Letter to the Editor
Levofloxacin as a possible cause of myasthenic crisis
Levofloxacino como posible causa de crisis miasténica
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Registro con electrodos de superficie en los músculos abductor del quinto dedo derecho y trapecio izquierdo, respectivamente. En condiciones basales (es decir, con el músculo previamente relajado), se observa una caída significativa (><span class="elsevierStyleHsp" style=""></span>10%) de la amplitud del 4.<span class="elsevierStyleSup">o</span> potencial de acción motor compuesto (flechas verdes) respecto al 1.<span class="elsevierStyleSup">o</span> (flechas azules) con trenes de estímulo a baja frecuencia (3<span class="elsevierStyleHsp" style=""></span>Hz), así como una ausencia del fenómeno de facilitación con trenes de estímulo a alta frecuencia (30<span class="elsevierStyleHsp" style=""></span>Hz) en ambos nervios (estrella). Se trata de un patrón característico de una alteración de transmisión neuromuscular de tipo postsináptico, compatible con miastenia gravis. El patrón de la estimulación repetitiva tras el esfuerzo (activación voluntaria del músculo) no es valorable en este caso al encontrarse el paciente bajo el efecto de la sedación.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Diego Durán Barata, Olga Fedirchyk, Celia Corral Tuesta" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Diego" "apellidos" => "Durán Barata" ] 1 => array:2 [ "nombre" => "Olga" "apellidos" => "Fedirchyk" ] 2 => array:2 [ "nombre" => "Celia" "apellidos" => "Corral Tuesta" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2387020623001651" "doi" => "10.1016/j.medcle.2023.01.011" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020623001651?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775323000234?idApp=UINPBA00004N" "url" => "/00257753/0000016000000010/v2_202305172125/S0025775323000234/v2_202305172125/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2387020623001626" "issn" => "23870206" "doi" => "10.1016/j.medcle.2023.04.006" "estado" => "S300" "fechaPublicacion" => "2023-05-26" "aid" => "6144" "copyright" => "Elsevier España, S.L.U." 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(A) Dorsocervical spine MRI showing a posterior epidural abscess (arrow). (B) Transesophageal echocardiography, long-axis longitudinal plane, showing a periannular aortic abscess (arrow).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Didac González Sans, Pau Carratalà Marín, Alfredo Guillen-del-Castillo" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Didac" "apellidos" => "González Sans" ] 1 => array:2 [ "nombre" => "Pau" "apellidos" => "Carratalà Marín" ] 2 => array:2 [ "nombre" => "Alfredo" "apellidos" => "Guillen-del-Castillo" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775323000325" "doi" => "10.1016/j.medcli.2023.01.014" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775323000325?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020623001675?idApp=UINPBA00004N" "url" => "/23870206/0000016000000010/v2_202311101432/S2387020623001675/v2_202311101432/en/main.assets" ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Levofloxacin as a possible cause of myasthenic crisis" "tieneTextoCompleto" => true "saludo" => "To the Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "464" "paginaFinal" => "466" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Diego Durán Barata, Olga Fedirchyk, Celia Corral Tuesta" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Diego" "apellidos" => "Durán Barata" "email" => array:1 [ 0 => "diego.duranb@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Olga" "apellidos" => "Fedirchyk" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Celia" "apellidos" => "Corral Tuesta" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Neumología, Hospital Universitario Ramón y Cajal, Universidad de Alcalá de Henares, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Neurofisiología, Hospital Universitario Ramón y Cajal, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Geriatría, Hospital Universitario Ramón y Cajal, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Levofloxacino como posible causa de crisis miasténica" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1285 "Ancho" => 2925 "Tamanyo" => 350222 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Repetitive nerve stimulation of the right ulnar (top) and left accessory nerves (bottom). Surface electrode recording on the right fifth finger abductor and left trapezius muscles, respectively. Under basal conditions (i.e., with the muscle previously relaxed), a significant drop (>10%) in the amplitude of the 4th compound motor action potential (green arrows) is observed with respect to the 1 st (blue arrows) with low frequency stimulation trains (3 Hz), as well as an absence of the facilitation phenomenon with high frequency stimulation trains (30 Hz) in both nerves (star). This is a characteristic pattern of a postsynaptic neuromuscular transmission disorder, compatible with myasthenia gravis. The pattern of repetitive stimulation after exertion (voluntary muscle activation) is not assessable in this case as the patient is under sedation.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">We report the case of a patient who developed severe respiratory failure in the context of a myasthenic crisis in probable relation to the use of levofloxacin, a very unusual cause of respiratory failure.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 76-year-old male, never a smoker, with a history of type 2 diabetes mellitus and hypertension, who came to the emergency department for grade 4 dyspnoea, according to the mMRC. The previous week he had seen his primary care doctor, who prescribed levofloxacin for a respiratory infection. At 72 h from the start of treatment, he started with dyspnoea, associated with marked weakness for cervical extension and mobilisation of the proximal muscles of the 4 limbs. In addition, he had had dysphagia for liquids for 2 years, worsening during this episode. He did not report diplopia, or disturbances in visual acuity or ocular motility.</p><p id="par0015" class="elsevierStylePara elsevierViewall">On arrival at the emergency department, he was tachypnoeic at rest, requiring a Ventimask® at 50% to maintain an oxygen saturation of 93%. Physical examination (including cardiopulmonary auscultation) was normal, except for minimal bilateral ptosis. A full laboratory work-up, including D-dimer, was performed, showing no significant findings. Echocardiogram and chest X-ray were normal, so a computed tomography (CT) scan was requested, where only small bibasilar opacities were observed, in a probable relation with bronchial aspiration pneumonia.</p><p id="par0020" class="elsevierStylePara elsevierViewall">After a few hours, the patient developed a significant respiratory deterioration, requiring orotracheal intubation and admission to the Intensive Care Unit (ICU). During admission to the ICU, a lumbar puncture and cranial CT scan were performed, both of which were normal. The neurological examination was inconclusive due to the effects of sedation, although Neurology noted that the stretch reflexes were preserved. Subsequently, a neurophysiological study was performed, including repetitive nerve stimulation, which showed a characteristic pattern of postsynaptic neuromuscular transmission disorder, compatible with myasthenia gravis (MG) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The autoimmunity study detected anti-striated muscle and anti-acetylcholine receptor antibodies, both tests confirming the diagnosis of MG.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Specific treatment was initiated, including high-dose glucocorticoids, plasmapheresis (5 sessions) and, subsequently, pyridostigmine. The patient showed significant clinical improvement, allowing extubation 72 h after initiation of treatment. He was admitted to the hospital ward after 7 days and discharged home on the ninth day. On discharge, the only pathological findings on neurological examination were left eye ptosis covering the pupillary border, with fatigability without diplopia and weakness of the neck muscles after fatigability manoeuvres.</p><p id="par0030" class="elsevierStylePara elsevierViewall">A score of 5 was obtained when performing a Naranjo-type algorithm to show causality, establishing a probable relationship between levofloxacin intake and myasthenic crisis.</p><p id="par0035" class="elsevierStylePara elsevierViewall">MG is an autoimmune disease characterised by dysfunction of the motor endplate at the postsynaptic level. Myasthenic crisis is its most severe and life-threatening expression. Cases admitted to the ICU for severe myasthenic crisis have a mortality rate of 5–12 %, with higher mortality in older people, late onset myasthenia and presence of more than 3 comorbidities.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">There are different situations described as possible triggers for myasthenic crises, such as late onset of the disease, the presence of other autoimmune diseases or the use of certain drugs.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Regarding the latter, some are capable of triggering a new-onset myasthenic crisis, such as checkpoint inhibitors. However, many others, including fluoroquinolones, by interacting with the motor endplate, tend to worsen symptoms in patients with pre-existing or undiagnosed MG, as in the case described above.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Fluoroquinolones (ciprofloxacin, levofloxacin, ofloxacin, etc.) are known for their potential to produce neuromuscular blockade, either pre- or post-synaptic, and are dose-dependent. Worsening of myastheniform symptoms may occur within a relatively short period of time, between 15 min and 6 days after administration, and will depend on the severity of the pre-existing symptoms and the dose administered.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Our case illustrates the importance of knowing which drugs are contraindicated or should be avoided in patients with MG. Moreover, cases such as this one highlight the need for a multidisciplinary approach in the treatment of this type of patient, as well as the importance of specific complementary tests, which help to establish a correct diagnosis and therefore early treatment.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Ethical considerations</span><p id="par0055" class="elsevierStylePara elsevierViewall">Informed consent has been obtained.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Funding</span><p id="par0060" class="elsevierStylePara elsevierViewall">We confirm that there has been no funding for this paper.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflict of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">We confirm that there is no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Ethical considerations" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Funding" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflict of interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1285 "Ancho" => 2925 "Tamanyo" => 350222 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Repetitive nerve stimulation of the right ulnar (top) and left accessory nerves (bottom). Surface electrode recording on the right fifth finger abductor and left trapezius muscles, respectively. Under basal conditions (i.e., with the muscle previously relaxed), a significant drop (>10%) in the amplitude of the 4th compound motor action potential (green arrows) is observed with respect to the 1 st (blue arrows) with low frequency stimulation trains (3 Hz), as well as an absence of the facilitation phenomenon with high frequency stimulation trains (30 Hz) in both nerves (star). This is a characteristic pattern of a postsynaptic neuromuscular transmission disorder, compatible with myasthenia gravis. The pattern of repetitive stimulation after exertion (voluntary muscle activation) is not assessable in this case as the patient is under sedation.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Myasthenic crisis demanding mechanical ventilation: A multicenter analysis of 250 cases" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Neumann" 1 => "K. Angstwurm" 2 => "P. Mergenthaler" 3 => "S. Kohler" 4 => "S. Schönenberger" 5 => "J. Bösel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1212/WNL.0000000000008688" "Revista" => array:7 [ "tituloSerie" => "Neurology." "fecha" => "2020" "volumen" => "94" "numero" => "3" "paginaInicial" => "e299" "paginaFinal" => "e313" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31801833" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Factors associated with acute exacerbations of myasthenia gravis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "R.R. Gummi" 1 => "N.A. Kukulka" 2 => "C.B. Deroche" 3 => "R. 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