Letter to the Editor
Myoclonus secondary to use of anti-flu drug
Mioclonías secundarias a fármaco antigripal
A. Velázquez
, S. Santos, E. Bellosta, C. Iñiguez
Corresponding author
Servicio de Neurología, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
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Velázquez, S. Santos, E. Bellosta, C. Iñiguez" "autores" => array:4 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "Velázquez" "email" => array:1 [ 0 => "albavelazquez83@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "S." "apellidos" => "Santos" ] 2 => array:2 [ "nombre" => "E." "apellidos" => "Bellosta" ] 3 => array:2 [ "nombre" => "C." "apellidos" => "Iñiguez" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Neurología, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Mioclonías secundarias a fármaco antigripal" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Drug-induced movement disorders are relatively frequent. In fact, a high number of drugs have been found to be linked to myoclonus. We present the case of a patient who developed myoclonus secondary to combined treatment with dextromethorphan and chlorphenamine, 2 widely used drugs. The literature describes one case of myoclonus associated with dextromethorphan use; no cases of myoclonus secondary to chlorphenamine use had been reported to date.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Our patient was a 64-year-old male smoker with no relevant medical history. He was receiving no medications and exercised regularly.</p><p id="par0015" class="elsevierStylePara elsevierViewall">A few days previously, he presented general unease, fever (39<span class="elsevierStyleHsp" style=""></span>°C), holocranial headache, and nasal congestion. After a pharmacist identified the patient's flu-like symptoms, the patient began taking an anti-flu preparation containing paracetamol, dextromethorphan, chlorphenamine, ascorbic acid, and caffeine citrate.</p><p id="par0020" class="elsevierStylePara elsevierViewall">After taking the first tablet orally, our patient experienced intense restlessness and involuntary movements of the face and upper limbs which interfered with night-time sleep.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Upon arriving at the emergency department, he had no fever and his vital signs were within normal limits. He denied use of any other drugs or intoxicating substances. The physical examination, including auscultation and examination of the upper respiratory tract, revealed no abnormalities. The emergency blood analysis, chest radiography, and brain CT scan yielded normal results.</p><p id="par0030" class="elsevierStylePara elsevierViewall">A neurological examination revealed sudden-onset short involuntary movements in the upper limbs, present during rest and exacerbating with movement. These movements were accompanied by decreased muscle tone and dropping of both upper limbs; after this, our patient was able to lift them immediately. Furthermore, he reported generalised restlessness and involuntary contraction affecting facial muscles on both sides. These contractions did not disappear with distraction movements. He displayed no alterations in strength or sensitivity and no signs of cranial nerve involvement. Likewise, he showed no signs of meningeal irritation, increased muscle tone, or regressive reflexes.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Suspicion of drug-induced generalised myoclonus led to treatment with intravenous benzodiazepines. After doctors discontinued the anti-flu drug and administered intravenous diazepam (3 doses of 10<span class="elsevierStyleHsp" style=""></span>mg every 8<span class="elsevierStyleHsp" style=""></span>hours), symptoms resolved completely and the patient became asymptomatic. He has experienced no recurrences and displayed no other neurological symptoms in the subsequent months. We recommended that he avoid such anti-flu drugs or their derivatives.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Myoclonus belongs to the spectrum of hyperkinetic movement disorders; it is described as sudden-onset quick involuntary jerking movements.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> It is caused by either muscle contractions (positive myoclonus) or brief lapses of loss of muscle activity (negative myoclonus).</p><p id="par0045" class="elsevierStylePara elsevierViewall">Depending on its various origins within the nervous system, myoclonus can be classified as cortical (multifocal, very brief duration, occurring especially during activity), subcortical (longer duration, occurring both at rest and during activity), or spinal (focal, longer duration, occurring especially at rest).<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In our patient, myoclonus seemed to be negative and of subcortical origin. Aside from myoclonus, drug-induced movement disorders include a wide range of symptoms such as dystonia, tremor, drug-induced parkinsonism, dyskinesia, akathisia, and even serotonin syndrome or neuroleptic malignant syndrome.</p><p id="par0055" class="elsevierStylePara elsevierViewall">All of them share a direct temporal relationship between use of a certain drug and symptom onset, and between drug discontinuation and symptom resolution (except for late-onset symptoms).<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Drugs responsible for such syndromes have included levodopa, antidepressants, lithium, dopamine agonists, antiepileptics, opioids, antineoplastics, anxiolytics, and antibiotics.</p><p id="par0065" class="elsevierStylePara elsevierViewall">In our patient, the drug included several active ingredients, which raises the question of whether myoclonus was caused by one of the components or rather by the synergistic effect of a combination of them.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Dextromethorphan is a widely used cough suppressant that can either be used alone or in anti-flu drug complexes. It has been linked to myoclonus in the context of renal failure,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> as well as to serotonin syndrome in more severe conditions<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> and when combined with other drugs (especially serotonin reuptake inhibitors). Immediate discontinuation of the drug is recommended if either condition arises. Multiple drugs, including diazepam, have been suggested as treatment for myoclonus, although no specific indications have been established.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Chlorphenamine is a first-generation antihistamine with central nervous system side effects that included tremor, epileptic seizures, sedation, and somnolence. However, an association with myoclonus has not been described.</p><p id="par0080" class="elsevierStylePara elsevierViewall">In our patient, myoclonus probably was an unexpected likely adverse reaction to the drug (according to the causality criteria for adverse reactions); as such, it was reported to the appropriate pharmacovigilance authority. However, we have no conclusive data on the underlying mechanism.</p><p id="par0085" class="elsevierStylePara elsevierViewall">Although no studies have reported a higher risk of movement disorders in patients with a history of drug-induced myoclonus, it seems reasonable to think that these patients would have a higher risk of recurrences after using that particular drug or its derivatives.</p><p id="par0090" class="elsevierStylePara elsevierViewall">To the best of our knowledge, no similar cases have been described in the literature to date.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0095" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare. This study has not been presented elsewhere.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Velázquez A, Santos S, Bellosta E, Iñiguez C. Mioclonías secundarias a fármaco antigripal. Neurología. 2017;32:133–135.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Myoclonus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "V.C. Chang" 1 => "S.J. Frucht" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Curr Treat Options Neurol" "fecha" => "2008" "volumen" => "10" "paginaInicial" => "222" "paginaFinal" => "229" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18579026" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mioclonías: características clínicas y neurofisiológicas, etiología y tratamiento" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.E. Erro" 1 => "M.C. 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Burkhard" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S1353-8020(13)70027-0" "Revista" => array:7 [ "tituloSerie" => "Parkinsonism Relat Disord" "fecha" => "2014" "volumen" => "20" "numero" => "Suppl. 1" "paginaInicial" => "S108" "paginaFinal" => "S112" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24262159" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Myoclonus after dextromethorphan administration in peritoneal dialysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Tanaka" 1 => "T. Nagamatsu" 2 => "M. Yamaguchi" 3 => "A. Nomura" 4 => "F. Nagura" 5 => "K. Maeda" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1345/aph.1P301" "Revista" => array:5 [ "tituloSerie" => "Ann Pharmacother" "fecha" => "2011" "volumen" => "45" "paginaInicial" => "e1" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21228393" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Síndrome serotoninérgico por administración de un inhibidor de la recaptación de serotonina y dextrometorfano" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "F. Sánchez" 1 => "S. Marín" 2 => "E. Merchán" 3 => "I. 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