the Management of Epilepsy in Egypt

-  To determine whether the patient might have had an epileptic seizure, the patient's and eyewitness's (where possible) detailed histories should be taken . (strong recommendation) 

-  A  neurological examination  should be performed since recurrence can be predicted through an abnormal examination after a first seizure. (strong recommendation)  .

-  In children and young people, a specialist neurologist with good training and expertise in epilepsy should establish the diagnosis of epilepsy  (strong recommendation).

-  We recommend referral to a more specialized Epilepsy clinic If the epilepsy diagnosis cannot be definitely confirmed. (strong recommendation)

-  A normal EEG should not exclude the diagnosis of epilepsy . (strong recommendation)  .

-  Epilepsy is a clinical diagnosis; however, EEG can be indicated  .(conditional recommendation)  .

-  If  there is clinical doubt, EEG  should be used to classify epileptic seizures and epilepsy syndromes . (strong recommendation) 

-  In case of equivocal epilepsy diagnosis or suspected non-epileptic events, refer to tertiary center (strong recommendation) 

- When findings of a standard EEG have not supported epilepsy diagnosis or classification, a sleep EEG should be performed . (strong recommendation) 

-  Increasing recording time to 60 minutes on conventional EEG is a more convenient and cost-effective method of enhancing the EEG diagnostic yield compared to multiple conventional EEGs (strong recommendation)  ..

- In the case of patients with a likelihood of a non-convulsive epileptic seizure, as suggested by the clinical history, the finding of epileptiform abnormalities in EEG is specific to assess the risk of seizure recurrence . (strong recommendation)  .

-  We strong recommend using 21 electrodes should be used (10-20 system) periods when the eyes are closed and open should be included in the recordings (strong recommendation)  .

- During EEG Photic stimulation, sleep deprivation, and hyperventilation can be used routinely (unless contraindicated ) (conditional recommendation)  .

-  In all patients with blackouts,  we recommend the 12-lead electrocardiography (ECG) in  older age groups with blackouts (strong recommendation) .

- Consider ECG as a routine channel during EEG recording and should be performed as a baseline before starting ASM (conditional recommendation)  .

-  Magnetic resonance imaging (MRI) epilepsy protocol should follow the ILAE consensus on the"recommendations for using structural MRI in the care of PWE" (strong recommendation)

-  We recommend MRI  for brain imaging in PWE (before the age of two years and in adults) (strong recommendation).

- Any patient with focal onset on history, EEG, or examination (unless clear evidence of benign focal epilepsy) is indicated for MRI(strong recommendation). 

-  We recommend Referral for neuropsychological for any PWE who is suffering from learning or occupational challenges and as a part of the pre-surgical evaluation (strong recommendation).

- In adults, appropriate blood tests should be considered (complete blood count (CBC), glucose, calcium, thyroid-stimulating hormone (TSH), plasma electrolytes) to specify possible causes and/or any significant comorbidity(strong recommendation).

-  In adolescents and adults, urine toxicology screening should be done if addiction is suspected (strong recommendation). 

-  We recommend lumbar puncture (LP) for a child <6 months, a patient who fails to return to baseline /meningeal signs, or suspects high intracranial pressure (imaging before LP is mandatory) (strong recommendation).

-  In children and young people, other investigations should be considered in special situations (including urine and blood biochemistry) to identify an underlying cause of epilepsy and exclude other diagnoses (strong recommendation)..

-  In case of failure of the initial ASM (due to continued seizures or adverse effects), initiation of an additional drug should take place and then escalate up to an adequate or maximum tolerated dose (this drug may be an alternative first‐line or second‐line drug). Afterward, slow tapering off the first drug should be done and caution is needed during the changeover period (strong recommendation).

-  In case the second drug is worthless, consider tapering of it or the first drug  (conditional recommendation).

-  We recommend combination therapy with the newer antiepipetic drugs in  patients who do not achieve seizure freedom on monotherapy . (strong recommendation).

-  We recommend Drug withdrawal  after a minimum of 2-5 years without a seizure based on risk of seizure recurrence. Gradual withdrawal over 2-6 months is recommended.

If seizures recur, the effective well tolerated drug previously used should be restarted using the last effective dose . (strong recommendation).

-  In self-limited epilepsy with centrotemporal spikes first line are carbamazepine, oxcarbazepine, valproate. And adjuvant therapy are eslicarpazepine, lacozamide, lamotrigine, levetiracetam, zonisamide (strong recommendation)  .          

-  In self-limited epilepsy with autonomic seizures first line are carbamazepine, sodium valproate. And adjuvant therapy are eslicarpazepine, lacozamide, lamotrigine, levetiracetam, zonisamide (conditional recommendation)  .

-  In childhood occipital visual epilepsy first line are carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, valproate. And adjuvant therapy are eslicarpazepine, lacozamide, lamotrigine, levetiracetam, zonisamide (strong recommendation)  .

-  In photosensitive occipital lobe epilepsy first line is avoid factors that provoke seizures, valproate and adjuvant therapy are benzodiazepines, levetiracetam (strong recommendation)  .

-  In childhood absence epilepsy first line are ethosuximide, valproic acid. And adjuvant therapy are a combination of ethosuximide and valproic acid or lamotrigine (strong recommendation)  .

-  In epilepsy with myoclonic absence first line are ethosuximide, valproic acid.and adjuvant therapyare a combination of ethosuximide and valproic acid. other options are lamotrigine (strong recommendation) .

-  In epilepsy with eyelid myoclonia first line are ethosuximide, valproic acid.and adjuvant therapy are clonazepam, ethosuximide, valproic acid (conditional recommendation)  .

-  In myoclonic atonic epilepsy first line are valproate in GTCS, ethosuximide in absence seizures, steroids in the periods with multiple atonic seizures, and frequent, prolonged episodes of nonconvulsive status. and adjuvant therapy are lamotrigine, ketogenic diet (conditional recommendation)  .

-  In lennox-gastaut syndrome first line are lamotrigine, topiramate, valproate.and adjuvant therapy are lamotrigine, topiramate, valproate, rufinamide (strong recommendation)  .

-  In developmental and/or epileptic encephalopathy with spike-wave activation during sleep first line are standard ASMs, VPA, benzodiazepines, ethosuximide, ACTH or prednisone, high-dose benzodiazepines, intravenous immunoglobulins, epilepsy surgery.other options: acetazolamide, clobazam, lacozamide, lamotrigine, levetiracetam (conditional recommendation)  .

-  IN Febrile infection-related epilepsy syndrome First line ARE benzodiazepines and barbiturates for treatment of the acute event.And adjuvant therapy is ketogenic diet.other options: IVIG, cannabidiol, anakinra, immunomodulation such as tocilizumab or canakinumab, epilepsy surgery  (strong recommendation).

-  In hemiconvulsion, hemiplegia epilepsy syndrome first line are Steroids, NMDA receptor blocker as memantine, amantadine.and adjuvant therapy are carbamazepine, phenytoin in cases of persistent seizures.other options: lamotrigine, perampanel, rufinamide, topiramate, valproate, epilepsy surgery (conditional recommendation)   .

-  In juvenile absence epilepsy (JAE) first line are ethosuximide, lamotrigine, sodium valproate.and adjuvant therapy are a combination of any of the first lines (strong recommendation) .

-  In juvenile myoclonic epilepsy (JME) first line aresodium valproate, topiramate.and adjuvant therapy are acetazolamide, lamotrigine, levetiracetam .  (strong recommendation). .

-  In idiopathic generalized tonic–clonic seizures first line are lamotrigine, sodium valproate. And adjuvant therapy are consider carbamazepine, oxcarbazepine (exacerbating myoclonic and absence seizures) (strong recommendation). .

- In focal aware and impaired awareness seizures first line are carbamazepine, eslicarpazepine acetate, lacozamide, lamotrigine, levetiracetam, oxcarbazepine, sodium valproate.and adjuvant/ add-on: lamotrigine, phenobarbital, phenytoin, topiramate, vigabatrin, zonisamide (strong recommendation).

-  In focal to bilateral tonic-clonic seizure and generalized onset tonic-clonic seizure first line; lamotrigine, sodium valproate.and adjuvant/ add-on: levetiracetam, topiramate (strong recommendation). .

- In generalized non-motor (Absence) seizures first line: ethosuximide, sodium valproate,and adjuvant: clonazepam, lamotrigine, levetiracetam, topiramate, zonisamide (strong recommendation) .

- In myoclonic seizures first line: levetiracetam, sodium valproate, topiramate.and adjuvant are clonazepam, levetiracetam, piracetam (strong recommendation).  .

- In tonic & atonic seizures first line: sodium valproateand adjuvant: lamotrigine, topiramate(strong recommendation) .

-   In status Epilepticus (SE) the diagnostic evaluation begins in parallel with emergent Initial Therapy :

o   For diagnosis, finger stick glucose should be checked, pulse oximeter and cardiac monitoring should be started as soon as possible. Blood and serum laboratory evaluation typically includes a CBC, basic metabolic panel, calcium and magnesium determinations (conditional recommendation) .

o   In the case of febrile patients or if there is a suspected subarachnoid haemorrhage or central nervous system infection, LP should be performed, preferably after obtaining the CT scan. Non-contrast CT of the brain is the first imaging study to be considered in the Emergency Department (ED) if MRI is not feasible (conditional recommendation) .

o   Emergent prehospital treatment with benzodiazepines is needed and assess any abnormalities (hypoxia, hypoglycemia, or hypotension must be managed accordingly) (strong recommendation)  .

o   If benzodiazepines are not administered to the patient before ED arrival and are still seizing, IV benzodiazepines should be included in the initial dosing when IV access is immediately available (strong recommendation)  .

o   When IV access is not available, IM, per rectum (PR), buccal, or intranasal benzodiazepines should be administered together with IV placement (strong recommendation)   .

o   Unless IV access is immediately available, initiate IM. In adults or children over 40 kg, IM midazolam 10 mg. In children 13–40 kg, the IM midazolam dose is 5 mg, and in children <13 kg, the IM midazolam dose is 0.2 mg/ kg  (strong recommendation)  .

o   Among second-line ASMs, the first-line choice will be either phenytoin or levetiracetam in their standard loading doses. Also lacosamide can be used if the previous ASM failed or is unavailable. It would be better to start the second line simultaneously with the initial benzodiazepine rather than waiting for a response for benzodiazepine (strong recommendation)  .

o   If seizures have stopped after the initial ASM, and the patient had awakened, a maintenance dose of loading ASMs should be started if indicated and can be given either orally or intravenously  (strong recommendation)  .

l  For treatment of Refractory SE early (within one hour) drug-induced coma with continuous IV infusion of an anaesthetic drug is recommended for RSE with EEG target of burst suppression (strong recommendation)   .

l  The recommended loading dose of IV midazolam infusion is 0.2 mg/kg at 2 mg/min. Then, repeated boluses every 5 min of 0.2–0.4 mg/kg should be administered until the seizures stop, up to a maximum loading dose of 2 mg/kg. Then, a continuous infusion at 0.05–2 mg/kg/h should be started (strong recommendation)   .

-  Propofol IV infusions are an alternative at 1–2 mg/kg IV over 3–5 min as a loading dose and then repeated boluses every 3–5 min of the same amount until the seizures stop  (strong recommendation).

-   The propofol infusion at a rate of 30–200 mcg/kg/min should then be maintained .Pentobarbital at 5 mg/kg as a loading dose, which is followed by a maintenance infusion of 1–3 mg/ kg may be used in children with refractory SE more frequently because of adverse effects with propofol (strong recommendation)   .

-  For treatment of Super-Refractory SE Thiopental should be initiated in the recommended dose with progressive weaning of the previous anesthetic over the following 24 hours (conditional recommendation).

-  If a burst-suppression EEG pattern without epileptic activity has been achieved during 24 hours under thiopental and SE recurs after thiopental weaning, adding phenobarbital should be considered in therapeutic dose for at least 24 hours, after which weaning should again be tried .thiopental anesthesia (epileptiform discharges), then ketamine in the recommended dose should be associated with thiopental (conditional recommendation)   .

-  In case of persistence or recurrence of SRSE despite the adoption of all previous recommendations and the patient in burst suppression so should be maintained under combined anesthesia with thiopental and ketamine, and all of the following therapeutics should be considered (according to availability and applicability):

A. magnesium sulfate – intravenous bolus (4 g) followed by a continuous infusion (2 - 6 g/h) aiming for plasma levels of 3.5 mmol/L (conditional recommendation).

B. Immunotherapy (conditional recommendation)   .

C. Ketogenic diet (conditional recommendation)  .

D. Vagus nerve stimulation (conditional recommendation)   .

F. Epilepsy surgery (conditional recommendation)   .

G. electroconvulsive therapy (conditional recommendation)   .

-  Patients with focal Drug resistant epilepsy should be referred for evaluation in a specialized/tertiary epilepsy care facility. The expertise of multidisciplinary teams should include psychology, psychiatry, neuroradiology, social work, counseling, clinical nurse specialists, occupational therapy, neurology, neuroanesthesia, neurophysiology, and neurosurgery  (conditional recommendation)  .

-  Once referred to a specialized/tertiary epilepsy facility the patient should undergo :

A.    Video-EEG to characterize the epilepsy types and rule out PNES (conditional recommendation)  .

B.    Imaging (MRI- HARNESS protocol) studies must be scrutinized once epilepsy diagnosis is confirmed to ascertain the presence of an epileptogenic focus and facilitate a possible surgical work-up  (conditional recommendation)  .

C.    In presence of high suspicion of focal seizures; if no epileptogenic lesion is found on MRI, other ancillary tests include:

1.     Ictal single-photon emission computed tomography (SPECT) (conditional recommendation)  .

2.     Positron emission tomography (PET) (strong recommendation)  .

3.     Functional MRI for eloquent regions of the brain (strong recommendation)  .

4.     Invasive EEG can be considered in case of unclear localization, or in case a more precise definition of the relationship of the eloquent cortex to the epileptic cortex is needed (strong recommendation)   .

l  In case of the localized epileptogenic zone (i.e. for lesional focal epilepsy in concordance with semiology and EEG, or non-lesional focal epilepsy with the localized epileptogenic zone); For extra-temporal lobe epilepsy related to eloquent areas but not included in the epileptogenic zone; awake craniotomy, mapping techniques, and ECoG guided resection should be applied (conditional recommendation) .

 

-  In case of the localized epileptogenic zone (i.e. for lesional focal epilepsy in concordance with semiology and EEG, or non-lesional focal epilepsy with the localized epileptogenic zone); For extra-temporal lobe epilepsy with eloquent areas included in the epileptogenic zone; implementation of procedure such as MST, VNS, or RNS should be applied (strong recommendation).

-  In case of the localized epileptogenic zone (i.e. for lesional focal epilepsy in concordance with semiology and EEG, or non-lesional focal epilepsy with the localized epileptogenic zone); For unilateral temporal lobe epilepsy with lateral temporal involvement, ATL should be applied (strong recommendation).

-  In case of the localized epileptogenic zone (i.e. for lesional focal epilepsy in concordance with semiology and EEG, or non-lesional focal epilepsy with the localized epileptogenic zone); For unilateral temporal lobe epilepsy with no lateral temporal involvement, either surgical procedures (ATL or SAH) or minimally invasive procedures (LITT or SRS) should be applied  (strong recommendation).

-  In the case of the localized epileptogenic zone (i.e. for lesional focal epilepsy in concordance with semiology and EEG, or non-lesional focal epilepsy with the localized epileptogenic zone); For bilateral temporal lobe epilepsy, either VNS or RNS should be applied (conditional recommendation)  .

-  In the case of hemispheric generalized or multifocal epilepsy, either hemispherectomy (anatomical or functional) or VNS should be applied (conditional recommendation)  .

-  In the case of generalized poorly localized epilepsy with mostly atonic attacks, palliative management with corpus callosotomy should be applied (conditional recommendation) .

- In case of generalized poorly localized epilepsy with minor atonic attacks, palliative management with VNS or DBS of the anterior nucleus of the thalamus should be applied (strong recommendation) .