Medication Summary
The only specific treatment available for neuronal ceroid lipofuscinoses (NCLs) is cerliponase alfa (Brineura) for neuronal ceroid lipofuscinosis type 2 (CLN2, also known as tripeptidyl peptidase 1 [TPP1] deficiency). [27]
Seizures in neuronal ceroid lipofuscinoses (NCLs) should be treated with standard anticonvulsants. Anticonvulsant agents used in NCL include the following:
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Carbamazepine (Tegretol, Carbatrol, Epitol, Equetro)
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Oxcarbazepine (Trileptal)
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Phenytoin (Dilantin, Phenytek)
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Valproic acid (Depakote, Depakene, Depacon, Stavzor)
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Gabapentin (Neurontin)
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Lamotrigine (Lamictal)
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Topiramate (Topamax)
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Tiagabine (Gabitril)
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Felbamate (Felbatol)
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Phenobarbital
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Zonisamide (Zonegran)
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Levetiracetam (Keppra)
Enzyme Replacement
Class Summary
The first enzyme replacement therapy for CLN2 disease (TPP1 deficiency) has been approved by the FDA.
Cerliponase alfa (Brineura, Recombinant human tripeptidyl peptidase 1 (rhtpp1))
Recombinant form of human tripeptidyl peptidase (TPP1) that provides enzyme replacement therapy. The enzyme results in a restored breakdown of the lysosomal storage materials that cause CLN2 disease.
Anticonvulsants
Class Summary
These agents are used to terminate clinical and electrical seizure activity as rapidly as possible and to prevent seizure recurrence.
Carbamazepine (Tegretol, Carbatrol, Epitol, Equetro)
Carbamazepine is effective for the treatment of complex partial seizures. It appears to act by reducing polysynaptic responses and blocking posttetanic potentiation. Carbamazepine's major mechanism of action is the reduction of sustained, high-frequency, repetitive neural firing.
Oxcarbazepine (Trileptal)
Oxcarbazepine's pharmacologic activity comes primarily from its 10-monohydroxy metabolite. Oxcarbazepine may block voltage-sensitive sodium channels, inhibit repetitive neuronal firing, and impair synaptic impulse propagation. Its anticonvulsant effect may occur through the drug's affect on potassium conductance and high-voltage, activated calcium channels. Oxycarbazepine's pharmacokinetics are similar in older children (>8 y) and adults. Young children (< 8 y) have a 30-40% increased clearance, compared with older children and adults. Children younger than 2 years have not been studied in controlled clinical trials.
Phenytoin (Dilantin, Phenytek)
A phosphorylated formulation, fosphenytoin, is available for parenteral use and may be given intramuscularly or intravenously.
Valproic acid (Depakote, Depakene, Depacon, Stavzor)
Valproic acid is chemically unrelated to other drugs used to treat seizure disorders. Although its mechanism of action not established, the activity of valproic acid may be related to increased brain levels of gamma-aminobutyric acid (GABA) or enhanced GABA action. Valproate may potentiate postsynaptic GABA responses, affect potassium channels, or have a direct membrane-stabilizing effect.
Gabapentin (Neurontin)
Gabapentin has properties in common with other anticonvulsants. However, its exact mechanism of action is not known. Gabapentin is structurally related to GABA but does not interact with GABA receptors.
Lamotrigine (Lamictal)
Lamotrigine is a triazine derivative that is useful in the treatment of seizures and neuralgic pain. It inhibits the release of glutamate and also inhibits voltage-sensitive sodium channels, stabilizing the neuronal membrane.
Topiramate (Topamax)
Topiramate is a sulfamate-substituted monosaccharide. It has a broad spectrum of antiepileptic activity that may have state-dependent sodium channel–blocking action, potentiating the inhibitory activity of the neurotransmitter GABA. In addition, topiramate may block glutamate activity.
Tiagabine (Gabitril)
Tiagabine's mechanism of antiseizure effect is unknown. However, the effect is believed to be related to tiagabine's ability to enhance the activity of GABA, a major inhibitory neurotransmitter in the CNS. Tiagabine may block GABA uptake into presynaptic neurons, permitting more GABA to be available for receptor binding on the surfaces of postsynaptic cells. The drug also possibly prevents the propagation of neural impulses that contribute to seizures by GABAergic action. The modification of concomitant AEDs is not necessary unless clinically indicated.
Felbamate (Felbatol)
Felbamate is an oral antiepileptic agent with weak inhibitory effects on GABA-receptor binding and benzodiazepine-receptor binding. It interacts as an antagonist at the strychnine-insensitive glycine recognition site of the N-methyl-D-aspartate (NMDA) receptor ̶ ionophore complex.
Felbamate is not indicated as a first-line antiepileptic treatment. The drug is recommended for use only in patients whose epilepsy is so severe that felbamate's benefits outweigh the risks of aplastic anemia or liver failure.
Phenobarbital
Phenobarbital exhibits anticonvulsant activity in anesthetic doses and can be administered orally. If the intramuscular route is chosen, inject the drug into one of large muscles, such as the gluteus maximus or vastus lateralis, or into another area where there is little risk of encountering a nerve trunk or major artery. Injection into or near peripheral nerves may result in permanent neurologic deficit. Restrict intravenous use to conditions in which other routes of administration are not feasible, either because the patient is unconscious, as in cases of cerebral hemorrhage, eclampsia, or status epilepticus, or because prompt action is imperative.
Zonisamide (Zonegran)
One of newer antiepileptics recently introduced in the US market, zonisamide has been studied extensively in Japan and Korea and seems to have broad-spectrum properties. It blocks T-type calcium channels, prolongs sodium channel inactivation, and is a carbonic anhydrase inhibitor.
Levetiracetam (Keppra, Keppra XR, Spritam)
Levetiracetam is indicated for primary generalized tonic-clonic seizures in adults and children aged 6 years or older, as well as for use in juvenile myoclonic epilepsy and for partial seizures.
