**2. Neonatal epileptic encephalopathies: early infantile epileptic encephalopathy with suppression-burst pattern (Ohtahara syndrome) and early myoclonic encephalopathy (EME)**

### **2.1 Overview**

Early myoclonic epilepsy and early infantile epileptic encephalopathy (or Ohtahara syndrome) are age-dependent EEs that occur in the earliest stages of life. Although they share some clinical, electroencephalographic and prognostic characteristics, they are distinguished by their clinical presentations and different etiologies [6].

In 1976, Ohtahara et al. report an epileptic syndrome that affected very young babies with a typical electroencephalographic pattern, and they called it "early infant epileptic encephalopathy with suppression-burst" [7]. Ohtahara observed that this disorder progressed frequently to West syndrome (WS) and then to a Lennox-Gastaut syndrome (LGS) [8]. Ohtahara syndrome (OS), as it has been called since the 1980s, has also been known for other terms, such as myoclonic epilepsy with neonatal onset, neonatal epileptic encephalopathy with periodic electroencephalographic bursts, and early myoclonic epileptic encephalopathy.

In 2001, the ILAE Classification and Terminology Working Group included both OS and EME within EEs [3]. Both syndromes are similar in terms of age of onset, a characteristic of suppression-burst EEG, and the presence of several types of superimposed seizures; due to this, their differentiation is difficult and often impossible at the beginning of the disease [9]. On the other hand, motor manifestations at this age are difficult to classify.

### **2.2 Seizures: symptoms and semiology**

In both syndromes, seizures begin almost after birth, usually during the first month of life [9]. In OS, the most typical seizures are epileptic spasms and tonic

**79**

*2.3.3 Ictal EEG*

*Epileptic Encephalopathies in Infants and Children DOI: http://dx.doi.org/10.5772/intechopen.85378*

**2.3 Electroencephalography features**

tics in wakefulness or sleep [11].

discharges can be observed [12].

associated with bursts of spikes and polyspikes.

*2.3.2 Interictal abnormalities*

*2.3.1 Background*

seizures, in groups or isolated [10]. In patients with hemispheric structural lesions, seizures can be unilateral or at least asymmetric. On the other hand, in the EME, myoclonic (axial, segmental, or erratic) seizures are more characteristic. The frequency of seizures is flexible and can be almost continuous. Erratic and segmental myoclonus usually occurs in the first days [11]. In erratic myoclonus, the jerking seems to change arbitrarily from one area of the body to another, mainly in the face and extremities, although axial myoclonus could also appear. Subtle focal or clonic seizures may continue to myoclonus. Additionally, the complex motor manifestations that are associated with bursts of paroxysmal activity on the EEG are difficult to classify as spasms or myoclonus. Both conditions can present focal seizures commonly; these can be with deviation of the eyes, tonic posture, or hemiconvulsions; subtle attacks can also occur with autonomic phenomena, such as flushing or apnea [9].

The EEG may be normal at the beginning of the EME, which is why successive EEGs must be repeated to define the diagnosis. When the clinical presentation is complete, there is no temporal or spatial organization or physiological characteris-

The typical pattern is the suppression-burst (S-B); it consists of bursts of highvoltage asynchronous delta or theta waves, interspersed with spikes and polyspikes from 150 to 350 μV that last from 1 to 6 seconds and alternate with low voltage (<10 μV) or complete suppression activity intervals of 2–5 seconds in duration [8]. In the EME, the bursts are shorter, and the suppression periods are much longer [11]; the S-B pattern in OS occurs in both wakefulness and sleep, while the S-B pat-

The S-B pattern may vary in configuration and the interhemispheric synchronization of the bursts; they may predominate in one hemisphere, especially when associated with lateralized structural anomalies, such as focal cortical dysplasia or hemimegalencephaly [11]. During the suppression periods, focal epileptiform

The S-B pattern may persist beyond the first year of life, or it may progress to hypsarrhythmia between 3 and 6 months of age; it's coinciding with the development of epileptic spasms in the WS context [11]. The early transition to hypsarrhythmia is more common in the OS, while in the EME the S-B can continue in the infancy until a transient evolution to hypsarrhythmia in the middle and late infancy [10]. There are reports of evolution to the slow spike-wave pattern characteristic of LGS.

During tonic spasms, EEG shows desynchronization with or without rapid activity [8]. By means of video-electroencephalography (video-EEG) with electromyographic recordings from deltoid muscles, we observe that each burst is to be associated with tonic contraction of variable duration [13]. The erratic myoclonus of EME habitually has no EEG correlate, whereas limb/axial myoclonus are usually

Complex stereotyped movements that are difficult to classify as either spasms or myoclonias are also associated with bursts of activity. There is no correlation between

tern in EME, which usually is present only during sleep [9].

*Epileptic Encephalopathies in Infants and Children DOI: http://dx.doi.org/10.5772/intechopen.85378*

seizures, in groups or isolated [10]. In patients with hemispheric structural lesions, seizures can be unilateral or at least asymmetric. On the other hand, in the EME, myoclonic (axial, segmental, or erratic) seizures are more characteristic. The frequency of seizures is flexible and can be almost continuous. Erratic and segmental myoclonus usually occurs in the first days [11]. In erratic myoclonus, the jerking seems to change arbitrarily from one area of the body to another, mainly in the face and extremities, although axial myoclonus could also appear. Subtle focal or clonic seizures may continue to myoclonus. Additionally, the complex motor manifestations that are associated with bursts of paroxysmal activity on the EEG are difficult to classify as spasms or myoclonus. Both conditions can present focal seizures commonly; these can be with deviation of the eyes, tonic posture, or hemiconvulsions; subtle attacks can also occur with autonomic phenomena, such as flushing or apnea [9].

## **2.3 Electroencephalography features**

## *2.3.1 Background*

*Epilepsy - Advances in Diagnosis and Therapy*

broad spectrum of severity.

**2.1 Overview**

brain function." In 2006, Engel defined EE as disorders in which the evidence suggests the idea that neurological impairment depends on epilepsy and not on an underlying metabolic, degenerative, or encephalitic process, so that it excludes these progressive etiologies from the possible etiologies of EE [4]. Engel also emphasizes the importance of distinguishing between the deficits that are due to the cause of epilepsy, those that

The ILAE Working Group of 2010 pointed out the recognition achieved by the scientific community in relation to the EE [5]. The notion that epileptic activity itself may contribute to cognitive and behavioral deficiencies that exceed beyond what might be expected from causal pathology alone underlies the concept of EE. Deficits caused by epileptic discharges can be global or focal and can occur in a

In 2012, Capovilla proposed the term epileptogenic encephalopathy. They refer to progressive disorders of various etiologies that can cause deterioration and epilepsy, such as brain tumors, neurodegenerative or metabolic diseases, and presumed inflammatory or autoimmune conditions [1]. In epileptogenic encephalopathies, deterioration is independent of epilepsy, even if epilepsy could worsen the clinical picture; in some cases, the same etiology can produce encephalopathy without epilepsy. This distinction is important for the treatment; in the EE the treatment must be aggressive. On the other hand, if the deterioration is due to the etiology, there is a risk of unjustified excessive treatment. It is known that drugs, especially in

polytherapy, can aggravate the neuropsychological deficits in these patients.

**2. Neonatal epileptic encephalopathies: early infantile epileptic** 

Early myoclonic epilepsy and early infantile epileptic encephalopathy

**and early myoclonic encephalopathy (EME)**

**encephalopathy with suppression-burst pattern (Ohtahara syndrome)** 

(or Ohtahara syndrome) are age-dependent EEs that occur in the earliest stages of life. Although they share some clinical, electroencephalographic and prognostic characteristics, they are distinguished by their clinical presentations and different etiologies [6]. In 1976, Ohtahara et al. report an epileptic syndrome that affected very young babies with a typical electroencephalographic pattern, and they called it "early infant epileptic encephalopathy with suppression-burst" [7]. Ohtahara observed that this disorder progressed frequently to West syndrome (WS) and then to a Lennox-Gastaut syndrome (LGS) [8]. Ohtahara syndrome (OS), as it has been called since the 1980s, has also been known for other terms, such as myoclonic epilepsy with neonatal onset, neonatal epileptic encephalopathy with periodic electroencephalographic bursts, and early myoclonic epileptic encephalopathy.

In 2001, the ILAE Classification and Terminology Working Group included both OS and EME within EEs [3]. Both syndromes are similar in terms of age of onset, a characteristic of suppression-burst EEG, and the presence of several types of superimposed seizures; due to this, their differentiation is difficult and often impossible at the beginning of the disease [9]. On the other hand, motor manifestations at this

In both syndromes, seizures begin almost after birth, usually during the first month of life [9]. In OS, the most typical seizures are epileptic spasms and tonic

are due to pharmacotherapy, and those that are due to epilepsy itself.

**78**

age are difficult to classify.

**2.2 Seizures: symptoms and semiology**

The EEG may be normal at the beginning of the EME, which is why successive EEGs must be repeated to define the diagnosis. When the clinical presentation is complete, there is no temporal or spatial organization or physiological characteristics in wakefulness or sleep [11].

### *2.3.2 Interictal abnormalities*

The typical pattern is the suppression-burst (S-B); it consists of bursts of highvoltage asynchronous delta or theta waves, interspersed with spikes and polyspikes from 150 to 350 μV that last from 1 to 6 seconds and alternate with low voltage (<10 μV) or complete suppression activity intervals of 2–5 seconds in duration [8]. In the EME, the bursts are shorter, and the suppression periods are much longer [11]; the S-B pattern in OS occurs in both wakefulness and sleep, while the S-B pattern in EME, which usually is present only during sleep [9].

The S-B pattern may vary in configuration and the interhemispheric synchronization of the bursts; they may predominate in one hemisphere, especially when associated with lateralized structural anomalies, such as focal cortical dysplasia or hemimegalencephaly [11]. During the suppression periods, focal epileptiform discharges can be observed [12].

The S-B pattern may persist beyond the first year of life, or it may progress to hypsarrhythmia between 3 and 6 months of age; it's coinciding with the development of epileptic spasms in the WS context [11]. The early transition to hypsarrhythmia is more common in the OS, while in the EME the S-B can continue in the infancy until a transient evolution to hypsarrhythmia in the middle and late infancy [10]. There are reports of evolution to the slow spike-wave pattern characteristic of LGS.

### *2.3.3 Ictal EEG*

During tonic spasms, EEG shows desynchronization with or without rapid activity [8]. By means of video-electroencephalography (video-EEG) with electromyographic recordings from deltoid muscles, we observe that each burst is to be associated with tonic contraction of variable duration [13]. The erratic myoclonus of EME habitually has no EEG correlate, whereas limb/axial myoclonus are usually associated with bursts of spikes and polyspikes.

Complex stereotyped movements that are difficult to classify as either spasms or myoclonias are also associated with bursts of activity. There is no correlation between the duration of the burst and the type of seizure [11]. Focal seizures and subclinical phenomena are associated with focal discharges of spikes or sharp wave [8].
