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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
CASE REPORT  
Year : 2019  |  Volume : 30  |  Issue : 2  |  Page : 513-516
Thiocolchicoside associated with epileptic seizures in a chronic hemodialysis patient


1 Department of Nephrology, Antalya Atatürk StateHospital, Antalya, Turkey
2 Department of Oral and Maxillofacial Radiology, Faculty of Dentistry, Akdeniz University, Antalya, Turkey
3 Department of Nephrology, Ankara Numune Education and Research Hospital, Ankara, Turkey

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Date of Submission14-Apr-2018
Date of Acceptance07-Mar-2018
Date of Web Publication23-Apr-2019
 

   Abstract 


Thiocolchicoside (TCC) is a widely used centrally acting muscle relaxant. Epileptic seizures from the use of TCC are rarely reported. A 67-year-old male patient with endstage renal disease that was caused by hypertension was on maintenance hemodialysis (HD) for 22 months. He had taken TCC 8 mg capsules twice daily for four days due to painful myofascial spasm in neck and face muscles. At the end of the HD session, he had generalized tonic–clonic seizures. Epileptic seizures were brought under control with sodium valproate, and no recurrence of epileptic seizures was observed.

How to cite this article:
Yilmaz F, Günen Yılmaz S, Keleş M. Thiocolchicoside associated with epileptic seizures in a chronic hemodialysis patient. Saudi J Kidney Dis Transpl 2019;30:513-6

How to cite this URL:
Yilmaz F, Günen Yılmaz S, Keleş M. Thiocolchicoside associated with epileptic seizures in a chronic hemodialysis patient. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2019 Jul 21];30:513-6. Available from: http://www.sjkdt.org/text.asp?2019/30/2/513/256859



   Introduction Top


Thiocolchicoside (TCC) is a widely used drug, especially in muscular spasm and myo-fascial pain syndrome, due to centrally acting muscle relaxant, anti-inflammatory, and analgesic effects.[1] Information about the pharmaco-kinetics and metabolism of TCC is limited. However, it is generally a relatively safe drug with few known side effects.[2]

In addition to the known effects of TCC, recently anticancer properties and prevention of cerebral vasospasm after subarachnoid hemorrhage have been shown in cell culture and animal studies.[3],[4] In the literature, epileptic seizures due to the use of TCC have been reported in a small number of patients, and these patients are often patients with acute brain injury and epilepsy.[5],[6] In this study, we present a patient on chronic hemodialysis (HD) who developed epileptic seizures after use of TCC.


   Case Report Top


A 67-year-old man patient with the end-stage renal disease that was caused by hypertension was on maintenance HD for 22 months. He was continuously using sodium polystyrene sulfonate (25 g/day) for hyperkalemia and benidipine (4 mg/day) and doxazosin mesilate (4 mg/day) for hypertension. He was not receiving any antiepileptic drug or erythro-poietin treatment. The patient had been operated on three months earlier for cervical disc herniation. He had taken TCC 8 mg capsules twice daily for four days due to painful myofascial spasm in face and neck muscles. He took the last dose 8 h before the start of the HD session. At the end of the HD session, he had a sudden generalized tonic–clonic seizures. He had no previous history of epileptic seizures and cerebrovascular disease.

On examination, the body temperature was 36.8°C, blood pressure was 145/80 mm Hg, and the heart rate was 76 bpm. The systemic and neurological examination was normal. The results of other laboratory tests are listed in [Table 1]. The electroencephalograhy, 4 h after the seizure was normal. Brain computed tomography and magnetic resonance imaging (MRI) were normal.
Table 1: Laboratory results of the patient.

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The TCC was discontinued. Epileptic seizure was brought under control with sodium valproate. Sodium valproate therapy was continued for three months, and during the following year, no recurrence of epileptic seizures was observed. We believe that the seizures were due to TCC because benidipine, doxazosin mesilate, and other drugs had shown no particular neurologic adverse effects and the patient had not used antiepileptic drug and did not have a history of cerebrovascular disease such as epilepsy. Furthermore, the absence of epileptic seizures after discontinuation of TCC and antiepileptic drug therapy in the patient is further proof that TCC may be responsible.

Informed consent was obtained from the patient before reporting the case.


   Discussion Top


TCC is a semi-synthetic derivative of colchicine, a natural glycoside of Gloriosa superba[7],[8] The chemical structure of TCC is 3,10-di (demethoxy) -3-glucupyrosyloxy-10-methyl thiocolchicine. Preclinical studies have indicated that the TCC metabolite is 3-demethyl thiocolchicine.[9] The muscle relaxant and analgesic effects of TCC may be due to interaction with γ-aminobutyric acid receptors.

It has been shown that TCC has strong convulsive effects, especially in humans and animals.[9] It has been observed that colchicinecosine causes generalized tonic–clonic seizures and death in rats.[5] Epileptic seizures following TCC ingestion have been reported in a few animal studies and cases.[5],[6],[9] Peak plasma level is reached within 30 min following oral intake and its plasma half-life is 7.7 h.[1] TCC can be used topically, orally and intramuscularly. Side effects associated with the use of TCC include liver injury, severe cutaneous disorder, pancreatitis, rhabdomyolysis, reproductive disorders, and seizures.[10] Epileptic seizures related to TCC were observed in rats at the total dose of 6–12 mg/kg.[9] Our patient was 71 kg, and the total dose of TCC that he received was 0.90 mg/kg (cumulative dose: 64 mg).

According to previous case reports, TCC-induced epileptic seizures are associated with symptomatic brain lesions. The total cumulative amount of TCC in De Riu et al’s study, in the treatment of three patients who developed seizures after the use TCC, was reported as 52 mg in the first patient, 72 mg in the second patient, and 4 mg in the third patient.[6] The first of these patients had a history of epilepsy and was using antiepileptic drugs (phenytoin and carbamazepine). The other two patients did not have epileptic seizures for seven and nine years. The third patient had a cerebral contusion in the left frontobasal region of the brain on CT along with a mandibular fracture after a traffic accident.[6] In this patient, epileptic seizure developed after a single dose of TCC. The central nervous system pathology was present in all three patients. In the report of Giavina-Bianchi et al, epileptic seizures were observed after a total of 20 mg TCC, and in that patient brain CT showed focal cortical hyperperfusion in the left frontal lobe, MRI revealed microhemorrhages in the right frontal and left occipital lobes.[5] In the case published by Havali et al, a healthy three-month-old female infant developed epileptic seizure due to TCC passing through the mother’s milk.[11] In the case of Ugurel et al, a 40-year-old male patient developed delirium after a single dose of intramuscular TCC and no central nervous system pathology was detected.[12] Brain CT and MRI were normal in this patient.

TCC has been shown to interact with gammaaminobutyric acid type A receptors and strychnine-sensitive glycine receptors in the central nervous system of rats and facilitates the development of epileptic seizures by lowering the seizure threshold.[5],[13]


   Conclusion Top


Patients with epilepsy and central nervous system pathology (trauma and hemorrhage) may experience epileptic seizures after TCC use. In addition, epileptic seizures due to TCC through the mother’s milk have been reported during infancy when the blood–brain barrier is not fully developed.

Conflict of interest: None declared.



 
   References Top

1.
Janbroers JM. Review of thetoxicology, pharmacodynamics and pharmacokinetics of thiocolchicoside, a GABA-agonist muscle relaxant with anti-inflammatory and analgesic actions. Acta Ther 1987;13:221-7.  Back to cited text no. 1
    
2.
Trellu M, Filali-Ansary A, Françon D, et al. New metabolic and pharmacokinetic characteristics of thiocolchicoside and its active metabolite in healthy humans. Fundam Clin Pharmacol 2004;18:493-501.  Back to cited text no. 2
    
3.
Reuter S, Prasad S, Phromnoi K, et al. Thiocolchicoside exhibits anticancer effects through downregulation of NF-κB pathway and its regulated gene products linked to inflammation and cancer. Cancer Prev Res (Phila) 2010;3:1462-72.  Back to cited text no. 3
    
4.
Kertmen H, Gürer B, Yilmaz ER, et al. The effect of thiocolchicoside on cerebral vasospasm following experimental subarachnoid hemorrhage in the rabbit. Acta Neurochir (Wien) 2012;154:1431-6.  Back to cited text no. 4
    
5.
Giavina-Bianchi P, Giavina-Bianchi M, Tanno LK, Ensina LF, Motta AA, Kalil J. Epileptic seizure after treatment with thiocolchicoside. Ther Clin Risk Manag 2009;5:635-7.  Back to cited text no. 5
    
6.
De Riu PL, Rosati G, Sotgiu S, Sechi G. Epileptic seizures after treatment with thiocolchicoside. Epilepsia 2001;42:1084-6.  Back to cited text no. 6
    
7.
Nautiyal OP. Isolation of 3-demethylcolchicine from Glorisa superba sludge and coupling with α-acetobromoglucose to yield colchicoside and thiocolchicoside. J Nat Prod 2011;4:87-93.  Back to cited text no. 7
    
8.
Ketenci A, Basat H, Esmaeilzadeh S. The efficacy of topical thiocolchicoside (Muscoril) in the treatment of acute cervical myofascial pain syndrome: A single-blind, randomized, prospective, phase IV clinical study. Agri 2009;21:95-103.  Back to cited text no. 8
    
9.
Sechi G, De Riu P, Mameli O, Deiana GA, Cocco GA, Rosati G. Focal and secondarily generalised convulsive status epilepticus induced by thiocolchicoside in the rat. Seizure 2003;12:508-15.  Back to cited text no. 9
    
10.
Thiocolchicoside: Review of adverse effects. Prescrire Int 2016;25:41-3.  Back to cited text no. 10
    
11.
Havali C, Gucuyener K, Gurkas E, Demir E. Temporary seizure in an infant who had been exposed to G-amino butyric acid receptor antagonist thiocolchicoside. Pediatr Emerg Care 2017;May 8.  Back to cited text no. 11
    
12.
Ugurel B, Sahin O, Oztürk V. An encephalopathy case developed after intramuscular injection of thiocolchicoside. J Neurol Sci [Turk] 2009;26:97-101.  Back to cited text no. 12
    
13.
Carta M, Murru L, Botta P, et al. The muscle relaxant thiocolchicoside is an antagonist of GABAA receptor function in the central nervous system. Neuropharmacology 2006;51: 805-15.  Back to cited text no. 13
    

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Correspondence Address:
Fatih Yilmaz
Department of Nephrology, Antalya Atatürk State Hospital, Antalya
Turkey
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DOI: 10.4103/1319-2442.256859

PMID: 31031388

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