Nystagmus in Infantile Pompe Disease: a new feature?

We describe a 3 month-old female floppy infant with hypertrophic cardiomyopathy, serum enzyme levels, which were characterized by an aspartate aminotransferase level of 144 U/l, alanine transaminase 240 U/L and creatine kinase level of 543 U/l. On the basis of the clinical signs and laboratory results,  acid α-glucosidase activity was determined from dried blood spots resulting lower than the normal range (0.2 mmol/L/h: normal reference range: 1,86-21,9 mmol/L/h) and leading to a diagnosis of infantile Pompe disease. She also showed multi-directional nystagmus. Refractive errors, ptosis and strabismus are described in infantile Pompe Disease, while nystagmus is rarely reported before. Therefore with this paper we highlight an atypical ocular symptom, whose uncertain pathogenesis, to be taken into consideration, because by now, with increasing survival with ERT, new phenotypes of Pompe disease are taking shape.

Risk factors for neonatal seizures: A case-control study in the province of Parma, Italy.

PURPOSE: The present study evaluated the risk factors for electroencephalographic (EEG)-confirmed seizures during the whole neonatal period in preterm and term neonates born in the province of Parma between January 2009 and December 2014. METHODS: We selected as cases the infants that presented EEG-confirmed neonatal seizures (NS). Two population controls for each case were matched by gestational age (GA), sex, hospital, and period of birth. Information on the mother, the pregnancy, the labor and delivery, and the neonates were taken from the Emilia-Romagna Certificate of Delivery Assistance database and from hospital charts and ICD-9-CM codes. RESULTS AND INTERPRETATION: In the 6-year period of this study, 22 patients were recorded with NS. The association between at least one pregnancy complication and at least one neonatal complication, a low Apgar score, the need for resuscitation at birth, intraventricular hemorrhages (IVH) grades II-IV for preterm, and acute perinatal asphyxia/hypoxic-ischemic encephalopathy (HIE) for term infants were all statistically significant among cases. Neonates presenting these risk factors are more prone to develop NS and have to be strictly monitored.

Incidence of neonatal seizures, perinatal risk factors for epilepsy and mortality after neonatal seizures in the province of Parma, Italy.

OBJECTIVE: Information about the incidence of neonatal seizures (NS) is scarce. Previous studies relied primarily on a clinical diagnosis of seizures. This population-based, retrospective study evaluated the incidence of electroencephalography (EEG)-confirmed seizures in neonates born in the province of Parma and the perinatal risk factors for mortality and epilepsy. METHODS: All neonates with suspected seizures or with medical conditions at high risk for seizures from the study area were recorded in the neonatal intensive care unit (NICU) of the Parma University Hospital. NS were EEG confirmed. Perinatal risk factors for mortality and epilepsy after NS were evaluated with Cox's proportional hazards models. RESULTS: In a 13-year period, 112 patients presented with NS: 102 newborns had electroclinical seizures (46 full-term and 56 preterm), whereas 10 presented only electrical seizures. The incidence was 2.29/1000 live births (95% confidence interval [CI] 1.87-2.72), with higher rates in preterm neonates (14.28/1000 in preterm vs 1.10/1000 in full-term infants). The incidence increased with decreasing gestational age (31-36 weeks of gestation: 5.01/1000, 28-30: 54.9/1000, and <28: 85.6/1000) and with decreasing birth weight (≥2500 g: 1.19/1000, <1000 g: 127.57/1000). Twenty-eight patients (25%) died, 16 (14.3%) had a diagnosis of epilepsy, 33 (29.5%) had cerebral palsy, and 39 (34.8%) had a developmental delay. Among the perinatal risk factors considered, the multivariate analysis showed an association between a 5-minute Apgar score of 0-7 and etiology with increased mortality and between female gender and status epilepticus with epilepsy. SIGNIFICANCE: The incidence of NS is inversely associated with gestational age and birth weight. The etiology and a low Apgar score are strongly related to mortality; female gender and status epilepticus are risk factors for the development of epilepsy.

A novel temporal pattern of childhood cerebral X-linked adrenoleukodystrophy.

We report a 9-year-old boy, with childhood cerebral X-linked adrenoleukodystrophy (CCALD), presenting with an episode of loss of consciousness, fixed gaze, hypotonia and vomit with spontaneous resolution and post-ictal sleep. Behavioural impairment has been observed since the previous five months. Magnetic Resonance Images (MRI) revealed isolated bilateral, symmetric, confluent temporal white matter lesions involving also corticospinal tracts, with sparing of the parieto-occipital and frontal white matter. This report outlines an atypical neuroradiological localization of X-linked adrenoleukodystrophy and neuropsychological findings not specifically related to the brain involvement seen at the MRI.

Reflex Myoclonic Epilepsy of Infancy: Seizures Induced by Tactile Stimulation.

Myoclonic epilepsy with reflex seizures in infancy is an extremely rare condition, in which seizures are provoked mainly by auditory or auditory-tactile stimuli. To increase the awareness of pediatricians regarding this underrecognized condition, we describe a child with seizures provoked only by the tactile stimulation of specific areas of the head and face.

Epileptic and non-epileptic paroxysmal motor phenomena in newborns.

OBJECTIVE: The aim of this study is to provide an extensive overview of the clinical features of neonatal paroxysmal motor phenomena, both self-limited, related to the immaturity of the central nervous system, and pathological (epileptic and non-epileptic), in order to help the diagnostic approach. METHODS: We reviewed the scientific literature about epileptic and non-epileptic paroxysmal motor phenomena in newborns. RESULTS: Paroxysmal motor phenomena in newborns represent a challenge for the clinicians due to the different underlying pathophysiological mechanisms. A proper differential diagnosis is required. CONCLUSIONS: There are some clinical features that may help clinicians with the differentiation among physiological and pathological, epileptic, and non-epileptic events. However, further investigations are often needed to identify the cause. A continuous synchronized video-electroencephalogram (EEG)-recording, interpreted by an expert in neonatal neurology, remains the gold standard to prove the epileptic origin of a paroxysmal motor phenomenon.

Neonatal seizures in preterm newborns: A predictive model for outcome.

BACKGROUND: With a reported prevalence of 22.2%, seizures in preterm newborns represent an emergent challenge, because they are often related to adverse outcome. The electroclinical features of preterm infants with neonatal seizures were evaluated in order to predict outcome. METHODS: From 154 newborns with video-EEG confirmed neonatal seizures admitted to Parma University Hospital between January 1999 and December 2012, we collected 76 preterm newborns with neonatal seizures. Outcome was assessed at least at one year. Student t-test for unpaired data was used to compare means of continuous variables. We applied the χ(2) test to compare nominal data between preterm newborns with favorable versus adverse outcome, and between those with seizures versus those with status epilepticus. Then we determined the independent risk factors for adverse outcome with multivariate logistic regression analysis. RESULTS: Birth weight, Apgar at 1st minute, neurologic examination, EEG, US brain scans and the presence of neonatal status epilepticus were different between preterm newborns with favorable and adverse outcome (p ≤ .049). Furthermore, birth weight, seizure onset, neurologic examination and EEG were different between the group with or without status (p ≤ .031). None of the infants with status epilepticus had a favorable outcome compared to 22.3% of those with neonatal seizures (p = .004). We also identified a predictive model that correctly classified outcome in 85.5% of subjects, with a high sensitivity for adverse outcome (>91.5%). CONCLUSION: The presence of neonatal seizures in preterm newborns is highly related to an adverse outcome that can be predicted since the first days of life.

Hereditary Hemorrhagic Telangiectasia presenting as migraine: a case report.

BACKGROUND: Hemorrhagic Hereditary Telangiectasia (HHT) is an autosomal dominant disease characterized by the presence of multiple arteriovenous malformations (AVMs). Migraine is described in association with HHT in adulthood, while only few paediatric cases are reported in the literature. AIM: In this paper, we describe an atypical case of HHT in a 7-year-old boy, who presented severe and recurrent episodes of migraine-like headache as the first symptom of the disease. METHODS: The patient was accurately investigated both clinically (general, neurological and dermatological examinations), instrumentally (electroencephalogram, brain magnetic resonance, transcranic Eco-color-Doppler, contrast echocardiography and enhanced chest computed tomography) and genetically. RESULTS: Familial history was positive for HHT in the paternal line. Both general and neurological examination were normal. Brain magnetic resonance imaging showed a minor old infarct in the right parietal and occipital lobes. Transcranic Eco-color-Doppler, contrast echocardiography and enhanced chest computed tomography revealed a pulmonary AVM. Cephalalgia resolved after transcatheter embolotherapy. A genetic test, identifying the mutation in endoglin gene both in the patient and in the father, confirmed the suspected diagnosis of HHT. CONCLUSIONS: Although headache is rarely reported in children as the first symptom of HHT, we warn clinicians on this possible link, as a promptly diagnosis is advisable in order to prevent potential complications.

Paroxysmal nonepileptic motor phenomena in newborn.

INTRODUCTION: Understanding the pathophysiological meaning of paroxysmal nonepileptic motor phenomena in newborns represents a challenge for the clinicians of the Neonatal Intensive Care Unit. METHODS: This paper provides an extensive review of the most frequent paroxysmal nonepileptic motor phenomena in newborns, in order to improve the knowledge about this sub-topic of the neonatal pathology and to guide the diagnostic-therapeutic approach. RESULTS: The correct identification of an epileptic form, among different motor phenomena, which may clinically mimic seizures, is essential for a correct management, avoiding overtreatment. However, it is likewise important to know and to be able to identify other rare neurological conditions, such as hyperekplexia, spinal muscular atrophy, acute bilirubin encephalopathy, that could make a first appearance with paroxysmal motor manifestations, needing specific diagnostic work-up and treatment. CONCLUSIONS: These clinical events should not be underestimated because, even if many times they are physiological and age-related, sometimes they could be the visible signs of an underlying epileptic or nonepileptic neurological disease.

Epilepsy after neonatal seizures: literature review.

INTRODUCTION: Acute neonatal seizures are the most frequent neurological complication in the neonatal intensive care units and the seizing newborns have an increased risk of long-term morbidity. However, the relationship between neonatal seizures and the development of epilepsy later in life is still unclear. METHODS: We performed a literature review using the search terms "neonatal seizures AND outcome", "neonatal seizures AND epilepsy", "neonatal seizures AND post-neonatal epilepsy", including secondary sources of data such as reference lists of articles reviewed. From the studies in which data were available, the incidence of epilepsy was calculated by dividing the number of all subjects who developed epilepsy in the different studies considered with the number of all newborns enrolled to the studies less the number of patients lost at follow-up. RESULTS: We found 44 studies published between 1954 and 2013, of which 4 were population-based studies and the remaining were hospital-based case series. The overall population evaluated was 4538 newborns and 17.9% developed post-neonatal epilepsy, with an onset within the first year of life in 68.5% of the patients. In 80.7%, epilepsy was associated with other neurological impairments. CONCLUSION: Estimates on epilepsy after neonatal seizures vary widely depending on selection criteria and length of the follow-up. However, it represents a common outcome of these newborns, especially in those with severe brain injury and additional neurodevelopmental disabilities.

Real-time automated detection of clonic seizures in newborns.

OBJECTIVE: The aim of this study is to apply a real-time algorithm for clonic neonatal seizures detection, based on a low complexity image processing approach extracting the differential average luminance from videotaped body movements. METHODS: 23 video-EEGs from 12 patients containing 78 electrographically confirmed neonatal seizures of clonic type were reviewed and all movements were divided into noise, random movements, clonic seizures or other seizure types. Six video-EEGs from 5 newborns without seizures were also reviewed. Videos were then separately analyzed using either single, double or triple windows (these latter with 50% overlap) each of a 10s duration. RESULTS: With a decision threshold set at 0.5, we obtained a sensitivity of 71% (corresponding specificity: 69%) with double-window processing for clonic seizures diagnosis. The discriminatory power, indicated by the Area Under the Curve (AUC), is higher with two interlaced windows (AUC=0.796) than with single (AUC=0.788) or triple-window (AUC=0.728). Among subjects without neonatal seizures, our algorithm showed a specificity of 91% with double-window processing. CONCLUSIONS: Our algorithm reliably detects neonatal clonic seizures and differentiates them from either noise, random movements and other seizure types. SIGNIFICANCE: It could represent a low-cost, low complexity, real-time automated screening tool for clonic neonatal seizures.