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Epilepsy With Myoclonic-Atonic Seizures (Doose Syndrome)

Etiologies: It may involve complex/polygenic inheritance with variable penetrance (it may be related to gene variations such as SLC2A1, SCN2A, GABRB3, SLC6A1, SPTAN1, SCN1A, SCN1B and KCNA2). About 1/3 patients have a family history of epilepsy or febrile seizures [1-6].

Age of onset: onset of seizures between 6 months and 6 years of age (peak 2 to 4 years).

Seizure characteristics: In 2/3 children febrile seizures and generalized tonic-clonic seizures precede the onset of myoclonic-atonic and atonic seizures, and later myoclonic atonic seizures occur (this process is often very short, sometimes only hundreds of milliseconds. Most clinical observations can only see falls, it is difficult to determine whether there is myoclonic seizure in front. Therefore, it is very important to install electromyography at the same time when doing EEG examination). In addition, there may be separate myoclonic, atonic and absence seizures, and about 1/3 of the patients may have non convulsive status epilepticus (manifested in varying degrees of consciousness turbidity and indifference, sometimes lasting for hours or even weeks, accompanied by myoclonic and atonic seizures). Generally, tonic seizures not occur (a few can occur in the later stage), epileptic spasms and focal seizures. The incidence rate of male is about 2 times that of female [7-8].

EEG: Background: It can be normal in the early stage, and paroxysmal theta activity dominated by bilateral central and parietal areas can be seen later. Interictal: It can be normal in the early stage, with the progress of the disease, generalized spike-and-wave and polyspike-and-wave occur. Ictal: During myoclonic seizure, EEG can show generalized (poly)spike-and-wave discharge, and EMG mostly shows the involvement of both upper limbs. The average latency between EEG negative spike wave and the starting point of EMG outbreak is about 30ms; During myoclonic-atonic seizures, EEG also shows generalized (poly)spike-and-wave discharge. Usually, the slow wave component with extremely high amplitude is slower than that in myoclonic seizure. The myoclonic component is associated with a generalized spike and polyspike. The atonic component is associated with the after going high voltage slow wave. The absence seizure is characterized by generalized 2-3Hz spike-and-wave bursts, which is usually slower and less rhythmic than the typical absence seizure [7-8].

Brain MRI: Most of them are normal.

Developmental progress: It is often normal before seizure onset, however impairments may develop at or after seizure onset.

Treatment:

National Institute for health and Clinical Excellence (NICE) epilepsy guidelines 2022:

First-line treatment: levetiracetam, valproate.

Second-line treatment: ketogenic die (monotherapy or add-on treatment).

Third-line treatment: If the above first-line and second-line treatment schemes are unsuccessful, one of the following treatment can be added (If the first choice is unsuccessful, consider the other add-on options): clobazam, ethosuximide, topiramate, zonisamide.

Be aware that the following drugs may exacerbate seizures: carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, vigabatrin.

Chinese clinical diagnosis and treatment guidelines epilepsy volume 2015:

First line drugs: valproate, topiramate, clonazepam, clobazam.

Drugs that can be added: lamotrigine, levetiracetam.

Be aware that the following drugs may exacerbate seizures: carbamazepine, oxcarbazepine, phenytoin sodium, gabapentin, pregabalin, tiagabine, vigabatrin.

2022 International League Against Epilepsy (ILAE) diagnostic criteria [9]:

Mandatory: Myoclonic–atonic seizures; EEG show generalized 2–6 Hz spike-wave or polyspike-and-wave abnormalities.

Alerts: Tonic seizures within 12 months of epilepsy onset; EEG show generalized paroxysmal fast activity in sleep, Generalized slow spike-and-wave complexes of <2 Hz, photoparoxysmal response at low frequencies (suggests neuronal ceroid lipofuscinosis type 2  (CLN2) disease); Moderate to severe developmental delay preceding seizure onset;Focal neurological findings.

Exclusionary: Epileptic spasms or infantile epileptic spasms syndrome (IESS) prior to diagnosis, Focal seizures; EEG show persistent focal abnormalities or Hypsarrhythmia; Age at onset <6 months or >8 years; Causal lesion on MRI.

 

References

  1. Mullen SA., et al. (2011): Glucose transporter 1 deficiency asa treatable cause of myoclonic astatic epilepsy. Arch Neurol 68: 1152-1155.
  2. Wolff M., et al., Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders. Brain 140:1316-1336.
  3. Moller, R.S., et al., Mutations in GABRB3: From febrile seizures to epileptic encephalopathies. Neurology, 2017. 88(5): p. 483-492.
  4. Johannesen, K.M., et al., Defining the phenotypic spectrum of SLC6A1 mutations. Epilepsia, 2018. 59(2): p. 389-402.
  5. Syrbe S., et al., Delineating SPTAN1 associated phenotypes: from isolated epilepsy to encephalopathy with progressive brain atrophy. Brain 2017; 140: 2322-2336.
  6. McTague, A., et al., The genetic landscape of the epileptic encephalopathies of infancy and childhood. Lancet Neurol, 2016. 15(3): p. 304-16.
  7. Panayiotopoulos.  癫痫综合征及临床治疗.  北京 : 人民卫生出版社, 2012.
  8. 刘晓燕.  临床脑电图学. 第2版.  北京 : 人民卫生出版社, 2017.
  9. Specchio, N., et al., International League Against Epilepsy classification and definition of epilepsy syndromes with onset in childhood: Position paper by the ILAE Task Force on Nosology and Definitions. Epilepsia, 2022.