Letter to the Editor
Recurrent lacunar ischaemic stroke due to resistance to antiplatelet treatment: examining the need for personalised antithrombotic therapy
Ictus lacunar recurrente por resistencia al tratamiento antiagregante plaquetario: hacia la necesidad de una terapia antitrombótica individualizada
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A) Octubre de 2006: ictus lacunar protuberancial izquierdo subagudo (flecha). B) Septiembre de 2008: ictus lacunar bulbar izquierdo subagudo (flecha). C) Abril de 2011: ictus lacunar protuberancial derecho subagudo (flecha).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M.G. Delgado, J.R. Corte, A. Sáiz, S. Calleja" "autores" => array:4 [ 0 => array:2 [ "nombre" => "M.G." "apellidos" => "Delgado" ] 1 => array:2 [ "nombre" => "J.R." "apellidos" => "Corte" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Sáiz" ] 3 => array:2 [ "nombre" => "S." 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Tratamiento endovascular en pacientes con oclusión de la arteria de Percheron" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1013 "Ancho" => 1350 "Tamanyo" => 261349 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Right vertebral artery prior to thrombolysis: right hypoplastic P1 segment with occlusion (arrow) is observed. (B) Lateral view of right carotid artery with adequate filling of the right posterior cerebral artery. (C) Microguide wire in the right posterior cerebral artery prior to balloon placement (arrow). (D) The end of the microguide wire was left in the posteromedial choroidal artery after several manoeuvres with the balloon deflated (arrow). (E) Both paramedian arteries have a common origin in the right P1 artery (arrows); recanalisation of the right P1 segment connected to the right posterior cerebral artery can be seen.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "E. Jiménez Gómez, I. Bravo Rey, J.J. Ochoa-Sepúlveda, F. de A. Bravo-Rodríguez" "autores" => array:4 [ 0 => array:2 [ "nombre" => "E." "apellidos" => "Jiménez Gómez" ] 1 => array:2 [ "nombre" => "I." "apellidos" => "Bravo Rey" ] 2 => array:2 [ "nombre" => "J.J." "apellidos" => "Ochoa-Sepúlveda" ] 3 => array:2 [ "nombre" => "F. de A." 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Delgado, J.R. Corte, A. Sáiz, S. Calleja" "autores" => array:4 [ 0 => array:4 [ "nombre" => "M.G." "apellidos" => "Delgado" "email" => array:1 [ 0 => "mglezdelgado@yahoo.es" ] "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" => "J.R." "apellidos" => "Corte" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "A." "apellidos" => "Sáiz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "S." "apellidos" => "Calleja" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Neurología, Hospital Universitario Central de Asturias, Oviedo, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Hematología, Hospital Universitario Central de Asturias, Oviedo, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Radiología, Hospital Universitario Central de Asturias, Oviedo, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Ictus lacunar recurrente por resistencia al tratamiento antiagregante plaquetario: hacia la necesidad de una terapia antitrombótica individualizada" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 708 "Ancho" => 1647 "Tamanyo" => 168257 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Cranial MRI, coronal T2-weighted sequences. (A) October 2006. Subacute left-sided lacunar pontine stroke (arrow). (B) September 2008. Subacute left-sided lacunar medullary stroke (arrow). (C) April 2011. Subacute right-sided lacunar pontine stroke (arrow).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">A significant percentage of patients with stroke will experience recurrence.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1,2</span></a> Some of these cases of recurrence may arise due to resistance to antiplatelet treatment.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a> We describe the case of a patient who suffered several recurrent strokes, a situation attributed to insufficient analysis of risk factors; however, the possibility of resistance to antiplatelet treatment was not examined.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Our patient was a 51-year-old woman who was hospitalised for dysarthria in October 2006. Her cardiovascular risk factors comprised heavy smoking habit (2.5 packs of cigarettes daily), diabetes (with diabetic retinopathy), arterial hypertension, and dyslipidaemia. There was no other relevant family or personal history. She was treated with atorvastatin 20<span class="elsevierStyleHsp" style=""></span>mg, insulin, and acetylsalicylic acid (ASA) 500<span class="elsevierStyleHsp" style=""></span>mg. At time of admission, the patient displayed mild right-sided hemiparesis and dysarthria. Cranial magnetic resonance imaging (MRI) revealed a left pontine stroke (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). The neurovascular study (MRI angiography and carotid duplex ultrasound) showed clinically diffuse silent carotid atheromatosis causing stenosis of 60% on the right side. Cardiology study results were normal. A blood panel revealed high triglyceride levels (190<span class="elsevierStyleHsp" style=""></span>mg/dL) and high glycaemia (265<span class="elsevierStyleHsp" style=""></span>mg/dL). The stroke was attributed to microangiopathy and the patient's drug regimen was adjusted by adding clopidogrel and increasing the statin dose to 80<span class="elsevierStyleHsp" style=""></span>mg daily.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">In September 2008, the patient came to the emergency department because of right-sided hypoaesthesia. Neurological examination revealed facio-brachio-crural hypoaesthesia preceded by mild paresis. Duplex carotid ultrasound showed bilateral carotid atheromatosis similar to that in the previous study. Transcranial duplex ultrasound yielded normal results. The blood count, including microbiology study and antiphospholipid antibodies, showed no abnormalities. Cranial MRI revealed a left medullary stroke (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B). The patient remained on clopidogrel; low molecular-weight heparin (nadroparin calcium 0.6<span class="elsevierStyleHsp" style=""></span>mL SC daily) was added and later withdrawn after the cardiology study. The transthoracic ultrasonography in that study revealed ventricular hypertrophy and discrete left atrial enlargement. A routine CT angiography showed diffuse atheromatosis with no other alterations.</p><p id="par0020" class="elsevierStylePara elsevierViewall">In April 2011, the patient was hospitalised for left hemiparesis. A neurological examination recorded exacerbation of initial dysarthria, left hemiparesis (3/5 in arm, 2/5 in leg), mild right hemiparesis, and bilateral Babinski sign. Cranial MRI revealed a right pontine stroke (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C), and CT angiography indicated diffuse atheromatosis. High blood pressure and hyperglycaemia were also recorded while the patient was hospitalised. Once again, the diagnostic impression was microangiopathy plus poor control over cerebrovascular risk factors, and the patient continued to take antiplatelet drugs.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In November 2011, the patient stopped taking all drugs due to difficulty swallowing and was admitted due to poor clinical status. A neurological examination yielded similar results to previous ones, in addition to severe dysphagia. The patient could walk using supports and required assistance with most activities, including basic tasks. In light of the recurrent strokes and worsening clinical state, doctors suspected a neoplastic aetiology and performed a full work-up to rule out that suspicion. The haematology department completed a platelet study that yielded the following results: Platelet Function Analyser (PFA) collagen/epinephrine test 94<span class="elsevierStyleHsp" style=""></span>seconds (85-165), PFA collagen/ADP 86<span class="elsevierStyleHsp" style=""></span>seconds (71-118), and PFA P2Y 71<span class="elsevierStyleHsp" style=""></span>seconds (0-106). These tests did not show an antiplatelet effect occurring with either ASA or clopidogrel, even after raising the dose to 150<span class="elsevierStyleHsp" style=""></span>mg/day. The patient began treatment with cilostazol.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Earlier studies have described lacunar strokes as being the most frequently responsible for pure motor hemiparesis. Their main localisations are the internal capsule and the pons, as is the case in our patient.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> Recurrence in lacunar stroke entails progressive motor and cognitive impairment. These patients will come to be dependent on others for activities of daily living, and this situation is costly. Today, tight control over cerebrovascular risk factors and use of antiplatelet drugs are the pillars of treating lacunar stroke. However, despite the benefits of antiplatelet drugs, many patients experience recurrent strokes.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">2–4</span></a> This phenomenon may be explained in part by resistance to antiplatelet treatment,<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> defined as failure by the agent to block its target even when used at the correct dosage.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">5,6</span></a> In our hospital, platelet function is measured using the PFA collagen/epinephrine and PFA collagen/ADP tests for ASA and the PFA P2Y test for clopidogrel. In our patient, results on all tests were below the threshold for an antiplatelet effect. Higher doses of ASA (≥325<span class="elsevierStyleHsp" style=""></span>mg/day) and strict adherence to treatment may successfully overcome resistance to ASA in some patients.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a> Maintaining clopidogrel at 150<span class="elsevierStyleHsp" style=""></span>mg/day is an option for patients who are poor responders.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a> Although both approaches were used in our case, we observed no response. On the other hand, results from the SPS3 study, showing that antiplatelet bitherapy with ASA and clopidogrel was not superior to ASA in monotherapy in patients with lacunar stroke, influenced the decision to not administer this treatment to our patient.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">We believe that this case illustrates the importance not only of strict control over cerebrovascular risk factors, but also of administering personalised antiplatelet drugs. Measuring the response to antiplatelet drugs is an option in clinical practice that may help establish effective antithrombotic treatment, and should be carried out at least in those patients with recurrent cerebral infarcts.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Delgado MG, Corte JR, Sáiz A, Calleja S. Ictus lacunar recurrente por resistencia al tratamiento antiagregante plaquetario: hacia la necesidad de una terapia antitrombótica individualizada. Neurología. 2015;30:376–378.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 708 "Ancho" => 1647 "Tamanyo" => 168257 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Cranial MRI, coronal T2-weighted sequences. (A) October 2006. Subacute left-sided lacunar pontine stroke (arrow). (B) September 2008. Subacute left-sided lacunar medullary stroke (arrow). (C) April 2011. Subacute right-sided lacunar pontine stroke (arrow).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0040" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical study of 222 patients with pure motor stroke" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Arboix" 1 => "I. Padilla" 2 => "J. Massons" 3 => "L. García-Eroles" 4 => "E. Comes" 5 => "C. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 8 | 1 | 9 |
| 2024 October | 32 | 5 | 37 |
| 2024 September | 50 | 6 | 56 |
| 2024 August | 23 | 9 | 32 |
| 2024 July | 35 | 9 | 44 |
| 2024 June | 35 | 8 | 43 |
| 2024 May | 44 | 2 | 46 |
| 2024 April | 34 | 9 | 43 |
| 2024 March | 56 | 8 | 64 |
| 2024 February | 67 | 7 | 74 |
| 2024 January | 66 | 4 | 70 |
| 2023 December | 43 | 3 | 46 |
| 2023 November | 50 | 8 | 58 |
| 2023 October | 59 | 10 | 69 |
| 2023 September | 40 | 3 | 43 |
| 2023 August | 30 | 4 | 34 |
| 2023 July | 59 | 11 | 70 |
| 2023 June | 70 | 7 | 77 |
| 2023 May | 74 | 6 | 80 |
| 2023 April | 62 | 5 | 67 |
| 2023 March | 62 | 3 | 65 |
| 2023 February | 60 | 3 | 63 |
| 2023 January | 77 | 11 | 88 |
| 2022 December | 57 | 3 | 60 |
| 2022 November | 76 | 13 | 89 |
| 2022 October | 49 | 12 | 61 |
| 2022 September | 52 | 14 | 66 |
| 2022 August | 44 | 10 | 54 |
| 2022 July | 50 | 15 | 65 |
| 2022 June | 28 | 16 | 44 |
| 2022 May | 42 | 7 | 49 |
| 2022 April | 65 | 14 | 79 |
| 2022 March | 83 | 10 | 93 |
| 2022 February | 90 | 11 | 101 |
| 2022 January | 71 | 4 | 75 |
| 2021 December | 54 | 13 | 67 |
| 2021 November | 53 | 8 | 61 |
| 2021 October | 68 | 12 | 80 |
| 2021 September | 35 | 8 | 43 |
| 2021 August | 43 | 7 | 50 |
| 2021 July | 24 | 10 | 34 |
| 2021 June | 33 | 13 | 46 |
| 2021 May | 46 | 14 | 60 |
| 2021 April | 119 | 18 | 137 |
| 2021 March | 66 | 15 | 81 |
| 2021 February | 49 | 10 | 59 |
| 2021 January | 57 | 20 | 77 |
| 2020 December | 47 | 13 | 60 |
| 2020 November | 38 | 10 | 48 |
| 2020 October | 37 | 5 | 42 |
| 2020 September | 26 | 29 | 55 |
| 2020 August | 28 | 33 | 61 |
| 2020 July | 24 | 12 | 36 |
| 2020 June | 21 | 10 | 31 |
| 2020 May | 31 | 17 | 48 |
| 2020 April | 26 | 9 | 35 |
| 2020 March | 35 | 4 | 39 |
| 2020 February | 26 | 7 | 33 |
| 2020 January | 32 | 10 | 42 |
| 2019 December | 37 | 2 | 39 |
| 2019 November | 32 | 15 | 47 |
| 2019 October | 22 | 3 | 25 |
| 2019 September | 37 | 11 | 48 |
| 2019 August | 43 | 16 | 59 |
| 2019 July | 59 | 14 | 73 |
| 2019 June | 98 | 31 | 129 |
| 2019 May | 201 | 18 | 219 |
| 2019 April | 87 | 15 | 102 |
| 2019 March | 20 | 4 | 24 |
| 2019 February | 25 | 8 | 33 |
| 2019 January | 12 | 9 | 21 |
| 2018 December | 14 | 7 | 21 |
| 2018 November | 23 | 2 | 25 |
| 2018 October | 39 | 6 | 45 |
| 2018 September | 34 | 13 | 47 |
| 2018 August | 9 | 8 | 17 |
| 2018 July | 7 | 7 | 14 |
| 2018 June | 10 | 2 | 12 |
| 2018 May | 13 | 13 | 26 |
| 2018 April | 20 | 2 | 22 |
| 2018 March | 12 | 0 | 12 |
| 2018 February | 7 | 6 | 13 |
| 2018 January | 9 | 1 | 10 |
| 2017 December | 8 | 1 | 9 |
| 2017 November | 18 | 4 | 22 |
| 2017 October | 20 | 3 | 23 |
| 2017 September | 23 | 5 | 28 |
| 2017 August | 21 | 5 | 26 |
| 2017 July | 8 | 2 | 10 |
| 2017 June | 24 | 16 | 40 |
| 2017 May | 31 | 7 | 38 |
| 2017 April | 22 | 4 | 26 |
| 2017 March | 22 | 4 | 26 |
| 2017 February | 21 | 2 | 23 |
| 2017 January | 18 | 1 | 19 |
| 2016 December | 21 | 10 | 31 |
| 2016 November | 17 | 7 | 24 |
| 2016 October | 52 | 7 | 59 |
| 2016 September | 109 | 7 | 116 |
| 2016 August | 47 | 12 | 59 |
| 2016 July | 28 | 6 | 34 |
| 2016 June | 40 | 20 | 60 |
| 2016 May | 48 | 38 | 86 |
| 2016 April | 48 | 31 | 79 |
| 2016 March | 33 | 20 | 53 |
| 2016 February | 36 | 23 | 59 |
| 2016 January | 35 | 18 | 53 |
| 2015 December | 32 | 11 | 43 |
| 2015 November | 31 | 9 | 40 |
| 2015 October | 25 | 12 | 37 |
| 2015 September | 30 | 12 | 42 |
| 2015 August | 54 | 25 | 79 |
| 2015 July | 42 | 23 | 65 |
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