Mizrahi Abstracts KZ


First International Congress on Clinical Neurophysiology of Commonwealth of Independent States (CIS), Shanghai Cooperation Organization (SCO), Asisa and Europe

Eli M. Mizrahi, MD
Chair, Department of Neurology
Professor of Neurology and Pediatrics
James A. Quigley Endowed Chair in Pediatric Neurology
Baylor College of Medicine
Houston, Texas USA

Neurophysiology of Neonates and Infants with Seizure Disorders

The clinical goal of the application of neurophysiology in the care of neonates and infants include the assessment of brain function (presence and degree of diffuse and focal dysfunction) and identification of seizures (surveillance, classification and persistence). Most often EEG is used to assess neonatal encephalopathy characterized by both altered mental status and seizures, making this technique ideal for this application. While there are significant difference in the neurophysiology of early life compared to older children and adults, there are important universal considerations: in both age groups EEG is valued in cerebral function assessment and seizure identification. In neonates and infants, the added complexity in EEG interpretation is that rapid brain growth and development determine variable findings of normal and abnormal features at various conceptional ages. There are a number of neurophysiologic techniques available for this age group, each with its advances and limitations, including: routine EEG, amplitude-integrated EEG (aEEG) and prolonged EEG monitoring (with and without video). The character of the background may correlate with the presence and degree of brain injury, with serial recording providing the most accurate findings. Electrographic seizures in the neonatal period have varied manifestations in terms of onset, focality, morphology, amplitude, duration and evolution. Prolonged monitoring not only provides data concerning presence or absence of seizures but time of onset, persistence and response to antipepiletic drug (AED) therapy. Synchronized EEG/video monitoring has been the basis for classification and characterization of neonatal seizures, providing insight into clinical identification and the differentiation of clinical seizures of epileptic origin from clinical events which do not have an epileptic basis. Prolonged monitoring can also inform treatment with AEDs. The sequence of response of an electroclinical seizure to AED treatment is initial control of the clinical seizure with persistence of the electrographic seizure, making prolonged monitoring valuable in determining the impact of therapy. The characterization of neonatal seizures with EEG/video monitoring can also help inform translational scientists as they develop experimental models of human disease.
Early Severe Neonatal and Infantile Epileptic Encephalopathy
Epileptic encephalopathy is a severe brain disorder of early age characterized by abnormal electrographic paroxysmal activity; seizures; cognitive, behavioral and neurological deficits; and poorlong term outcome. There are age-dependent manifestations among various epileptic encephalopathies although the common feature is that the interaction between seizure activity, EEG abnormalities and brain maturation may contribute to the progressive neurological and behavioral decline experienced by affected infants. Two such recognized electroclinical syndromes are early myoclonic encephalopathy (EME) (onset with in the first month of life) and early infant epileptic encephalopathy (EIEE) which is also referred to as Ohthara syndrome (OS) (onset within the first three months of life). While each have distinct features there are also some features held in common which suggest they may represent one disorder with a wide spectrum of clinical and EEG manifestations. The primary seizure type of EME is erratic and fragmentary myoclonus with onset of tonic seizures later in the course of the illness. The primary seizure type of EIEE is tonic spasms which may occur in clusters and eventually in association with partial seizures. The neurological examination at onset for infants with both syndromes is abnormal with altered consciousness, although those with EIEE have asymmetric findings. Each has suppression-burst findings on EEG and both may eventually evolve to hysparrhythmia. Traditionally the etiology for EME has been considered primarily metabolic and, to a lesser extent, genetic; and for EIEE the etiology has been considered structural brain abnormalities associated with congenital anomalies. More recently genetic mutations have been recognized as important etiologies for both EME and EIEE with a genetic etiology reportedly found between 29% and 61% of patients. In half of the EME/EIEE cases of genetic origin the following mutations have been found: KCNQ2, STXBP1, SCN2A. Treatment options for both EME and EIEE are limited. Etiology directed therapy is most successful in the cases of metabolic etiology. Surgical approaches have been applied to those with structural brain lesions. Steroid therapy has typically been used, although with limited success. The outcome for both EME and EIEE has been poor, with high death rates and, in survivors, neurological impairment. Some survivors, particularly with EIEE, transition to other age-dependent epileptic encephalopathies including West syndrome and Lennox-Gastuat syndrome.
Electroencephalography and Prognosis in Neonatal Hypoxic-Ischemic Encephalopathy
Electroencephalography is an important tool in the evaluation of neonates with hypoxic-ischemic encephalopathy (HIE). This is an etiology responsible for approximately 40-50% of infants with perinatal encephalopathy and is associated with global developmental delay (in approximately 43% of survivors), cerebral palsy (31% of survivors) and epilepsy (32% of survivors), with considerable overlap of these outcome measures. The contributing factors and time course of the disorder have some variability between pre-term and full-term infants, with pre-term infants more greatly affected by intrapartum factors. The HIE syndrome may evolve over time following its first recognition and this variability is most apparent in the most severely affected infants. There are also variable patterns of associated brain injury: selective neuronal necrosis, parasagittal cerebral injury, periventricular leukomalacia and focal/multifocal ischemic brain necrosis (stroke). The EEG abnormalities associated with HIE are conceptional age (CA) dependent, determined by the possible range of normal background activity expected at a given epoch of CA. Such findings include: prolonged interburst duration (25-28 weeks CA), depressed voltage (27-28 weeks CA), dyschronism (29-30 weeks CA), generalized voltage attenuations (34-35 weeks CA), absence of sleep cycling (36-37 weeks CA), depressed and undifferentiated background (36-37 weeks CA), and suppression-burst activity (36-37 weeks CA). In considering EEG andprognosis, in general the greater the EEG abnormality, the more grave the prognosis will be. However, because some abnormal EEGs resolve over time, the findings of serial EEGs add accuracy in assessing prognosis. On the other hand a normal initial EEG reliably suggests a good prognosis. These findings are typically associated with significant neurological impairment: electrocerebral silence, suppression-burst, severe depressed and undifferentiated background, and in the pre-term infant, prolonged interburst intervals. These findings, although abnormal, are suggestive, but not definitive of a neurological impairment: moderate depressed and undifferentiated background, non-reactive background, aberrant sleep architecture, delayed maturation in serial recordings, absence of expected developmental elements, and dyschronism. Serial EEG recordings, and more recently, prolonged EEG and EEG/video monitoring, are used to assess prognosis. Prolonged EEG and EEG/video monitoring has been utilized in association with hypothermia therapy in HIE (continuous EEG over 72 hours of treatment); a therapy which has been shown to effectively reduce morbidity and mortality in affected infants. Samples of EEGs at 36 hours and 48 hours most accurately predict outcome, while samples at 24 hours do not. In considering outcome, important factors include etiology, gestational age and the presence or absence of seizures and their degree of control with antiepileptic drugs.
Master Class in Neonatal Electroencephalopathy
An orderly approach to the interpretation of neonatal electroencephalography can be the basis for accurate and clinically valuable information in the care of newborn infants. This presentation will present methods of interpretation through the review of recording techniques, age-dependent normal and abnormal findings, and environmental electrical artifacts. Initially the basic issues of recording techniques will be considered. The normal findings of the EEG will be considered in terms of continuity, synchrony, development of grapho-elements, and wake/sleep cycles. These will be described according to increasing conceptional age from the pre-term to term infant. Abnormal findings – background and focal features - will also be described on an age-dependent basis in relation to stage of brain development. The features of electrographic seizures will be discussed in terms of onset, focality, morphology, amplitude, and duration. The application of EEG will also be considered in relation to specific clinical questions relating to the degree and distribution of brain injury, the determination of prognosis, the correlation of EEG findings to etiology, and the response to therapies. In addition, because neonatal EEG is so often recorded in the setting of the neonatal intensive care unit with its potential for environmental electrical interference, electrical artifact in the neonate will also be reviewed.