PDF | Epileptic encephalopathies are motor-mental retardations or cognitive Although genetic factors are unknown, a study reported relation with familial .. “ Epileptic encephalopathy in infancy and early childhood, ” in A. Epileptic encephalopathies are severe brain disorders of early age that manifest with: (1) electrographic EEG paroxysmal activity that is often. Epileptic Encephalopathy in Infants and Children . These promising experimental findings await clinical correlation in the epileptic encephalopathies.
The electroencephalogram EEG which records the electrical activity in the brain is usually normal early in this condition. Later, by the time the child is 18 months old, there is evidence of epileptic activity with spike and wave or polyspike discharges, which occur either as single event or in bursts.
These may be generalized involving the whole brain or occurring just from on small area of the brain. Some children show EEG evidence of sensitivity to flashing lights but this does not occur in all. Brain scans are usually normal.
It is likely that other mutations will also be found in children with SMEI. The mutation can be looked for in a simple blood test and this has been very helpful in making or confirming a diagnosis of this epilepsy syndrome. SMEI is very resistant to anti-epileptic drugs. Phenobarbital, sodium valproate Epilimand lamotrigine Lamictal are usually tried first.
However, lamotrigine may actually make the myoclonic seizures worse in many children. Other options include a medication called stiripentol, topiramate Topamaxclonazepam Rivotriland clobazam Frisium.
Epileptic Encephalopathies in Adults and Childhood
A combination of sodium valproate with either topiramate or stiripentol may be the most helpful. A short course of a steroid called prednisolone and the ketogenic diet may also be helpful. Because children with SMEI always have learning difficulties, they will also need full educational assessment and support [ 1617 ].
Epileptic Encephalopathy Syndromes in Childhood 3. The syndrome is characterized by multiple seizure types; mental retardation or regression; abnormal findings on electroencephalogram EEGwith paroxysms of fast activity and generalized slow spike and wave discharges 1.
The most common seizure types are tonic-axial, atonic, and absence seizures, but myoclonic, generalized tonic-clonic, and partial seizures can be observed see clinical presentation. Neuroimaging is an important part of the search for an underlying etiology. LGS can be classified according to its suspected etiology as either idiopathic or symptomatic. Patients may be considered to have idiopathic LGS if normal psychomotor development occurred prior to the onset of symptoms, no underlying disorders or definite presumptive causes are present, and no neurologic or neuroradiologic abnormalities are found.
In contrast, symptomatic LGS is diagnosed if a likely cause can be identified as being responsible for the syndrome. LGS is more common in boys than in girls.
The prevalence is 0. The mean age at epilepsy onset is 26—28 months range, 1 d to 14 y. The peak age at epilepsy onset is older in patients with LGS of an identifiable etiology than in those whose LGS has no identifiable etiology.
The difference in age of onset between the group of patients with LGS and a history of West syndrome infantile spasm and those with LGS without West syndrome is not significant. The average age at diagnosis of LGS in Japan was 6 years range, 2—15 y. Epidemiologic studies in industrialized countries e.
The prevalence of LGS is 0. The annual incidence of LGS in childhood is approximately 2 perchildren. Long-term prognosis overall is unfavorable but variable in LGS. A variety of therapeutic approaches are used in LGS, ranging from conventional antiepileptic agents to diet and surgery.
Unfortunately, much of the evidence supporting these approaches is not robust, and treatment is often ineffective. The medical treatment options for patients with LGS can be divided into the following 3 major groups: The medical treatment options for patients with LGS include the use of antiepileptic drugs such as valproic acid and benzodiazepines such as clonazepam, nitrazepam and clobazam, vigabatrin, zonisamide, lamotrigine, topiramate and rufinamide proven effective by double-blind placebo-controlled studies e.
The ketogenic diet may be useful in patients with LGS refractory to medical treatment. Surgical options for LGS include corpus callosotomy, vagus nerve stimulation, and focal cortical resection [ 18 — 21 ].
EEG in Lennox-Gastaut syndrome with paroxysms of fast activity and generalized slow spike and wave discharges 1. The clinical manifestations of this syndrome include a status heterogeneous epileptic disorder, deterioration of neuropsychological functions associated with or independent from the epileptic disorder, and deterioration of motor functions.
The typical EEG pattern of continuous spikes and waves during slow sleep Figures 5 and 6 is also an essential and absolute feature for the recognition of the syndrome. The age at which the first seizure occurs ranges between 2 months and 12 years, with a peak around 4 and 5 years.
This event can be preceded by either normal psychomotor development or abnormal signs indicating preexisting encephalopathy such as hemiparesis, hemiplegia, spastic quadriplegia, diffuse hypotonia, and ataxia.
The seizure types occurring in the disorder can be both partial and generalized. They include unilateral or bilateral clonic seizures, generalized tonic-clonic seizure, absences, partial motor seizures, complex partial seizures, or epileptic falls.
They may occur during wakefulness or sleep. Tonic seizures, however, never occur. The first seizures are reported to be nocturnal and of unilateral type in almost one-half of the cases reported.
At onset, the frequency of seizure attacks is low. At the time of discovery of the typical nocturnal EEG pattern, however, the epileptic seizures frequently change in severity and frequency. Absences and epileptic falls herald the appearance of continuous spikes and waves during slow sleep and seizure frequency increases, both during wakefulness and sleep.
The characteristic feature of this disorder is the appearance of continuous spike-wave discharges on the EEG during slow sleep. The typical EEG changes appear 1 year to 2 years after the first seizure and are associated with behavioral deterioration.
Focal and generalized interictal spikes occur before this time and persist during wakefulness and REM sleep after the appearance of continuous spike waves during slow-wave sleep [ 24 ].
The cause of electrical status epilepticus during slow sleep is unknown. Long-lasting persistence of continuous spike waves during sleep is postulated to be responsible for the neuropsychiatric abnormalities in electrical status epilepticus during slow sleep; secondary bilateral synchrony is the mechanism underlying continuous spikes and waves during slow sleep.
In this respect the apparent generalized seizures absences, tonic-clonic attacks occurring in this condition have in fact a focal onset as demonstrated by interhemispheric peak latencies of their EEG correlates, phase reversal of spikes on unilateral frontal regions, and studies of coherence and phase analyses.
A localized metabolic abnormality has been also revealed by means of PET studies.
Therefore, although electrical status epilepticus during slow sleep is currently classified among the epilepsies undetermined whether focal or generalized, consistent data support the view that this syndrome is to be included in the domain of localization-related epilepsies, of cryptogenic or symptomatic nature [ 23 — 25 ].
Electrical status epilepticus during slow sleep is a rare order. One study revealed an incidence of 0. There is no obvious gender preponderance [ 23 ]. The seizures in electrical status epilepticus during slow sleep are self-limited and disappear in the midteens.
The good seizure outcome is independent of the etiology and is observed also in cases with cortical malformations such as multilobar polymicrogyria. The characteristic EEG patterns during slow-wave sleep also disappear at approximately the same time, but focal interictal spikes may persist.
Improvement in language dysfunction, mental retardation, and psychiatric disturbances generally occurs but it is variable and individualized.
The majority of affected children never return to normal levels, particularly in the verbal area and attention [ 2526 ].
Epileptic seizures may or may not respond to a variety of drugs including benzodiazepines, valproate, ethosuximide, carbamazepine, and phenytoin. Despite of the fact that the seizures may be refractory to therapy for months to years, the long-term prognosis of epilepsy is favorable with the disappearance of seizures in all cases.
Only benzodiazepines and adrenocorticotrophic hormone have been reported to suppress the electrical status and perhaps to improve language function. However, the positive effects are often transient [ 23 ].
In individual cases, chronic oral treatment with clobazam, lorazepam, and clonazepam associated with other antiepileptic drugs usually valproate seemed to have a long-lasting effect. Short cycles 3 to 4 weeks of relatively high doses of diazepam 0. At the present time, the combined use of benzodiazepines and valproate is considered the treatment of choice in this condition. On the other hand, polytherapy should be avoided. A detailed evaluation of antiepileptic regimens in 88 patients demonstrated that the reduction in polytherapy coincided with an improvement of the syndrome.
It was also suggested that the drug overload and some medications such as carbamazepine could play a role in the maintenance of continuous spikes and waves during slow sleep. In cases of electrical status epilepticus during sleep with severe language impairment, a progressive and long-lasting improvement of the language function has been obtained applying the surgical procedure of multiple subpial transections of the region of focal epileptic discharges [ 27 ].
Electrical status epilepticus during slow sleep ESESdisappearance of spike waves with eye opening arrows. Acquired Epileptic Aphasia Landau-Kleffner Syndrome LKS Acquired epileptic aphasia typically develops in healthy children who acutely or progressively lose receptive and expressive language ability coincident with the appearance of paroxysmal electroencephalographic EEG changes [ 28 ].
Epileptic Encephalopathies in Adults and Childhood
In most cases described in detail, a clearly normal period of motor and language development occurs before acquired epileptic aphasia symptoms appear. In one case, expressive language deteriorated instead of receptive language, whereas in another case, a brief period of normal language development single words was followed by language regression with abnormal EEG findings. Acquired epileptic aphasia must be differentiated from autism with minimal language regression, especially when it is associated with isolated EEG abnormalities.
The duration also varies, from 2—4 weeks to 3—6 months. The risk of infection is particularly high. Vigabatrin Vigabatrin is a relatively new alternative to hormonal therapy in West syndrome. Its efficacy has been documented in open and control studies. Vigabatrin has a quick beneficial effect that usually occurs at the fourth day of treatment with a range of 1—14 days.
These patients may be more vulnerable to psychomotor deterioration. The beneficial effect of vigabatrin is sometimes transient, despite continued treatment.
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Relapses and other types of seizures occur in approximately half of patients who are initially improved. Vigabatrin is effective in some children who are resistant to ACTH or steroids and vice versa. Vigabatrin is definitely superior to hydrocortisone in the treatment of West syndrome of tuberous sclerosis.
In comparative trials, the incidence of adverse events was statistically lower for vigabatrin than for steroids. Most of the events were relatively mild neuropsychological effects. However, there is still unresolved realistic concern regarding irreversible visual field defects induced by vigabatrin.
If the seizures are not controlled within 2 weeks, this should be replaced with ACTH. Continuation of the treatment after 3—6 months may be debatable, as with ACTH.
Pyridoxine Vitamin B6 Customarily, children in whom the aetiology of West syndrome cannot be definitely established receive an infusion of — mg of pyridoxine intravenously during EEG monitoring. Infants with pyridoxine dependency, which is rarely the cause of epileptic spasms, usually improve within minutes. However, its long-term effects on the prognosis have not been studied.
Lamotrigine, levetiracetam, sulthiame, topiramate, zonisamide, a ketogenic diet, immunoglobulin therapy, felbamate and thyrotropin-releasing hormone have all been used for the treatment of West syndrome with variable results. Improvement is usually temporary. However, this is still in the provisional stage provided for hopeless cases that may need multi-lobar resection or hemispherectomy.
On a practical level it is necessary to ask the parents to demonstrate and imitate the attacks physically rather than merely describe them. If in doubt, demonstrating or showing a video with typical attacks is often conclusive: Benign phenomena such as a Moro reflex, attacks of colic or even attempts to sit up may be a cause of confusion that can be avoided by remembering that epileptic spasms occur in clusters.
Singular events are rare. Dravet Syndrome Severe Myoclonic Epilepsy in Infancy Dravet syndrome — is a rare progressive epileptic encephalopathy that is mostly genetically determined. There is significant recent progress in the understanding of the genetics and the diagnostic borders of this syndrome. Demographic Data Onset is always within the first year of life, with a peak age of 5 months, affecting previously normal children. Twice as many boys are affected. There are approximately reported cases with Dravet syndrome.
The incidence is approximately 1 per 30, The complete tetrad of febrile clonic convulsions, myoclonic jerks, absences and complex focal seizures is seen in more than half of cases. In the others, one or another type of seizure may not occur.
Myoclonic jerks, initially considered as the defining seizure type, may not be present in one-fifth of patients or may precede the initial febrile clonic convulsions.
Thus, neither myoclonic jerks nor absences are a prerequisite for diagnosis. The sequence of polymorphic seizures, their resistance to treatment and the progression to mental and neurological deterioration is characteristic of Dravet syndrome. There are three periods of evolution.
The first period is relatively mild pre-seismic period with febrile convulsions and febrile convulsive status epilepticus. The second period is relentlessly aggressive seismic period with the appearance of intractable polymorphic seizures. The third period is static post-seismic period with improvement of seizures, but with serious residual mental and neurological abnormalities.
First Period of Mainly Febrile Convulsions The first period is relatively mild pre-seismic period with seizures usually occurring during febrile illnesses and consisting of clonic convulsions that are unilateral or generalised, brief or prolonged.
Convulsive seizures start before the age of 12 months with a peak at 5 months in all patients and these are typically febrile at onset. They consist of unilateral and less often bilateral clonic convulsions intermixed with some tonic components. They are usually long lasting more than 10 min and often in approximately one-quarter of cases progress to convulsive status epilepticus.
The characteristics include a family history of epilepsy or febrile convulsions, normal development before onset, seizures beginning during the first year of life in the form of generalised or unilateral febrile clonic seizures, secondary appearance of myoclonic jerks and often partial seizures. EEGs show generalised spikes and waves and polyspikes and waves, early photosensitivity and focal abnormalities.
Psychomotor development is retarded from the second year of life and ataxia, pyramidal signs and inter-ictal myoclonus appear. This type of epilepsy is very resistant to all forms of treatment. They can be clearly generalised, clonic and tonic clonic, or unilateral, hemiclonic.
More often, they have peculiar clinical and EEG features that do not permit classification under generalised clonic or tonic-clonic seizures. They are characterized by clonic or tonic components, initially predominating in the head and the face, evolving to variable, bilateral localisation, and loss of consciousness.
When they are short in duration there are no autonomic symptoms. They were named falsely generalised or unstable. Isolated episodes of focal myoclonic jerking and, more rarely, focal seizures may predate or appear just before the febrile convulsions. These seizures recur frequently within 6—8 weeks and later may also be non-febrile. This period lasts for 2 weeks to 6 months before progressing to the second stage. Second Relentlessly Aggressive Period The second period is relentlessly aggressive seismic period with the emergence of other multiple-seizure types and severe neurocognitive deterioration.
Various forms of febrile and non-febrile convulsive seizures, myoclonic fits, atypical absences and complex focal seizures occur on a daily basis and frequently evolve to status epilepticus.
Convulsive Seizures Febrile and Non-Febrile These are similar but more frequent and more prolonged than in the first period. Myoclonic Seizures Myoclonic seizures usually appear between the ages of 1 and 4 years, after an average of 1—2 years from onset. In some cases myoclonic jerks may also occur at a much earlier age, sometimes clustering prior to the onset of febrile clonic convulsions.
Myoclonic seizures may be segmental or generalised. Segmental jerks affect facial muscles and the limbs, mainly distally.
Generalised jerks predominantly affect the axial body muscles causing flexion or extension and often falls. Myoclonic jerks are as a rule very frequent several times per day and may cluster in myoclonic status epilepticus without impairment of consciousness.
However, other patients may have jerks only hours or days prior to a convulsive seizure. Myoclonic jerks are usually violent, forceful and massive, but they may also be mild and inconspicuous as revealed by appropriate clinical testing or video— EEG monitoring.
One-fifth of patients have segmental myoclonic jerks that are not violent.
Complex Focal Seizures Focal seizures occur in nearly half of patients. They manifest with a number of symptoms such as atonic or adversive components, autonomic phenomena pallor and peri-oral cyanosis and automatisms. They occasionally progress to GTCS. One seizure recorded by Dravet may be an illustrative example.
This was a 2-year-old girl who, upon awakening, had deviation of the eyes to the right, arrhythmic bilateral myoclonic jerks of the deltoids and loss of consciousness. The seizure ended within 80 s with a hiccup, pallor, cyanosis of the lips and rare myoclonias. Status Epilepticus Myoclonic, atypical absence, complex focal and convulsive status epilepticus, alone or in combination, are common and frequent.
Epileptic Encephalopathies: An Overview
Unexpected EEG findings have recently been reported [ 112830 ]. Treatment is resistant to several medications. Carbamazepine and lamotrigine are shown to exacerbate the seizures.
Effects of other anticonvulsants vary. In Europe, more successful results are achieved by combining stiripentol, a cytochrome P inhibitor, with clobazam CLB and VPA, especially in prevention of status epilepticus [ 1231 ]. Recent studies indicate that addition of a voltage-gated calcium channel blocker, such as verapamil, to anticonvulsant therapy is beneficial. Ketogenic diet is another method for management or minimizing seizure frequency [ 31 — 37 ].
Myoclonic-Astatic Epilepsy or Doose Syndrome Myoclonic-astatic epilepsy or Doose syndrome is a form of generalized epilepsy developing between 7 months and 6 years of life with myoclonic attacks, absence and tonic seizures [ 13839 ]. Peak age is 1—5 and males are more prone than females. One-third of cases have history of febrile convulsion [ 115 ]. EEG may show spike-wave, wave-multiple spike complexes in ictal period with 2—4 Hz frequency.
It is initially normal in interictal period, 3 Hz wave-spike discharges may be observed in sleep in later periods [ 40 — 42 ]. Cases with mental deterioration are usually resistant to treatment. Seizures may be managed after 3 years in a certain percentage of patients [ 224243 ].
Neuroradiological findings are generally normal [ 41 ]. Genetical basis is not clear [ 223839 ]. VPA and ethosuximide ESM are still the commonly preferred medications for management of myoclonic seizures [ 4042 ]. Although BDZ and clonazepam CZP are beneficial for management of generalized seizures, they are not preferred since they cause behavior changes [ 41 ].
Lamotrigine LTG can be used for generalized seizures [ 4445 ]. Ketogenic diets are effective but difficult to maintain for long periods [ 4049 ].
Progressive myoclonic epilepsies, that is, MERRF syndrome myoclonus epilepsy with ragged-red fibers can be mistaken for with Unverricht-Lundborg disease, and late-infantile neuronal ceroid lipofuscinosis; however, neurological development in later stage, continuity and persistence of the disease facilitate differential diagnosis.
Prevalence is not known, but incidence is reported to be 0. Equal male-female incidence is defined in early studies; extended studies indicate higher incidence in males. Generalized tonic-clonic seizures, atypical absence, myoclonic and atonic seizures may be observed. Mental retardation, lower IQ secondary to deterioration, and motor loss such as aphasia, behaviour disorder, ataxia, and dyspraxia accompany the seizures. Clinical course is composed of 3 stages: Cases solely presenting with mental retardation or behaviour disorder with no seizures are also noted [ 1052 — 56 ].