Carlotta Spagnoli

Neonatal status epilepticus: Differences between preterm and term newborns

BACKGROUND Despite the many studies on neonatal seizures, neonatal status epilepticus (NSE) remains a controversial entity, with no general consensus about its definition. We report the characteristics of newborns with NSE in order to assess whether they showed homogeneous features or displayed clinical and/or instrumental differences depending on gestational age (GA). Preterm and term neonates were compared and risk factors for adverse outcome evaluated. METHODS From 154 newborns with video-EEG confirmed neonatal seizures admitted to the NICU of Parma University Hospital between January 1999 and December 2012, we collected a cohort of 47 newborns (19 preterm, 28 full-term) with NSE. NSE was defined as continuous seizure activity for at least 30 min or recurrent seizures lasting a total of 30 min without definite return to the baseline neurologic condition between seizures. Outcome was assessed at least at one year. We applied the χ(2) test to compare nominal data, and multivariate logistic regression analysis to determine independent risk factors for adverse outcome. RESULTS Only Apgar scores and neurologic examination (p ≤ .02) were different between the groups. None of the preterm newborns had a favourable outcome compared to 25% of the full-term ones (p = .032). Moreover, 52.6% of preterm neonates died compared to 17.8% of the full-term newborns (p = .01; OR = 5.11). The only variable related to outcome was Apgar score at 5 min (p = .02). CONCLUSION Newborns with NSE represented a quite homogeneous group regardless of the GA. Outcome was unfavourable in most of the subjects; however adverse outcome and death were more represented in preterm newborns.

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.

Neonatal Seizures: A Review of Outcomes and Outcome Predictors

The majority of neonatal seizures are of acute symptomatic origin, and their occurrence is associated with higher mortality and morbidity compared with the general population, even if there is conflicting evidence of a detrimental effect per se. Etiology is considered the main determinant of outcome, but other factors, including gestational age, brain damage severity, neonatal neurological examination, and electroencephalographically (EEG) interictal and ictal characteristics are also related to neurodevelopmental outcome or death. Therefore, accuracy in early prognostication since the neonatal period can be improved by conveniently integrating different clinical and instrumental findings.The aim of this review is first to review the outcome of newborns with seizures (mortality, epilepsy, cerebral palsy, and intellectual disability), second to review the risk factors for adverse outcome after seizures in the newborn period, considering clinical, EEG/amplitude-integrated EEG, and neuroimaging findings associated with adverse outcome and lack of response to treatment, and finally to review published scoring systems for predicting neurologic outcome after neonatal seizures.

A wire-free, non-invasive, low-cost video processing-based approach to neonatal apnoea detection

In this paper, we present a non-invasive, low-cost, wire-free video processing-based approach to neonatal apnoea detection. Our method consists in evaluating the presence or absence of apnoea events through an innovative analysis of a motion signal extracted from a video live capturing or recording of a patient. In particular, we pre-process the video by a recently proposed selective magnification algorithm, which has the purpose of emphasizing respiratory movements. Subsequently, by relying on a motion detection method based on the difference of consecutive frames, we extract a signal representative of the “quantity” of movement. Then, since breathing is characterized by periodic movements of specific body parts (e.g., the chest), using the Maximum Likelihood (ML) criterion we detect the presence or absence of a periodic component in the motion signal, so that the presence/absence of the respiratory movements and, therefore, of apnoea episodes can be inferred. Our method is tested on a newborn with recurrent apnoea events, affected by Congenital Central Hypoventilation Syndrome (CCHS). With the proposed method, we can identify 90-100% of the apnoea events detected by polysomnography, depending on the acceptable detection delay. The results, although preliminary, are thus very promising and show that apnoea events can be identified with non-invasive, low-cost, wire-free devices.

Expanding phenotype of PRRT2 gene mutations: A new case with epilepsy and benign myoclonus of early infancy.

BACKGROUND Mutations in the gene PRRT2 have been identified in a variety of early-onset paroxysmal disorders. To date associations between PRRT2 mutations and benign myoclonus of early infancy have not been reported. CLINICAL REPORT We describe a baby affected by PRRT2 mutation and benign infantile epilepsy, with an episode of focal status epilepticus. During follow-up he developed benign myoclonus of early infancy. DISCUSSION We hypothesize a pathogenic role of PRRT2 mutation in inducing benign myoclonus of early infancy, similarly to that at the origin of other PRRT2-related paroxysmal movement disorders, such as paroxysmal kinesigenic dyskinesia. CONCLUSIONS Currently the function of PRRT2 is poorly understood, even if a marked pleiotropy and variable penetrance of its mutations are well known. Our case concurs in expanding the broad clinical spectrum of PRRT2-related disorders.

Neonatal seizures therapy: we are still looking for the efficacious drug

Therapeutic options currently available for neonatal seizures are still unsatisfactory both in terms of efficacy and of risk for long-term neurotoxicity, even if there is growing recognition of their potential to worsen neurodevelopmental outcome. A recent paper by Slaughter and colleagues entitled “Pharmacological treatment of neonatal seizures: a systematic review” has been published with the aim to provide a treatment algorithm, but, due to the relative paucity of clinical studies, it relies mainly on traditional antiepileptic drugs and does not distinguish between different neonatal populations, especially preterm and hypothermic neonates, who might require a dedicated approach in order to improve seizure control and reduce side effects.

Monitoring infants by automatic video processing

A unified approach to contact-less and low-cost video processing for automatic detection of neonatal diseases characterized by specific movement patterns is presented. This disease category includes neonatal clonic seizures and apneas. Both disorders are characterized by the presence or absence, respectively, of periodic movements of parts of the body-e.g., the limbs in case of clonic seizures and the chest/abdomen in case of apneas. Therefore, one can analyze the data obtained from multiple video sensors placed around a patient, extracting relevant motion signals and estimating, using the Maximum Likelihood (ML) criterion, their possible periodicity. This approach is very versatile and allows to investigate various scenarios, including: a single Red, Green and Blue (RGB) camera, an RGB-depth sensor or a network of a few RGB cameras. Data fusion principles are considered to aggregate the signals from multiple sensors. In the case of apneas, since breathing movements are subtle, the video can be pre-processed by a recently proposed algorithm which is able to emphasize small movements. The performance of the proposed contact-less detection algorithms is assessed, considering real video recordings of newborns, in terms of sensitivity, specificity, and Receiver Operating Characteristic (ROC) curves, with respect to medical gold standard devices. The obtained results show that a video processing-based system can effectively detect the considered specific diseases, with increasing performance for increasing number of sensors.

Epileptic and non-epileptic paroxysmal motor phenomena in newborns

Abstract 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.

Children's Headache: Drawings in the Diagnostic Work Up.

OBJECTIVES This study aims to evaluate the drawings effectiveness in childhood headache assessment. BACKGROUND Headache is a common cause of pain in children. Although drawings have been used in childhood to recognize psychological insights and pain perception, they were rarely used for headache characterization. METHODS We collected drawings from 67 subjects with cephalalgia during a 22-month timeframe. The clinical diagnosis was made according to the 2nd edition of The International Headache Classification. Drawings were independently categorized as migraine or tension-type headache (TTH) by two child neuropsychiatrists blinded to the clinical data. Cohen kappa for interrater agreement, sensitivity, specificity, and positive predictive value (PPV) were calculated. Subjects were also divided into three age groups to assess the influence of age. Finally, a control group of 90 subjects was collected and K-means cluster analysis was performed. RESULTS The drawings had a sensitivity of 85.71 and 81.48%, a specificity of 81.48 and 85.71%, and a PPV of 85.71 and 81.48%, for migraine and TTH diagnosis, respectively. Drawings by the older age group showed the highest predictability degree. Finally, by mean of cluster analysis, 59 of the 67 patients were correctly classified, whereas control subjects were similarly distributed between the two clusters. CONCLUSIONS Drawings are a useful instrument for migraine and TTH differential diagnosis. Thus, we suggest their inclusion in childhood headache diagnostic assessment.

Acute symptomatic neonatal seizures in preterm neonates (etiologies and treatments)

Acute symptomatic neonatal seizures in preterm newborns are a relevant clinical challenge due to the presence of many knowledge gaps. Etiology-wise, acute symptomatic seizures have an age-specific epidemiology, with intraventricular hemorrhage and its complications representing the first cause in extremely and very preterm neonates, whereas other etiologies have similar occurrence rates as in full-term infants. Specific treatment strategies for the premature neonates are not yet available. Studies suggest a similarly low response rate with even more unfavorable prognosis than in full-term infants. Pharmacodynamic and pharmacokinetic changes are likely under way during the preterm period, with the potential to affect both effectiveness and safety of antiepileptic drugs in these patients. However, due to the lack of clear evidence to guide prioritization of second-line drugs, off-label medications are frequently indicated by review papers and flow-charts, and are prescribed in clinical practice. We therefore conclude by exploring potential future lines of research.