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The diagnosis or suspicion of LGS is often a question of probability rather than certainty. This is because the varied presentations of LGS share features with other disorders, many of which may be said to have overlapping characteristics.
The diagnosis is more obvious when the epilepsy has frequent and manifold attacks, with the classic pattern on the electro-encephalogram (EEG); the latter is a slowed rhythm with Spike-wave-pattern, or with a multifocal and generalizing Sharp-slow-wave-discharges at 1.5–2.5 Hz. During sleep, frequently, tonic patterns can be seen. But variations of these patterns are known in patients with no diagnosis other than LGS, and they can differ bilaterally, and from time to time, within the same patient.
General medical investigation usually reveals developmental delay and cognitive deficiencies in children with true LGS. These may precede development of seizures, or require up to two years after the seizures begin, in order to become apparent.
Exclusion of organic or structural brain lesions is also important in establishing a correct diagnosis of LGS; this may require magnetic resonance imaging (MRI) or computerized tomography (CT). An important differential diagnosis is 'Pseudo-Lennox-Syndrome', which differs from LGS, in that there are no tonic seizures; sleeping EEG provides the best basis for distinguishing between the two.
Differentiating an epileptic seizure from other conditions such as syncope can be difficult. Other possible conditions that can mimic a seizure include: decerebrate posturing, psychogenic seizures, tetanus, dystonia, migraine headaches, and strychnine poisoning. In addition, 5% of people with a positive tilt table test may have seizure-like activity that seems to be due to cerebral hypoxia. Convulsions may occur due to psychological reasons and this is known as a psychogenic non-epileptic seizure. Non-epileptic seizures may also occur due to a number of other reasons.
An electroencephalography is only recommended in those who likely had an epileptic seizure and may help determine the type of seizure or syndrome present. In children it is typically only needed after a second seizure. It cannot be used to rule out the diagnosis and may be falsely positive in those without the disease. In certain situations it may be useful to prefer the EEG while sleeping or sleep deprived.
Diagnostic imaging by CT scan and MRI is recommended after a first non-febrile seizure to detect structural problems inside the brain. MRI is generally a better imaging test except when intracranial bleeding is suspected. Imaging may be done at a later point in time in those who return to their normal selves while in the emergency room. If a person has a previous diagnosis of epilepsy with previous imaging repeat imaging is not usually needed with subsequent seizures.
In adults, testing electrolytes, blood glucose and calcium levels is important to rule these out as causes, as is an electrocardiogram. A lumbar puncture may be useful to diagnose a central nervous system infection but is not routinely needed. Routine antiseizure medical levels in the blood are not required in adults or children. In children additional tests may be required.
A high blood prolactin level within the first 20 minutes following a seizure may be useful to confirm an epileptic seizure as opposed to psychogenic non-epileptic seizure. Serum prolactin level is less useful for detecting partial seizures. If it is normal an epileptic seizure is still possible and a serum prolactin does not separate epileptic seizures from syncope. It is not recommended as a routine part of diagnosis epilepsy.
Intravenous immunoglobulin therapy has been used in Lennox–Gastaut syndrome as early as 1986, when van Rijckevorsel-Harmant and colleagues used it in seven patients with ostensibly idiopathic LGS and saw EEG improvement and decreased seizure frequency in six of them.
Continuous prophylactic antiepileptic drug (AED) treatment may not be needed particularly for children with only 1-2 or brief seizures. This is probably best reserved for children whose seizures are unusually frequent, prolonged, distressing, or otherwise significantly interfering with the child’s life. There is no evidence of superiority of monotherapy with any particular common AED.
Autonomic status epilepticus in the acute stage needs thorough evaluation for proper diagnosis and assessment of the neurologic/autonomic state of the child. "Rescue" benzodiazepines are commonly used to terminate it. Aggressive treatment should be avoided because of the risk of iatrogenic complications, including cardiovascular arrest. There is some concern that intravenous lorazepam and/or diazepam may precipitate cardiovascular arrest. Early parental treatment is more effective than late emergency treatment. Buccal midazolam is probably the first choice medication for out of hospital termination of autonomic status epilepticus which should be administered as soon as the child shows evidence of onset of its habitual autonomic seizures.
Parental education about Panayiotopoulos syndrome is the cornerstone of correct management. The traumatizing, sometimes long-lasting effect on parents is significant particularly because autonomic seizures may last for many hours compounded by physicians’ uncertainty regarding diagnosis, management, and prognosis.
Between 10 and 30% of people who have status epilepticus die within 30 days. The great majority of these people have an underlying brain condition causing their status seizure such as brain tumor, brain infection, brain trauma, or stroke. However, people with diagnosed epilepsy who have a status seizure also have an increased risk of death if their condition is not stabilized quickly, their medication and sleep regimen adapted and adhered to, and stress and other stimulant (seizure trigger) levels controlled.
However, with optimal neurological care, adherence to the medication regimen, and a good prognosis (no other underlying uncontrolled brain or other organic disease), the person—even people who have been diagnosed with epilepsy—in otherwise good health can survive with minimal or no brain damage, and can decrease risk of death and even avoid future seizures.
The distinctive clinical features particularly lengthy seizures and ictus emeticus means that the diagnosis of Panayiotopoulos syndrome is easy. However, these are frequently mistaken as nonepileptic conditions such as acute encephalitis, syncope, migraine, cyclic vomiting syndrome, motion sickness, sleep disorder, or gastroenteritis. The consequence is avoidable misdiagnosis, high morbidity, and costly mismanagement.
Autonomic seizures and autonomic status epilepticus as occur in Panayiotopoulos syndrome have not been described in other epileptic syndromes in that sequence though 10–20 per cent of children with the same seizure semiology may have cerebral pathology. The major problem is to recognize emetic and other autonomic manifestations as seizure events and not to dismiss them or erroneously to consider them as unrelated to the ictus and a feature of encephalitis, migraine, syncope or gastro-enteritis.
The lack of generally recognized clinical recommendations available are a reflection of the dearth of data on the effectiveness of any particular clinical strategy, but on the basis of present evidence, the following may be relevant:
- Epileptic seizure control with the appropriate use of medication and lifestyle counseling is the focus of prevention.
- Reduction of stress, participation in physical exercises, and night supervision might minimize the risk of SUDEP.
- Knowledge of how to perform the appropriate first-aid responses to seizure by persons who live with epileptic people may prevent death.
- People associated with arrhythmias during seizures should be submitted to extensive cardiac investigation with a view to determining the indication for on-demand cardiac pacing.
- Successful epilepsy surgery may reduce the risk of SUDEP, but this depends on the outcome in terms of seizure control.
- The use of anti suffocation pillows have been advocated by some practitioners to improve respiration while sleeping, but their effectiveness remain unproven because experimental studies are lacking.
- Providing information to individuals and relatives about SUDEP is beneficial.
According to the Dravet Syndrome Foundation, the diagnostic criteria for DS requires the patient to present with several of the following symptoms:
- Onset of seizures in the first year of life in an otherwise healthy infant
- Initial seizures are typically prolonged and are generalized or unilateral
- Presence of other seizure types (i.e. myoclonic seizures)
- Seizures associated with fever due to illness or vaccinations
- Seizures induced by prolonged exposure to warm temperatures
- Seizures in response to strong lighting or certain visual patterns
- Initially normal EEGs and later EEGs with slowing and severe generalized polyspikes
- Normal initial development followed by slow development during the first few years of life
- Some degree of hypotonia
- Unstable gait and balance issues
- Ankle pronation and flat feet and/or development of a crouched gait with age
In epilepsy surgery a distinction can be made between resective and disconnective procedures. In a resective procedure the area of the brain that causes the seizures is removed. In a disconnective procedure the neural connections in the brain that allow the seizures to spread are disconnected. In most cases epilepsy surgery is only an option when the area of the brain that causes the seizures - the so-called epileptic focus can be clearly identified and is not responsible for critical functions such as language. Several imaging techniques such as magnetic resonance tomography and functional techniques like electrocorticography are used to demarcate the epileptic focus clearly.
Definitions vary, but currently it is defined as one continuous, unremitting seizure lasting longer than five minutes, or recurrent seizures without regaining consciousness between seizures for greater than five minutes. Previous definitions used a 30-minute time limit.
NCSE is believed to be under-diagnosed.
Epilepsy with myoclonic-astatic seizures has a variable course and outcome. Spontaneous remission with normal development has been observed in a few untreated cases. Complete seizure control can be achieved in about half of the cases with antiepileptic drug treatment (Doose and Baier 1987b; Dulac et al. 1990). In the remainder of cases, the level of intelligence deteriorates and the children become severely intellectually disabled. Other neurologic abnormalities such as ataxia, poor motor function, dysarthria, and poor language development may emerge (Doose 1992b). However, this proportion may not be representative because in this series the data were collected in an institution for children with severe epilepsy.
The outcome is unfavorable if generalized tonic-clonic, tonic, or clonic seizures appear at the onset or occur frequently during the course. Generalized tonic-clonic seizures usually occur during the daytime in this disorder, at least in the early stages. Nocturnal generalized tonic-clonic seizures, which may develop later, are another unfavorable sign. If tonic seizures appear, prognosis is poor.
Status epilepticus with myoclonic, astatic, myoclonic-astatic, or absence seizures is another ominous sign, especially when prolonged or appearing early.
Failure to suppress the EEG abnormalities (4- to 7-Hz rhythms and spike-wave discharges) during therapy and absence of occipital alpha-rhythm with therapy also suggest a poor prognosis (Doose 1992a).
Seizures in Dravet syndrome can be difficult to manage but may be reduced by anticonvulsant medications such as clobazam, stiripentol, topiramate and valproate. Because the course of the disorder varies from individual to individual, treatment protocols may vary. A diet high in fats and low in carbohydrates may also be beneficial, known as a ketogenic diet. Although diet adjustment can help, it does not eliminate the symptoms. Until a better form of treatment or cure is discovered, those with this disease will have myoclonic epilepsy for the rest of their lives.
Certain anticonvulsant drugs that are classed as Sodium Channel Blockers are now known to make seizures worse in most Dravet patients. These drugs include carbamazepine, gabapentin, lamotrigine, and phenytoin.
Treatments include cognitive rehabilitation through psychomotor and speech therapy. In addition, valproate is often administered to prevent recurrence of febrile seizures and benzodiazapine is used for long lasting seizures, but these treatments are usually insufficient.
Stiripentol was the only drug for which a double-blind placebo trial was performed and this drug showed efficacy in trials. It acts as a GABAergic agent and as a positive allosteric modulator of GABA receptor. Stiripentol, can improve focal refractory epilepsy, as well as Dravet's syndrome, supplemented with clobazam and valproate was approved in Europe in 2007 as a therapy for Dravet syndrome and has been found to reduce overall seizure rate by 70%. In cases with more drug resistant seizures, topiramate and the ketogenic diet are used as alternative treatments.
Cannabidiol (CBD) has received orphan drug status in the United States, for treatment of Dravet syndrome which will allow it to be studied.
The cause of FIRES is not known. It does not happen twice in the same family, but the medical community does not know if it is genetic. It happens in boys more than girls. After the initial status, life expectancy is not affected directly. Issues such as overdose of medications or infections at a food tube site are examples of things that would be secondary to the status.
Any number of medications may be used to both prevent and treat seizures.
Generally after three medications are tried, different treatment should be considered. It should also be noted that some medications are harmful to those with this syndrome and can increase seizures.
if the source of seizures is a lesion for example a scar tissue from a brain injury a tumor or malformed blood vessels this lesion can be removed surgically in a lesionectomy.
No single cause of OS has been identified. In most cases, there is severe atrophy of both hemispheres of the brain. Less often, the root of the disorder is an underlying metabolic syndrome. Although it was initially published that no genetic connection had been established, several genes have since associated with Ohtahara syndrome. It can be associated with mutations in "ARX", "CDKL5", "SLC25A22", "STXBP1", "SPTAN1", "KCNQ2", "ARHGEF9", "PCDH19", "PNKP", "SCN2A", "PLCB1", "SCN8A", and likely others.
Treatment outlook is poor. Anticonvulsant drugs and glucocorticoid steroids may be used to try to control the seizures, but their effectiveness is limited. Most therapies are related to symptoms and day-to-day living.
The ring 20 abnormality may be limited to as few as 5% of cells, so a screen for chromosomal mosaicism is critical. Newer array technology will not detect the ring chromosome and the standard metaphase chromosome analysis has been recommended. A karyotype analysis examining at least 50 cells should be requested to properly detect mosaicism.
Seven anti-epileptic drugs are approved for use in cases of suspected primary generalized epilepsy:
- Felbamate
- Levetiracetam
- Zonisamide
- Topiramate
- Valproate
- Lamotrigine
- Perampanel
Valproate, a relatively old drug, is often considered the first-line treatment. It is highly effective, but its association with fetal malformations when taken in pregnancy limits its use in young women.
All anti-epileptic drugs (including the above) can be used in cases of partial seizures.
Epilepsy surgery has been performed since the 1860s and doctors have observed that it is highly effective in producing freedom from seizures. However, it was not until 2001 that a scientifically sound study was carried out to examine the effectiveness of temporal lobectomy.
Temporal lobe surgery can be complicated by decreased cognitive function. However, after temporal lobectomy, memory function is supported by the opposite temporal lobe; and recruitment of the frontal lobe. Cognitive rehabilitation may also help.
Most generalized epilepsy starts during childhood. While some patients outgrow their epilepsy during adolescence and no longer need medication, in others, the condition remains for life, thereby requiring lifelong medication and monitoring.
A wide array of phenomena may resemble epileptic seizures, which may lead to people who do not have epilepsy being misdiagnosed. Indeed, a significant percentage of people initially diagnosed with epilepsy will later have this revised. In one study, the majority of children referred to a secondary clinic with "fits, faints and funny turns" did not have epilepsy, with syncope (fainting) as the most common alternative. In another study, 39% of children referred to a tertiary epilepsy centre did not have epilepsy, with staring episodes in mentally challenged children as the most common alternative. In adults, the figures are similar, with one study reporting a 26% rate of misdiagnosis.
Differentiation of a non-epileptic attack from an epileptic seizure includes the patient keeping their eyes closed and rarely causing themselves harm (both more common in non-epileptic attacks)
Over the past decade or so, researchers have been attempting to discover less invasive, safer and more efficient technologies that enable surgeons to remove epileptogenic focal zones without causing any damage to neighboring cortical areas. One such technology that has emerged and has great promise, is the use of gamma knife radiosurgery to either excise a brain tumor or repair a vascular malformation.
In Gamma Knife radiosurgery, intersecting gamma radiation beams are applied directly to the tumor site or vascular malformation site that had been established using neuroimaging. Although each beam itself is not strong enough to damage brain tissue, when the beams interesect they are strong enough to destroy the specific brain tissue that is to be excised. This process is extremely efficient and entirely non-invasive and is therefore much safer than actual neurosurgery itself.
Recently researchers and surgeons alike have begun to use Gamma Knife radiosurgery to treat cases of epilepsy by removing tumors responsible for causing the seizures. The early success rates in being able to alleviate seizures seem to be similar to those of temporal resective surgery however Gamma Knife radiosurgery has less associated risk factors. Current research on this topic is aimed at improving the technique in order to increase success rates as well as developing non-invasive forms of physiologic monitoring in order to determine the epileptogenic focus conclusively.
Where surgery is not recommended, further management options include new (including experimental) anticonvulsants, and vagus nerve stimulation. The ketogenic diet is also recommended for children, and some adults. Other options include brain cortex responsive neural stimulators, deep brain stimulation, stereotactic radiosurgery, such as the gamma knife, and laser ablation.
Like other forms of epilepsy, nocturnal epilepsy can be treated with anti-convulsants.
Despite the effectiveness of anti-convulsants in people who suffer from nocturnal epilepsy, the drugs are shown to disrupt a person's sleeping structure. This may cause concern in people who suffer specifically from nocturnal epilepsy because undisrupted sleep is important for these people, as it lowers the likeliness of epileptic symptoms to arise.
One particular study by V. Bradley and D. O'Neill analysed the different forms of epilepsy, including nocturnal epilepsy and its relationship with sleep. They found that some patients only experienced epileptic symptoms while they are asleep (nocturnal epilepsy), and that maintaining good sleep helped in reducing epileptic symptoms. Another study determined that anti-convulsant medications can minimize epilepsy not just in people who are awake, but also in people who are asleep. However, some of these anti-convulsant medications did also have adverse effects on subjects' sleeping structures, which can exacerbate epileptic symptoms in people who suffer from nocturnal epilepsy.
To minimize epileptic seizures in these people, it is important to find an anti-convulsant medication that does not disrupt a person's sleeping structure. The anti-convulsant medications that were tested to meet this criteria are: phenobarbital, phenytoin, carbamazepine, valproate, ethosuximide, felbamate, gabapentin, lamotrigine, topiramate, vigabatrin, tiagabine, levetiracetam, zonisamide, and oxcarbazepine. Oxcarbazepine is shown to have the least amount of adverse effects on sleep. Another study shows that it enhances slow wave-sleep and sleep continuity in patients with epilepsy.