns in the DS and non-DS groups was not delayed. In DS the myelination was delayed between ages 2 months-6 years (17/29; 58.6%) up to 12 months, and 12/29 (41.4%) aged 2-6 years, while in non-DS aged 2-6 months only. The myelination delay affected tracts with late beginning and slow cycle of myelination, mainly the associated and intercortical fibers of the fronto-temporal lobes. In 3/7 of DS cases (ages 3, 4, 6 years) less advanced myelination of U fibers was noted. In both groups the myelination delay seemed also to depend on the systemic diseases which affected the subjects during the time of myelination. In DS where CHD was present the myelination delay was found in 14/29 (48.2%) in contrast to 3/5 (60%) non-DS. Also, in 28/129 (23%) DS cases dates regarding the developmental milestones were available and some correlation was found between developmental and myelination delay.(ABSTRACT TRUNCATED AT 250 WORDS)     

Epileptic seizures in infants and children with mitochondrial diseases

The purpose of this study is to describe the characteristics of epileptic seizures in infants and children with mitochondrial diseases. From 1984 to December 2010, data from 46 of 76 patients diagnosed as having mitochondrial diseases with epileptic seizures were reviewed. Age at seizure onset, epileptic phenotypes, electroencephalogram findings, magnetic resonance imaging features, and treatment outcome in patients with syndromic or nonsyndromic mitochondrial diseases were analyzed. Thirty (65%) of 46 patients manifested seizures before the age of 1 year; 43% had Leigh syndrome and 53% had nonsyndromic mitochondrial diseases. Twenty-eight (61%) of 46 patients exhibited seizures as the manifesting complaint. Nineteen (68%) of 28 patients had nonsyndromic mitochondrial diseases. The most frequently observed electroencephalogram finding was background slow activity (28/46; 61%) in both groups. The most common cortical abnormality relevant to clinical seizures was diffuse brain atrophy on the brain magnetic resonance imaging (26/45; 58%), which was commonly observed in patients with nonsyndromic mitochondrial diseases (16/26; 62%). Despite treatment, 49% of patients experienced less than 50% seizure reduction rate, 77% of whom had nonsyndromic mitochondrial diseases. Leigh syndrome and nonsyndromic mitochondrial diseases often manifest as infantile seizures. Epileptic seizure as the initial complaint, diffuse brain atrophy, and refractory epilepsy were more common in patients with nonsyndromic mitochondrial diseases.     

Oxcarbazepine in infants and young children with partial seizures

In this open-label study, the safety, tolerability, and pharmacokinetics of oxcarbazepine as monotherapy or adjunctive therapy were studied in infants and young children with partial seizures. In a 30-day treatment phase, oxcarbazepine was titrated from 10 mg/kg/day to 60 mg/kg/day. Blood samples for analysis of the oxcarbazepine metabolite, the 10-monohydroxy derivative (MHD), were obtained at regular intervals. Patients completing the treatment phase entered a 6-month extension phase. Safety and tolerability were assessed throughout the study. Twenty-four patients (mean [range] age, 20.4 [2-45] months) were enrolled. Nineteen (79%) patients completed the treatment phase and, together with one patient who discontinued prematurely during the treatment phase, entered the extension phase. Thirteen of 20 (65%) patients completed the extension phase. The most common adverse events were pyrexia, ear infection, and irritability. Whether patients (n = 23) received enzyme-inducing antiepileptic drugs or not, MHD concentrations were consistent with those predicted from a linear, one-compartment, population-pharmacokinetic model based on a model previously fitted for 3- to 17-year-old children. Oxcarbazepine was safe and well tolerated in infants and young children. The pharmacokinetic profile of MHD was predicted by extension of a model based on older children.     

Detection of SARS-coronavirus-2 in the central nervous system of patients with severe acute respiratory syndrome and seizures

Journal of NeuroVirology - This study was designed to evaluate whether severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can directly target the central nervous system (CNS). We present...     

Hypomotor seizures in infants and children

PURPOSE: Hypomotor seizures (characterized by diminished behavioral activity with indeterminate level of consciousness) have been identified as an important seizure type in infants. Our goal was to investigate further the clinical and EEG features of hypomotor seizures. METHODS: We retrospectively reviewed 110 hypomotor seizures from 34 patients recorded with video-EEG. RESULTS: Twenty-seven (79%) patients were younger than 48 months, and seven (21%) were aged 4 to 15 years. Seventy-one (64%) seizures had regional or lateralized EEG onset, arising predominantly from temporal or parietal lobe regions. The other 39 (35%) seizures had generalized onset, usually with abrupt onset of diffuse rhythmic high-amplitude theta activity or diffuse electrodecrement and only rarely (two patients) with slow spike-wave complexes or 3-Hz spike-wave complexes. Hypomotor seizures with generalized EEG onset were significantly shorter than those with regional or lateralized onset (p = 0.01, GEE model). Unsustained head or eye movements and subtle mouth automatisms were commonly seen in hypomotor seizures with either focal or generalized onset. Seventeen percent of hypomotor seizures with focal onset evolved to include version of head and eyes or jerking of one arm, whereas 2% of generalized hypomotor seizures evolved to a cluster of spasms. CONCLUSIONS: Hypomotor seizures may be either focal or generalized. Regional EEG onsets were most often temporal or parietal, suggesting that focal hypomotor seizures may be a bland form of "complex partial" seizures with no or minimal automatisms, seen predominantly in infants. Generalized hypomotor seizures were rarely associated with an ictal pattern of generalized spike-wave complexes, suggesting a different mechanism from absence seizures seen later in life.     

Cognitive sequelae in acute respiratory distress syndrome patients with and without recall of the intensive care unit.

Some critically ill patients have dramatic recollections of the intensive care unit (ICU), whereas 23-50% have little or no recollection of their ICU stay. In addition, cognitive impairments are common following critical illness and ICU treatment. Little is known regarding the relationship between cognitive sequelae and ICU recall. We assessed recall of the ICU and its relationship to cognitive functioning at hospital discharge and 1 and 2 years after discharge in 70 consecutive acute respiratory distress syndrome (ARDS) patients. Seventeen patients (24%) had no recall of the ICU. Patients without ICU recall had increased rates of cognitive sequelae at hospital discharge and 1-year follow-up compared with the ICU recall group. Patients without ICU recall had a greater magnitude of cognitive impairments at hospital discharge, but not at 1- or 2-year follow-up. Profile analysis showed significant group differences in general intellectual functioning, executive function, processing speed, and spatial skills at hospital discharge, but not at 1- or 2-year follow-up. Estimated premorbid intelligence scores were inversely related to the magnitude of cognitive sequelae, suggesting greater "cognitive reserve" in patients with fewer cognitive decrements.     

Predicting school readiness from neurodevelopmental assessments at age 2 years after respiratory distress syndrome in infants born preterm

Aim To determine whether neurodevelopmental outcomes at the age of 2 years accurately predict school readiness in children who survived respiratory distress syndrome after preterm birth. Method Our cohort included 121 preterm infants who received surfactant and ventilation and were enrolled in a randomized controlled study of inhaled nitric oxide for respiratory distress syndrome. Abnormal outcomes at the age of 2 years were defined as neurosensory disability (cerebral palsy, blindness, or bilateral hearing loss) or delay (no neurosensory disability but Bayley Scales of Infant Development mental or performance developmental index scores <70). School readiness (assessed at a mean age of 5y 6mo, SD 1y) was determined using neurodevelopmental assessments of motor, sensory, receptive vocabulary, perceptual, conceptual, and adaptive skills. Results The mean birthweight of the cohort (57 males, 64 females) was 987g (SD 374), and the mean gestational age was 27.3 weeks (SD 2.6). At the age of 2 years, the neurodevelopmental classification was ‘disabled’ in 11% and ‘delayed’ in 23%. At the age of 5 years 6 months, intensive special education was required for 11% and some special education for 21%. Disability and delay at the age of 2 years were 92% and 50% predictive of lack of school readiness respectively, whereas only 15% of children who were normal at the age of 2 years were not school ready at the later assessment. Children with delay at 2 years were more likely to need special education if they were socially disadvantaged. Interpretation Without preschool developmental supports, preterm survivors living in poverty will require more special education services.     

A case of combined paraneoplastic neurological syndrome, with Lambert-Eaton myasthenic syndrome manifesting as severe respiratory failure, and anti-Hu syndrome]

A 63-year-old man complained of rapidly progressive respiratory failure, requiring a control respiration. He subsequently, presented with muscle weakness involving the neck and all the extremities, superimposed by painful paresthesia. He was proven to carry small-cell lung cancer (SCLC). Neurophysiological examinations revealed the waxing phenomenon at 30 Hz repetitive motor nerve stimulation. Positive serum autoantibodies were detected to voltage-gated calcium channel and Hu proteins. He received diagnosis of combined Lambert-Eaton myasthenic syndrome (LEMS) and anti-Hu syndrome. The initial chemotherapy for SCC alleviated his respiratory and neurological symptoms. But he developed multiple cranial palsies and fatal respiratory distress two months later. There is only a few reports about LEMS complicated by respiratory failure as an initial presentation. Various clinical manifestations including respiratory failure at the onset could be best explained by the combination of LEMS and anti-Hu syndrome in this case.