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Dravet, syndrome
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(Severe myoclonic epilepsy of childhood, severe infantile multifocal epilepsy)
Rare form of epilepsy (1/20,000 to 1/40,000 births). Autosomal dominant transmission but de novo mutation in 95 % of cases.
It is due
- either to a mutation of the SCN1A gene (2q24.3) leading to a loss of function of the alpha subunit of the Na voltage-gated channel Nav1.1(75 % of cases), the most important Na channel of the inhibitory interneurones; this mutation leads to a neuronal hyperexcitability state
- or to a mutation in the PCDH19 gene (chromosomeX) coding for protocadherin 19 (20 % of the cases among girls).
It starts before one year of age with clonic convulsions (or a status epilepticus), with or without fever,that are complex (often affecting a hemi-body) and occurring in a child whose development was until then normal; at that age, the EEG and imaging are normal. These repeated focal seizures persist until about 2-3 years of age. At that time, onset of generalized seizures (febrile or not) with a tendency to easily progress to status epilepticus associated with a significant risk of mortality (SUDEP: Sudden Unexpected Death in Epilepsy).
Other forms of seizures (myoclonic seizures, atypical absences etc...) gradually add to the initial clinical presentation. There is also hyperkinesia and psychomotor instability.
This epilepsy is resistant to treatment and typically requires a triple therapy: valproate, clobazam and striripentol, even ketogenic diet. Carbamazepine, phenytoin, lamotrigine, and vigabratin which inhibit the neuronal channel Nav1.1 should be avoided because they aggravate the seizures. Repeated seizures eventually result in moderate to severe mental retardation.
Experimental treatments:
- marijuana extract orally twice daily (cannabidiol antagonizes CB1 and CB2 receptors without psychotropic effects).
- fenfluramine 0,2 to 0,7 mg/kg/d: significantly less frequent convulsive crises
Anesthetic implications:
Epilepsy, mental retardation; possible interactions with the cannabis extract(CYP1A2, CYP3A4, CYP2C9, CYP2C19 cytochromes); temperature monitoring and prevention of hyperthermia. Careful use of the local anesthetics (lidocaine ?) which are also known as Nav1.1 channel inhibitors.
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- take advice from the neuropediatrician: efficacy of the diet, which treatment in case of seizure, side effects (urinary lithiases ?) - evaluation: RBC, WC, platelets, electrolytes, urea, creatinine, Ca, Mg, albumin and prealbumin (nutrition). SGOT and SGPT levels are often moderately elevated - avoid prolonged fasting: clear unsweetened fluids allowed - avoid sweetened fluids in the premedication - avoid IV administration of carbohydrates containing IV fluids - check glycemia at induction: ideally 50-80 mg/dL |
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anesthesia |
- propofol: OK for induction but avoid TIVA: source of glycerol, risk of PRIS and pancreatitis - fluids: 0.9 % NaCl (risk of worsening metabolic acidosis) or Ringer lactate (but lactate promotes gluconeogenesis); ideal: a solution without glucose but containing acetate (Plasmalyte&®) - avoid corticosteroids: dexamethasone? - avoid carbohydrate-containing medications (glucose, mannitol, glycerol) if possible - the transfusion of labile blood products is a hidden intake of carbohydrates - in case of hypoglycemia, correct with low doses of glucose (0.25g/kg) - monitor glycemia, pH, electrolytes, NaHCO3 |
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postoperative |
- resume the ketogenic diet as soon as possible - check ketone bodies (urine): between 40 and 160 mg/dL or at least 2 ++ |
Ketogenic diet: perianesthetic recommendations
References :
- Flannery KM, D’Souza G, Agarwal R.
Perioperative management of the pediatric patient on medicinal marijuana: what anesthesiologists should know.
Anesth Analg 2019, 129:1339-43
- Conover ZR, Talai A, Klockau KS, Ing RJ, Chaterjee D.
Perioperative management of children on ketogenic dietary therapies.
Anesth Analg 2020 ; 131 :1872-82.
- MacDonald-Laurs E, Corlette S, Davidson A, Howell KB.
Anesthetic considerations in Dravet syndrome.
Pediatr Anesth 2022 ; 32 :1166-8
Updated: September 2022