ABSTRACT
Intermediate CAG expansions in the gene ataxin-2 (ATXN2) are a known risk factor for ALS, but little is known about their role in FTD risk. Moreover, their contribution to the risk and phenotype of patients might vary in populations with different genetic backgrounds. The aim of this study was to assess the relationship of intermediate CAG expansions in ATXN2 with the risk and phenotype of ALS and FTD in the Spanish population. Repeat-primed PCR was performed in 620 ALS and 137 FTD patients in three referral centers in Spain to determine the exact number of CAG repeats. In our cohort, ≥27 CAG repeats in ATXN2 were associated with a higher risk of developing ALS (odds ratio [OR] = 2.666 [1.471-4.882]; p = 0.0013) but not FTD (odds ratio [OR] = 1.446 [0.558-3.574]; p = 0.44). Moreover, ALS patients with ≥27 CAG repeats in ATXN2 showed a shorter survival rate compared to those with <27 repeats (hazard ratio [HR] 1.74 [1.18, 2.56], p = 0.005), more frequent limb onset (odds ratio [OR] = 2.34 [1.093-4.936]; p = 0.028) and a family history of ALS (odds ratio [OR] = 2.538 [1.375-4.634]; p = 0.002). Intermediate CAG expansions of ≥27 repeats in ATXN2 are associated with ALS risk but not with FTD in the Spanish population. ALS patients carrying an intermediate expansion in ATXN2 show more frequent limb onset but a worse prognosis than those without expansions. In patients carrying C9orf72 expansions, the intermediate ATXN2 expansion might increase the penetrance and modify the phenotype.
ABSTRACT
OBJECTIVE: To accurately categorize the phenotypes of individuals with collagen VI-related dystrophies (COL6-RDs) during the first years of life to predict long-term motor function and pulmonary function, to provide phenotype-specific anticipatory care, and to improve clinical trial readiness. METHODS: This retrospective, multicenter, international study analyzed the relationship of long-term motor and pulmonary function with the initial maximal motor ability achieved in individuals with COL6-RD. RESULTS: We studied 119 patients with COL6-RD from Spain (n = 54) and the United States (n = 65). The early maximal motor milestones of ability to rise from the floor unassisted and ability to climb 4 steps without holding onto a railing demonstrated reliability in distinguishing between 3 COL6-RD phenotypic subgroups: (1) Ullrich congenital muscular dystrophy, (2) intermediate COL6-RD, and (3) Bethlem myopathy. Long-term motor function and pulmonary function are strongly correlated with the maximal motor ability achieved during the first years of life. Maximal motor capacity can predict other disease-relevant events such as the age at loss of ambulation and the need for the initiation of nocturnal noninvasive ventilation. CONCLUSION: This work proposes a prospective phenotypic classification for COL6-RDs that will enable an accurate prediction of a patient's COL6-RD phenotype during the first years of life. The ability to establish a patient's COL6-RD phenotypic classification early will enable a more accurate prognosis of future motor and pulmonary function, thus improving anticipatory clinical care, and it will be instrumental in aiding the design of future clinical trials by allowing early stratification of trial cohorts.
Subject(s)
Collagen Type VI/genetics , Muscular Dystrophies/genetics , Muscular Dystrophies/psychology , Psychomotor Performance , Adolescent , Adult , Aged , Child , Child, Preschool , Disease Progression , Female , Genotype , Humans , Kaplan-Meier Estimate , Lung/physiopathology , Male , Middle Aged , Muscular Dystrophies/physiopathology , Respiratory Function Tests , Retrospective Studies , Spain , Treatment Outcome , United States , Walking , Young AdultABSTRACT
Oropharyngeal dysphagia (OD) is highly prevalent (up to 80%) in patients with motor neuron disease (MND), influencing the prognosis of the disease. The clinical assessment of dysphagia is complex. There are assessment scales and screening questionnaires, but they have not been tested in patients with MND. In a sample of 46 patients with MND, the sensitivity and specificity of the EAT-10 and SwalQoL questionnaires, as well as the ALS-SS and FOIS scales, were tested and compared to the gold standard technique (videofluoroscopy, VFS). The patients were stratified using the DOSSc variable according to the video fluoroscopic examination with (n = 37) or without (n = 8) signs of dysphagia, and the results were compared with the scores obtained in the dysphagia questionnaires. None of the studied questionnaires was more sensitive than the others, but one stood out for its high specificity (= 1): the SwalQoL revised FS. The symptom frequency section of the SwalQoL questionnaire with some modifications, (SwalQoL revised FS) may be a useful tool in the clinical assessment of dysphagia because it's capable to detect the patients that really don't have dysphagia. The ALS-SS showed the greatest validity as a severity scale of dysphagia among the sample studied. A specific questionnaire for screening for dysphagia in MND needs to be developed. Until that time, the proposal is to use a combination of the existing questionnaires for other pathologies (EAT-10 and SwalQoL) and the specific scale for MND, the ALS-SS, to make an accurately clinical assessment of OD in MND patients before to perform a videofluoroscopy.
Subject(s)
Amyotrophic Lateral Sclerosis , Deglutition Disorders , Motor Neuron Disease , Amyotrophic Lateral Sclerosis/complications , Deglutition Disorders/diagnosis , Deglutition Disorders/etiology , Humans , Motor Neuron Disease/complications , Motor Neuron Disease/diagnosis , Sensitivity and Specificity , Surveys and QuestionnairesABSTRACT
Objetivo. Describir la información aportada por el dúplex color transcraneal (DCTC) en pacientes con ictus isquémico agudo, analizando la relación entre los hallazgos del DCTC, la gravedad y el pronóstico, así como su utilidad en la toma de decisiones terapéuticas. Pacientes y métodos. Analizamos los DCTC realizados a pacientes con ictus agudo de menos de seis horas de evolución. Recogimos la existencia de oclusión arterial empleando las clasificaciones TIBI (Thrombolysis in Brain Ischemia) y COGIF (Consensus on Grading Intracranial Flow Obstruction). Determinamos la recanalización arterial a las 24 horas del ictus empleando criterios TIBI y COGIF. Consideramos buena evolución funcional puntuaciones en la escala de Rankin de 0 a 2 a los tres meses. Resultados. Realizamos DCTC en 104 pacientes, 85 tratados con trombólisis intravenosa. Objetivamos oclusión arterial en el 79,8%. La detección de una oclusión arterial mediante DCTC permitió indicar tratamiento endovascular en el 23,1% de los pacientes. La presencia de oclusión arterial se asoció a mayor gravedad del ictus. Detectamos recanalización arterial en el 44,1% según los criterios TIBI y en el 45,8% según los criterios COGIF. El 80,8% de los pacientes que recanalizaron y sólo el 39,5% de los que no recanalizaron obtuvieron una buena evolución funcional a los tres meses. La recanalización dependió de la localización de la oclusión arterial. Conclusiones. El DCTC es útil para detección y localización de oclusión arterial, aporta información pronóstica valiosa y permite seleccionar pacientes para el empleo de terapias endovasculares. La información aportada por las clasificaciones TIBI y COGIF es equiparable (AU)
Aim. To describe the information provided by transcranial color-coded duplex (TCCD) sonography for therapeutic decision making in patients with acute ischemic stroke and to analyze the relationship between TCCD findings and the severity and prognosis of stroke. Patients and methods. TCCD performed within the six first hours after an acute ischemic stroke were analyzed in our institution. The presence of an arterial occlusion and its location were collected using TIBI (Thrombolysis in Brain Ischemia) and COGIF (Consensus on Grading Intracranial Flow Obstruction) criteria. Arterial recanalization within 24 hours after stroke was determined using TIBI and COGIF criteria. Favorable functional outcome was defined as a modified Rankin scale from 0 to 2 at three months. Results. TCCD was performed in 104 patients, 85 were treated with intravenous thrombolysis. Arterial occlusion was detected in 79.8% of patients. The detection of arterial occlusion with TCCD allowed the selection for endovascular treatment in 23.1% of patients. Arterial occlusion was associated with a higher severity of stroke. Recanalization was detected in 44.1% using TIBI and 45.8% according to COGIF criteria. 80.8% of recanalized patients and only 39.5% of not recanalized had a favorable functional outcome at three months. Recanalization rate depended on the location of arterial occlusion. Conclusion. TCCD is a useful technique for the detection and location of arterial occlusion. It provides valuable prognostic information and allows selecting patients for endovascular recanalizing therapies. TIBI and COGIF scores provide a comparable information (AU)
