Treatment options in AHC have proved of limited success to date. A variety of strategies targeted toward episode prophylaxis can be helpful in some individuals, including avoidance of specific stressors or triggers, using daily prophylactic medications such as flunarizine or topiramate, or implementing strategies to induce sleep as a management tactic.[1]
Medications and Their Uses
Disease-modifying therapy of alternating hemiplegia of childhood does not exist, and several agents such as benzodiazepines, flunarizine, topiramate, ketogenic diet, triheptanoin, steroid, amantadine, memantine, aripiprazole, oral ATP, coenzyme Q, acetazolamide, dextromethorphan, and vagus nerve stimulator have been tried with various rates of success by aborting attacks or reducing the frequency or severity of paroxysmal spells.[2]
Research papers have covered the following treatment options:
- Acute attack management include benzodiazepines (administered orally, rectally, or via nasal administration),
- Sleep inducers include chloral hydrate, phenobarbitol,
- Antiepileptic agents if appropriate in children with concomitant epilepsy.
- Behavioral and mood disturbances become increasingly prevalent in later childhood and adolescence, and antipsychotic agents and mood stabilizing medications may be of value.
- Epilepsy is often reasonably managed with standard antiepileptic agents; however, it is important to try to distinguish nonepileptic from epileptic episodes and treat appropriately.
- The most frequent drugs used in AHC are flunarizine, benzodiazepines, carbamazepine, barbiturates and valproic acid. It has been wildly demonstrated that flunarizine and benzodiazepines show a greater improvement in dystonic or plegic episodes. Numerous studies have demonstrated that flunarizine, a calcium antagonist, reduces the duration, severity, and frequency of the hemiplegic attacks in up to 80% of AHC patients.[3]
Flunarizine
Flunarizine remains a mainstay of prophylactic therapy, although it is not currently Food and Drug Administration approved in the United States and has never been adequately tested in a sufficiently powered placebo-controlled trial; nonetheless, anecdotal reports of benefit are compelling in a disorder with limited treatment options. No definitive mechanistic explanation for potential efficacy has been proven, although flunarizine has been demonstrated to block voltage-dependent Na+- and Ca2+-dependent channels and alters synaptic transmission, and the utility of flunarizine in epilepsy and migraine has been previously documented.68 A recently published cohort of Japanese patients suggests a potential protective benefit of the medication in severe cases of AHC, and these investigators have previously reported an abrupt deterioration in the setting of withdrawal of flunarizine in some patients.[4]
Facts on Flunarizine (factdr.com)
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The effects of Flunarizine are cumulative and can take up to 2 to 3 weeks to show.
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Flunarizine is mainly used for the prevention of migraine attacks and lowering their severity.
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Flunarizine is well absorbed from the gastrointestinal tract, 85 % is absorbed after oral administration.
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99% of Flunarizine is transported in the body bound to Plasma proteins.
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Flunarizine has an elimination half-life of up to 18 days.
Other Interventions
Ketogenic diet, oral ATP, coenzyme Q and vagus nerve stimulator have been tried with various rates of success by aborting attacks or reducing the frequency or severity of paroxysmal spells. However, most of the reports of efficacy were from single case reports or case series of only a handful of patients.[5]
[1] Sweney MT, Newcomb TM, Swoboda KJ. The expanding spectrum of neurological phenotypes in children with ATP1A3 mutations, Alternating Hemiplegia of Childhood, Rapid-onset Dystonia-Parkinsonism, CAPOS and beyond. Pediatr Neurol. 2015;52(1):56-64.
[2] Samanta D. Management of Alternating Hemiplegia of Childhood: A Review. Pediatr Neurol. 2020 Feb;103:12-20.
[3] Capuano A, Garone G, Tiralongo G, Graziola F. Alternating Hemiplegia of Childhood: Understanding the Genotype-Phenotype Relationship of ATP1A3 Variations. Appl Clin Genet. 2020;13:71-81.
[4] Sweney MT, Newcomb TM, Swoboda KJ. The expanding spectrum of neurological phenotypes in children with ATP1A3 mutations, Alternating Hemiplegia of Childhood, Rapid-onset Dystonia-Parkinsonism, CAPOS and beyond. Pediatr Neurol. 2015;52(1):56-64.
[5] Samanta D. Management of Alternating Hemiplegia of Childhood: A Review. Pediatr Neurol. 2020 Feb;103:12-20.
