Aspiration and injection of joints (2).
Authors: P Williams, M Gumpel
Journal: BMJ (1980)

<h3>Objective:</h3> To detect the clinical characteristics of ALS patients carrying an intermediate ATXN2 polyQ expansion. <h3>Background:</h3> An intermediate-length CAG expansion (encoding ≥31 glutamines, polyQ) in the <i>ataxin 2</i> (<i>ATXN2</i>) gene, already known as the cause of spinocerebellar ataxia type 2 (SCA2), is also associated with an increased risk of developing ALS. In addition, it could be a modifier of survival. <h3>Design/Methods:</h3> A total of 1,048 patients (482 female [47.8%], mean age at onset 65.5 [SD 11.1] years) were enrolled. Patients were identified through the Piemonte and Valle d’Aosta Register for ALS (PARALS) in the period 2007–2015. All patients were prospectively followed up to death or censor date (June 30<sup>th</sup>, 2021). In 672 patients. the <i>ATXN2</i> polyQ repeat expansion was detected using repeat primed PCR, while whole-genome sequencing was analyzed to count the repeat number in 376 patients. <h3>Results:</h3> We detected 35 cases (3.3%) in which the ATXN2 polyQ repeat number was greater than 30 (ALS-ATXN2+). Compared to patients without intermediate ATXN2 polyQ expansion (ALS-ATXN2−), ALS-ATXN2+ patients had less frequent bulbar onset disease (8.6% vs 32.8%, p=0.001), had a shorter diagnostic delay (7.7 [SD 6.6] months vs 11.7 [10.4], p=0.024), and a higher mean monthly ALSFRS-R decline (1.81 [SD 2.52] vs 0.96 [1.16], p=0.0001). The rate of FVC% decline did not differ between ALS-ATXN2+ and ALS-ATXN2− patients, and cognitive impairment was similarly distributed in the two groups. Nevertheless, the median survival time among ALS-ATXN2+ patients was 1.8 years (IQR 1.3–2.5) compared to 2.8 (IQR 2.7–5.3) in ALS-ATXN2− patients (p=0.0001). <i>ATXN2</i> intermediate expansion remained independently related to survival (HR 1.55, CI 1.09–2.29, p=0.015) in Cox multivariable analysis. <h3>Conclusions:</h3> Our population-based study found that ALS patients carrying the <i>ATXN2</i> intermediate PolyQ expansion have a distinctive phenotype characterized by a predominant spinal onset and a more rapid clinical decline measured with ALSFRS-R and survival. <b>Disclosure:</b> Dr. Chio has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cytokinetics. Dr. Chio has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi. Dr. Chio has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Cristina Moglia has nothing to disclose. Antonio Canosa has nothing to disclose. Dr. Manera has nothing to disclose. Maura Brunetti has nothing to disclose. Ruth Chia has nothing to disclose. Jinhui Ding has nothing to disclose. J. Raphael Gibbs has received research support from NIH. The institution of J. Raphael Gibbs has received research support from Michael J Fox Foundation. Clifton Dalgard has nothing to disclose. Sandra D9Alfonso has nothing to disclose. Lucia Corrado has nothing to disclose. Fabiola De Marchi has nothing to disclose. Letizia Mazzini has nothing to disclose. The institution of Dr. Traynor has received research support from ALS Association. The institution of Dr. Traynor has received research support from Merck. The institution of Dr. Traynor has received research support from Myasthenia Gravis Foundation. Dr. Traynor has received intellectual property interests from a discovery or technology relating to health care. Dr. Calvo has nothing to disclose.