Spasm, infantile

Drugs with unknown mechanism of action are gabapentin, bromides (but see above effects on GABAergic transmission) and adrenocorticotropic hormone (ACTH), which is used in infantile spasms. 

Historically the only melanocortin peptide to be used clinically is the parent hormone from which all these peptides are derived from namely ACTH (see above). It has also been used in the treatment infantile spasms for epilepsy, where it is administered as an intramuscular injection only over a 2-12 weeks period. Obvious side effects include weight gain, puffy face, high blood pressure and an increased risk of infection and should never be administered to patients with diabetics, renal or heart failure. ACTH is also used as a stimulation test to measure adrenal cortex activity, i.e. production of cortisol and is used to ascertain whether someone has Addison s disease. 

Infantile spasms A seizure syndrome that occurs in infants less than 1 year of age. It is characterized by a specific EEG pattern and spasms or jitters and is also known as West s syndrome. Infants with infantile spasms often develop other seizure types and epilepsies later in life. 

Clinically, ACTH stimulation of the adrenals is used diagnostically to detect adrenal insufficiency plasma cortisol levels are measured before and 60 minutes following an intravenous injection of cosyntropin. Adrenocortical insufficiency is known as Addison s disease Addison s classic description, in 1855, namely general debility, remarkable feebleness of the heart, irritability of the stomach, and a peculiar change of the colour of the skin , summarizes the clinical features of this disease, which is uniformly fatal if undetected and untreated. Therapeutically, corticotropin therapy has been essentially abandoned in favor of the direct administration of glucocorticoids. However, ACTH is still rarely used in the treatment of the infantile spasm seizure disorder. 

It is indicated in typical and atypical absence seizure, infantile spasms, myoclonic epilepsy, atonic seizures, minor motor seizures of childhood, refractory grandmal epilepsy or temporal lobe epilepsy and seizures not controlled by conventional antiepileptics. 

It is a benzodiazepine useful in the treatment of petitmal epilepsy, myoclonic seizures and infantile spasms. It is used in the treatment of petitmal epilepsy not responding to ethosuximide and sodium valproate. Clonazepam and diazepam act by increasing the effectiveness of the inhibitory neurotransmitter GABA, within the central nervous system. 

An epileptic syndrome rather than a specific seizure type drugs useful in infantile spasms will be reviewed separately. 

Phenobarbital is useful in the treatment of partial seizures and generalized tonic-clonic seizures, although the drug is often tried for virtually every seizure type, especially when attacks are difficult to control. There is little evidence for its effectiveness in generalized seizures such as absence, atonic attacks, and infantile spasms it may worsen certain patients with these seizure types. 

Clonazepam As for diazepam >80% bioavailability extensively metabolized but no active metabolites fiy2 20-50 h Absence seizures, myoclonic seizures, infantile spasms Toxicity Similar to diazepam Interactions Minimal... 

Clobazam Indications include absence seizures, myoclonic seizures, infantile spasms ... 

Vigabatrin Irreversibly inhibits GABA-transaminase 70% bioavailable not bound to plasma proteins not metabolized, ti/2 5-7 h (not relevant because of mechanism of action) Partial seizures, infantile spasms Toxicity Drowsiness, dizziness, psychosis, visual field loss Interactions Minimal... 

Elterman RD et al Randomized trial of vigabatrin in patients with infantile spasms. Neurology 2001 57 1416. 

Desmodium triquetrum (L.) DC Hu Lu Cao (leaf) Potassium oxide, silicic acid, tannins.50-60 A tonic for dyspepsia, hemorrhoids, infantile spasms, insecticide, vermicide. 

Drowsiness, hypotonia, and irritability were observed in 37% of infants given corticotropin in a randomized comparison of corticotropin with vigabatrin in the treatment of infantile spasms (SEDA-22, 442 11). 

Renal calcinosis can develop as a result of hypercalciuria and is a major concern in the treatment of infantile spasms with corticotropin. In 16 infants, corticotropin, often associated with anticonvulsants, results in increased urinary excretion of calcium and phosphate, with increased parathormone serum concentrations and in some cases generalized aminoaciduria (26). This makes it imperative that the dose of corticotropin and the duration of treatment be kept to the minimum required to ensure efficacy. In one case in which calcified stones were removed surgically, recurrence was apparently prevented, despite the presence of a Cushingoid state, by long-term chlorothiazide (27). 

Hiraishi S, Iwanami N, Ogawa N. Images in cardiology. Enlargement of cardiac rhabdomyoma and myocardial ischaemia during corticotropin treatment for infantile spasm. Heart 2000 84(2) 170. 

Hrachovy RA, Frost JD Jr, Glaze DG. High-dose, long-duration versus low-dose, short-duration corticotropin therapy for infantile spasms. J Pediatr 1994 124(5 Pt l) 803-6. 

Konishi Y, Yasujima M, Kuriyama M, Konishi K, Hayakawa K, Fujii Y, Ishii Y, Sudo M. Magnetic resonance imaging in infantile spasms effects of hormonal therapy. Epilepsia 1992 33(2) 304-9. 

Konishi Y, Hayakawa K, Kuriyama M, Saito M, Fujii Y, Sudo M. Effects of ACTH on brain midline structures in infants with infantile spasms. Pediatr Neurol 1995 13(2) 134-6. 

Vigevano F, Cilio MR. Vigabatrin versus ACTH as first-line treatment for infantile spasms a randomized, prospective study. Epilepsia 1997 38(12) 1270-4. 

Liebling MS, Stare TJ, McAlister WH, Ruzal-Shapiro CB, Abramson SJ, Berdon WE. ACTH induced adrenal enlargement in infants treated for infantile spasms and acute cerebellar encephalopathy. Pediatr Radiol 1993 23(6) 454-6. 

Perheentupa J. Disturbed calcium and phosphate homeostasis during treatment with ACTH of infantile spasms. Arch Dis Child 1986 61(7) 671-6. 

Dunagan DP, Rubin BK, Fasano MB. Pneumocystis carinii pneumonia in a child receiving ACTH for infantile spasms. Pediatr Pulmonol 1999 27(4) 286-9. 

Vigabatrin is used as an adjunctive antiepileptic in patients with resistant partial epilepsy with or without secondary generalization, unresponsive to other therapy [2]. Nowadays, vigabatrin is rarely used in the treatment of partial seizures due to several irreversible visual field constrictions associated with its chronic use [57-62], It is regarded by many authorities as a drug of choice in infants with west syndrome (infantile spasms), particularly in cases associated with tuberous sclerosis [62],... 

The recommended initial dose of vigabatrin as adjunctive therapy in adults is 1.0 g daily by mouth, increased if necessary in increments of 0.5 g at weekly intervals to a maximum of 3.0 g daily. A recommended initial dose in children is 40 mg/kg body-weight daily. For infantile spasms the dose is from 50 mg to 150 mg/kg daily [2]. 

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