Utilidad de la midodrina para controlar el síncope vasovagal: ¿la recomienda la evidencia? / Usefulness of Midodrine for the Control of Recurrent Vasovagal Syncope: Does the Evidence Recommend it? / Utilidade da midodrina no controle da síncope vasovagal: as evidencias a recomendam?

Introducción:El síncope vasovagal es la principal causa de pérdida transitoria de la conciencia, y es un motivo de consulta cada vez más frecuente en pediatría y medicina del adulto. La midodrina es un agonista de los recepto-res alfa, de acción periférica, empleada principalmente en el manejo de la hipotensión ortostática; sin embargo, también se ha evaluado en el síncope vasovagal, con resultados prometedores.Objetivo:Analizar la evidencia más reciente sobre la utilidad de la midodrina para el control y la prevención del síncope vasovagal.Materiales y métodos: Se realizó una búsqueda bibliográfica utilizando términos de búsqueda como Vasovagal Syncope y Midodrine, así como sinónimos, que se combinaron con operadores booleanos, en cinco bases de datos, hasta octubre del 2022. Se incluyeron estudios originales, revisiones sistemáticas y metanálisis, publicados tanto en inglés como en español.Resultados:Ensayos controlados aleatorizados y revisiones sistemáticas y metanálisis difieren ligeramente entre resultados, pero estos demuestran un efecto global protector. La evidencia más reciente y completa indica que utilizar este agente reduce significativamente la positividad al realizar la prueba de la mesa inclinada y que previene la aparición de episodios sincopales.Conclusiones:Aunque la evidencia actual sobre la eficacia de la midodrina respecto a la prevención y control del síncope vasovagal es limitada, se observa un efecto protector significativo, porque disminuye el riesgo de sufrir un episodio sincopal, aproximadamente hasta en un 50 %.Palabras clave: midodrina; síncope vasovagal; síncope; adrenérgicos; medicina basada en la evidencia

Introduction: Vasovagal syncope is the main cause of transient loss of consciousness, being an in-creasingly frequent reason for consultation in pediatrics and adult medicine. Midodrine, a periphe-rally acting alpha-receptor agonist, is mainly used in the management of orthostatic hypotension. However, it has also been evaluated in vasovagal syncope, with promising results. Objective: To analyze the most recent evidence on the usefulness of midodrine for the control and prevention of vasovagal syncope. Materials and Methods: A literature search was performed using search terms such as "Vasovagal Syncope" and "Midodrine," as well as synonyms, which were combined with Boolean operators, in 5 databases until October 2022. Original studies, systematic reviews and meta-analyses, published in both English and Spanish, were included. Results: Randomized controlled trials and systematic reviews and meta-analyses differ slightly between results, but these demonstrate an overall protective effect. The most recent and complete evidence shows that using this agent significantly reduces the probability of positivity when performing the tilt table test and prevents the occurrence of syncopal episodes. Conclusions: Although current evidence on the efficacy of midodrine with respect to the prevention and control of vasovagal syncope is limited, a significant protective effect is observed, reducing the risk of suffering syncopal episode by approximately up to 50%

Introdução: a síncope vasovagal é a principal causa de perda transitória de consciência e é um motivo cada vez mais comum de consulta em pediatria e medicina de adultos. A midodrina é um agonista do receptor alfa de ação periférica usado principalmente no tratamento da hipotensão ortostática; no entanto, ela também foi avaliada na síncope vasovagal, com resultados promissores. Objetivo: Revisar as evidências mais recentes sobre a utilidade da midodrina para o controle e a pre-venção da síncope vasovagal. Materiais e métodos: Foi realizada uma pesquisa na literatura usando termos de pesquisa como Va-sovagal, Syncope e Medodrine, bem como sinônimos, que foram combinados com operadores boo-leanos, em cinco bancos de dados, até outubro de 2022. Foram incluídos estudos originais, revisões sistemáticas e metanálises, publicados em inglês e espanhol. Resultados: Os ensaios clínicos randomizados, as revisões sistemáticas e as metanálises diferem ligei-ramente entre os resultados, mas demonstram um efeito protetor geral. As evidências mais recentes e abrangentes indicam que o uso desse agente reduz significativamente a positividade no teste de inclinação da mesa e evita a ocorrência de episódios de síncope. Conclusões: Embora as evidências atuais sobre a eficácia da midodrina em relação à prevenção e ao controle da síncope vasovagal sejam limitadas, observa-se um efeito protetor significativo, pois ela diminui o risco de sofrer um episódio sincopal em aproximadamente 50%

Use of fludrocortisone for intradialytic hypotension

Intradialytic hypotension during dialysis adversely affects a patient's prognosis and increases mortality. We report a case in which intradialytic hypotension that persisted after the administration of midodrine was relieved after the use of fludrocortisone. Administration of 0.2 mg of fludrocortisone occurred 30 minutes before dialysis. We compared 45 sessions of dialysis without fludrocortisone administration and 45 sessions of dialysis with fludrocortisone administration in one patient. The number of times in which systolic blood pressure became lower than 80 mmHg and the number of early terminations of dialysis due to a decrease in systolic blood pressure were higher in the sessions without fludrocortisone administration than in the sessions with fludrocortisone administration (P < 0.05). Fludrocortisone may be helpful for the treatment of intradialytic hypotension that does not respond to midodrine administration.

Effect of Alpha-1-Adrenergic Agonist, Midodrine for the Management of Long-Standing Neurogenic Shock in Patient with Cervical Spinal Cord Injury: A Case Report / 대한신경손상학회지

We report a rare case of a 71-year-old male patient who had suffered from long-lasting neurogenic shock for 13 weeks after cervical spinal cord injury (SCI) caused by a bicycle accident. The neurogenic shock was resolved dramatically 2 weeks after the administration of alpha-1-adrenergic agonist, midodrine hydrochloride. In usual cases, neurogenic shock tends to improve between 2 and 6 weeks after SCI; however, in a few cases, the shock lasts for several months. In our case, spinal shock lasted for 13 weeks and exhibited very sensitive decline of blood pressure for even a slight decrease of dopamine despite recovered bulbospongiosus reflex. Three days after midodrine hydrochloride was added, hypotension improved dramatically. We discuss our rare case with pertinent literatures.

Predictive value of baseline plasma midregional fragment of pro-adrenomedullin level on long-term outcome of postural tachycardia syndrome children treated with midodrine hydrochloride / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the predictive value of baseline plasma midregional fragment of pro-adrenomedullin level (MR-proADM) on long-term survival of postural tachycardia syndrome (POTS) children treated with midodrine hydrochloride.</p><p><b>METHODS</b>Fifty-three children (male 26, mean age (14.5 ± 4.5) years old) with POTS were included in this study, and all of them were diagnosed as POTS in our department from December 2007 to January 2010. Fifty-three children with POTS were divided into two groups according to the baseline plasma content of MR-proADM. Group I consisted of 35 POTS children with plasma content of MR-proADM > 61.5 ng/L, and the group II consisted of 18 POTS children with plasma content of MR-proADM ≤ 61.5 ng/L. The mean follow-up time was (67 ± 7) months. The orthostatic intolerance symptom score and the symptom free survival were compared between the 2 groups.</p><p><b>RESULTS</b>At the 60 months follow-up, the symptom score of children in group I was significantly lower than that in group II (χ(2) = 4.985, P < 0.05). At 72 months follow up, the symptom score was similar between the 2 groups (χ(2) = 0.004, P > 0.05) while the symptom free survival of group I was significantly higher than that in group II (χ(2) = 4.566, P < 0.05).</p><p><b>CONCLUSION</b>The baseline plasma MR-proADM level is value in predicting the long-term survival of POTS children treated with midodrine hydrochloride.</p>

Prognostic analysis of orthostatic intolerance using survival model in children / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Orthostatic intolerance (OI) is a common disease at pediatric period which has a serious impact on physical and mental health of children. The purpose of this study was to investigate the effect of related factors on the prognosis of children with OI.</p><p><b>METHODS</b>The subjects were 170 children with OI, including 71 males (41.8%) and 99 females (58.2%) with age from 6 to 17 (12.0±2.6) years. The effect of related factors on the prognosis of children was studied by using univariate analysis. Then, the impact of children's age, symptom score, duration, disease subtype, and treatment on patient's prognosis was studied via analysis of COX proportional conversion model.</p><p><b>RESULTS</b>Among 170 cases, 48 were diagnosed with vasovagal syncope, including 28 cases of vasoinhibitory type, 16 cases of mixed type, and 4 cases of cardioinhibitory type; 115 cases were diagnosed with postural tachycardia syndrome and 7 cases with orthostatic hypotension. By using univariate analysis of Cox regression, the results showed that symptom score had a marked impact on the time of symptoms improvement of children after taking medication (P < 0.05), while other univariates had no impact (P > 0.05). Multivariate analysis using Cox proportional hazards regression model showed that the symptom score at diagnosis had a significant effect on holding time of symptoms improvement of children after taking medication (P < 0.05). Kaplan-Meier curve showed that symptom-free survival was higher in children with symptom score equal to 1 than children with symptom score equal to or greater than 2 during follow-up (P < 0.05).</p><p><b>CONCLUSION</b>Symptom score is an important factor affecting the time of symptom improvement after treatment for children with OI.</p>

Noradrenalin versus the combination of midodrine and octreotide in patients with hepatorenal syndrome: randomized clinical trial

Hepatorenal syndrome [HRS] is known as development of acute renal failure in a patient who usually has advanced liver disease. The aim of the present study was to determine the safety and the efficacy of noradrenalin in comparison with midodrine-octreotide in patients with HRS. This study was registered to the Iranian Registry of Clinical trials [IRCT]. This study was a single-center, randomized, clinical trial that performed in Alzahra hospital, Isfahan, Iran. Since March 2011 to January 2012, twenty-three patients were enrolled in the study. Eligible patients were allocated in 2 groups. In the first group, patients received infusion of NA with the dose of 0.1-0.7 micro g/kg/min, and in the other groups, patients received octreotide 100-200 micro g subcutaneously 3 times daily and midodrine 5-15 mg orally 3 times daily. In both study groups, patient received albumin infusion in addition to noradrenalin or midodrine-octreotide. Complete response of HRS was observed in 8 of the 11 patients [73%] treated with noradrenalin and in 9 of the 12 patients [75%] treated with midodrine-octreotide [P > 0.05]. HRS recurred after treatment withdrawal in 2 of 11 in NA and 3 of 12 in MO group. That shows no significant difference between 2 groups [P > 0.05]. We deduce that NA has the same efficacy and safety with MO and can induce a complete response in high percentage of the patients. Moreover, we observed no significant differences in the recurrence rate and outcomes after 3 months among the patients in both study groups; this result could support the use of NA in HRS management

Therapies for postural tachycardia syndrome in children / 中华儿科杂志

<p><b>OBJECTIVE</b>This study was designed to compare the short-term and long-term effects of oral rehydration salts, oral rehydration salts plus metoprolol or oral rehydration salts plus midodrine hydrochloride on the treatment of postural tachycardia syndrome (POTS) in children.</p><p><b>METHOD</b>A total of 118 children with POTS were divided into oral rehydration salts group (n = 39), metoprolol group (oral rehydration salts plus metoprolol, n = 10) or midodrine hydrochloride group (oral rehydration salts plus midodrine hydrochloride, n = 69). The patients were followed up in clinics or over telephone for 3 - 18 months, with a mean of (11.7 ± 4.1) months. The symptom scores were recorded before treatment, after 3 months and at the end of the follow-up. Reduction of the score by 2 points or more was considered that the treatment was effective. The effective rate in 3 months was applied to evaluate short-term effects of 3 different therapies by chi-square test. Taking futility as events, Kaplan-Meier curves were drawn to compare long-term effects of the 3 different therapies in treating POTS in children.</p><p><b>RESULT</b>No significant differences among the 3 groups were found in sex, age, body height, weight, the symptom scores before treatment or hemodynamic variables. Oral rehydration salts, metoprolol and midodrine hydrochloride improved clinical symptoms after 3 months. The symptom scores of the 3 groups before treatment and after 3 months were 2.4 ± 3.2 vs. 5.5 ± 2.9, 2.2 ± 3.0 vs. 6.1 ± 3.0 and 1.9 ± 1.6 vs. 5.9 ± 2.7, respectively. The difference was significant (P < 0.05). Descending order of the short-term effective rate was 91.3% in midodrine hydrochloride group, 80.0% in metoprolol group and 74.4% in oral rehydration salts group. The difference was significant (χ(2) = 5.85, P < 0.05). All the 3 different therapies improved clinical symptoms at the end of follow-up. The symptom scores were 2.6 ± 3.2 vs. 5.6 ± 2.9, 2.5 ± 3.1 vs. 6.1 ± 3.0 and 2.2 ± 2.1 vs. 6.0 ± 2.7, respectively. (P < 0.05). The result of the Kaplan-Meier curves showed that the long-term effect of midodrine hydrochloride was significantly superior to metoprolol group and oral rehydration salts group (P < 0.05). There was no significant difference between the latter two groups.</p><p><b>CONCLUSION</b>Oral rehydration salts plus midodrine hydrochloride or plus metoprolol improved the efficacy of drugs in children with POTS. And the efficacy of midodrine hydrochloride was superior to that of metoprolol.</p>

Persistent Autonomic Dysfunction in Guillain-Barre Syndrome: A case report

Autonomic dysfunction is a common manifestation in Guillain-Barre syndrome (GBS), but it rarely persists. We report a case involving a 22-year-old man who presented with glove-and-stocking type sensory loss, symmetric weakness, urinary distension, orthostatic hypotension, decreased perspiration, and the syndrome of inappropriate secretion of antidiuretic hormone. He was subsequently diagnosed as having GBS with autonomic failure that persisted for more than six months, despite regaining muscle strength. Orthostatic hypotension progressively improved after rehabilitation and administration of midodrine and fludrocortisone. Extensive evaluation and management should be performed in patients with GBS because severe autonomic dysfunction is a major source of disability.

Effect of selective alpha1 receptor agonist in the treatment of children with postural orthostatic tachycardia syndrome / 中华儿科杂志

<p><b>OBJECTIVE</b>The study was designed to examine the effect of selective alpha1 receptor agonist midodrine hydrochloride in the treatment of children with postural orthostatic tachycardia syndrome.</p><p><b>METHODS</b>Fifty-five children (23 male, 32 female, age 5 - 19 yrs, mean age 12.3 +/- 3.1 yrs) who came from Peking University First Hospital were included in the study and clinical investigations as well as standing test, basic head-up tilt test and sublingual nitroglycerin-provocated head-up tilt test under quiet circumstance were conducted. They were randomly divided into treatment group (with midodrine hydrochloride and oral rehydration salt treatment) and control group (with oral rehydration salt treatment only). At last, the disease-free rate, improvement rate and effective rate of symptoms, and the rate of HUT from positive to negative response were compared between control group and treatment group. SPSS 10.0 software was used for the statistical analysis of these data.</p><p><b>RESULTS</b>The symptom improvement rate in treatment group was significantly higher than that of control group after three and six weeks of treatment (100.0% vs. 42.4%, P < 0.001; 100.0% vs. 42.4%, chi2 = 19.352, P < 0.001). The disease-free rate at follow-up end-point in treatment group was significantly higher than that of control group (77.3% vs. 27.3%, chi2 = 13.239, P < 0.001). The effective rate at follow-up end-point in treatment group was also significantly higher than that of control group (100.0% vs. 36.4%, chi2 = 22.647, P < 0.001). The rate of HUT changing from positive to negative response between two groups after three weeks of treatment was not significantly different (31.8% vs. 12.1%, P > 0.05), but it was significantly different (81.0% vs. 48.5%, P < 0.05) after six weeks of treatment.</p><p><b>CONCLUSION</b>Selective alpha1 receptor agonist midodrine hydrochloride is effective in the treatment of children with postural orthostatic tachycardia syndrome.</p>

The Effect of Midodrine on Exercise-induced Hypotension in Cervical Cord Injury Patients

OBJECTIVE: To evaluate the effect of midodrine, an alpha(1) agonist, on symptom and hemodynamic response during standing and arm bicycle ergometer exercise in patients with cervical cord injury. METHOD: Twelve cervical spinal cord injury patients with orthostatic hypotension symptoms and post-exercise hypo- tension were enrolled. They were positioned on a 90degrees standing frame for 3 minutes. After 15 minutes of resting on supine position, 5 minutes of arm bicycle ergometer exercise was done. These tests were done without midodrine initially, but, with 5 mg midodrine on the next day. Heart rate, self-perceived presyncope score (PPS), systolic and diastolic blood pressure were measured before, during and after the exercise. RESULTS: With 5 mg midodrine, the decrease of systolic and diastolic blood pressures after 3 minutes' standing was significantly smaller than without midodrine (p<0.05). PPS was also significantly decreased with midodrine on standing frame test. Arm ergometer exercise induced less systolic blood pressure decrease and better PPS on immediate and 5 minutes after exercise with midodrine (p<0.05). The change of diastolic blood pressure and heart rate was not significant after the exercise with midodrine. CONCLUSION: In cervical spinal cord injury patients with orthostatic and post-exercise hypotension, 5 mg midodrine significantly improved the symptoms and the systolic blood pressures.

Disautonomía: un problema médico poco conocido / Dysautonomia: a not well known medical problem

La disautonomía es una condición médica frecuente, que por lo general cursa sin ser diagnosticada y es causada de problemas crónicos y mala calidad de vida. Estos enfermos muchas veces peregrinan de mÚdico en médico, se les hacen múltiples exámenes, se plantean múltiples hipótesis, pero el diagnóstico preciso no se hace, ya que no se tiene en cuenta la disautonomía. Una vez confirmado el diagnóstico con un Tilt test, se puede tratar sintomßticamente con bastante éxito. Hemos visto que la disautonomía frecuentemente se asocia al síndrome de hiperlaxitud articular, que es una forma frustra de las alteraciones hereditarias de la fibra colágena, que es muy prevalente en Chile.

Efecto de la midodrina en la hipotensión sintomática en hemodiálisis / Effects of midodrine on orthostatic hypotension during hemodialysis

Background: Hypotension occurs in 20 percent of hemodialysis procedures. Aim: To study the effects of midodrine on hypotension during hemodialysis. Patients and methods: Ten patients on chronic hemodialysis and with a history of hypotension during the procedure, were studied. They received midodrine 10 mg per os or placebo during 5 dialytic procedures each, in a double blind cross over design. Results: Blood pressure levels prior to dialysis were similar during the midodrine or placebo administration periods. During dialysis, systolic blood pressure fell 19.3ñ28 mmHg with midodrine and 23.4ñ28 mmHg with placebo. Diastolic blood pressure fell 7.3ñ11.5 mmHg with midodrine and 11.1ñ12 mmHg with placebo. The reduction in median arterial pressure was also less pronounced with midodrine. Conclusions: Midodrine lessens the fall in arterial pressure during hemodialysis, in patients with symptomatic hypotension

Midodrine for the Treatment of Hypotension in a Tetraplegic Patient with Cervical Cord Injury in ICU: A case report / 대한구급학회지

Cervical spinal cord injury results in significant dysfunction of the sympathetic nervous system. Reduced sympathetic activity below the level of spinal cord injury is associated with low resting blood pressure,orthostatic hypotension,and reflex bradycardia.Hypotension can be treated with vasoactive agents,such as dopamine,epinephrine,norepinephrine, and phenylephine .Orally administered midodrine is an alpha adrenergic receptor agonist that increases blood pressure with vasoconstriction.Its action is fast and effective in treating hypotension in patients with spinal cord injury,and it has less severe side effects.A 70-year-old tetraplegic patient with fracture and dislocation of C6-7 after a motor vehicle accident was admitted to ICU and underwent anterior cervical intervertebral body fusion.Symptomatic hypotension following postural changes was treated with intravenous infusion of dopamine,but it was difficult to reduce the dose of dopamine without causing severe hypotension.Midodrine was prescribed and the patient was well tolerated without any adverse effect.With adequately maintained blood pressure,intravenous infusion of dopamine was successfully switched to the oral midodrine.This case suggests that the midodrine is effective for the treatment of hypotension in tetraplegic patients with spinal cord injury and enables patients to participate in early rehabilitation therapies.

Uso de midodrín y congelación de semen en el tratamiento de las alteraciones del transporte espermático: caso clínico / Use of midodrine and frozen/thawed semen to treat semen transport disturbances: report of 2 cases

Retrograde ejaculation severely compromises male fertility. The use of sympathicomimetics for the treatment of this condition has poor results, except in patients with partial retrograde ejaculation, whose semen has a higher spermatozoa concentration. The semen of two patients with partial retrograde ejaculation was collected and frozen after the injection of a sympathicomimetic (Midodrine). The frozen/thawed samples were mixed with fresh semen recently ejaculated to obtain a minimal number of motile spermatozoa, and used for intrauterine insemination (> de 1 x 106 motile spermatozoa/ml). In both cases, pregnancies that developed satisfactorily, were obtained

Nonocclusive mesenteric ischemia in a patient on maintenance hemodialysis

Nonocclusive mesenteric ischemia (NOMI) is known to occupy about 25+ACU- to 60+ACU- of intestinal infarction. NOMI has been reported to be responsible for 9+ACU- of the deaths in the dialysis population and the postulated causes of NOMI include intradialytic hypotension, atherosclerosis and medications, such as diuretics, digitalis and vasopressors. Clinical manifestations, such as fever, diarrhea and leukocytosis, are nonspecific, which makes early diagnosis of NOMI very difficult. Case: A 66-year-old woman on maintenance hemodialysis for 5 years was admitted with syncope, abdominal pain and chilly sensation. Since 7 days prior to admission, blood pressure on the supine position during hemodialysis had frequently fallen to 80/50 mmHg. Four days later, she complained of progressive abdominal pain. Rebound tenderness and leukocytosis (WBC 13900/mm3) with left shift were noted. Stool examination was positive for occult blood. Abdominal CT scan showed a distended gall bladder with sludge. Under the impression of acalculous cholecystitis, she was operated on. Surgical and pathologic findings of colon colon were compatible with NOMI. Because of recurrent intradialytic hypotension, we started midodrine 2.5 mg just before hemodialysis and increased the dose up to 7.5 mg. After midodrine therapy, blood pressure during dialysis became stable and the symptoms associated with hypotension did not recur. CONCLUSION: As NOMI may occur within several hours or days after an intradialytic hypotensive episode, abdominal pain should be carefully observed and NOMI should be considered as a differential diagnosis. In addition, we suggest that midodrine be considered to prevent intradialytic hypotensive episodes.

Síncope neurocardiogénico cardio-inhibitorio en niños y adolescentes: características clínicas, tratamiento y evolución / Neurocardiogenic syncope in children and adolescents: clinical course and treatment

Los síndromes de hipotensión arterial ortostáticos constituyen las principales causas que explican muchos de los síncopes de etiología no precisada. En la mayoría de los pacientes pediátricos se documenta síncope neurocardiogénico mixto y vasodepresor t, en menor proporción, síncope cardioinhibitorio. El pronóstico de este último subgrupo no está del todo dilucidado. El objetivo del presente trabajo fue evaluar las características clínicas, tratamiento y evolución de los síncopes cardio-inhibitorios, definidos como IIA y IIB según clasificación del grupo VASIS, en un grupo de niños y adolescentes. Se estudió prospectivamente a 100 niños y adolescentes de 8 a 16 años de edad, con síncope o pre-síncope de etiología no precisada, desde 1/1/98 hasta 1/7/99. Se practicó test de Tilt a todos según recomendaciones del ACC Expert Consensus Document. 52 por ciento no presentó alteraciones. 10 por ciento presentó síncope neurocardiogénico cardioinhibitorio, 34 por ciento síncope neurocardiogénico mixto y vasodepresor, 4 por ciento pooling venoso patológico, 3 por ciento síndrome de taquicardia postural ortostática, 1 por ciento prolongación del QT. En el grupo de pacientes con síncope cardio-inhibitorio, la edad promedio fue de 12 ñ 2 años (4 mujeres y 6 hombres). Ninguno requirió isoprotenol para reproducir el síncope cardio-inhibitorio. 5/10 presentaron mioclonías y no hubo traumatismos secundarios. Casi todos presentaron más de 5 episodios sincopales (8/10) e historia de más de 1 año de evolución (9/10). 9/10 fueron síncopes cardio-inhibitorios tipo IIA y 1/10 de tipo IIB. El tipo de tratamiento fue individual y dependió del médico tratante. Un paciente requirió marcapaso (tipo IIB). El seguimiento promedio fue de 6 meses (3 a 13 meses), con excelente respuesta clínica. Conclusiones: En población pediátrica, 10 por ciento de los síncopes de etiología no precisada correspondió a síncope cardioinhibitorio. La mayoría recibió tratamiento farmacológico por períodos relativamente breves (2-3 meses) o no recibió tratamiento, con excelente respuesta clínica a los 6 meses de seguimiento (3-13 meses)