Long-term response to aminopyridines in a cohort of patients with ataxia associated with downbeat nystagmus due to the FGF14 GAA expansion
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Bibliographic record
Abstract
Ataxia with downbeat nystagmus (A-DBN) has recently been associated with an intronic GAA repeat expansion in the FGF14 gene. The objectives of our study were to describe the clinical, radiological, and genetic findings, as well as the long-term response to aminopyridine (AP) treatment, in a cohort of patients with ataxia with DBN. Demographic, clinical, and radiological data were obtained through medical records. Genetic analysis of the FGF14 GAA expansion was performed. All patients were under compassionate treatment with AP. Scale for Assessment and Rating of Ataxia (SARA) score pre-treatment was compared with the current SARA score. Patient Clinical Global Impression (CGI-p) and the presence of adverse events were also assessed. Eight patients were included. Median (quartiles 1 and 3) age at disease onset was 63.5 (54–67) years. Before treatment, patients complained of gait instability with daily fluctuations and visual disturbances. They showed DBN with predominant involvement of gait and posture on the SARA. Brain MRI disclosed mainly vermian atrophy. An FGF14 GAA expansion (>250 repeats) was demonstrated in all patients. After a median AP treatment duration of 43 (14.25–137.25) months, the CGI-p showed a median improvement of 65% (60–80%) in their disability, and the total SARA score remained without significant changes ( P = .348). Only one patient complained of transient gastric upset and nausea with AP treatment. Patients with A-DBN due to the FGF14 GAA expansion predominately show an axial involvement with fluctuating disability. Long-term treatment with AP is well tolerated and effective, and seems to slow disease progression in our patients. La ataxia con nistagmo vertical hacia abajo (A-DBN) se ha asociado recientemente con una expansión intrónica de repeticiones GAA en el gen FGF14 . Nuestros objetivos fueron describir los hallazgos clínicos, radiológicos y genéticos, así como la respuesta a largo plazo al tratamiento con aminopiridinas (AP), en una cohorte de pacientes con A-DBN. Los datos demográficos, clínicos y radiológicos se obtuvieron a través de las historias clínicas. Se realizó un análisis genético de la expansión GAA en FGF14 . Todos los pacientes estaban en tratamiento compasivo con AP. La puntuación de la escala SARA pretratamiento se comparó con la puntuación actual. También se evaluó la impresión clínica global del paciente (CGI-p) y la presencia de eventos adversos. Se incluyeron ocho pacientes. La mediana (IQR) de la edad de inicio de la enfermedad fue de 63,5 (54-67) años. Antes del tratamiento, los pacientes se quejaban de inestabilidad en la marcha con fluctuaciones diarias y alteraciones visuales. En el examen mostraban DBN con afectación predominante de la marcha y la postura en la SARA. La RM cerebral evidenció principalmente atrofia vermiana. En todos los pacientes se demostró una expansión de GAA >250 repeticiones. Después de 43 meses (14,25-137,25) de tratamiento con AP, la CGI-p mostró una mejoría del 65% (60%-80%). La puntuación total de la SARA se mantuvo sin cambios significativos (p = 0,348). Sólo un paciente refirió malestar gástrico transitorio y náuseas con el tratamiento con AP. Los pacientes A-DBN debido a la expansión GAA en FGF14 muestran predominantemente una afectación axial con discapacidad fluctuante. El tratamiento a largo plazo con AP es bien tolerado, eficaz y parece enlentecer la progresión de la enfermedad en nuestros pacientes.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it