Neurol Sci DOI 10.1007/s10072-015-2108-2
LETTER TO THE EDITOR
Acute dystonic reaction associated with cefalexine Svetlana Tomic • Tatjana Rotim • Marina Hlavati Ruzica Palic Kramaric • Tea Mirosevic Zubonja
•
Received: 9 December 2014 / Accepted: 9 February 2015 Ó Springer-Verlag Italia 2015
Introduction
Case report
Dystonia is a movement disorder defined as a syndrome of sustained muscle contractions, frequently causing twisted and repetitive movements or abnormal postures. While dystonic reactions due to a neurodegenerative disease develop slowly in the progressive fashion, acute drug-induced dystonic reactions usually occur within the first 4 days of the treatment. Typically, cranial pharyngeal and cervical muscles are affected with prompt relief after the introduction of anticholinergics in treatment [1]. The most common cases of drug-induced movement disorders are caused with neuroleptics and antiemetics [2]. We present a patient with acute dystonic reaction associated with betalactam antibiotic cefalexine.
A 24-year-old female patient came to our emergency department due to involuntary contractions of the neck muscle. The day before she started with the treatment of pharyngitis with cefalexine (1 g twice a day). After the second dose of the cefalexine, she developed involuntary movements that were represented with painful contractions of the platysma muscles. All other neurological exams were completely normal. She has not been taking other drugs. In her medical history, it was stated that she was suffering from the lack of alpha 1 antitrypsin. She had hyperthyreosis that was improved with the therapy. Previously, she has never had any involuntary movements or dystonic reactions. In her family history one half-sister had psychosis and no one had movement disorders. All examinations were normal (CT scan of the brain, toxicology for barbiturates, tricyclic antidepressants, cannabinoids, amphetamine/methamphetamine, cocaine, methadon, opiates and thyroid hormones), except of mild elevation of GGT (62), lack of potassium (3,7), and left shift in white blood count with mild leucocytosis and lymphopenia. In the treatment, we stopped with cefalexine and gave her biperiden lactate ampoule of 10 mg twice. After the second ampoule of biperiden lactate, involuntary movements have completely disappeared and she was discharged from hospital with completely normal neurological examination.
S. Tomic (&) R. P. Kramaric T. M. Zubonja Department of Neurology, University Hospital Center Osijek, J. Huttlera 4, 31000 Osijek, Croatia e-mail: [email protected] S. Tomic Medical School of Josip Juraj Strossmayer in Osijek, Osijek, Croatia T. Rotim Department of Radiology, University Hospital Center Osijek, Osijek, Croatia M. Hlavati Department of Neurology, General Hospital Nasice, Nasice, Croatia
Discussion We present a patient with acute dystonic reaction developed after the second dose of cefalexine. Examinations did not reveal other causative agents for this condition. Withdrawal of the cefalexine from therapy and administration of
123
Neurol Sci
the anticholinergics resulted in disappearance of the symptoms. Alpha 1 antitrypsin deficiency could not explain adverse reaction to cefalexine as toxicity reaction due to the fact that cefalexine is mostly (over 90 %) excreted unchanged in the urine by glomerular filtration and tubular secretion [2]. While neuroleptics and antiemetics are common causes of the acute dystonic reaction, cefalexine has been never connected to this adverse event [2]. Naranjo Adverse Drug Reaction Probability Scale indicates the dystonic reaction as a probable (score of 6) adverse reaction to cefalexine. The mechanism of acute drug-induced dystonic reaction is unclear with few hypotheses about its origin. One hypothesis is that dopaminergic hypofunction results in a relative overactivity of cholinergic mechanisms. The other hypothesis proposes that there is paradoxical dopaminergic hyperfunction induced by dopaminereceptor blocking agents through blocking of presynaptic dopamine receptors. The third hypothesis proposes involvement of sigma opiate receptors [1]. Also, there is no clear evidence about anatomical circuits involved in pathophysiology of adult onset focal dystonias. There are more results confirming that for development of focal dystonia, involvement of cerebellum is more crucial than basal ganglia circuits [1]. The mechanism of how betalactam antibiotics can induce acute drug dystonic reaction could be explained with involvement of glutamate neurotransmitters system in cerebellum. Lipski and coauthors [3] have found that beta-lactam antibiotics are able to pass freely via the blood–brain barrier and up-regulate the functional expressions of glutamate transporter as well as glutamate transporter subtype 1 (GLT1). GLT1 has been investigated as the predominant glutamate transporter, which is essential to recycle glutamate and maintain a
123
relatively low level of extracellular glutamate [4]. On the other hand, Fan et al. have found that glutamate receptor activation, specifically AMPA receptor, was necessary to evoke dystonia. They found out that AMPA receptor agonists induced dystonia, and AMPA receptor antagonists reduced the dystonia induced by glutamate receptor agonists [5].
Conclusion This case report for the first time describes acute dystonic reaction associated with cefalexine possible through involvement of the glutamate neurotransmitter system and cerebellum. Conflict of interest of interest.
The authors declare that they have no conflict
References 1. Jankovic J, Tolosa E (2007) Parkinson‘s disease and movement disorders. Lippincott Williams & Wilkins, Wolters Kluwer Business, Philadelphia 2. MIMS (web page). http://www.mims.com. Accessed 24 July 2014 3. Lipski J, Wan CK, Bai JZ, Pi R, Li D, Donnelly D (2007) Neuroprotective potential of ceftriaxone in in vitro models of stroke. Neuroscience 146:617–629 4. Kanai Y, Hediger MA (2003) The glutamate and neutral amino acid transporter family: physiological and pharmacological implications. Eur J Pharmacol 479:237–247 5. Fan X, Hughes KE, Jinnah HA, Hess EJ (2012) Selective and sustained a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor activation in cerebellum induces dystonia in mice. J Pharmacol Exp Ther 340:733–741
LETTER TO THE EDITOR
Acute dystonic reaction associated with cefalexine Svetlana Tomic • Tatjana Rotim • Marina Hlavati Ruzica Palic Kramaric • Tea Mirosevic Zubonja
•
Received: 9 December 2014 / Accepted: 9 February 2015 Ó Springer-Verlag Italia 2015
Introduction
Case report
Dystonia is a movement disorder defined as a syndrome of sustained muscle contractions, frequently causing twisted and repetitive movements or abnormal postures. While dystonic reactions due to a neurodegenerative disease develop slowly in the progressive fashion, acute drug-induced dystonic reactions usually occur within the first 4 days of the treatment. Typically, cranial pharyngeal and cervical muscles are affected with prompt relief after the introduction of anticholinergics in treatment [1]. The most common cases of drug-induced movement disorders are caused with neuroleptics and antiemetics [2]. We present a patient with acute dystonic reaction associated with betalactam antibiotic cefalexine.
A 24-year-old female patient came to our emergency department due to involuntary contractions of the neck muscle. The day before she started with the treatment of pharyngitis with cefalexine (1 g twice a day). After the second dose of the cefalexine, she developed involuntary movements that were represented with painful contractions of the platysma muscles. All other neurological exams were completely normal. She has not been taking other drugs. In her medical history, it was stated that she was suffering from the lack of alpha 1 antitrypsin. She had hyperthyreosis that was improved with the therapy. Previously, she has never had any involuntary movements or dystonic reactions. In her family history one half-sister had psychosis and no one had movement disorders. All examinations were normal (CT scan of the brain, toxicology for barbiturates, tricyclic antidepressants, cannabinoids, amphetamine/methamphetamine, cocaine, methadon, opiates and thyroid hormones), except of mild elevation of GGT (62), lack of potassium (3,7), and left shift in white blood count with mild leucocytosis and lymphopenia. In the treatment, we stopped with cefalexine and gave her biperiden lactate ampoule of 10 mg twice. After the second ampoule of biperiden lactate, involuntary movements have completely disappeared and she was discharged from hospital with completely normal neurological examination.
S. Tomic (&) R. P. Kramaric T. M. Zubonja Department of Neurology, University Hospital Center Osijek, J. Huttlera 4, 31000 Osijek, Croatia e-mail: [email protected] S. Tomic Medical School of Josip Juraj Strossmayer in Osijek, Osijek, Croatia T. Rotim Department of Radiology, University Hospital Center Osijek, Osijek, Croatia M. Hlavati Department of Neurology, General Hospital Nasice, Nasice, Croatia
Discussion We present a patient with acute dystonic reaction developed after the second dose of cefalexine. Examinations did not reveal other causative agents for this condition. Withdrawal of the cefalexine from therapy and administration of
123
Neurol Sci
the anticholinergics resulted in disappearance of the symptoms. Alpha 1 antitrypsin deficiency could not explain adverse reaction to cefalexine as toxicity reaction due to the fact that cefalexine is mostly (over 90 %) excreted unchanged in the urine by glomerular filtration and tubular secretion [2]. While neuroleptics and antiemetics are common causes of the acute dystonic reaction, cefalexine has been never connected to this adverse event [2]. Naranjo Adverse Drug Reaction Probability Scale indicates the dystonic reaction as a probable (score of 6) adverse reaction to cefalexine. The mechanism of acute drug-induced dystonic reaction is unclear with few hypotheses about its origin. One hypothesis is that dopaminergic hypofunction results in a relative overactivity of cholinergic mechanisms. The other hypothesis proposes that there is paradoxical dopaminergic hyperfunction induced by dopaminereceptor blocking agents through blocking of presynaptic dopamine receptors. The third hypothesis proposes involvement of sigma opiate receptors [1]. Also, there is no clear evidence about anatomical circuits involved in pathophysiology of adult onset focal dystonias. There are more results confirming that for development of focal dystonia, involvement of cerebellum is more crucial than basal ganglia circuits [1]. The mechanism of how betalactam antibiotics can induce acute drug dystonic reaction could be explained with involvement of glutamate neurotransmitters system in cerebellum. Lipski and coauthors [3] have found that beta-lactam antibiotics are able to pass freely via the blood–brain barrier and up-regulate the functional expressions of glutamate transporter as well as glutamate transporter subtype 1 (GLT1). GLT1 has been investigated as the predominant glutamate transporter, which is essential to recycle glutamate and maintain a
123
relatively low level of extracellular glutamate [4]. On the other hand, Fan et al. have found that glutamate receptor activation, specifically AMPA receptor, was necessary to evoke dystonia. They found out that AMPA receptor agonists induced dystonia, and AMPA receptor antagonists reduced the dystonia induced by glutamate receptor agonists [5].
Conclusion This case report for the first time describes acute dystonic reaction associated with cefalexine possible through involvement of the glutamate neurotransmitter system and cerebellum. Conflict of interest of interest.
The authors declare that they have no conflict
References 1. Jankovic J, Tolosa E (2007) Parkinson‘s disease and movement disorders. Lippincott Williams & Wilkins, Wolters Kluwer Business, Philadelphia 2. MIMS (web page). http://www.mims.com. Accessed 24 July 2014 3. Lipski J, Wan CK, Bai JZ, Pi R, Li D, Donnelly D (2007) Neuroprotective potential of ceftriaxone in in vitro models of stroke. Neuroscience 146:617–629 4. Kanai Y, Hediger MA (2003) The glutamate and neutral amino acid transporter family: physiological and pharmacological implications. Eur J Pharmacol 479:237–247 5. Fan X, Hughes KE, Jinnah HA, Hess EJ (2012) Selective and sustained a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor activation in cerebellum induces dystonia in mice. J Pharmacol Exp Ther 340:733–741
