Acta Neurol Scand 2015: 132: 143–146 DOI: 10.1111/ane.12395
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd ACTA NEUROLOGICA SCANDINAVICA
Clinical Commentary
Eyelid myokymia in patients with migraine taking topiramate Medrano-Martınez V, Perez-Sempere A, Molt o-Jorda JM, FernandezIzquierdo S, Frances-Pont I, Mallada-Frechin J, Piqueras-Rodrıguez L. Eyelid myokymia in patients with migraine taking topiramate. Acta Neurol Scand 2015: 132: 143–146. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Objective – Although ocular side effects of topiramate are common, neuroophthalmologic manifestations such as blepharospasm, myokymia and oculogyric crisis are scarcely reported. Methods – We present a serie of 8 patients with migraine who developed eyelid myokymia after treatment with topiramate. We reviewed all patients with migraine treated with topiramate attending the headache outpatient clinic of our hospital from January 2008 to December 2012. Results – During the study period, a total of 140 patients with migraine were treated with topiramate in our headache clinic. Eight presented eyelid myokymia after beginning treatment with topiramate ( 5,7% ). Topiramate was stopped and myokymia disappeared in all patients, it was prescribed again and eyelid myokymia reappeared with their previous characteristics in all patients. Conclusions – Eyelid myokymia is an underreported side-effect of topiramate in patients with migraine, of unknown cause, so that in future, further studies are need to examine whether patients with migraine are predisposed or not to this adverse effect.
Introduction
Myokymia consists of involuntary, fine, and undulating fascicular contractions that spread across the affected striated muscle. The term myokymia is derived from the Greek word kyma, meaning wave. Myokymia is characterized electrophysiologically by rhythmic or semi-rhythmic bursts of a single motor unit discharging at a rate of 3–8 Hz. These spontaneous discharges are not initiated by voluntary movement, although they may increase with voluntary movement (1). Eyelid myokymia is typically unilateral and involves the orbicularis oculi muscle of one of the lower eyelids. In most cases, eyelid myokymia is benign and self-limited, occurring in normal individuals during periods of severe fatigue, stress, and physical exertion, as well as with excessive caffeine intake. Eyelid myokymia usually lasts for only a few days, although occasionally it persists for several weeks or even a few months before
V. Medrano-Martınez1, A. PerezSempere2, J. M. Molto-Jorda3, S. Fernandez-Izquierdo1, I. FrancesPont1, J. Mallada-Frechin1, L. Piqueras-Rodrıguez1 1 Department of Neurology, Hospital General Universitario Virgen De La Salud, Elda, Spain; 2 Department of Neurology, Hospital General Universitario De Alicante, Alicante, Spain; 3Department of Neurology, Hospital Verge Dels Lliris, Alcoi, Spain
Key words: migraine; topiramate; neuro-ophthalmologic manifestations; ocular side effects; isolated myokymia; eyelid myokymia V. Medrano-Martínez, Neurology department, Hospital general Universitario Virgen De La salud, Carretera Elda-Sax, s/n. Elda/Alicante. CP: 03600. Spain. Tel.: +34 966989000 Fax: +34 966989000 e-mail: [email protected] Accepted for publication February 23, 2015
resolving (2). Myokymia has been reported with the use of several drugs, such as flunarizine (3), clozapine (4), and gold salts (5). In a review of ocular side effects associated with topiramate use, two cases of blepharospasm and only one case of eyelid myokymia were reported (6). We present a series of 8 patients with migraines who developed eyelid myokymia after treatment with topiramate. Methods
After observing myokymia in two patients just spontaneously reporting it, we immediately began a retrospective study to determine the incidence of myokymia in patients with migraines during treatment with topiramate. We reviewed all patients with migraines treated with topiramate attending the headache outpatient clinic of our hospital from January 2008 to December 2012. We ask specifically for eyelid myokymia, but we include only those that had visible eyelid 143
Medrano-Martınez et al. unilateral, either right or left, but was bilateral in two of our patients. It affected only the lower portion of the orbicularis oculi muscle. All patients were being treated with topiramate as a monotherapy when they developed myokymia. Eyelid myokymia was noticed by the patients within the first month of treatment. Seven of the eight patients had never noticed eyelid myokymia before topiramate use. Brain MRI did not reveal significant abnormalities. Serum potassium and calcium levels and thyroid function test were within the normal range in all patients with myokymia. When topiramate was stopped, myokymia disappeared in all patients. Because the drug had been effective in the prevention of migraine, topiramate was prescribed again, and eyelid myokymia and its previous characteristics reappeared in all patients. Eyelid myokymia was well tolerated and did not lead to a withdrawal from topiramate in any patient.
myokymia. Migraine diagnosis was made according to the International Classification of Headache Disorders (ICHD-II). In our clinic, topiramate was used as a first-line drug to prevent migraines, along with propranolol and flunarizine. The initial dose was 25 mg once daily, with weekly 25 mg increases up to the recommended dose of 100 mg daily divided into 2 doses. If the patient did not tolerate 100 mg daily, a lower dose of 50 mg daily was used instead. Doses higher than 100 mg of topiramate were administered in selected cases. Patients who developed eyelid myokymia underwent brain neuroimaging studies and a blood test with serum potassium and calcium level, and thyroid function test. Eyelid myokymia was diagnosed clinically. The examinations were carried out retrospectively when the patients presented myokymia. Electrophysiological examinations (EMG) were not ‘performed. Four patients gave their consent to be videotaped. All patients remained on TPM after a rechallenge. The concomitant drugs were evaluated. Topiramate was stopped, and if myokymia subsided, a rechallenge with the drug was offered to the patient. It was a retrospective study and was not scrutinized necessarily by an independent ethics committee, but informed consent was obtained from each patient.
Discussion
Among nine trials of topiramate vs placebo, seven specific adverse events were reported in at least three trials: anorexia, fatigue, memory problems, nausea, paresthesia, taste disturbance, and weight loss. Although ocular side effects of topiramate are common, neuro-ophthalmological manifestations, such as blepharospasm, myokymia, and oculogyric crisis, are scarcely reported (7). In a review of 115 patients with ocular side effects associated with topiramate use, there was only one case of eyelid myokymia with a positive rechallenge (6). In our study, 5.7% of patients with migraines treated with topiramate developed this side effect, suggesting that it is underreported. Considering the temporal relationship between the administration of topiramate and the appearance
Results
During the study period, a total of 140 patients with migraines were treated with topiramate in our headache clinic. Eight presented eyelid myokymia after beginning treatment with topiramate. They had a mean age of 39 years, seven were women, and all were of Caucasian origin. Their clinical characteristics are summarized in Table 1. The location of myokymia was primarily
Table 1 Demographic and clinical features of the patients with eyelid myokymia related to topiramate Patient number
1
2
3
4
5
6
7
40 F Episodic whit aura
39 F Chronic whit aura
41 F Chronic
Bilateral Intermittent None Normal 50
Alternating Continuous Paresthesias Normal 100
Right Continuous None Normal 150
4.3
4.5
3.8
Age (years) Sex Type of migraine
43 F Chronic
34 F Chronic
46 F Chronic
33 F Episodic
Eyelid myokymia Myokymia quality Other adverse effects Brain MRI Daily topiramate dose (mg) Serum potassium level (mEq/l)
Left Continuous Paresthesias Normal 100
Right Intermittent None Normal 100
Bilateral Intermittent Paresthesias Normal 200
Right Continuous Dysgeusia paresthesias Normal 100
38 M Episodic whit aura Left Continuous None Normal 50
4.6
4.4
4.1
4.7
3.9
F, female; M, male.
144
8
Eyelid myokymia and topiramate of myokymia, as well as the responses to withdrawal of the drug and to the positive rechallenge, we consider eyelid myokymia to be a probable side effect of topiramate. Brain neuroimaging studies and blood tests showed no evidence supporting alternative causes of eyelid myokymia. It is important to note that this side effect was well tolerated and did not cause a withdrawal from topiramate in any patient. The cause of isolated eyelid myokymia is not well defined. The chronic, localized nature of the process and the absence of a progression to other ipsilateral facial muscle groups suggest that the lesion is peripheral. However, no electrophysiological studies have been performed on this particular subset of patients to confirm that myokymia is caused by a peripheral lesion (2). The underlying cause of myokymia most likely involves a biochemical change in the microenvironment and/or the membranes of motor axons (8). The disorders that produce myokymia affect motor axons through mechanisms that include autoimmune processes, genetic changes, radiation, demyelination, toxic effects, ischemia, hypoxia, and edema. Voltage-gated potassium channels are widespread throughout the peripheral, autonomic, and central nervous systems and play a key role in controlling neuronal excitability (9). Peripheral nerve hyperexcitability may be immunological (10); genetic, such as in episodic ataxia/myokymia syndrome associated with mutations in the human potassium channel gene, KCNA1 (11); toxic, as in the case of rattlesnake envenomation (12); and pharmacological in response to drugs, such as flunarizine (3), clozapine (4), and gold salts (5). Flunarizine is a piperazine derivate and a highly selective T-type calcium channel antagonist that is used to prevent migraines and vertigo. There was a report of acquired peripheral nerve hyperexcitability syndrome associated with flunarizine treatment. This response was suggested to be related to a blocking effect on voltage-gated K–current, similar to the effect of dihydropyridine, an L-type calcium channel antagonist (3, 13). Clozapine is a calmodulin antagonist, whereas calmodulin regulates calcium uptake and the activity of certain kinases (4). Topiramate is a sulfamate-substituted monosaccharide that is used to treat epilepsy and for migraine headache prophylaxis. It acts through several mechanisms: blocking neuronal voltagedependent sodium channels while acting on high-voltage activated (L-type) Ca2+ channels, enhancing GABA(A) activity, antagonizing AMPA/ kainate glutamate receptors, inhibiting carbonic anhydrase, and increasing potassium conductance
(14). Topiramate use is linked with the development of acidosis, hypokalemia, hyperuricemia, and hypocitraturia (15). Although topiramate, directly or indirectly, acts on calcium and potassium channels related to myokymia, the exact cause of myokymia in these patients is unknown. In conclusion, eyelid myokymia is an underreported side effect of topiramate in patients with migraines of unknown cause. Further studies should examine whether patients with migraines are predisposed to this adverse effect. Clinical relevance summary
-The article is clinically based. -Eyelid myokymia is benign and self-limited. -Myokymia has been reported with the use of several drugs, such as flunarizine, clozapine, and gold salts. -Although ocular side effects of topiramate are common, neuro-ophthalmological manifestations, such as blepharospasm, myokymia, and oculogyric crisis, are scarcely reported. -In our study, 5.7% of patients with migraines treated with topiramate developed this side effect, suggesting that it is underreported. -Although topiramate, directly or indirectly, acts on calcium and potassium channels related to myokymia, the exact cause of myokymia in these patients is unknown.
Acknowledgment The author would like to acknowledge the following individuals for their contribution to the research: Dr. Julio Pascual, Director Area de Neurociencias and Profesor Titular, Neurologıa Hospital Universitario Central de Asturias ( Oviedo ).
Contributorship statement V. Medrano-Martınez participated in research project, statistical analysis, and manuscript preparation. A. Perez-Sempere participated in research project, statistical analysis, and manuscript preparation. J.M. Molt o-Jord a participated in statistical analysis and manuscript preparation. S. Fern andezIzquierdo, I. Frances-Pont, J. Mallada-Frechin, and L. Piqueras-Rodrıguez participated in manuscript preparation.
Conflict of interest and disclosure The authors declare that there are not additional disclosures to report.
Funding No specific funding was received for this work, and the author declares that there are not conflict of interests relevant to this work.
145
Medrano-Martınez et al. Supporting Information Additional Supporting Information may be found in the online version of this article. Video S1. Myokymia 1. Video S2. Myokymia 2.
References 1. MILLER NR. Eyelid Myokymia. Surv Ophthal 2011;2:277. 2. BANIK R, MILLER NR. Chronic myokymia limited to the eyelid is a benign condition. J Neuroophthalmol 2004;24:290–2. 3. KIZILAY F, EKMEKCI B, GUNGOR H, UYSAL H. Flunarizine-induced fasciculation myokymia. J Clin Neuromuscul Dis 2011;12:246–7. 4. DAVID WS, SHARIF AA. Clozapine-induced myokymia. Muscle Nerve 1998;21:827–8. 5. NICHOLSON D, SCALETTAR R, JACOBS RP. Rheumatoid rigor: gold induced myokymia. A report and review of the literature. J Rheumatol 1986;13:195–6. 6. FRAUNFELDER FW, FRAUNFELDER FT, KEATES EU. Topiramate-associated acute, bilateral, secondary angle-closure glaucoma. Ophthalmology 2004;111:109–11. 7. ABTAHI MA, ABTAHI SH, FAZEL F et al. Topiramate and the vision: a systematic review. Clin Ophthalmol 2012;6:117–31.
146
8. GUTMANN L, GUTMANN L. Myokymia and neuromyotonia 2004. J Neurol 2004;251:138–42. 9. HART IK, MADDISON P, NEWSOM-DAVIS J, VINCENT A, MILLS KR. Phenotypic variants of autoimmune peripheral nerve hyperexcitability. Brain 2002;125:1887–95. 10. MADDISON P, VINCENT A, MILLS K, DAVIS CF. Persistent facial myokymia: an autoimmune aetiology? J Neurol 2000;247:554–5. 11. BROWNE DL, GANCHER ST, NUTT JG et al. Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium cannel gene KCNA1. Nat Genet 1994;8:136–40. 12. VOHRA R, CANTRELL FL, WILLIAMS SR. Fasciculations after rattlesnake envenomations: a retrospective statewide poison control system study. Clin Toxicol 2008;46:117– 21. 13. ZHANG XL, GOLD MS. Dihydropyridine block of voltage-dependent K+ currents in rat dorsal root ganglion neurons. Neuroscience 2009;161:184–94. 14. PORTER RJ, MELDRUM BS. Chapter 24. Antiseizure Drugs. In: KATZUNG BG, MASTERS SB, TREVOR AJ, eds. Basic & Clinical Pharmacology, 12e. New York, NY: McGraw-Hill, 2012;403–427. 15. DELL’ORTO VG, BELOTTI EA, GOEGGEL-SIMONETTI B et al. Metabolic disturbances and renal stone promotion on treatment with topiramate: a systematic review. Br J Clin Pharmacol 2013;77:958–64.
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd ACTA NEUROLOGICA SCANDINAVICA
Clinical Commentary
Eyelid myokymia in patients with migraine taking topiramate Medrano-Martınez V, Perez-Sempere A, Molt o-Jorda JM, FernandezIzquierdo S, Frances-Pont I, Mallada-Frechin J, Piqueras-Rodrıguez L. Eyelid myokymia in patients with migraine taking topiramate. Acta Neurol Scand 2015: 132: 143–146. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Objective – Although ocular side effects of topiramate are common, neuroophthalmologic manifestations such as blepharospasm, myokymia and oculogyric crisis are scarcely reported. Methods – We present a serie of 8 patients with migraine who developed eyelid myokymia after treatment with topiramate. We reviewed all patients with migraine treated with topiramate attending the headache outpatient clinic of our hospital from January 2008 to December 2012. Results – During the study period, a total of 140 patients with migraine were treated with topiramate in our headache clinic. Eight presented eyelid myokymia after beginning treatment with topiramate ( 5,7% ). Topiramate was stopped and myokymia disappeared in all patients, it was prescribed again and eyelid myokymia reappeared with their previous characteristics in all patients. Conclusions – Eyelid myokymia is an underreported side-effect of topiramate in patients with migraine, of unknown cause, so that in future, further studies are need to examine whether patients with migraine are predisposed or not to this adverse effect.
Introduction
Myokymia consists of involuntary, fine, and undulating fascicular contractions that spread across the affected striated muscle. The term myokymia is derived from the Greek word kyma, meaning wave. Myokymia is characterized electrophysiologically by rhythmic or semi-rhythmic bursts of a single motor unit discharging at a rate of 3–8 Hz. These spontaneous discharges are not initiated by voluntary movement, although they may increase with voluntary movement (1). Eyelid myokymia is typically unilateral and involves the orbicularis oculi muscle of one of the lower eyelids. In most cases, eyelid myokymia is benign and self-limited, occurring in normal individuals during periods of severe fatigue, stress, and physical exertion, as well as with excessive caffeine intake. Eyelid myokymia usually lasts for only a few days, although occasionally it persists for several weeks or even a few months before
V. Medrano-Martınez1, A. PerezSempere2, J. M. Molto-Jorda3, S. Fernandez-Izquierdo1, I. FrancesPont1, J. Mallada-Frechin1, L. Piqueras-Rodrıguez1 1 Department of Neurology, Hospital General Universitario Virgen De La Salud, Elda, Spain; 2 Department of Neurology, Hospital General Universitario De Alicante, Alicante, Spain; 3Department of Neurology, Hospital Verge Dels Lliris, Alcoi, Spain
Key words: migraine; topiramate; neuro-ophthalmologic manifestations; ocular side effects; isolated myokymia; eyelid myokymia V. Medrano-Martínez, Neurology department, Hospital general Universitario Virgen De La salud, Carretera Elda-Sax, s/n. Elda/Alicante. CP: 03600. Spain. Tel.: +34 966989000 Fax: +34 966989000 e-mail: [email protected] Accepted for publication February 23, 2015
resolving (2). Myokymia has been reported with the use of several drugs, such as flunarizine (3), clozapine (4), and gold salts (5). In a review of ocular side effects associated with topiramate use, two cases of blepharospasm and only one case of eyelid myokymia were reported (6). We present a series of 8 patients with migraines who developed eyelid myokymia after treatment with topiramate. Methods
After observing myokymia in two patients just spontaneously reporting it, we immediately began a retrospective study to determine the incidence of myokymia in patients with migraines during treatment with topiramate. We reviewed all patients with migraines treated with topiramate attending the headache outpatient clinic of our hospital from January 2008 to December 2012. We ask specifically for eyelid myokymia, but we include only those that had visible eyelid 143
Medrano-Martınez et al. unilateral, either right or left, but was bilateral in two of our patients. It affected only the lower portion of the orbicularis oculi muscle. All patients were being treated with topiramate as a monotherapy when they developed myokymia. Eyelid myokymia was noticed by the patients within the first month of treatment. Seven of the eight patients had never noticed eyelid myokymia before topiramate use. Brain MRI did not reveal significant abnormalities. Serum potassium and calcium levels and thyroid function test were within the normal range in all patients with myokymia. When topiramate was stopped, myokymia disappeared in all patients. Because the drug had been effective in the prevention of migraine, topiramate was prescribed again, and eyelid myokymia and its previous characteristics reappeared in all patients. Eyelid myokymia was well tolerated and did not lead to a withdrawal from topiramate in any patient.
myokymia. Migraine diagnosis was made according to the International Classification of Headache Disorders (ICHD-II). In our clinic, topiramate was used as a first-line drug to prevent migraines, along with propranolol and flunarizine. The initial dose was 25 mg once daily, with weekly 25 mg increases up to the recommended dose of 100 mg daily divided into 2 doses. If the patient did not tolerate 100 mg daily, a lower dose of 50 mg daily was used instead. Doses higher than 100 mg of topiramate were administered in selected cases. Patients who developed eyelid myokymia underwent brain neuroimaging studies and a blood test with serum potassium and calcium level, and thyroid function test. Eyelid myokymia was diagnosed clinically. The examinations were carried out retrospectively when the patients presented myokymia. Electrophysiological examinations (EMG) were not ‘performed. Four patients gave their consent to be videotaped. All patients remained on TPM after a rechallenge. The concomitant drugs were evaluated. Topiramate was stopped, and if myokymia subsided, a rechallenge with the drug was offered to the patient. It was a retrospective study and was not scrutinized necessarily by an independent ethics committee, but informed consent was obtained from each patient.
Discussion
Among nine trials of topiramate vs placebo, seven specific adverse events were reported in at least three trials: anorexia, fatigue, memory problems, nausea, paresthesia, taste disturbance, and weight loss. Although ocular side effects of topiramate are common, neuro-ophthalmological manifestations, such as blepharospasm, myokymia, and oculogyric crisis, are scarcely reported (7). In a review of 115 patients with ocular side effects associated with topiramate use, there was only one case of eyelid myokymia with a positive rechallenge (6). In our study, 5.7% of patients with migraines treated with topiramate developed this side effect, suggesting that it is underreported. Considering the temporal relationship between the administration of topiramate and the appearance
Results
During the study period, a total of 140 patients with migraines were treated with topiramate in our headache clinic. Eight presented eyelid myokymia after beginning treatment with topiramate. They had a mean age of 39 years, seven were women, and all were of Caucasian origin. Their clinical characteristics are summarized in Table 1. The location of myokymia was primarily
Table 1 Demographic and clinical features of the patients with eyelid myokymia related to topiramate Patient number
1
2
3
4
5
6
7
40 F Episodic whit aura
39 F Chronic whit aura
41 F Chronic
Bilateral Intermittent None Normal 50
Alternating Continuous Paresthesias Normal 100
Right Continuous None Normal 150
4.3
4.5
3.8
Age (years) Sex Type of migraine
43 F Chronic
34 F Chronic
46 F Chronic
33 F Episodic
Eyelid myokymia Myokymia quality Other adverse effects Brain MRI Daily topiramate dose (mg) Serum potassium level (mEq/l)
Left Continuous Paresthesias Normal 100
Right Intermittent None Normal 100
Bilateral Intermittent Paresthesias Normal 200
Right Continuous Dysgeusia paresthesias Normal 100
38 M Episodic whit aura Left Continuous None Normal 50
4.6
4.4
4.1
4.7
3.9
F, female; M, male.
144
8
Eyelid myokymia and topiramate of myokymia, as well as the responses to withdrawal of the drug and to the positive rechallenge, we consider eyelid myokymia to be a probable side effect of topiramate. Brain neuroimaging studies and blood tests showed no evidence supporting alternative causes of eyelid myokymia. It is important to note that this side effect was well tolerated and did not cause a withdrawal from topiramate in any patient. The cause of isolated eyelid myokymia is not well defined. The chronic, localized nature of the process and the absence of a progression to other ipsilateral facial muscle groups suggest that the lesion is peripheral. However, no electrophysiological studies have been performed on this particular subset of patients to confirm that myokymia is caused by a peripheral lesion (2). The underlying cause of myokymia most likely involves a biochemical change in the microenvironment and/or the membranes of motor axons (8). The disorders that produce myokymia affect motor axons through mechanisms that include autoimmune processes, genetic changes, radiation, demyelination, toxic effects, ischemia, hypoxia, and edema. Voltage-gated potassium channels are widespread throughout the peripheral, autonomic, and central nervous systems and play a key role in controlling neuronal excitability (9). Peripheral nerve hyperexcitability may be immunological (10); genetic, such as in episodic ataxia/myokymia syndrome associated with mutations in the human potassium channel gene, KCNA1 (11); toxic, as in the case of rattlesnake envenomation (12); and pharmacological in response to drugs, such as flunarizine (3), clozapine (4), and gold salts (5). Flunarizine is a piperazine derivate and a highly selective T-type calcium channel antagonist that is used to prevent migraines and vertigo. There was a report of acquired peripheral nerve hyperexcitability syndrome associated with flunarizine treatment. This response was suggested to be related to a blocking effect on voltage-gated K–current, similar to the effect of dihydropyridine, an L-type calcium channel antagonist (3, 13). Clozapine is a calmodulin antagonist, whereas calmodulin regulates calcium uptake and the activity of certain kinases (4). Topiramate is a sulfamate-substituted monosaccharide that is used to treat epilepsy and for migraine headache prophylaxis. It acts through several mechanisms: blocking neuronal voltagedependent sodium channels while acting on high-voltage activated (L-type) Ca2+ channels, enhancing GABA(A) activity, antagonizing AMPA/ kainate glutamate receptors, inhibiting carbonic anhydrase, and increasing potassium conductance
(14). Topiramate use is linked with the development of acidosis, hypokalemia, hyperuricemia, and hypocitraturia (15). Although topiramate, directly or indirectly, acts on calcium and potassium channels related to myokymia, the exact cause of myokymia in these patients is unknown. In conclusion, eyelid myokymia is an underreported side effect of topiramate in patients with migraines of unknown cause. Further studies should examine whether patients with migraines are predisposed to this adverse effect. Clinical relevance summary
-The article is clinically based. -Eyelid myokymia is benign and self-limited. -Myokymia has been reported with the use of several drugs, such as flunarizine, clozapine, and gold salts. -Although ocular side effects of topiramate are common, neuro-ophthalmological manifestations, such as blepharospasm, myokymia, and oculogyric crisis, are scarcely reported. -In our study, 5.7% of patients with migraines treated with topiramate developed this side effect, suggesting that it is underreported. -Although topiramate, directly or indirectly, acts on calcium and potassium channels related to myokymia, the exact cause of myokymia in these patients is unknown.
Acknowledgment The author would like to acknowledge the following individuals for their contribution to the research: Dr. Julio Pascual, Director Area de Neurociencias and Profesor Titular, Neurologıa Hospital Universitario Central de Asturias ( Oviedo ).
Contributorship statement V. Medrano-Martınez participated in research project, statistical analysis, and manuscript preparation. A. Perez-Sempere participated in research project, statistical analysis, and manuscript preparation. J.M. Molt o-Jord a participated in statistical analysis and manuscript preparation. S. Fern andezIzquierdo, I. Frances-Pont, J. Mallada-Frechin, and L. Piqueras-Rodrıguez participated in manuscript preparation.
Conflict of interest and disclosure The authors declare that there are not additional disclosures to report.
Funding No specific funding was received for this work, and the author declares that there are not conflict of interests relevant to this work.
145
Medrano-Martınez et al. Supporting Information Additional Supporting Information may be found in the online version of this article. Video S1. Myokymia 1. Video S2. Myokymia 2.
References 1. MILLER NR. Eyelid Myokymia. Surv Ophthal 2011;2:277. 2. BANIK R, MILLER NR. Chronic myokymia limited to the eyelid is a benign condition. J Neuroophthalmol 2004;24:290–2. 3. KIZILAY F, EKMEKCI B, GUNGOR H, UYSAL H. Flunarizine-induced fasciculation myokymia. J Clin Neuromuscul Dis 2011;12:246–7. 4. DAVID WS, SHARIF AA. Clozapine-induced myokymia. Muscle Nerve 1998;21:827–8. 5. NICHOLSON D, SCALETTAR R, JACOBS RP. Rheumatoid rigor: gold induced myokymia. A report and review of the literature. J Rheumatol 1986;13:195–6. 6. FRAUNFELDER FW, FRAUNFELDER FT, KEATES EU. Topiramate-associated acute, bilateral, secondary angle-closure glaucoma. Ophthalmology 2004;111:109–11. 7. ABTAHI MA, ABTAHI SH, FAZEL F et al. Topiramate and the vision: a systematic review. Clin Ophthalmol 2012;6:117–31.
146
8. GUTMANN L, GUTMANN L. Myokymia and neuromyotonia 2004. J Neurol 2004;251:138–42. 9. HART IK, MADDISON P, NEWSOM-DAVIS J, VINCENT A, MILLS KR. Phenotypic variants of autoimmune peripheral nerve hyperexcitability. Brain 2002;125:1887–95. 10. MADDISON P, VINCENT A, MILLS K, DAVIS CF. Persistent facial myokymia: an autoimmune aetiology? J Neurol 2000;247:554–5. 11. BROWNE DL, GANCHER ST, NUTT JG et al. Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium cannel gene KCNA1. Nat Genet 1994;8:136–40. 12. VOHRA R, CANTRELL FL, WILLIAMS SR. Fasciculations after rattlesnake envenomations: a retrospective statewide poison control system study. Clin Toxicol 2008;46:117– 21. 13. ZHANG XL, GOLD MS. Dihydropyridine block of voltage-dependent K+ currents in rat dorsal root ganglion neurons. Neuroscience 2009;161:184–94. 14. PORTER RJ, MELDRUM BS. Chapter 24. Antiseizure Drugs. In: KATZUNG BG, MASTERS SB, TREVOR AJ, eds. Basic & Clinical Pharmacology, 12e. New York, NY: McGraw-Hill, 2012;403–427. 15. DELL’ORTO VG, BELOTTI EA, GOEGGEL-SIMONETTI B et al. Metabolic disturbances and renal stone promotion on treatment with topiramate: a systematic review. Br J Clin Pharmacol 2013;77:958–64.
