(Read Only) Camposano_Cardiology_book_temp 16/02/2010 10:11 Page 82
Epilepsy
Vigabatrin in the Treatment of Infantile Spasms
Susana E Camposano, MD
1
and Elizabeth A Thiele, MD, PhD
2
1. Instructor of Neurology, Harvard Medical School, and Research Coordinator, Herscot Center for Tuberous Sclerosis Complex,
Massachusetts General Hospital; 2. Associate Professor of Neurology, Harvard Medical School, and
Director, Pediatric Epilepsy Program, and Director, Herscot Center for Tuberous Sclerosis Complex, Massachusetts General Hospital
Abstract
Vigabatrin (VGB) is an effective treatment of infantile spasms (IS) that controls spasms of all etiologies in about 50% of patients when used as
monotherapy. In tuberous sclerosis complex, VGB controls spasms in up to 95% of patients and should be used as the drug of choice. Higher
VGB doses correlate with shorter times to response and higher response rates. Its most serious side effect is retinal toxicity characterized by
irreversible bilateral concentric constriction of the visual fields (BCCVF). Maximum VGB dose, total VGB dose, and duration of VGB treatment
constitute risk factors for BCCVF. In each particular patient, dose and duration of treatment should be kept at a minimum, while ensuring
effectiveness and preventing relapse. Every effort should be made to evaluate retinal function, even though it may require specialized
ophthalmological services. The addition of this new US Food and Drug Administration (FDA)-approved drug as an alternative in the treatment
of IS represents a major contribution to an armamentarium that contains only one other treatment.
Keywords
Vigabatrin, tuberous sclerosis complex, infantile spasms, visual field constriction, children, side effect
Disclosure: The authors have no conflicts of interest to declare.
Received: April 22, 2009 Accepted: October 20, 2009
Correspondence: Susana E Camposano, MD, Herscot Center for Tuberous Sclerosis Complex, Neurology Department, Massachusetts General Hospital, 175 Cambridge Street,
Suite 340, Boston, MA 02114. E:
scamposano@partners.org
Vigabatrin in Infantile Spasms When VGB is compared with hormonal (corticosteroid) treatment for
Vigabatrin (VGB) was only recently approved by the US Food and Drug IS, the response to hormonal treatment is faster and initially benefits
Administration (FDA) as monotherapy for infantile spasms (IS). a higher percentage of patients. However, assessed again at 14
Nonetheless, considerable experience is available, since VGB has months of age, patients exhibit comparable response rates as a result
been used for more than 10 years in other countries. The delay in of fewer subsequent relapses following VGB use.
7,14
Early studies had
approval in the US relates in part to its safety profile, since it can cause suggested that symptomatic IS respond better to VGB than idiopathic
irreversible retinal toxicity. IS,
15
particularly IS resulting from cerebral malformations.
16
These
results have not been replicated in the more recent studies.
VGB is an irreversible inhibitor of gamma-aminobutyric acid
transaminase (GABA-T), which has a favorable pharmacokinetic Cognitive outcomes overall seem to be similar with VGB or hormonal
profile since it is not metabolized by the liver, is excreted by the treatment, but infants with no known underlying cause have better
kidney, has low protein binding, and has a long effective half-life, cognitive outcomes following hormonal treatment.
9
On the other
allowing once- or twice-daily dosing. Interaction with other hand, superior cognitive outcome has been reported with VGB in
antiepileptic drugs is minimal.
1
TSC
17
and with other etiologies.
18
Ample evidence has been provided to support the use of VGB in the The exact dosing of VGB treatment is still being debated. Elterman
10
treatment of IS, and for many years European neurologists have established that in children receiving higher doses (100–148mg/
considered VGB to be the drug of choice for the symptomatic day versus 18–36mg/day), times to response were shorter and
treatment of IS.
2–4
Used as a first line of treatment in monotherapy, the response rates significantly higher. An earlier review of 20 patients
percentage of children who are rendered seizure-free averages found that some individuals responded to doses as low as 25mg/kg
around 50%.
5–10
Efficacy is lower in refractory cases, but still and suggested starting at a low dose and gradually increasing
approaches total control in 30% of children.
11,12
Tuberous sclerosis until IS control was achieved.
19
Since in some studies retinal
complex (TSC) represents a particularly successful story for the use of toxicity correlates with the highest VGB level, this risk has to be
VGB, since the drug controls spasms in up to 95% of patients.
10,11,13
weighed against the potential benefits of faster control of IS
82 © TOUCH BRIEFINGS 2009
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92 |
Page 93 |
Page 94 |
Page 95 |
Page 96 |
Page 97 |
Page 98 |
Page 99 |
Page 100