You are in: eMedicine Specialties > Neurology > Pediatric Neurology Neuronal Ceroid LipofuscinosesArticle Last Updated: Apr 24, 2006AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: Celia H Chang, MD, Associate Health Sciences Clinical Professor, Department of Neurology, University of California at Davis Celia H Chang is a member of the following medical societies: American Academy of Neurology and Child Neurology Society Editors: Beth A Pletcher, MD, Associate Professor, Co-Director of The Neurofibromatosis Center of New Jersey, Department of Pediatrics, University of Medicine and Dentistry of New Jersey; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Kenneth J Mack, MD, PhD, Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic; Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital; Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants Author and Editor Disclosure Synonyms and related keywords: Batten disease, Parry's disease, Spielmeyer-Sjögren disease, Bielschowsky disease, Kufs disease, Santavuori-Haltia disease, neuronal ceroid lipofuscinoses, NCLs INTRODUCTIONSection 2 of 10
  BackgroundThe neuronal ceroid lipofuscinoses (NCLs), also known as Batten disease, are a group of neurodegenerative disorders. They are considered the most common of the neurogenetic storage diseases with a prevalence of 1 in 12,500 in some populations. They are associated with variable yet progressive symptoms including seizures, dementia, visual loss, and/or cerebral atrophy. In 1826, Stengel described the first patients—4 siblings in Norway. Batten made the first clinicopathologic correlation in 1903 and referred to NCL as "familial cerebromacular degeneration." Batten was also the first person to differentiate NCL from Tay-Sachs disease in 1914. Vogt, Spielmeyer, Bielschowsky, and Kufs also described older patients with similar symptoms. In 1939, Klenk discovered increased gangliosides in Tay-Sachs disease but in not "juvenile amaurotic idiocy" (an early name for NCL). NCL was later so named because of the accumulation of autofluorescent lipopigments resembling ceroid and lipofuscin. In 1959, Koppang described English setters with the same phenotype as patients with NCL. Although NCLs are generally autosomal recessive disorders, in 1971 Boehme also described autosomal dominant inheritance of the same disease in the Parry family of New Jersey. The enzymatic abnormalities were better defined in the 1980s and the molecular genetics are now being described in some variants of NCL. PathophysiologyIn CLN1, a lysosomal enzyme, palmitoyl protein thioesterase (PPT), is deficient. PPT, which removes fatty acyl groups from cysteine residues on fatty acid modified proteins, remains in the endoplasmic reticulum where it is inactive, causing sapsosins A and D to accumulate in the lysosomes. Mutations have been found in all 9 exons of the CLN1 gene. Although CLN1 usually had onset in infancy, later onset including in adulthood has also been described. More than 40 mutations have been described in CLN1. Subunit C of the mitochondrial ATP synthase complex accumulates in the lysosomes of patients with some variants of NCL, including CLN2, CLN3, CLN4, CLN5, CLN6, CLN7, and CLN8. Subunit C also accumulates in some animal models of NCL, including the bovine and several canine variants. Subunit C, an extremely hydrophobic 75-amino-acid protein, is encoded by 2 separate genes, P1 and P2. P1 is on chromosome 17 and P2 is on chromosome 12. The mRNA for P2 is the predominant form. Subunit C is part of a transmembrane proton channel located on the inner mitochondrial membrane. Each ATP synthase complex has 10-12 copies of subunit C. Patients with CLN2 are deficient in a pepstatin-insensitive lysosomal peptidase—tripeptidyl peptidase 1 (TTP1). TTP1 removes tripeptides from the N-terminal of polypeptides. Mutations have been reported in all 13 exons of the CLN2 gene. Some mutations result in a more protracted course. Although onset is usually in late infancy, later onset has been described. More than 52 mutations have been described in CLN2. The CLN3 gene encodes a 438 amino acid protein that is thought to be a part of the lysosomal membrane. The most common mutation of CLN3 is a 1.02-kb deletion that involves loss of exons 7 and 8. Most patients with the classic phenotype of JNCL are homozygous for the 1.02-kb deletion. Patients who are compound heterozygotes for this deletion may have atypical phenotypes. Munroe reported 2 patients who were compound heterozygotes with visual failure, only one of whom had seizures; both patients were able to hold full-time employment as adults. Wisniewski et al reported similar patients who initially presented with psychiatric or behavioral symptoms but otherwise had a typical course. More than 31 mutations have been described in CLN3. The exact function of CLN3 is unknown, but its expression is highest in secretory/glandular tissues and in gastrointestinal cells. All patients with CLN3 have had visual failure by age 10. The adult form of NCL (ANCL) is associated with mutations of the CLN4 gene. The CLN4 gene has not been mapped yet. Mutations in another gene, CLN5 is associated with Finnish variant LINCL (fLINCL). It occurs predominantly in the Finnish population. CLN5 encodes a 407 amino acid transmembrane protein. CLN5 only occurs in vertebrae. The expression of CLN5 increases during cortical neurogenesis. Four mutations have been described in CLN5. The CLN6 gene is associated with variant LINCL (vLINCL). Disease caused by CLN6 mutations are also referred to as the Czech or Indian variant. The CLN6 gene has been mapped to band 15q21-q23 and encodes a 311 amino acid membrane protein. More than 18 mutations have been described in CLN6. Affected individuals with CLN6 mutations are primarily of Portuguese, Indian, Pakistani, or Czech ancestry. The CLN7 gene has been assigned to the tLINCL variant and has not yet been mapped. Individuals with the tLINCL variant originate from Turkey. CLN8 encodes a 286 amino acid transmembrane protein, which localizes to the endoplasmic reticulum and endoplasmic reticulum-Golgi intermediate complex. The exact function of the CLN8 protein is unknown. Five mutations have been described in CLN8. Four mutations cause vLINCL, but a missense mutation (R24G) results in progressive epilepsy with mental retardation (PEMR) or Northern epilepsy, which is a protracted disease. Schulz et al reported that CLN9 produces a protein that may be a regulator of dihydroceramide synthetase. Even though the CLN8 sequence was normal, transfection with CLN8 corrected growth and apoptosis in CLN9 deficient cells. FrequencyUnited StatesEstimates suggest that approximately 25,000 families in the United States are affected with a form of NCL. InternationalCLN1: In the Finnish population, incidence is 1 in 20,000 with a carrier frequency of 1 in 70. CLN2: Worldwide prevalence is 0.6-0.7 per million inhabitants, with an incidence of 0.46 per 100,000 live births. CLN3: Worldwide, CLN3 is the second most common form of NCL. Incidence is 7 cases per 100,000 live births in Iceland. Mortality/MorbidityPatients with NCL have shortened life expectancy; impact on life span clearly depends on the type of NCL. RaceThe prevalence of NCL is highest in the Scandinavian countries, especially Finland, where the estimated carrier frequency is a little less than 1 in 100 or 1%. AgeAlthough the age of onset depends in part upon the type of NCL, molecular genetic discoveries have revealed more clinical overlap than was appreciated previously. Most cases of CLN1 in the Finnish population have an infantile onset. Only 50% of the CLN1 cases have an infantile onset in the United States. The other cases have late infantile, juvenile, or adult onset. CLINICALSection 3 of 10
HistoryThe NCLs originally were defined by their age of onset and clinical symptoms; however, they soon may be reclassified on the basis of newer molecular findings, which have provided evidence of far more overlap for the different genetic variants than what was previously suggested by the clinical phenotypes.
PhysicalPlease see History section. CausesPlease see Pathophysiology. DIFFERENTIALSSection 4 of 10
Absence Seizures Benign Childhood Epilepsy Benign Neonatal Convulsions Complex Partial Seizures Diseases of Tetrapyrrole Metabolism: Refsum Disease and the Hepatic Porphyrias Disorders of Carbohydrate Metabolism Dopamine-Responsive Dystonia Epilepsia Partialis Continua Epilepsy in Adults with Mental Retardation Epilepsy in Children with Mental Retardation First Seizure in Adulthood: Diagnosis and Treatment First Seizure: Pediatric Perspective Friedreich Ataxia Frontal Lobe Epilepsy Frontal Lobe Syndromes Hallervorden-Spatz Disease HIV-1 Associated CNS Complications (Overview) Huntington Disease Inherited Metabolic Disorders Lysosomal Storage Disease Peroxisomal Disorders Seizures and Epilepsy: Overview and Classification Temporal Lobe Epilepsy
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| Drug Name | Carbamazepine (Tegretol) |
|---|---|
| Description | Effective for treatment of complex partial seizures. Appears to act by reducing polysynaptic responses and blocking posttetanic potentiation. Major mechanism of action is to reduce sustained high-frequency repetitive neural firing. |
| Adult Dose | 200 mg PO bid (100 mg qid of suspension); increase at weekly intervals by no more than 200 mg/d using tid/qid regimen (2 times/d with extended release) until best response obtained; generally not to exceed 1600 mg/d |
| Pediatric Dose | <6 years: 10-20 mg/kg/d bid/tid (qid with suspension); increase weekly to achieve optimal clinical response administered tid/qid 6-12 years: 100 mg bid (50 mg qid of suspension); increase at weekly intervals gradually by adding 100 mg/d using tid/qid regimen (bid with extended release) until best response obtained >12 years: Administer as in adults; generally not to exceed 1000 mg/d in children aged 12-15 years or 1200 mg/d in patients older than 15 years |
| Contraindications | Documented hypersensitivity; because it has effect on ventricular automaticity, do not use in sino-atrial block, sinus bradycardia, second- or third-degree AV block, or Adams-Stokes syndrome |
| Interactions | Danazol may increase serum levels significantly within 30 days (avoid combination whenever possible); do not coadminister with MAOIs; cimetidine may increase toxicity, especially if taken in first 4 wk of therapy; may decrease primidone and phenobarbital levels (their coadministration may increase carbamazepine levels) |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | Do not use to relieve minor aches or pains; caution with increased intraocular pressure; obtain CBC and serum iron at baseline prior to treatment, during first 2 months, and yearly or every other year thereafter; can cause drowsiness, dizziness, and blurred vision; caution while driving or performing other tasks requiring alertness |
| Drug Name | Phenytoin (Dilantin) |
|---|---|
| Description | Primary site of action of hydantoins, such as phenytoin, appears to be motor cortex, where it may inhibit spread of seizure activity. May reduce maximal activity of brain stem centers responsible for tonic phase of grand mal seizures. Dose should be individualized. If daily dosage cannot be divided equally, larger dose should be given before retiring. Phosphorylated formulation, fosphenytoin, available for parenteral use and may be given IM or IV. |
| Adult Dose | 100 mg (125 mg suspension) PO/IV tid initially; 300-400 mg/d PO/IV divided tid for maintenance dose, or qd/bid if using extended release; increase to 600 mg/d (625 mg/d suspension) may be necessary; not to exceed 1500 mg/d |
| Pediatric Dose | 5 mg/kg/d PO/IV divided bid/tid; 4-8 mg/kg PO/IV divided bid/tid for maintenance >6 years: May require minimum adult dose (300 mg/d); not to exceed 300 mg/d |
| Contraindications | Documented hypersensitivity; sino-atrial block, second- or third-degree AV block, sinus bradycardia, or Adams-Stokes syndrome |
| Interactions | Amiodarone, benzodiazepines, chloramphenicol, cimetidine, fluconazole, isoniazid, metronidazole, miconazole, phenylbutazone, succinimides, sulfonamides, omeprazole, phenacemide, disulfiram, ethanol (acute ingestion), trimethoprim, and valproic acid may increase toxicity Barbiturates, diazoxide, ethanol (chronic ingestion), rifampin, antacids, charcoal, carbamazepine, theophylline, and sucralfate may decrease effects May decrease effects of acetaminophen, corticosteroids, dicumarol, disopyramide, doxycycline, estrogens, haloperidol, amiodarone, carbamazepine, cardiac glycosides, quinidine, theophylline, methadone, metyrapone, mexiletine, oral contraceptives, valproic acid |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | Rapid IV infusion may result in death from cardiac arrest, marked by QRS widening Perform blood counts and urinalyses when therapy is begun and at monthly intervals for several months thereafter to monitor for blood dyscrasias; discontinue use if skin rash appears and do not resume use if rash is exfoliative, bullous, or purpuric; caution in acute intermittent porphyria and diabetes (may elevate blood glucose); discontinue use if hepatic dysfunction occurs |
| Drug Name | Valproic acid (Depakote, Depakene, Depacon) |
|---|---|
| Description | Chemically unrelated to other drugs used to treat seizure disorders. Although mechanism of action not established, activity may be related to increased brain levels of GABA, or enhanced GABA action. Valproate may potentiate postsynaptic GABA responses, affect potassium channel, or have direct membrane-stabilizing effect. For conversion to monotherapy, concomitant AED dosage ordinarily can be reduced by approximately 25% every 2 wk. This reduction may be started at initiation of therapy or delayed by 1-2 wk if concern that seizures are likely to occur with reduction. Monitor patients closely during this period for increased seizure frequency. As adjunctive therapy, divalproex sodium may be added to patient's regimen at dosage of 10-15 mg/kg/d. Dosage may be increased by 5-10 mg/kg/wk to achieve optimal clinical response. Ordinarily, optimal clinical response achieved at daily doses <60 mg/kg/d. |
| Adult Dose | 10-15 mg/kg/d in 1-3 divided doses and increase by 5-10 mg/kg/wk until seizures controlled or adverse effects prevent further increases; not to exceed 60 mg/kg/d; use same regimen as in adults; if total daily dose is >250 mg, give in divided doses |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity; hepatic disease/dysfunction |
| Interactions | Cimetidine, salicylates, felbamate, and erythromycin may increase toxicity; rifampin may reduce levels significantly; in children, salicylates decrease protein binding and metabolism of valproate; may result in variable changes of carbamazepine concentrations with possible loss of seizure control; may increase diazepam and ethosuximide toxicity (monitor closely); may increase phenobarbital and phenytoin levels while either one may decrease valproate levels; may displace warfarin from protein-binding sites (monitor coagulation tests); may increase zidovudine levels in HIV-seropositive patients |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | Thrombocytopenia and abnormal coagulation parameters have occurred; risk of thrombocytopenia increases significantly at total trough valproate plasma concentrations >110 mcg/mL in females and >135 mcg/mL in males; before initiating therapy, at periodic intervals, and prior to surgery, determine platelet counts and bleeding time; reduce dose or discontinue therapy if hemorrhage, bruising, or hemostasis/coagulation disorder occurs; hyperammonemia may occur, resulting in hepatotoxicity; monitor patients closely for appearance of malaise, weakness, facial edema, anorexia, jaundice, and vomiting; may cause drowsiness |
| Drug Name | Gabapentin (Neurontin) |
|---|---|
| Description | Has properties in common with other anticonvulsants. However, exact mechanism of action not known. Structurally related to GABA but does not interact with GABA receptors. |
| Adult Dose | Day 1: 100 mg tid or 300 mg PO hs Day 2: Increase dose to 400 mg PO tid over 3-d interval and titrate dose prn; increases in daily dose best tolerated when done slowly; not to exceed 1200 mg PO qid |
| Pediatric Dose | <12 years: Not established >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Antacids may reduce bioavailability significantly (administer at least 2 h following antacids); may increase norethindrone levels significantly |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in severe renal disease |
| Drug Name | Lamotrigine (Lamictal) |
|---|---|
| Description | Triazine derivative useful in treatment of both seizures and neuralgic pain. Inhibits release of glutamate and inhibits voltage-sensitive sodium channels, which stabilizes neuronal membrane. Follow manufacturer's recommendation for dose adjustments. |
| Adult Dose | Adjunctive therapy with enzyme-inducing anticonvulsant: Weeks 1-2: 50 mg/d PO Weeks 3-4: 100 mg/d PO in 2 divided doses; 300-500 mg/d in 2 divided doses for maintenance (to achieve maintenance, increase dose by 100 mg/d q1-2wk) Adjunctive therapy with anticonvulsant regimen containing valproate: Weeks 1-2: 25 mg PO qod Weeks 3-4: 25 mg/d PO; 100-200 mg/d for maintenance as qd or bid dose (to achieve maintenance, increase dose by 25-50 mg/d every 1-2 wk) Conversion from single enzyme-inducing anticonvulsant to lamotrigine monotherapy: Weeks 1-2: 50 mg/d PO Weeks 3-4: 100 mg/d PO for weeks 3 and 4 in 2 divided doses; 300-500 mg/d in 2 divided doses for maintenance (to achieve maintenance, increase dose by 100 mg/d every 1-2 wk); enzyme-inducing anticonvulsant is gradually withdrawn over 4-wk interval in 20% decrements per wk |
| Pediatric Dose | 2-12 years Adjunctive therapy with enzyme-inducing anticonvulsant: Weeks 1-2: 0.6 mg/kg/d PO in 2 divided doses, rounded down to nearest 5 mg Weeks 3-4: 1.2 mg/kg/d PO in 2 divided doses, rounded down to nearest 5 mg; 5-15 mg/kg/d for maintenance; not to exceed 400 mg/d divided bid To achieve usual maintenance dose, increase subsequent doses every 1-2 wk as follows: Calculate 1.2 mg/kg/d PO and round down to nearest 5 mg; add this amount to previously administered daily dose As concomitant therapy with valproic acid: Weeks 1-2: 0.15 mg/kg/d PO qd or divided bid, rounded down to nearest 5 mg; If initial calculated daily dose 2.5-5 mg, then take 5 mg on alternate days for first 2 wk Weeks 3-4: 0.3 mg/kg/d PO qd or divided bid, rounded down to nearest 5 mg 1-5 mg/kg/d PO for maintenance; not to exceed 200 mg/d qd or divided bid; to achieve usual maintenance dose, increase subsequent doses every 1-2 wk as follows: Calculate 0.3 mg/kg/d PO, and round down to nearest 5 mg; add amount to previously administered qd dose >12 years As adjunctive therapy with enzyme-inducing anticonvulsant: Weeks 1-2: 50 mg/d PO Weeks 3-4: 100 mg/d PO divided bid; 300-500 mg/d divided bid for maintenance (to achieve maintenance, increase dose by 100 mg/d every 1-2 wk) Concomitant therapy with valproic acid: Weeks 1-2: 25 mg PO qod Weeks 3-4: 25 mg PO qd; 100-400 mg/d qd or divided bid for maintenance (to achieve maintenance, increase dose by 25-50 mg/d every 1-2 wk) |
| Contraindications | Documented hypersensitivity |
| Interactions | Acetaminophen increases renal clearance of medication, decreasing effects; similarly, phenobarbital and phenytoin increase lamotrigine metabolism, causing decrease in lamotrigine levels; valproic acid increases half-life |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in impaired renal or hepatic function; associated with rash in 5% of patients; children who take lamotrigine with valproate have significantly increased risk of severe allergic drug reactions |
| Drug Name | Topiramate (Topamax) |
|---|---|
| Description | Sulfamate-substituted monosaccharide with broad spectrum of antiepileptic activity that may have state-dependent sodium channel–blocking action, potentiates inhibitory activity of neurotransmitter GABA. In addition, may block glutamate activity. Not necessary to monitor plasma concentrations to optimize therapy. On occasion, addition of topiramate to phenytoin may require adjustment of phenytoin dose to achieve optimal clinical outcome. |
| Adult Dose | 50 mg/d PO; titrate by 50 mg/d at 1-wk intervals to target dose of 200 mg bid; not to exceed 1600 mg/d |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity |
| Interactions | Phenytoin, carbamazepine, and valproic acid can decrease levels significantly; reduces digoxin and norethindrone levels; carbonic anhydrase inhibitors may increase risk of renal stone formation and should be avoided; CNS depressants may have additive effect in CNS depression, as well as other cognitive or neuropsychiatric adverse events—use extreme caution |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Risk of developing kidney stone increased 2-4 times that of untreated population; risk may be reduced by increasing fluid intake; caution in renal or hepatic impairment |
| Drug Name | Tiagabine (Gabitril) |
|---|---|
| Description | Mechanism of antiseizure effect unknown. However, believed to be related to its ability to enhance activity of GABA, major inhibitory neurotransmitter in CNS. May block GABA uptake into presynaptic neurons, permitting more GABA to be available for receptor binding on surfaces of postsynaptic cells and possibly prevents propagation of neural impulses that contribute to seizures by GABAergic action. Modification of concomitant AEDs not necessary, unless clinically indicated. |
| Adult Dose | 4 mg PO qd in 2 or 4 divided doses; increase by 4-8 mg/wk until clinical response achieved or until total daily dose of 56 mg/d administered; doses >56 mg/d have not been systematically evaluated in adequate well-controlled trials |
| Pediatric Dose | <12 years: Not established 12-18 years: 4 mg PO qd; increase by 4 mg at beginning of wk 2; thereafter, total daily dose may be increased by 4-8 mg/wk until clinical response achieved or until 32 mg/d administered; doses >32 mg/d have been tolerated in small number of adolescent patients for relatively short duration |
| Contraindications | Documented hypersensitivity |
| Interactions | Cleared more rapidly in patients treated with carbamazepine, phenytoin, primidone, or phenobarbital than in patients who have not received these drugs |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Patients receiving valproate monotherapy may require lower doses or slower dose titration of tiagabine for clinical response; moderately severe to incapacitating generalized weakness reported in as many as 1% of patients with epilepsy; weakness may resolve after reduction in dose or discontinuation; withdraw slowly to reduce potential for increased seizure frequency |
| Drug Name | Felbamate (Felbatol) |
|---|---|
| Description | Oral antiepileptic agent with weak inhibitory effects on GABA-receptor binding and benzodiazepine receptor binding but interacts as antagonist at strychnine-insensitive glycine recognition site of NMDA receptor-ionophore complex. Not indicated as first-line antiepileptic treatment. Recommended for use only in those patients whose epilepsy is so severe that benefits outweigh risks of aplastic anemia or liver failure. |
| Adult Dose | Monotherapy: 1200 mg/d PO divided tid/qid initially; titrate to 2400 mg/d with 600-mg increments every 2 wk and to 3600 mg/d if clinically indicated Conversion to monotherapy: 1200 mg/d PO divided tid/qid initially Week 1: Reduce dosage of concomitant AEDs by one third at initiation of felbamate therapy Week 2: Increase dosage to 2400 mg/d PO while reducing dosage of other AEDs by additional one third of their original dosage Week 3: Increase dosage to 3600 mg/d PO and continue to reduce dosage of other AEDs prn Adjunctive therapy: Week 1: 1200 mg/d PO; reduce dose of concomitant AEDs Week 2: 2400 mg/d PO; reduce original AEDs dose by 33% Week 3: 3600 mg/d PO; reduce other AEDs as clinically indicated |
| Pediatric Dose | <14 years: Not established; for adjunctive therapy, 15 mg/kg/d PO divided tid/qid while reducing doses of present AEDs by 20% to control plasma levels of concurrent phenytoin, valproic acid, phenobarbital, or carbamazepine (and its metabolites); increase felbamate dosage by 15 mg/kg/d increments weekly to 45 mg/kg/d; most adverse effects during adjunctive therapy resolve as dosage of concomitant AEDs is decreased >14 years: Administer as in adults |
| Contraindications | Documented hypersensitivity; blood dyscrasia; hepatic dysfunction |
| Interactions | May increase steady-state phenytoin levels?40% dose reduction of phenytoin may be necessary in some patients; phenytoin may double felbamate clearance, resulting in more than 45% decrease in steady-state levels; may cause increase in phenobarbital plasma concentrations; phenobarbital may reduce plasma levels; may decrease steady-state carbamazepine levels and increase steady-state carbamazepine metabolite levels; may increase steady-state valproic acid levels |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Associated with marked increase in incidence of aplastic anemia (monitor CBC periodically); marked increase in fatal hepatic failure reported; perform liver function testing (ALT, AST, bilirubin) before felbamate therapy and at 1-2 wk intervals during therapy; discontinue immediately if liver abnormalities detected during treatment |
| Drug Name | Phenobarbital (Luminal) |
|---|---|
| Description | Exhibits anticonvulsant activity in anesthetic doses and can be administered orally. If IM route chosen, inject into one of large muscles such as gluteus maximus, vastus lateralis, or other areas where little risk of encountering nerve trunk or major artery. Injection into or near peripheral nerves may result in permanent neurological deficit. Restrict IV use to conditions in which other routes not feasible, either because patient unconscious, as in cerebral hemorrhage, eclampsia, or status epilepticus, or because prompt action imperative. |
| Adult Dose | 60-100 mg/d PO 200-320 mg IV/IM q6h prn |
| Pediatric Dose | 3 to 6 mg/kg/d PO4-6 mg/kg/d for 7-10 d IV/IM to blood level of 10-15 mcg/mL, or 10-15 mg/kg/d IV/IM |
| Contraindications | Documented hypersensitivity; severe respiratory disease; marked impairment of liver function; nephritis |
| Interactions | May decrease effects of chloramphenicol, digitoxin, corticosteroids, carbamazepine, theophylline, verapamil, metronidazole, and anticoagulants (patients with coagulation parameters stabilized on anticoagulants may require dosage adjustments if added to or withdrawn from their regimen); alcohol may produce additive CNS effects and death; chloramphenicol, valproic acid, and MAOIs may increase toxicity; rifampin may decrease effects; induction of microsomal enzymes may result in decreased effects of oral contraceptives in women (must use additional contraceptive methods to prevent unwanted pregnancy); menstrual irregularities also may occur |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | In prolonged therapy, evaluate hematopoietic, renal, hepatic, and other organ systems; caution in fever, hyperthyroidism, diabetes mellitus, and severe anemia since adverse reactions can occur; caution in myasthenia gravis and myxedema |
| Drug Name | Oxcarbazepine (Trileptal) |
|---|---|
| Description | Pharmacologic activity primarily by 10-monohydroxy metabolite (MHD). May block voltage-sensitive sodium channels, inhibit repetitive neuronal firing, and impair synaptic impulse propagation. Anticonvulsant effect may occur by affecting potassium conductance and high-voltage activated calcium channels. Drug pharmacokinetics similar in older children (>8 y) and adults. Young children ( <8 y) have 30-40% increased clearance compared with older children and adults. Children <2 years of age have not been studied in controlled clinical trials. |
| Adult Dose | Adjunctive therapy: 600 mg/d PO divided bid initially; may increase by maximum of 600 mg/d at weekly intervals; recommended daily dose 1200 mg/d; monitor patients for anticonvulsant adverse effects Conversion to monotherapy: 600 mg/d PO divided bid initially; gradually reduce dose of concomitant AEDs over about 3-6 wk and gradually increase oxcarbazepine dose over 2-4 wk; may increase oxcarbazepine dose as needed by maximum increment of 600 mg/d at weekly intervals; monitor patients closely during this transition phase for anticonvulsant adverse effects Initiation of monotherapy: 600 mg/d PO divided bid initially; increase dose by 300 mg/d PO every third day to 1200 mg/d; monitor patients for anticonvulsant adverse effects |
| Pediatric Dose | 4-16 years Adjunctive therapy: 8-10 mg/kg/d PO divided bid, not to exceed 600 mg/d; gradually increase to target dose over 2 wk; target dose based on body weight as follows: 20-29 kg: 900 mg/d PO 29.1-39 kg: 1200 mg/d PO >39 kg: 1800 mg/d PO |
| Contraindications | Documented hypersensitivity |
| Interactions | Can inhibit CYP2C19 and induce CYP3A4/5; cytochrome P-450 inducers can decrease plasma concentrations; may decrease levels of dihydropyridine calcium antagonists and oral contraceptives; can reduce serum concentrations of carbamazepine, phenobarbital, phenytoin, and valproic acid; when given in doses >1200 mg/d, may increase phenytoin and phenobarbital serum concentrations significantly; cytochrome P-450 enzymes such as carbamazepine, phenytoin, and phenobarbital can decrease MHD serum concentration by about 29%-40%; can reduce serum concentrations of oral contraceptives and make oral contraceptives ineffective; can increase clearance of felodipine; verapamil may reduce MHD serum levels |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Can cause cognitive adverse effects such as psychomotor slowing, impaired concentration, impaired speech, and impaired language; in persons with impaired renal function (CrCl <30 mL/min), dose should begin at one half usual starting dose, and dose increments should be made more slowly; can cause hyponatremia (sodium <125 mmol/L); among persons with hypersensitivity to carbamazepine, 25-30% will have hypersensitivity to oxcarbazepine; rapid withdrawal of oxcarbazepine can cause exacerbation of seizures; observe for adverse effects and monitor plasma levels of concomitant AEDs during dose titration |
Neuronal Ceroid Lipofuscinoses excerpt
Article Last Updated: Apr 24, 2006
