Elisa Cainelli

Longitudinal Electroencephalographic (EEG) Findings in Pediatric Anti-N-Methyl-d-Aspartate (Anti-NMDA) Receptor Encephalitis The Padua Experience

To contribute to characterize electroencephalographic (EEG) activity in pediatric anti-N-methyl-d-aspartate (anti-NMDA) receptor encephalitis, we reviewed electroclinical data of 5 children with anti-NMDA receptor encephalitis diagnosed in our department. We identified 4 longitudinal electroencephalographic phases: in the early phase, background activity was normal, with intermixed nonreactive slow waves; in the florid phase, background activity deteriorated with appearance of sequences of peculiar rhythmic theta and/or delta activity unrelated to clinical changes, unresponsive to stimuli and antiepileptic medications; in the recovery phase, these sequences decreased and reactive posterior rhythm re-emerged; electroencephalogram normalized 2 to 5 months after onset. In conclusion, in the presence of evocative clinical history, recognizing a characteristic longitudinal electroencephalographic activity could provide ancillary aspects addressing the diagnosis and the overall management of children with anti-N-methyl-d-aspartate receptor encephalitis; in particular, knowing that peculiar and recurrent paroxysmal nonepileptic rhythmic theta-delta patterns can occur in these patients could help distinguish paroxysmal epileptic and nonepileptic electroencephalographic activity.

Cognitive dysfunction in pediatric multiple sclerosis.

Cognitive and neuropsychological impairments are well documented in adult multiple sclerosis (MS). Research has only recently focused on cognitive disabilities in pediatric cases, highlighting some differences between pediatric and adult cases. Impairments in several functions have been reported in children, particularly in relation to attention, processing speed, visual–motor skills, and language. Language seems to be particularly vulnerable in pediatric MS, unlike in adults in whom it is usually preserved. Deficits in executive functions, which are considered MS-specific in adults, have been inconsistently reported in children. In children, as compared to adults, the relationship between cognitive dysfunctions and the two other main symptoms of MS, fatigue and psychiatric disorders, was poorly explored. Furthermore, data on the correlations of cognitive impairments with clinical and neuroimaging features are scarce in children, and the results are often incongruent; interestingly, involvement of corpus callosum and reduced thalamic volume differentiated patients identified as having a cognitive impairment from those without a cognitive impairment. Further studies about pediatric MS are needed in order to better understand the impact of the disease on brain development and the resulting effect on cognitive functions, particularly with respect to different therapeutic strategies.

Long-Term Neurocognitive Outcome and Quality of Life in Pediatric Acute Disseminated Encephalomyelitis

BACKGROUND Acute disseminated encephalomyelitis is an inflammatory-demyelinating disorder of the central nervous system usually with a monophasic course and a favorable neurological outcome. Long-term neurocognitive sequelae and quality of life have not yet been fully investigated. AIM To examine neurocognitive outcome and quality of life in pediatric monophasic acute disseminated encephalomyelitis. METHODS Of the 36 patients diagnosed with acute disseminated encephalomyelitis at our institution, six were lost to follow-up and eight relapsed (two with multiphasic forms and six with multiple sclerosis). The outcome of the 22 remaining patients was evaluated using four subscales of the Wechsler Intelligence Scales for estimation of IQ, a battery of neuropsychological tests, and semistructured and PedsQL questionnaires for quality of life. The effect of age at onset, neuroradiological recovery, and time elapsed from the acute event on outcome was also investigated. RESULTS Estimated IQ, neuropsychological mean group scores, and quality of life at follow-up were within the normal range, but 23% of the patients had pathological scores in various neuropsychological functions, among which attention was the most clearly affected. The neuroradiological recovery was not correlated with the result of the neuropsychological tests. Age at onset correlated with linguistic skills, whereas the time elapsed from the acute event had a significant effect on attention tasks: scores were worse in the group of patients with a follow-up shorter than 7 years. CONCLUSION Our results suggest that pediatric monophasic acute disseminated encephalomyelitis has a favorable neurocognitive outcome. Patients with longer follow-up had a better outcome, suggesting a neurocognitive course that is different from that of multiple sclerosis and a potential for long-term recovery of affected functions.

De novo trisomy 20p characterized by array comparative genomic hybridization: report of a novel case and review of the literature.

We report on a boy with speech delay, mental retardation, motor clumsiness, hyperactivity, dysmorphic facial features, brachytelephalangy and short stature. Electrocardiogram, echocardiography, renal ultrasound, electroencephalogram, fundoscopic exam and auditory brainstem responses were all normal. Brain magnetic resonance imaging showed a left temporal arachnoid cyst and a small pineal gland cyst. High resolution karyotype and FISH analysis detected a de novo duplication of the short arm of chromosome 20. A molecular characterization of the chromosomal anomaly was performed by array-CGH, confirming a 17.98 Mb duplication of the short arm of chromosome 20 associated with a small duplication on chromosome 3p, that was shown to be maternally inherited. This is one of the few cases of de novo trisomy 20p with extensive workup, characterization at molecular level and close follow-up from the neonatal period to age 30 months. We also compared the phenotype of our patient with that previously reported in literature, therefore contributing to better define the trisomy 20p syndrome and helping pediatricians and geneticists to better counsel families about the developmental prognosis of these children.

Neonatal Cortical Auditory Evoked Potentials Are Affected by Clinical Conditions Occurring in Early Prematurity.

Purpose: Cortical auditory evoked potentials may serve as an early indicator of developmental problems in the auditory cortex. The aim of the study was to determine the effect on neonatal cortical auditory processing of clinical conditions occurring in early prematurity. Methods: Sixty-seven preterm infants born at 29 weeks mean gestational age (range, 23–34 weeks) were recorded at a mean postconception age of 35 weeks, before discharge from the third level neonatal intensive care unit. The average of 330 responses to standard 1000 Hz pure tones delivered in an oddball paradigm was recorded at frontal location. Data of 45 of 67 recruited premature infants were available for analysis. Mean amplitudes calculated from the data points of 30 milliseconds centered on P1 and N2 peaks in the waveforms of each subject were measured. The effect of perinatal clinical factors on cortical auditory evoked responses was evaluated. Results: The amplitude of P1 component was significantly lower in infants with bronco-pulmonary dysplasia (P = 0.004) and retinopathy of prematurity (P = 0.03). The multivariate analysis, done to evaluate the relative weight of gestational age and bronco-pulmonary dysplasia and/or retinopathy of prematurity on cortical auditory evoked potentials components, showed an effect of clinical factors on P1 (P = 0.005) and of gestational age on N2 (P = 0.02). Conclusions: Cortical auditory processing seems to be influenced by clinical conditions complicating extremely preterm birth.

Power spectral analysis of two-channel EEG in very premature infants undergoing heat loss prevention.

OBJECTIVE To evaluate whether wearing a wool cap, a routine practice used to prevent heat loss in premature infants, affects interpretation of electroencephalogram spectral analysis. METHODS Eighteen premature infants (median gestational age 28 weeks, range 23-32) without neurological complications were randomized to two channel (C3, C4 referred to Cz) digital electroencephalogram recordings with (90 min) and without (90 min) wearing wool cap, at 4 days of life. Electroencephalogram was analyzed automatically by measurement of burst suppression ratio and asymmetry index and by Fast Fourier Transform to calculate total absolute spectral power; relative spectral power in the δ (0.5-3.5 Hz), θ (4-7.5 Hz), α (8-12.5 Hz), and β (13-30 Hz) frequency bands; spectral edge frequency; and mean dominant frequency. RESULTS The use of wool cap had no effect on all electroencephalogram parameters considered. Gestational age showed an effect on relative spectral power of all considered bands, spectral edge frequency and mean dominant frequency, while no effect was seen on burst suppression ratio and asymmetry index. Neonates born at gestational weeks lower than 28 had significantly higher relative power in the δ band and lower relative power in the α and β bands. CONCLUSIONS Heat loss prevention using wool cap does not affect interpretation of spectral electroencephalogram. Spectral values in our group of very premature infants without neurological complications correspond to normal data reported in the literature. Maturation changes consist of reduction of relative power of the δ band, spectral edge frequency and mean dominant frequency.

Evoked potentials predict psychomotor development in neonates with normal MRI after hypothermia for hypoxic-ischemic encephalopathy

OBJECTIVES To assess the prognostic role of evoked potentials (EP) in neonates with normal magnetic resonance imaging (MRI) after therapeutic hypothermia (TH) for hypoxic-ischemic encephalopathy (HIE). METHODS Thirty-five neonates recruited for TH because of HIE, having normal neonatal MRI, performed neonatal somatosensory (SEP), visual (VEP) evoked potentials and electroencephalogram (EEG). The effect of SEP, VEP or EEG abnormalities on Griffiths developmental scales at 12 and 24 months was measured; positive (PPV) and negative (NPV) predictive value, sensitivity, specificity and accuracy were calculated. RESULTS At 24 months, 28% had global psychomotor impairment and 57% had isolated impairments. VEP abnormality was associated with impaired hearing-language score (p = 0.002) and performance score (p < 0.0001). VEP achieved best PPV (0.91, 95% C.I. 0.62-0.99) and specificity (0.93, 95% C.I. 0.70-0.99). The combination of neurophysiological tests achieved the best NPV (0.85, 95% C.I. 0.58-0.96), sensitivity (0.90, 95% C.I. 0.70-0.97), overall accuracy (0.83, 95% C.I. 0.67-0.92). CONCLUSIONS Psychomotor sequelae may occur in survivors of neonatal HIE with normal MRI. VEP is the single best neurophysiological prognostic marker but the combination of neurophysiological tests has a better value. SIGNIFICANCE When facing the challenge of neurodevelopmental prognosis in infants with normal MRI after TH, EPs are useful prognostic tools, complementary to EEG.

Bilateral loss of cortical SEPs predict severe MRI lesions in neonatal hypoxic ischemic encephalopathy treated with hypothermia

OBJECTIVE The introduction of therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy calls for reevaluation of the prognostic role of somatosensory evoked potentials (SEPs). METHODS Among 80 consecutive neonates undergoing hypothermia for hypoxic-ischemic encephalopathy, 58 performed SEPs and MRI at 4-14 days of life and were recruited in this multicenter study. SEPs were scored as: 0 (bilaterally/unilaterally recorded N20) or 1 (bilaterally absent N20). The severity of brain injury was scored using MRI. RESULTS Bilaterally absent N20 was observed in 10/58 neonates (17%); all had moderate/severe MRI abnormalities; 36/48 neonates (75%) with score 0 at SEPs had normal MRI. The positive predictive value of SEPs on MRI outcome was of 1.00, while the negative predictive value 0.72, sensitivity 0.48, specificity 1.00, with an accuracy of 0.78 (p < .001). CONCLUSIONS Bilateral absence of cortical SEPs predicts moderate/severe MRI pattern of injury. SIGNIFICANCE Therapeutic hypothermia does not seem to significantly affect prognostic reliability of SEPs.

7. Bilateral absence of cortical SEP and neuroimaging: Study of a cohort of 40 neonates suffering from hypoxic-ischemic encephalopathy treated with therapeutic hypothermia

The prognostic role of SEPs in neonatal hypoxic-ischemic encephalopathy (HIE) was documented before the advent of therapeutic hypothermia (HT). Brain MRI as an established role as outcome measure in neonatal HIE. The prognostic role of the SEP has not been studied. The aim of this study is to evaluate the prognostic role of SEP in neonatal HIE undergoing HT, using MRI as an outcome measure, since it has not been studied. We prospectively recruited 40 neonates with HIE treated with IT using TOBY’s criteria (2009–2011). The protocol includes SEP within the 1st week of life and brain MRI at the 2nd week of life. The recordings and the images were scored by Suppiej et al. (2010) and Glass et al. (2011), respectively. Bilateral absence of cortical SEP was associated to moderate and severe neuroimaging lesions with a PPV of 80% and NPV of 81% (sensitivity of 44% and specificity of 96%). Bilateral absence of cortical SEP is associated with MRI severe lesions, which are known to predict severe neuromotor disabilities. These data suggest that the prognostic role of SEPs is confirmed in neonatal HIE treated with IT.

114. Movement disorder and EEG patterns in anti-NMDAr antibodies encephalitis

Our aim was to investigate clinical picture, differential diagnosis between epileptic seizures and movement disorder and the significance of EEG patterns in paediatric anti- N-methyl-d-aspartate receptor (NMDAr) antibodies encephalitis. We reviewed clinical history, time course of the disease and EEG records. Clinical suspicion was confirmed by cell-based assay for detection of NMDAr antibodies in the serum and CSF in 3 and in serum in 1 of the patients. Four patients had the diagnosis of anti-NMDAr antibodies encephalitis in our Institution between 2007 and 2012 (the last three since 2011). All presented with movement disorders, epileptic seizures or seldom psychiatric disturbance, rapidly associated to abnormal sleep-wake cycle, hyporesponsivity and catatonia, followed by autonomic nervous system imbalance. In the acute phase epileptic seizures were clinically suspected in all patients but the EEG showed clear electro-clinical patterns in only one patient, one other receiving antiepileptic treatment before EEG recording had electrical seizure patterns. EEG recordings showed some similarities between the four subjects in the corresponding disease phases. Extensive diagnostic testing failed to detect neoplasms in all. All patients showed a marked improvement at follow up. Anti NMDAr antibodies encephalitis is increasingly recognised in the paediatric population. With respect to adults, movement disorder, seizures and rapid development of hyporesponsivity predominate at onset over discrete psychiatric symptoms. EEG features although not specific might help to suspect the disease in the early stages and aid in the differentiation between epileptic and non epileptic manifestations, with implications for treatment.