Background
Fabry disease (FD) is a rare inherited lysosomal storage disorder caused by the deficiency of the enzyme alpha-galactosidase A. This deficiency leads to an accumulation of ...glycosphingolipids leading to progressive and multisystemic disease, including renal, cardiac, and neurological damages. FD may also have neuro-otological and visual impairments, which can generate postural control alterations, inner ear, and vision being involved in this function. This study aimed to evaluate the impact of FD on postural control.
Methods
In total, fourteen adult patients (8 men/6 women, mean age = 37.6 ± 11.4 years) and two children (mean age = 11 years) with FD and 19 healthy adults (12 men/7 women, mean age = 36.5 ± 16.9 years) and two healthy children (mean age = 10.5 years) took part in this study. Postural control was evaluated by a sensory organization test combining three visual situations (eyes open, eyes closed, and sway referenced visual surround motion) with two platform situations (stable platform and sway referenced platform motion), aiming to calculate a composite equilibrium score (CES), a high score being representative of good postural control. Somatosensory (R
SOM
), visual (R
VIS
), and vestibular (R
VEST
) contributions to postural control were calculated, a low score reflecting a poor use of the indicated sensory input.
Results
The CES was lower in adult patients with FD compared with the healthy subjects (
p
< 0.001). R
VIS
(
p
= 0.001) and R
VEST
(
p
= 0.003) were lower in patients with FD compared with the control group, whereas no difference in R
SOM
was observed.
Conclusion
Inner ear and visual pathologies associated with the central nervous system impairments are factors of postural control impairments. Physical activities, which can also be rehabilitative, by maintaining or increasing the weight of proprioception, may help diminish dependency on altered sensorial inputs.
Bevacizumab, an anti-VEGF monoclonal antibody, has recently emerged as a new option for severe forms of hereditary hemorrhagic telangiectasia (HHT). Its utilization in this orphan disease has rapidly ...spread despite the lack of randomized trials and international guidelines. The objective of this study is to report the main clinical data (baseline characteristics, dose schedule, efficacy, adverse events and deaths) of HHT patients treated by intravenous bevacizumab in France.
Retrospective observational study of HHT patients treated with bevacizumab for a severe form of the disease in the 14 centers of the French HHT network.
Forty-six patients (median age: 68 years) were treated between March 2009 and May 2015. Ten patients were treated for high output cardiac failure, 20 patients for severe hemorrhages and 16 for both indications. The standard protocol (6 infusions of 5mg/kg every 2 weeks) was initially used in 89% of the cases but diverse strategies were subsequently applied. A clinical improvement was noted by the referent physician for 74% of the patients with a median effect's duration of 6 months. Wound healing complications led to 2 amputations. Arthralgia/arthritis and arterial hypertension occurred in 5 patients each. One third of the patients were dead at the time of the final update, coherently with age and the poor prognosis of these highly symptomatic patients.
Intravenous bevacizumab seems to provide a clinical benefice in severe HHT patients. Precautions concerning wound healing and vascular pathologies must be respected. Prospective double blinded versus placebo trials are needed.
To investigate the validity of the global APS score (GAPSS) to predict thrombosis in patients with autoimmune diseases.
This prospective cohort study included consecutive patients with aPL or SLE. ...aPL, aPS-PT and GAPSS were determined. A Cox proportional hazards model assessed the validity of GAPSS and identified other potential independent predictors of thrombosis.
One hundred and thirty-seven patients 43.5 (s.d. 15.4) years old; 107 women were followed up for a mean duration of 43.1 (s.d. 20.7) months. Mean GAPSS was significantly higher in patients who experienced a thrombotic event compared with those without 10.88 (s.d. 5.06) vs 8.15 (s.d. 5.31), respectively, P = 0.038. In univariate analysis, age hazard ratio (HR) = 1.04 (95% CI 1.01, 1.08) and GAPSS above 16 HR = 6.86 (95% CI 1.90, 24.77) were each significantly associated with thrombosis during follow-up, while history of arterial thrombosis HR = 2.61 (95% CI 0.87, 7.82) failed to reach significance. Among aPL assays, IgG aPS/PT--a component of the GAPSS--was significantly associated with thrombosis HR = 2.95 (95% CI 1.02, 8.51). In multivariate analysis, GAPSS above 16 remained the only significant predictor of thrombosis HR = 6.17 (95% CI 1.70, 22.40).
This first external validation study confirmed that GAPSS can predict thrombosis in patients with aPL and associated autoimmune diseases.
Different pulmonary hypertension (PH) mechanisms are associated with hereditary haemorrhagic telangiectasia (HHT).
We conducted a retrospective study of all suspected cases of PH ...(echocardiographically estimated systolic pulmonary artery pressure sPAP ≥ 40 mmHg) in patients with definite HHT recorded in the French National Reference Centre for HHT database. When right heart catheterization (RHC) was performed, PH cases were confirmed and classified among the PH groups according to the European guidelines. Among 2,598 patients in the database, 110 (4.2%) had suspected PH. Forty-seven of these 110 patients had RHC: 38/47 (81%) had a confirmed diagnosis of PH. The majority of these had isolated post-capillary PH (n = 20). We identified for the first time other haemodynamic profiles: pre-capillary pulmonary arterial hypertension (PAH) cases (n = 3) with slightly raised pulmonary vascular resistances (PVR), and combined post- and pre-capillary PH cases (n = 4). Compared to controls, survival probability was lower in patients with PAH.
This study revealed the diversity of PH mechanisms in HHT. The description of combined post- and pre-capillary PH with/or without high cardiac output (CO) suggests either a continuum between the pre- and post-capillary haemodynamic profiles or a different course in response to high CO.
Highlights • Ventilatory response to CO2 is reduced in myotonic dystrophy patients. • Reduced ventilatory response to CO2 appeared independent of lung function impairment. • Myotonic dystrophy ...patients showed a central cause of CO2 insensitivity.
Clinical features, complications and treatments of Gaucher's disease (GD), a rare autosomal-recessive disorder due to a confirmed lysosomal enzyme (glucocerebrosidase) deficiency, are described.
All ...patients with known GD, living in France, with ≥ 1 consultations (1980-2010), were included in the French GD registry, yielding the following 4 groups: the entire cohort, with clinical description; and its subgroups: patients with ≥ 1 follow-up visits, to investigate complications; recently followed (2009-2010) patients; and patients treated during 2009-2010, to examine complications before and during treatment. Data are expressed as medians (range) for continuous variables and numbers (%) for categorical variables.
Among the 562 registry patients, 265 (49.6%) were females; 454 (85.0%) had type 1, 22 (4.1%) type 2, 37 (6.9%) perinatal-lethal type and 21 (3.9%) type 3. Median ages at first GD symptoms and diagnosis, respectively, were 15 (0-77) and 22 (0-84) years for all types. The first symptom diagnosing GD was splenomegaly and/or thrombocytopenia (37.6% and 26.3%, respectively). Bone-marrow aspiration and/or biopsy yielded the diagnosis for 54.7% of the patients, with enzyme deficiency confirming GD for all patients. Birth incidence rate was estimated at 1/50,000 and prevalence at 1/136,000. For the 378 followed patients, median follow-up was 16.2 (0.1-67.6) years. Major clinical complications were bone events (BE; avascular necrosis, bone infarct or pathological fracture) for 109 patients, splenectomy for 104, and Parkinson's disease for 14; 38 patients died (neurological complications for 15 type-2 and 3 type-3 patients, GD complications for 11 type-1 and another disease for 9 type-1 patients). Forty-six had monoclonal gammopathy. Among 283 recently followed patients, 36 were untreated and 247 had been treated during 2009-2010; 216 patients received treatment in December 2010 (126 with imiglucerase, 45 velaglucerase, 24 taliglucerase, 21 miglustat). BE occurred before (130 in 67 patients) and under treatment (60 in 41 patients) with respective estimated frequencies (95% CI) of first BE at 10 years of 20.3% (14.1%-26.5%) and 19.8% (13.5%-26.1%).
This registry enabled the epidemiological description of GD in France and showed that BE occur even during treatment.
To describe the possible association (pathophysiologic and clinical features) between exertional heat stroke (EHS) and malignant hyperthermia (MH).
Both EHS and MH are acute and life-threatening ...disorders. It has repeatedly been shown that EHS can occur in well-trained patients with known MH-associated mutation in the RYR1 gene in the absence of any extreme environmental conditions or extreme physical activity, thereby supporting a possible link between EHS and MH. In this case, a highly trained 30-year-old male athlete suddenly collapsed while running. He had initial hyperthermia (40.2°C) and progressive multiple organ failure requiring medical management in an intensive care unit. After he recovered completely, a maximal exercise test was performed and showed an obvious abnormality of oxidative metabolism in muscle; genetic analysis of the RYR1 gene identified a heterozygous missense variation p.K1393R. Consequently, the athlete was given appropriate information and allowed to progressively return to sport competition.
Doping, use of drugs and toxic agents, exercise-associated hyponatremia, exertional heat illness.
Initial management started with the basic resuscitative guidelines of airway, breathing, and circulation (intubation). Cooling, administration of fresh frozen plasma, and intensive rehydration resulted in improvement.
To our knowledge, ours is the first description of this MH mutation (p.K1393R) in the RYR1 gene that was associated with exertional rhabdomyolysis involving a dramatic impairment of oxidative metabolism in muscle.
Common features are shared by EHS and MH. Careful attention must therefore be paid to athletes who experience EHS, especially in temperate climates or when there are no other predisposing factors.
Background
Several arrhythmias were reported in myotonic dystrophy (MD).
Objectives
To evaluate the prevalence of atrial fibrillation (AF) and atrial flutter (AFL) in MD and the clinical ...consequences.
Methods
One hundred sixty‐one patients, mean age 41 ± 14 years, were referred for a type 1 MD. All patients were asymptomatic except four patients and followed during 5 ± 4 years. Electrocardiogram (ECG), echocardiography assessing left ventricular ejection fraction, and Holter monitoring were obtained and repeated.
Results
Twenty‐seven patients (17%) presented sustained (>1 hour) AF (n = 15) or AFL (n = 12); two of them presented syncope‐related 1/1 AFL. In one of them, 16 years of age, cardiac defibrillator was implanted for a diagnosis of ventricular tachycardia, but the true diagnosis was established after inappropriate shocks. AFL ablation was performed in five patients, but four developed AF. The other seven patients with AFL developed AF. During the follow‐up, 22 patients died (14%) from cardiac and respiratory failure; eight patients with AF/AFL died (30%) while only 14 without AF/AFL died (10%; P < 0.01). Univariate analysis indicated that age >40 years (death: 48 ± 14 vs 40 ± 8 in alive patients), abnormal ECG, and occurrence of AF/AFL were significant factors of death. At multivariate analysis, AF at ECG (odds ratio: 3.12) and age >40 (odds ratio: 3.14) were the sole independent variables predicting death.
Conclusions
AF and AFL were frequent in MD and increased mortality. AFL could present as 1/1 AFL with a poor tolerance and a risk of misdiagnosis despite frequent conduction disturbances. This arrhythmia could explain wide QRS tachycardia occurring in MD and interpreted as VT.
Abstract Objective The aim of the study was to identify, in addition to conduction defects, possible predictors of cardiac events and death in patients with myotonic dystrophy (DM1). Methods and ...design A retrospective observational cohort study was undertaken. Baseline clinical and non-invasive cardiac and respiratory investigations were obtained from 107 DM1 patients, who were regularly re-examined. Primary end-points were occurrence of cardiac events (pacemaker implantation or tachyarrhythmia) or death. Probability of an event was calculated using the Kaplan–Meier method, while contributing factors were assessed using univariate and multivariate (Cox model) analyses. Results Cardiac events occurred in 34 patients (29%). Age, muscular impairment, infantile onset, restrictive lung disease (RLD), ECG conduction defects, left ventricular ejection fraction (LVEF) below 50%, and arrhythmia detected during Holter monitoring were predictors of cardiac events. Multivariate analysis indicated that age, RLD, ECG conduction defects, Holter arrhythmia and LVEF remained independent predictors. Probability of cardiac events was 2.5% (5%CI: 0–7%) at 1 year and 6% (5%CI: 0–14%) at 3 years in patients younger than 42 years with normal ECG, Holter, LVEF and lung volumes. Advancing age, distal or proximal weakness and RLD characterized all non-survivors (n = 14). Conclusion Cardiac events or death are predicted not only by conduction defects or cardiomyopathy in DM1, but also by RLD, muscular disability and advancing age. Addition of these criteria should modulate time intervals for patient follow-up examinations. In young patients with normal baseline investigations, screening investigations every 2 or 3 years seem to be sufficient.
Introduction: Multiple acyl‐coenzyme A dehydrogenase deficiency (MADD), also called glutaric aciduria type II, is an inherited metabolic disorder resulting from a deficiency in electron transfer ...flavoprotein (ETF) or of its ubiquinone oxidoreductase (ETF‐QO). It usually occurs in the neonatal period or in early infancy and, very rarely, in adolescents and young adult patients. Methods: We report the case of a 55‐year‐old woman who developed a painful subacute myopathy. Results: Lipid accumulation was found at biopsy. MADD was confirmed by plasma acylcarnitine profile and by assessment of ETF‐QO activity in muscle. Conclusions: This study demonstrates that metabolic myopathies usually found in infancy may be also diagnosed in older patients. MADD may be easily treated by riboflavin and coenzyme Q10 and therefore should be included in the differential diagnosis of adult‐onset painful myopathy. Muscle Nerve 43: 444–446, 2011
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