ReviewOhtahara syndrome: With special reference to its developmental aspects for differentiating from early myoclonic encephalopathy
Introduction
Ohtahara syndrome (OS) is a specific epileptic syndrome with onset mainly in neonatal period and has many clinicoelectrical characteristics, among which age dependency and evolutional change is specific (Ohtahara et al., 1976, Ohtahara et al., 1992). It is paid attention as the youngest form in the frame of the age-dependent epileptic encephalopathy (Ohtahara, 1977, Ohtahara, 1978).
This paper outlines its clinicoelectrical characteristics and clarifies the specificity of its developmental course and further refers to the diagnostic problems and differentiation from early myoclonic encephalopathy, the independence of Ohtahara syndrome (OS), although it has already become widely accepted.
Section snippets
Age-dependent epileptic encephaloapthy and Ohtahara syndrome
OS is one type, the earliest form, of the age-dependent epileptic encephalopathy, together with West syndrome (WS) and Lennox–Gastaut syndrome (LGS) (Ohtahara et al., 1992, Ohtahara and Yamatogi, 2003, Donat, 1992).
The age-dependent epileptic encephalopathy, proposed by Ohtahara (1977), has the following common characteristics:
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preferential age of onset at a specific developmental period of life (age dependency),
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frequent minor generalized seizures,
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severe and continuous epileptic EEG abnormality,
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Clinical features of Ohtahara syndrome
Age of seizure onset is confined to neonatal and very early infantile periods. It is noteworthy that 5 out of 16 cases (31.3%) had the onset of OS within 10 days of life, and 12 cases (75%) within 1 month (Yamatogi and Ohtahara, 2002).
The main seizure pattern was tonic spasms with or without clustering, and tonic spasms were seen in all cases. Their tonic spasms resemble those of WS, but have some differential points; appearance in both waking and sleeping states and without clustering (
Interictal EEG findings
The most specific EEG feature was the suppression-burst (SB). This pattern was characterized by high voltage bursts alternating with almost flat suppression phases at an approximately regular rate.
It should be stressed that distinguished features of SB in OS were consistent appearance in both waking and sleeping states and regular appearance of periodicity (Fig. 2).
This finding has decisive importance for the diagnosis of this syndrome (Ohtahara et al., 1992, Aicardi and Ohtahara, 2002).
SB
Etiologies
Etiology is heterogeneous as already mentioned, but development in neuroimaging technique, particularly MRI, disclosed structural abnormalities of the brain as the main cause of OS. Most have gross static brain pathology, i.e. severe cortical lesions, often asymmetric, from the early stage (Ohtsuka et al., 2000, Fusco et al., 2001, Yamatogi and Ohtahara, 2002). Furhermore, prenatal brain pathology such as cerebral dysgenesis is suspectd in most cases. Even cryptogenic cases may have
Evolutional change with age
Because OS is the earliest form of the age-dependent epileptic encephalopathy, it is very important to clarify the age dependency and developmental changes of clinical and EEG features by the follow-up study (Yamatogi and Ohtahara, 1981, Ohtahara et al., 1987, Ohtahara and Yamatogi, 1990).
Up to now, 16 cases were followed up for as long as 31 years, at the longest, and the youngest alive is now 7 years 11 months of age.
As shown in Fig. 3, suppression-burst pattern was recognized until six
Prognosis and treatment
Seizures are extremely intractable and prognosis is grave with severe psychomotor retardation (Yamatogi and Ohtahara, 2002). There are many early deaths in early infancy. Accordingly, this syndrome has become to be called as a catastrophic epilepsy with other forms of the age-dependent epileptic encephalopathy, i.e. WS and LGS.
As mentioned before, evolution into WS is often observed in surviving cases.
Concerning the treatment of OS in our series, ACTH was effective in two cases at the time of
Follow-up study and differentiation from early myoclonic encephalopathy
As well known, EME is another characteristic epileptic encephalopathy presenting in very early infancy (Aicardi and Goutieres, 1978, Dalla Bernardina et al., 1983, Aicardi and Ohtahara, 2002). OS and EME have some common characteristics, such as very early onset, intractability and SB in EEG.
The diagnostic criteria of EME following ILAE classification (1989) are: (1) early onset within 3 months of age, (2) fragmentary myoclonia as the main seizure type, (3) frequent association of erratic
Discussion
In addition to many characteristics, evolutional change of OS, on the basis of its developmental study, clearly demonstrated the distinctive feature of this syndrome as the earliest form of the age-dependent epileptic encephalopathy.
In comparison between OS and EME, decisive difference in the interictal EEG findings of both syndromes is well known among EEG specialists, but some misunderstanding and confusion might still exist among clinicians in distinguishing both syndromes (Lombroso, 1990,
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2019, SeizureCitation Excerpt :Suppression-burst (SB) is an electroencephalographic finding characterized by the alternating appearance of depressed background activity and bursts of mixed-frequency paroxysmal activity [1]. SB patterns are typically recorded in patients with forms of early-onset epileptic encephalopathy, such as Ohtahara Syndrome (OS) and Early Myoclonic Encephalopathy (EME) [2]. In patients with epilepsy of infancy with migrating focal seizures (EIMFS), typical interictal electroencephalogram (EEG) features include multifocal spikes with slow background activity [3].