ABSTRACT
Syncope is a common emergency of children and adolescents,which has serious influence on the quality of life.Neurally-mediated syncope,including postural tachycardia syndrome,vasovagal syncope,orthostatic hypotension and orthostatic hypertension,is the main cause of syncope in children and adolescents.The main manifestations of neurally-mediated syncope are diverse,such as dizziness,headache,chest tightness,chest pain,pale complexion,fatigue,pre-syncope and syncope.Although the clinical manifestations are similar,each subtype of syncope has its hemodynamic feature and optimal treatment option.The diagnosis rate of syncope in children has been greatly improved on account of the development of the diagnostic procedures and methods.In recent years,with the promotion of head-up tilt test and drug-provocated head-up tilt test,the hemodynamic classification of neurally-mediated syncope gets continually refined.In recent years,with the effort of clinicians,an appropriate diagnostic protocol for children with syncope has been established.The initial evaluation consists of history taking,physical examination,standing test and standard electrocardiography.After the initial evaluation,some patients could be diagnosed definitely,such as postural tachycardia syndrome,orthostatic hypotension,and situational syncope.Those with a specific entity causing syncope need selective clinical and laboratory investigations.Patients for whom the cause of syncope remained undetermined should undergo head-up tilt test.The precise pathogenesis of neurally-mediated syncope is not entirely clear.In recent years,studies have shown that neurally-mediated syncope may be related to several factors,including hypovolemia,high catecholamine status,abnormal local vascular tension,decreased skeletal muscle pump activity and abnormal neurohumoral factors.Currently based on the possible pathogenesis,the individualized treatment of neurally-mediated syncope has also been studied in-depth.Generally,the management of neurallymediated syncope includes non-pharmacological and pharmacological interventions.Patient education is the fundamental part above all.In addition to exercise training,the first-line treatments mainly include oral rehydration salts,beta adrenoreceptor blockers,and alpha adrenoreceptor agonists.By analyzing the patient's physiological indexes and biomarkers before treatment,the efficacy of medication could be well predicted.The individualized treatment will become the main direction in the future researches.
ABSTRACT
Objective:To deepen our understanding of Methylmalonic aciduria (MMA) associated pulmonary hypertension (PH) by analyzing the characteristics of clinical presentation,pulmonary high resolusion CT(HRCT),treatment response and gene mutation.Methods:This study includes 15 cases of pediatric patients with MMA associated PH diagnosed and treated in Peking University First Hospital pediatric department between May 2012 and May 2016 with symptoms of PH as their leading presentation.Clinical symptoms and signs were recorded,Routine blood laboratory examinations was done including arterial blood gas analysis.Plasma total homocysteine (Hcy) and brain natriuretic peptide (BNP) level were measured.MMA gene mutation was analyzed.Chest HRCT was done in most of the patients.Standard treatment strategy to MMA and PH was given and follow up study was done,and the related literature was reviewed.Statistical analysis was done.The diagnosis of MMA was made by methylmalonic acid level ＞ 100 times the normal value in the urine.The diagnosis of PH was made by pulmonary arterial systolic pressure (PASP) ＞ 40 mmHg,which was estimated by the measurement of tricuspid regurgitation velocity through Doppler Echocardiography.Results:(1) Patient characteristics:There were 10 male and 5 female patients diagnosed as MMA associated PH,aged 0.5 to 13.8 years,with an average of (5.0 ± 4.3) years.The age of onset of PH was (3.7 ± 3.5) years,with an early onset type MMA in 5 cases and late-onset type in 10 cases.(2) Clinical presentation:Among the 15 cases of MMA,the first symptoms were associated with PH in 10 cases,so PH and MMA were diagnosed at the same time,and PH was diagnosed 3 to 72 months post MMA presentation in the other 5 cases.The main presentations of PH were techypnea/dyspnea and cyanosis in 11 cases each,weakness and fatigue on exertion in 6 cases,and edema in 4 cases.PH WHO functional classification (WHO FC) was Class Ⅱ in 4,Class Ⅲ in 5 and Class Ⅵ in 6 cases,with an average of Class 3.1 ± 0.8.Multi-system involvements were common with the highest frequency in the kidney (14 cases).Macrocytic anemia was present in 8 cases and subclinical hypothyroidism in 5 cases,and mild to moderate mental retardation in 4 cases.(3) Laboratory examination:PASP of the 15 patients was from 49 to 135 mmHg,with an average of (90.3 ±23.9) mm Hg.Total blood Hcy level was severely elevated to (121.2 ± 48.2) μmol/L (range:35.0-221.0 μmol/L),and Hcy ＞ 100 μmoL/L within 11 cases.Plasma BNP level was also elevated,median 794 ng/ L (range:21.0-4 995.0 ng/L) with 12 cases ＞ 300 ng/L.Blood gas analysis showed low arterial blood oxygen saturation between 70％ and 94％,with an average of 81.4％ ±8.4％.(4) Chest HRCT:chest HRCT showed a diffuse ground-glass centrilobular nodular opacities with septal line thickening in the lungs in 9 cases,and with associated mediastinal lymph node enlargement in 1 case,which indicated pulmonary veno-occlusive disease (PVOD),a rare type of pulmonary arterial hypertension (PAH).There was lung infection or edema in 3 cases,and interstitial infiltration and mesh-like feature in other 3 cases,which was inferred to interstitial lung disease.(5) Gene mutation:Genetic testing was done in 10 cases,totally 5 reported disease-causing mutations were found.There were 100％ presence of MMACHC c.80A ＞ G mutation in all the 10 patients tested,with the allelic genes of c.609G ＞ A mutation in 6 patients,including a sister and a brother from the same parents.(6).Treatment and follow up:Intramus cular hydroxocobalamin or vitamin B12 was given to all of the patients,together with betaine,levocarnidtine,folinic acid and vitamin B6.According to the severity of PH,single or combined PAH targeted drugs was given to 11 cases.By an average of (20.0 ± 13.5) days of in-hospital treatment in 13 patients (excepting 1 case treated as outpatient),symptoms remarkably resolved,WHO FC reduced to an average of Class 2.4 ±0.9,PASP dropped to (69.4 ±21.3) mmHg,and plasma Hcy and BNP level were decreased to (74.9 ± 25.9) μmol/L and (341.6 ± 180.2) ng/L,respectively.The above values all reached statistical significance (P ＜ 0.05) compared with each related value before treatment.Therewere 2 patients who expired during hospitalization despite of treatment.At the end of 3 months' follow up,all of the 13 patients disposed oxygen,and PASP significantly dropped to 38.7 ± 7.9 mmHg,and plasma BNP returned to normal,but plasma Hcy level showed no further decline.At the last follow up of 27.5 ± 19.0 (range:11-64) months,all the patients' PASP remained normal except for the 13.8-year-old boy with 6 years-long history of MMA and almost 3.6 years' history of PH still having PASP 58 mmHg.Conclusion:PH is a severe complication of MMA combined type,especially cblC type,it is more often happens in late-onset type of male patients and can be the first and leading manifestations of MMA.Its clinical symptoms are urgent and severe,characterized by tachypnea/dyspnea and cyanosis,and sometimes right heart failure,hypoxemia is usually present,chest HRCT is often indicative of PVOD,lung edema and interstitial lung disease may occur.Rapid diagnosis and targeted treatment of MMA with appropriate anti-PAH mcdication can reverse PH and save life.MMACHC gene c.80A ＞ G mutation may be the hot point of MMA cblC type associated PH.
ABSTRACT
Objective:To explore the clinical characteristics of the co-morbidity of vasovagal syncope (VVS) and postural tachycardia syndrome (POTS) with allergic diseases in children.Methods:A retrospective analysis was launched to summarize the clinical data of children with VVS and POTS.They were divided into allergic group and non-allergic group according to the history of allergic diseases.The participants' clinical characteristics were compared between allergic group and non-allergic group using independent sample t test or rank sum test;composition comparisons were completed by Chi-square test.Bi-variate correlation analysis was used to explore the association between eosinophil percentage/count and symptom scores/frequency of syncope episodes.A P value ＜ 0.05 was defined as statistically significant.Results:Sixty-seven children complaining of orthostatic intolerance (43 patients diagnosed as VVS and 24 cases diagnosed as POTS) were enrolled.Totally 21 cases (31％) had allergic diseases,inclu ding allergic rhinitis,atopic eczema,asthma,as well as food allergy.And allergic rhinitis is the most common co-morbidity.There were no significant differences between the two groups in age,gender ratio,height,body weight and basement blood pressure.Compared with the non-allergic group,the allergic group showed later onset age (year) (11 ± 2 vs.9 ± 3,P ＜ 0.05) of orthostatic intolerance and shorter course of the diseases (month) [8.0 (0.1,0.1) vs.24.0 (0.1,144.0),P＜0.05].The frequency of syncope episodes in the allergic group among VVS children (times per month) [2.50 (0.08,30.00) vs.O.25 (0.03,5.00),P ＜ 0.05] was much higher than that in the non-allergic group.Additionally,the eosinophil percentage (％) [3.50 (0.70,0.59) vs.1.65 (0.30,6.20),P＜0.001] and eosino phil count (×109) [0.18 (0.05,0.71) vs.0.10 (0.02,0.38),P＜0.001] were increased in the allergic group.However,there were no remarkable differences in the results of head-up tilt test in children with VVS or in the maximum change of heart rate during standing test in children with POTS were involved.Conclusion:Allergic diseases are common co-morbidities in children with both VVS and POTS.Allergic rhinitis is the most common co-morbidity.Children with co-morbidity of VVS/POTS and allergic diseases had a later onset of symptoms of orthostatic intolerance,and were more likely to be hospitalized for intensive attacks of symptoms during a short period when compared with those without allergic diseases.Children diagnosed as VVS combined with allergic diseases had more frequent episodes of syncope.