Oligohydrosis and Hyperthermia: Pilot Study of a Novel Topiramate Adverse Effect

Lee

et al. 2010

E&S

Purpose: To investigate the effectiveness and tolerability of topiramate (TPM) in treating children with CNS anomalies and intractable epilepsy. Methods: We retrospectively searched the patient database in National Taiwan University Hospital for candidate children (younger than 18 years of age) with epilepsy and CNS anomalies from December 2002 to February 2004. The effectiveness and possible side effects of TPM were evaluated by questionnaire. Results: Twenty-two children (9 males, 13 females) aged from five months to fourteen years were enrolled in the present study. Underlying CNS anomalies were proliferation disorders (n=10), migration/organization disorders (n=10), and neurocutaneous syndromes (n=2). Types of epilepsy at TPM add-on were symptomatic partial epilepsy (n=11), infantile spasms (n=7), and Lennox-Gastaut syndrome (n=4). During the follow-up periods of six to 30 months, eight patients (36%) had more than 50% reduction of seizures and four patients (18%) were seizure-free. The average dosages

“…Oligohidrosis or hypohidrosis has been reported in patients taking TPM [26][27][28]. The incidence of hypohidrosis in the present study, however, was higher.…”

Section: Discussioncontrasting

confidence: 55%

Clinical experience with open-label topiramate use in epileptic children with CNS anomalies

Lee

et al. 2010

E&S

“…Long-term topiramate stimulation resulted in a reduction in the number of reactive sweat glands, without changes in sweat gland innervation, suggesting that the diminished responsiveness of the glands to heat exposure induced by topiramate might have resulted from a decrease in the intrinsic regulatory activity of sweat glands, as opposed to the loss of periglandular neurotransmitters or the impairment of the structure of the glands. [12][13][14][15][16][17]. While the effect was reversible, and disappeared with the cessation of the treatment, the mechanism underlying this effect on sweating has not been fully elucidated.…”

mentioning

confidence: 99%

“…It possesses a broad spectrum of anticonvulsant activity, mainly through the following mechanisms: attenuation of voltage-gated Na + currents [3]; negative modulatory effects on AMPA/KA subtype of glutamate receptors [4,5]; inhibition of glutamate and aspartate release from the nerve terminal [6]; inhibition of carbonic anhydrase (CA) isozymes, particularly, CA II and CA IV [7]; enhancement of γ -amino butyric acid A-mediated neurotransmission [8,9]; modulatory effects on K + channel currents [10] and inhibition of neuronal L-type high voltage-activated Ca 2+ channels [11]. Heat intolerance with hypohidrosis or anhidrosis has been recently reported in children undergoing epilepsy treatment with topiramate [12][13][14][15][16][17]. While the effect was reversible, and disappeared with the cessation of the treatment, the mechanism underlying this effect on sweating has not been fully elucidated.…”

mentioning

confidence: 99%

Effects of Topiramate on Mouse Eccrine Sweat Gland Responsiveness to Heat Exposure

Jiyu¹,

Huang²,

Deng³

et al. 2007

Basic Clin Pharma Tox

Young mice (2 weeks old) were given topiramate daily for 1 month, and sudomotor function was evaluated utilizing impression mould techniques to determine the number of sweat glands reactive to heat exposure and sweat output per gland on the plantar surface of mice hind-paws. Immunohistochemical quantitation of protein gene product 9.5, choline acetyltransferase and tyrosine hydroxylase in footpads was determined after topiramate treatment. While a 25% decrease in the number of secreting sweat glands and a 42% decline in sweat output per gland were observed following topiramate treatment, no significant differences were noted in sudomotor innervation, expressed as length of choline acetyltransferase, tyrosine hydroxylase and protein gene product 9.5 immunoreactive nerve profiles in single secretory coils or in sweat gland sizes within the secretory coil area. Long-term topiramate stimulation resulted in a reduction in the number of reactive sweat glands, without changes in sweat gland innervation, suggesting that the diminished responsiveness of the glands to heat exposure induced by topiramate might have resulted from a decrease in the intrinsic regulatory activity of sweat glands, as opposed to the loss of periglandular neurotransmitters or the impairment of the structure of the glands. [12][13][14][15][16][17]. While the effect was reversible, and disappeared with the cessation of the treatment, the mechanism underlying this effect on sweating has not been fully elucidated. The ability of human beings to dissipate heat during exercise and in hot environments depends mainly on the evaporation of sweat secreted by eccrine sweat glands. Consequently, sweat production is essential for heat tolerance, preventing hyperthermia, and influences performance during physical activity [18]. Sweat glands are innervated by sympathetic postganglionic axons, which, in contrast to the ordinary sympathetic innervation, use acetylcholine as the principal neurotransmitter [19][20][21].In the current study, we investigated the effects of topiramate on the responsiveness of mouse eccrine sweat glands to heat exposure and evaluated sudomotor function utilizing silicone imprints, a method that allows accurate quantitation of sweat gland secretion repeatedly over time, and following different types of nerve lesions or treatments [22][23][24][25][26][27]. Additionally, immunolabelling was used to examine the effects of topiramate on choline acetyltransferase (ChAT) in cholinergic sudomotor nerves, tyrosine hydroxylase (TH) in noradrenalinergic nerves, as well as total innervation of sweat glands (protein gene product 9.5, PGP9.5) and sweat gland acinar size. The aim of this study was to investigate whether topiramate reduced the responsiveness of the glands to heat exposure in mice, and whether the effects on the eccrine sweat glands were related to changes in periglandular neurotransmitters and/or sweat gland structure. Materials and MethodsExperimental design. Animals were housed under standard conditions with water and foo...

“…Pilocarpine iontophoresis has been used to document minimal sweat production in a young infant with recurrent hyperthermia [8]. Similar utility of the technique has been in the detection of oligohydrosis in children with hyperthermia who were on topiramate therapy [9].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Sweat Production by Pilocarpine Iontophoresis: A Noninvasive Screening Tool for Hypohidrosis in Ectodermal Dysplasia

2013

Ectodermal dysplasia (ED) is a genetic disorder affecting the skin, hair, nails, teeth and sweat glands. The clinical presentation is heterogenous; however, hypohidrotic (reduced sweat) ectodermal dysplasia (HED) being the commonest. Also known as anhidrotic ED, sweat glands are sparse or rudimentary, leading to dysregulation of body temperature and episodes of uncontrolled hyperthermia due to reduced sweating. Of the many aids to document hypohidrosis in HED, we present here the technique of pilocarpine iontophoresis to induce, collect and measure sweat. Evaluation of sweat generated (against normally obtained values) is a non-invasive alternative to establish hypohidrosis in disorders such as HED. This augments clinical decision levels to plan skin biopsy for confirmation of diagnosis and facilitates patient management and early discharge. We present two cases of HED that were primarily diagnosed with sweat gland dysplasia using pilocarpine iontophoresis, and later confirmed with skin biopsy findings.