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Migraine is a leading cause of disability worldwide, yet it remains underrecognized and undertreated, especially in the pediatric and adolescent population. Chronic migraine occurs approximately in 1% of children and adolescents requiring preventive treatment. Topiramate is the only FDA-approved preventative treatment for children older than 12 years of age, but there is conflicting evidence regarding its efficacy. OnabotulinumtoxinA is a known and approved treatment for the management of chronic migraine in people older than 18 years. Several studies examine its role in the pediatric population with positive results; however, the clear-cut benefit is still unclear. OnabotulinumtoxinA seems not only to improve disability scores (PedMIDAS) but also to improve the quality, characteristics, and frequency of migraines in the said population. This systematic review aims to summarize the evidence on the efficacy, dosing, administration, long-term outcomes, and safety of onabotulinumtoxinA in pediatric and adolescent migraine. Eighteen studies met the eligibility criteria and were included in this review. The mean monthly migraine days (MMDs), decreased from of 21.2 days per month to 10.7 after treatment. The reported treatment-related adverse effects were mild and primarily injection site related and ranged from 0% to 47.0%. Thus, this review provides compelling evidence suggesting that OnabotulinumtoxinA may represent a safe and effective preventive treatment option for pediatric migraine.
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Toxinas Botulínicas Tipo A , Trastornos Migrañosos , Humanos , Trastornos Migrañosos/prevención & control , Trastornos Migrañosos/tratamiento farmacológico , Toxinas Botulínicas Tipo A/uso terapéutico , Toxinas Botulínicas Tipo A/efectos adversos , Niño , Adolescente , Fármacos Neuromusculares/uso terapéutico , Fármacos Neuromusculares/efectos adversos , Resultado del TratamientoAsunto(s)
Fenotipo , ARN Polimerasa III , Humanos , ARN Polimerasa III/genética , ARN Polimerasa III/inmunología , Masculino , Femenino , MutaciónRESUMEN
BACKGROUND: Headache represents a significant proportion of disability globally in general practice, neurology outpatient settings, and emergency departments. There is scant literature regarding the impact of headache on healthcare services in Ireland. AIMS: We aimed to investigate headache burden across the emergency department, inpatient stays, and neurology outpatient department referrals in an Irish University teaching hospital. METHODS: We prospectively collected data regarding emergency department presentations, inpatient neurology consultations, and neurology outpatient referrals for patients with headache between 13th January and 8th March 2020. Data were analyzed using descriptive statistics. RESULTS: There were 180 emergency department attendances, 50 inpatient consultations, and 76 outpatient referrals with headache. Neurological examinations were often incomplete; neuroimaging was commonly employed. Migraine was the most frequent headache diagnosis at discharge in the emergency department and among inpatients after neurology review. Diagnostic uncertainty was identified-33% of patients left the emergency department with no diagnosis, and "unknown/unspecified headache" was recorded on 49% of outpatient referrals and 30% of inpatient consult requests. Medication overuse headache coexisted with migraine in nine patients in the inpatient group. Prophylaxis had been trialed in 56% of patients with migraine referred to outpatients. CONCLUSIONS: Primary headache disorders have a large impact on hospital services. Diagnostic uncertainty is common; neuroimaging is relied upon. Appropriate care pathways, education, and resource allocation should be prioritized.
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Trastornos de Cefalalgia , Trastornos Migrañosos , Neurología , Humanos , Pacientes Ambulatorios , Pacientes Internos , Universidades , Cefalea , Servicio de Urgencia en Hospital , Hospitales de Enseñanza , Derivación y ConsultaRESUMEN
Inherited cerebellar ataxias (CA) are heterogeneous progressive neurological conditions associated with significant functional limitations. This study aimed to assess the implications of inherited CA on patients' self-reported quality of life (QoL) and impairments in work and activities. 129 individuals with ataxia responded to a survey focused on QoL. Health-related QoL was measured using the RAND 36-Item Short Form Survey. An adaptation of the validated Work Productivity and Activity Impairment questionnaire was used to assess the effect of health on work productivity and ability to perform activities over the past week. Nine percent of respondents were currently employed. Individuals with inherited ataxia experienced significant activity impairment, and 75% required professional or informal care. Health-related quality of life (HRQoL) was significantly worse in all areas for the individuals with inherited ataxia compared with Irish population normative values. Participants with Friedreich's ataxia (n = 56) demonstrated worse physical functioning then those with undetermined ataxia (n = 55). Female gender, younger age at symptom onset, current employment, retirement due to age or ataxia, and living in a long-term care facility were associated with higher sub-scores in different domains of HRQoL, while disease duration correlated with worse physical functioning sub-scores. This study is the first cross-sectional study on HRQoL in patients with inherited ataxia in Ireland. It highlights high rates of unemployment, difficulty with daily activities and physical functioning limitations, which is worse than comparative international studies. Given the limited therapeutic options currently available, optimising HRQoL is an important aspect of managing ataxia.
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AIM: Hereditary sensory neuropathy (HSN) 1E is a neurodegenerative disorder caused by pathogenic variants in DNA methyltransferase 1 (DNMT1). It is characterised by sensorineural deafness, sensory neuropathy and cognitive decline. Variants in DNMT1 are also associated with autosomal dominant cerebellar ataxia, deafness and narcolepsy. METHODS: A 42-year-old man presented with imbalance, lancinating pain, numerous paucisymptomatic injuries, progressive deafness since his mid-20s, mild cognitive decline and apathy. Examination revealed abnormalities of eye movements, distal sensory loss to all modalities, areflexia without weakness and lower limb ataxia. MRI brain and FDG-PET scan demonstrated biparietal and cerebellar atrophy/hypometabolism. Whole exome sequencing detected a heterozygous likely pathogenic missense variant in DNMT1, c.1289G > A, p.Cys430Tyr. Cochlear implant was performed at 44 years for the bilateral high frequency sensorineural hearing loss with improvement in hearing and day-to-day function. RESULTS AND CONCLUSION: We describe a novel variant in DNMT1 and confirm that an overlapping HSN1E-cerebellar phenotype can occur. Only one prior case of cochlear implant in HSN1E has been reported to date but this case adds to that literature, suggesting that cochlear implant can be successful in such patients. We further explore the clinical and radiological signature of the cognitive syndrome associated with this disorder.
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Ataxia Cerebelosa , Sordera , Narcolepsia , Enfermedades Neurodegenerativas , Enfermedades del Sistema Nervioso Periférico , Humanos , Ataxia Cerebelosa/genética , ADN (Citosina-5-)-Metiltransferasa 1/genética , Narcolepsia/complicaciones , Enfermedades del Sistema Nervioso Periférico/complicaciones , Enfermedades Neurodegenerativas/complicaciones , Sordera/complicaciones , Sordera/genética , Estudios de Asociación Genética , Linaje , MutaciónRESUMEN
BACKGROUND/AIMS: Data are limited on the frequency of 'consensus decisions' between sub-specialists attending a neurovascular multidisciplinary meeting (MDM) regarding management of patients with extracranial carotid/vertebral stenoses and post-MDM 'adherence' to such advice. METHODS: This prospective audit/quality improvement project collated prospectively-recorded data from a weekly Neurovascular/Stroke Centre MDM documenting the proportion of extracranial carotid/vertebral stenosis patients in whom 'consensus management decisions' were reached by neurologists, vascular surgeons, stroke physicians-geriatricians and neuroradiologists. Adherence to MDM advice was analysed in asymptomatic carotid stenosis (ACS), symptomatic carotid stenosis (SCS), 'indeterminate symptomatic status stenosis' (ISS) and vertebral artery stenosis (VAS) patients, including intervals between index event to MDM + / - intervention. RESULTS: One hundred fifteen patients were discussed: 108 with carotid stenosis and 7 with VAS. Consensus regarding management was noted in 96.5% (111/115): 100% with ACS and VAS, 96.2% with SCS and 92.9% with ISS. Adherence to MDM management advice was 96.4% (107/111): 100% in ACS, ISS and VAS patients; 92% (46/50) in SCS patients. The median interval from index symptoms to revascularisation in 50-99% SCS patients was 12.5 days (IQR: 9-18.3 days; N = 26), with a median interval from MDM to revascularisation of 5.5 days (IQR: 1-7 days). Thirty patients underwent revascularisation. Two out of twenty-nine patients (6.9%) with either SCS or ISS had a peri-procedural ipsilateral ischaemic stroke, with no further strokes/deaths during 3-months follow-up. CONCLUSIONS: The high frequency of inter-specialty consensus regarding management and adherence to proposed treatment supports a collaborative/multidisciplinary model of care in patients with extracranial arterial stenoses. Service development should aim to shorten times between MDM discussion-intervention and optimise prevention of stroke/death.
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Isquemia Encefálica , Estenosis Carotídea , Endarterectomía Carotidea , Accidente Cerebrovascular , Humanos , Estenosis Carotídea/cirugía , Accidente Cerebrovascular/prevención & control , Constricción Patológica/etiología , Consenso , Resultado del Tratamiento , Factores de RiesgoRESUMEN
Inherited ataxias are a heterogenous group of neurodegenerative disorders characterised by progressive impairment of balance and coordination, typically leading to permanent and progressive disability. Diagnosis and management of these disorders incurs a range of direct and indirect financial costs. The aim of this study was to collect individual ataxia-related healthcare resources in a large cohort of individuals with different subtypes of inherited ataxia and calculate the associated cost of illness in the Republic of Ireland. One hundred twenty-nine respondents completed a cross-sectional study on healthcare resource utilisation for progressive ataxia in Ireland. Costs were calculated using a prevalence-based approach and bottom-up methodology. The COI for inherited ataxia in 2016 was 59,993 per person per year. Results were similar between participants with Friedreich's ataxia (FRDA, n = 56), non-FRDA (n = 18) and those with undetermined ataxia (n = 55). Indirect costs, based on productivity losses by participants or caregivers, accounted for 52% of the cost of illness. Inherited ataxia is associated with significant health and social care costs. Further funding for inherited ataxia to ease the financial burden on patients, caregivers and healthcare system and improve standards of care compliance is warranted.
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Ataxia Cerebelosa , Ataxia de Friedreich , Degeneraciones Espinocerebelosas , Estudios Transversales , Ataxia de Friedreich/epidemiología , Ataxia de Friedreich/genética , Ataxia de Friedreich/terapia , Humanos , Irlanda/epidemiología , Degeneraciones Espinocerebelosas/diagnóstico , Degeneraciones Espinocerebelosas/epidemiología , Degeneraciones Espinocerebelosas/genéticaRESUMEN
Ocular abnormalities occur frequently in Friedreich's ataxia (FRDA), although visual symptoms are not always reported. We evaluated a cohort of patients with FRDA to characterise the clinical phenotype and optic nerve findings as detected with optical coherence tomography (OCT). A total of 48 patients from 42 unrelated families were recruited. Mean age at onset was 13.8 years (range 4-40), mean disease duration 19.5 years (range 5-43), mean disease severity as quantified with the Scale for the Assessment and Rating of Ataxia 22/40 (range 4.5-38). All patients displayed variable ataxia and two-thirds had ocular abnormalities. Statistically significant thinning of average retinal nerve fibre layer (RNFL) and thinning in all but the temporal quadrant compared to controls was demonstrated on OCT. Significant RNFL and macular thinning was documented over time in 20 individuals. Disease severity and visual acuity were correlated with RNFL and macular thickness, but no association was found with disease duration. Our results highlight that FDRA is associated with subclinical optic neuropathy. This is the largest longitudinal study of OCT findings in FRDA to date, demonstrating progressive RNFL thickness decline, suggesting that RNFL thickness as measured by OCT has the potential to become a quantifiable biomarker for the evaluation of disease progression in FRDA.
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Ataxia de Friedreich , Enfermedades del Nervio Óptico , Ataxia de Friedreich/complicaciones , Ataxia de Friedreich/diagnóstico por imagen , Humanos , Estudios Longitudinales , Enfermedades del Nervio Óptico/complicaciones , Enfermedades del Nervio Óptico/diagnóstico , Tomografía de Coherencia Óptica/métodos , Agudeza VisualRESUMEN
Hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC) is a rare autosomal recessive condition characterised by early-onset severe progressive neuropathy, variable degrees of ACC and cognitive impairment. Mutations in SLC12A6 (solute carrier family 12, member 6) encoding the K+-Cl- transporter KCC3 have been identified as the genetic cause of HMSN/ACC. We describe fraternal twins with compound heterozygous mutations in SLC12A6 and much milder phenotype than usually described. Neither of our patients requires assistance to walk. The female twin is still running and has a normal intellect. Charcot-Marie-Tooth Examination Score 2 was 8/28 in the brother and 5/28 in the sister. Neurophysiology demonstrated a length-dependent sensorimotor neuropathy. MRI brain showed normal corpus callosum. Genetic analysis revealed compound heterozygous mutations in SLC12A6, including a whole gene deletion. These cases expand the clinical and genetic phenotype of this rare condition and highlight the importance of careful clinical phenotyping.
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Enfermedad de Charcot-Marie-Tooth , Simportadores , Adulto , Agenesia del Cuerpo Calloso , Femenino , Humanos , Masculino , Mutación , Fenotipo , Simportadores/genética , GemelosRESUMEN
BACKGROUND: Mutations in SPG7 are increasingly identified as a common cause of spastic ataxia. We describe a cohort of Irish patients with recessive SPG7-associated phenotype. METHODS: Comprehensive phenotyping was performed with documentation of clinical, neurophysiological, optical coherence tomography (OCT) and genetic data from individuals with SPG7 attending two academic neurology units in Dublin, including the National Ataxia Clinic. RESULTS: Thirty-two symptomatic individuals from 25 families were identified. Mean age at onset was 39.1 years (range 12-61), mean disease duration 17.8 years (range 5-45), mean disease severity as quantified with the scale for the assessment and rating of ataxia 9/40 (range 3-29). All individuals displayed variable ataxia and spasticity within a spastic-ataxic phenotype, and additional ocular abnormalities. Two had spasmodic dysphonia and three had colour vision deficiency. Brain imaging consistently revealed cerebellar atrophy (n = 29); neurophysiology demonstrated a length-dependent large-fibre axonal neuropathy in 2/27 studied. The commonest variant was c.1529C > T (p.Ala510Val), present in 21 families. Five novel variants were identified. No significant thinning of average retinal nerve fibre layer (RNFL) was demonstrated on OCT (p = 0.61), but temporal quadrant reduction was evident compared to controls (p < 0.05), with significant average and temporal RNFL decline over time. Disease duration, severity and visual acuity were not correlated with RNFL thickness. CONCLUSIONS: Our results highlight that recessive SPG7 mutations may account for spastic ataxia with peripheral neuropathy in only a small proportion of patients. RNFL abnormalities with predominant temporal RNFL reduction are common and OCT should be considered part of the routine assessment in spastic ataxia.
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Espasticidad Muscular , Paraplejía Espástica Hereditaria , ATPasas Asociadas con Actividades Celulares Diversas/genética , Adolescente , Adulto , Niño , Preescolar , Humanos , Discapacidad Intelectual , Metaloendopeptidasas/genética , Persona de Mediana Edad , Espasticidad Muscular/diagnóstico por imagen , Espasticidad Muscular/genética , Neurofisiología , Atrofia Óptica , Fenotipo , Paraplejía Espástica Hereditaria/diagnóstico por imagen , Paraplejía Espástica Hereditaria/genética , Ataxias Espinocerebelosas , Tomografía de Coherencia Óptica , Adulto JovenRESUMEN
Establishing a molecular diagnosis in patients with progressive ataxia is often challenging due to significant genetic and clinical heterogeneity and requires a methodical approach with expert clinical evaluation and investigations. We describe the 5-year experience of the National Ataxia Clinic (NAC), Ireland. All adults with ataxia attending the NAC between 2014 and 2019 were evaluated. All individuals underwent detailed clinical assessment and investigations including, where appropriate, genetic testing using next-generation sequencing. For all patients, acquired causes were ruled out. A total of 254 patients from 196 families were assessed; with growth of the clinic cohort by 82% from 133 to 242 over the 5-year period. The underlying genetic cause was identified in 128/196 probands (65.3%). The detection rate for repeat expansion disorder gene testing was 47.7% (82/172) and using NGS gene panel, a genetic diagnosis was obtained in 30/84 (35.7%). Whole exome sequencing identified the molecular diagnosis in 4/20 (20%), and whole genome sequencing provided genetic diagnosis in 1/5 (20%). The commonest diagnosis was Friedreich's ataxia (68/128, 53.1%). SPG7-associated ataxia was the second most common diagnosis (21/128, 16.4%), followed by ANO10-associated spastic ataxia, ataxia telangiectasia (AT), and other rarer phenotypes. Our results highlight that careful clinical phenotyping in a dedicated ataxia clinic is crucial for appropriate genetic testing in selected patients in a timely manner. Advanced genetic testing has significantly improved the diagnostic yield in patients with suspected genetic ataxia and should be considered in all individuals with negative repeat expansion testing.
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Ataxias Espinocerebelosas/genética , ATPasas Asociadas con Actividades Celulares Diversas/genética , Adolescente , Adulto , Anciano , Anoctaminas/genética , Estudios de Cohortes , Expansión de las Repeticiones de ADN , Femenino , Ataxia de Friedreich/genética , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Genoma Humano/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Irlanda , Imagen por Resonancia Magnética , Masculino , Metaloendopeptidasas/genética , Persona de Mediana Edad , Fenotipo , Estudios Retrospectivos , Secuenciación del Exoma , Adulto JovenRESUMEN
Ataxia pancytopenia (ATXPC) syndrome due to gain-of-function pathogenic variants in the SAMD9L gene has been described in 38 patients to date. It is characterized by variable neurological and hematological phenotypes including ataxia, pyramidal signs, cytopenias, and hematological malignancies. Peripheral neuropathy with slowing of conduction velocities has been reported in only two affected individuals. We describe a female with childhood onset neuropathy diagnosed as Charcot-Marie-Tooth disease type 1 with onset of cerebellar ataxia in her 50s. Cerebellar, pyramidal, and neuropathic features were found on examination. Additionally, she also had conjunctival telangiectasia. Nerve conduction studies confirmed a demyelinating neuropathy. MRI brain showed cerebellar atrophy with diffuse white matter hyperintensities. OCT demonstrated global thinning of the retinal nerve fiber layer (RNFL). Full blood count has always been normal. A previously described pathogenic variant in SAMD9L [c.2956C>T p.(Arg986Cys)] was identified on whole exome sequencing. This case extends the previously described phenotype to include conjunctival telangiectasia and RNFL thinning and suggests that ATXPC syndrome should be considered in the differential for inherited demyelinating neuropathies.
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Ataxia Cerebelosa/genética , Enfermedad de Charcot-Marie-Tooth/genética , Pancitopenia/genética , Proteínas Supresoras de Tumor/genética , Ataxia Cerebelosa/patología , Ataxia Cerebelosa/fisiopatología , Enfermedad de Charcot-Marie-Tooth/patología , Enfermedad de Charcot-Marie-Tooth/fisiopatología , Femenino , Mutación con Ganancia de Función , Humanos , Persona de Mediana Edad , Polirradiculoneuropatía/genética , Polirradiculoneuropatía/patología , Polirradiculoneuropatía/fisiopatología , Síndrome , Telangiectasia/genética , Telangiectasia/patología , Telangiectasia/fisiopatologíaRESUMEN
We describe a patient with chronic progressive external ophthalmoplegia (CPEO) due to a rare mitochondrial genetic variant. Muscle biopsy revealed numerous cytochrome c oxidase (COX)-deficient fibres, prompting sequencing of the entire mitochondrial genome in muscle which revealed a rare m.12334G>A variant in the mitochondrial (mt-) tRNALeu(CUN)(MT-TL2) gene. Analysis of several tissues showed this to be a de novo mutational event. Single fibre studies confirmed the segregation of high m.12334G>A heteroplasmy levels with the COX histochemical defect, confirming pathogenicity of the m.12334G>A MT-TL2 variant. This case illustrates the importance of pursuing molecular genetic analysis in clinically-affected tissues when mitochondrial disease is suspected.
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Deficiencia de Citocromo-c Oxidasa/genética , ADN Mitocondrial/genética , Oftalmoplejía Externa Progresiva Crónica/genética , ARN de Transferencia de Leucina/genética , HumanosRESUMEN
Mutations in apoptosis-inducing factor mitochondrion-associated-1 (AIFM1) cause X-linked peripheral neuropathy (Cowchock syndrome, CMT4X); however, more recently a cerebellar presentation has been described. We describe a large Irish family with seven affected males. They presented with a variable age of onset, 18 months to 39 years of age. All developed variably present sensorineural deafness, peripheral neuropathy, cerebellar ataxia, and pyramidal involvement. In addition, three had colour vision deficiency. Scale for the assessment and rating of ataxia ranged 2 to 23/40, while Charcot-Marie-Tooth neuropathy score 2 varied between 7 and 13/36. All individuals had normal cognitive assessment. Neurophysiology demonstrated length-dependent large-fibre sensorimotor axonal neuropathy, with particular involvement of superficial radial sensory responses. Brain imaging, performed in four, revealed varying extent of cerebellar atrophy, and white matter changes in one. Optical coherence tomography was abnormal in one, who had unrelated eye pathology. Four obligate female carriers were assessed clinically, two of them neurophysiologically; all were unaffected. Whole genome sequencing demonstrated a previously reported hemizygous AIFM1 mutation. Analysis for mutations in other genes associated with colour deficiency was negative. AIFM1-associated phenotype in this family demonstrated significant variability. To our knowledge, this is the first report of AIFM1-associated colour blindness. Superficial radial nerve was particularly affected neurophysiologically, which could represent a phenotypic marker towards this specific genetic diagnosis.
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Factor Inductor de la Apoptosis/genética , Ataxia Cerebelosa , Defectos de la Visión Cromática , Pérdida Auditiva Sensorineural , Neuropatía Hereditaria Motora y Sensorial , Adulto , Ataxia Cerebelosa/etiología , Ataxia Cerebelosa/genética , Ataxia Cerebelosa/fisiopatología , Defectos de la Visión Cromática/etiología , Defectos de la Visión Cromática/genética , Defectos de la Visión Cromática/fisiopatología , Pérdida Auditiva Sensorineural/etiología , Pérdida Auditiva Sensorineural/genética , Pérdida Auditiva Sensorineural/fisiopatología , Neuropatía Hereditaria Motora y Sensorial/complicaciones , Neuropatía Hereditaria Motora y Sensorial/genética , Neuropatía Hereditaria Motora y Sensorial/fisiopatología , Humanos , Irlanda , Masculino , Persona de Mediana Edad , Linaje , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Patients with 'suspected viral encephalitis' are frequently empirically treated with intravenous aciclovir. Increasing urea and creatinine are 'common', but rapidly progressive renal failure is reported to be 'very rare'. AIMS: To describe the clinical course and outcome of cases of aciclovir-induced acute kidney injury (AKI) encountered by the Liaison Neurology Service at AMNCH and to highlight the importance of surveillance and urgent treatment of this iatrogenic complication. METHODS: Retrospectively and prospectively collected data from the Liaison Neurology Service at AMNCH on patients who received IV aciclovir for suspected viral encephalitis and developed AKI were analysed. Aciclovir-induced AKI was defined by a consultant nephrologist in all cases as a rise in serum creatinine of > 26 µmol/L in 48 h or by ≥ 1.5 times the baseline value. Renal function, haematocrit, and fluid balance were monitored following AKI onset. RESULTS: Data from 10 patients were analysed. Median time to AKI onset was 3.5 days (range: 1-6 days). Aciclovir was stopped or the dose adjusted. All patients recovered with IV normal saline, aiming for a urine output > 100-150 ml/h. The interval between first rise in creatinine and return to normal levels varied between 5 and 19 days. CONCLUSIONS: Liaison neurologists and general physicians need to be aware that aciclovir may cause AKI attributed to distal intra-tubular crystal nephropathy. Daily fluid balance and renal function monitoring are essential because AKI may arise even with intensive pre-hydration. Prognosis is good if identified early and actively treated.
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Lesión Renal Aguda/inducido químicamente , Aciclovir/efectos adversos , Aciclovir/uso terapéutico , Antivirales/efectos adversos , Antivirales/uso terapéutico , Encefalitis Viral/tratamiento farmacológico , Lesión Renal Aguda/patología , Lesión Renal Aguda/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
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. CONCLUSIONS: A high proportion of FRDA have symptoms suggestive of LUTS, bowel and sexual dysfunction. This is more marked with greater disease duration and later disease onset. These symptoms need to be addressed by clinicians as they can have a detrimental effect on patients.
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Ataxia de Friedreich/complicaciones , Enfermedades Intestinales/etiología , Conducta Sexual , Enfermedades Urológicas/etiología , Adolescente , Adulto , Anciano , Recolección de Datos , Femenino , Ataxia de Friedreich/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Adulto JovenRESUMEN
Waardenburg syndrome (WS) is a rare disorder comprising sensorineural deafness and pigmentation abnormalities. Four distinct subtypes are defined based on the presence or absence of additional symptoms. Mutations in six genes have been described in WS. SOX10 mutations are usually associated with a more severe phenotype of WS with peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, and Hirschsprung disease. Here we report a 32-year-old man with a novel heterozygous missense variant in SOX10 gene, who presented with congenital deafness, Hirschsprung disease, iris heterochromia, foot deformity, and intermediate conduction velocity length-dependent sensorimotor neuropathy. This case highlights that the presence of other non-neuropathic features in a patient with presumed hereditary neuropathy should alert the clinician to possible atypical rare causes.