Abstract:Purpose: To assess the prevalence of LUTS, urinary tract and urodynamics changes in patients with Friedreich's Ataxia (FA), the most common form of hereditary ataxia.
Materials and Methods:This study evaluated 258 patients with genetically confirmed diagnoses of FA. Of the patients, 158 responded to a questionnaire which assessed their urinary symptoms. Patients with clinical changes underwent renal function examinations, ultrasound, and urodynamic studies (UDS). Results: The sample analyzed showed that 82% of… Show more
“…On the other hand, we strengthened our findings by means of an extensive screening procedure and accurate patient characterization in a cohort of genetically confirmed FRDAs. Notably, in most of previous studies potential confounders such as vitamin deficiency or impaired glucose intolerance, which may per se cause an autonomic neuropathy, were not considered [ 10 , 11 , 27 ]. Moreover, the lack of validated scales precluded correlations with disease severity.…”
BackgroundFriedreich ataxia (FRDA) is an inherited movement disorder which manifests with progressive gait instability, sensory loss and cardiomyopathy. Peripheral neuropathy is an established feature of FRDA. At neuropathological examination, a depletion of large, myelinated axons is evident, but also unmyelinated fibers are affected which may result in a variety of sensory and autonomic signs and symptoms. Impaired temperature perception, vasomotor disturbances of lower extremities and a high prevalence of urinary symptoms have been documented in FRDA, but data from autonomic function testing in genetically confirmed cases are lacking.MethodsGenetically confirmed FRDAs were recruited in an outpatient setting. In a screening visit, general and neurological examination, laboratory testing, ECG and echocardiography were performed. Autonomic functions were evaluated by means of systematic questionnaires (SCOPA-Aut, OHQ), skin sympathetic reflex and cardiovascular autonomic function testing (CAFT). For the latter, a comparison with matched healthy controls was performed.Results20 patients were recruited and 13 underwent CAFT. Symptoms referred to multiple autonomic domains, particularly bladder function, thermoregulation and sweating were reported. SCOPA-Aut scores were significantly predicted by disease severity. At CAFT, FRDAs did not differ from controls except for increased heart rate at rest and during orthostatic challenge. Two patients had non-neurogenic orthostatic hypotension (14%). Skin sympathetic responses were pathologic in 3 out of 10 patients (of whom 2 aged > 50).ConclusionsFRDA patients may experience several autonomic symptoms and overall their burden correlates with disease severity. Nonetheless, clinical testing shows no major involvement of sudomotor and cardiovascular autonomic function.
“…On the other hand, we strengthened our findings by means of an extensive screening procedure and accurate patient characterization in a cohort of genetically confirmed FRDAs. Notably, in most of previous studies potential confounders such as vitamin deficiency or impaired glucose intolerance, which may per se cause an autonomic neuropathy, were not considered [ 10 , 11 , 27 ]. Moreover, the lack of validated scales precluded correlations with disease severity.…”
BackgroundFriedreich ataxia (FRDA) is an inherited movement disorder which manifests with progressive gait instability, sensory loss and cardiomyopathy. Peripheral neuropathy is an established feature of FRDA. At neuropathological examination, a depletion of large, myelinated axons is evident, but also unmyelinated fibers are affected which may result in a variety of sensory and autonomic signs and symptoms. Impaired temperature perception, vasomotor disturbances of lower extremities and a high prevalence of urinary symptoms have been documented in FRDA, but data from autonomic function testing in genetically confirmed cases are lacking.MethodsGenetically confirmed FRDAs were recruited in an outpatient setting. In a screening visit, general and neurological examination, laboratory testing, ECG and echocardiography were performed. Autonomic functions were evaluated by means of systematic questionnaires (SCOPA-Aut, OHQ), skin sympathetic reflex and cardiovascular autonomic function testing (CAFT). For the latter, a comparison with matched healthy controls was performed.Results20 patients were recruited and 13 underwent CAFT. Symptoms referred to multiple autonomic domains, particularly bladder function, thermoregulation and sweating were reported. SCOPA-Aut scores were significantly predicted by disease severity. At CAFT, FRDAs did not differ from controls except for increased heart rate at rest and during orthostatic challenge. Two patients had non-neurogenic orthostatic hypotension (14%). Skin sympathetic responses were pathologic in 3 out of 10 patients (of whom 2 aged > 50).ConclusionsFRDA patients may experience several autonomic symptoms and overall their burden correlates with disease severity. Nonetheless, clinical testing shows no major involvement of sudomotor and cardiovascular autonomic function.
“…The urodynamic findings were consistent with larger case-series that have shown detrusor overactivity as the predominant finding, however, only 2 patients had these tests [ 26 , 27 ]. Other findings on urodynamic studies have included detrusor underactivity, detrusor acontractility and detrusor-sphincter dyssynergia [ 14 ]. This would account for the urinary disturbances reported by our patients as there were high scores in OAB indicating detrusor overactivity and LS indicating possible detrusor-sphincter dyssynergia due to pyramidal tract involvement or peripheral neuropathy.…”
Section: Discussionmentioning
confidence: 99%
“…Previous cohorts of FRDA patients have noted complaints of sphincter disturbance or urinary incontinence but this has not been clarified further [ 5 , 10 – 13 ]. Only one large study of 258 FRDA patients showed that 82% of patients reported LUTS and 22% related these symptoms to poorer quality of life [ 14 ]. Smaller case-series have evaluated LUT function in a select group of patients but this has not been extended to larger groups.…”
Background: Pelvic symptoms are distressing symptoms experienced by patients with Friedreich's Ataxia (FRDA). The aim of this study was to describe the prevalence of lower urinary tract symptoms (LUTS), bowel and sexual symptoms in FRDA. Methods: Questionnaire scores measuring LUTS, bowel and sexual symptoms were analysed with descriptive statistics as a cohort and as subgroups (Early/Late-onset and Early/Late-stage FRDA) They were also correlated with validated measures of disease severity including those of ataxia severity, non-ataxic symptoms and activities of daily living. Results: 80% (n = 46/56) of patients reported LUTS, 64% (n = 38/59) reported bowel symptoms and 83% (n = 30/36) reported sexual symptoms. Urinary and bowel or sexual symptoms were significantly likely to co-exist among patients. Late-onset FRDA patients were also more likely to report LUTS than early-onset ones. Patients with a longer disease duration reported higher LUTS scores and poorer quality of life scores related to urinary symptoms.
“…Micturition is only mildly affected with urgency and detrusor hypoactivity being the most frequent symptoms. In a series of FA patients, there was evidence for dilatation of the upper urinary tract without creatinine increase in 14% [16]. Systematic assessment of bowel function has not been published to date.…”
Friedreich ataxia (FA) represents the most frequent type of inherited ataxia. Most patients carry homozygous GAA expansions in the first intron of the frataxin gene on chromosome 9. Due to epigenetic alterations, frataxin expression is significantly reduced. Frataxin is a mitochondrial protein. Its deficiency leads to mitochondrial iron overload, defective energy supply and generation of reactive oxygen species. This review gives an overview over clinical and genetic aspects of FA and discusses current concepts of frataxin biogenesis and function as well as new therapeutic strategies.
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