EURO-NMD Board & Working Group Meetings - Winter 2020

EURO-NMD network stakeholders – please save the date!

Our next board meeting and associated group meetings is now scheduled to take place 8-11 December 2020.

As with all meetings being held in this current crisis we will be holding this online via a series of virtual meetings and larger scale webinar style events spread over the days.

Further details of our programme are available on the website and will of course update these as we receive further individual details of each session.

You will need to register for each session you wish to attend but please note that some of the sessions are by invitation only.

The board meeting itself which will take place on 11th December is restricted to board members or designated representatives only.

Registration is closes on 30th November!

Publication - Assessment of respiratory muscles and motor function in children with SMA treated by Nusinersen

Introduction
Nusinersen is associated with an improvement in motor function in children with spinal muscular atrophy (SMA) but data on respiratory muscles strength are scarce. Respiratory muscles performance and lung function were evaluated in children with SMA 1c and 2 after 6 injections of Nusinersen (M14). Results from SMA2 patients were compared to data of age‐matched historical controls. Motor function tests (MFM and HINE‐2) were assessed at baseline and M14 in the treated patients.

Results
Sixteen children (2 SMA type 1c, 14 SMA type 2), mean age 9.4±2.3 years, were included. The data of 14 historical SMA 2 controls (mean age 9.3±1.9 years) were gathered. The strength of the global inspiratory muscles of SMA 2 treated with nusinersen, assessed on maximal static inspiratory pressure, forced vital capacity, and esophageal pressure during a maximal sniff, was significantly better compared to historical controls (p<.05). A significant improvement in MFM and HINE‐2 was observed in the 16 SMA patients treated with nusinersen after 14 months as compared to baseline.

Conclusion
In children with SMA type 2, respiratory muscle performance was significantly better after 6 injections of nusinersen as compared to age‐matched SMA type 2 historical controls.

Publication - hATTR Pathology: Nerve Biopsy Results from Italian Referral Centers

Pathological evidence of amyloid on nerve biopsy has been the gold standard for diagnosis in hereditary transthyretin amyloidosis polyneuropathy (hATTR-PN) for a long time. In this article, we reviewed the pathological findings of a large series of sural nerve biopsies from a cohort of hATTR-PN patients, collected by different Italian referral centers.

Patients and Methods: We reviewed clinical and pathological data from hATTR-PN patients, diagnosed and followed in five Italian referral centers for peripheral neuropathies. Diagnosis was formulated after a positive genetic test for transthyretin (TTR) mutations. Sural nerve biopsy was performed according to standard protocols.

Results: Sixty-nine sural nerve biopsies from hATTR-PN patients were examined. Congo red positive deposits were found in 73% of cases. Only the Phe64Leu mutation failed to show amyloid deposits in a high percentage of biopsies (54%), as already described. Unusual pathological findings, such as myelin abnormalities or inflammatory infiltrates, were detected in occasional cases.

Conclusions: Even if no longer indicated to confirm hATTR-PN clinical suspicion, nerve biopsy remains, in expert hands, a rapid and inexpensive tool to detect amyloid deposition. In Italy, clinicians should be aware that a negative biopsy does not exclude hATTR-PN, particularly for Phe64Leu, one of the most frequent mutations in this country.

Publication - Intravenous immunoglobulins as first-line treatment in idiopathic inflammatory myopathies: a pilot study

Objectives.
We explored efficacy and safety of IVIg as first-line treatment in patients with an idiopathic inflammatory myopathy.

Methods.
In this investigator-initiated phase 2 open-label study, we included 20 adults with a newly diagnosed, biopsy-proven idiopathic inflammatory myopathy, and a disease duration of less than 9 months. Patients with IBM and prior use of immunosuppressants were excluded. The standard treatment regimen consisted of IVIg (Privigen) monotherapy for 9 weeks: a loading dose (2 g/kg body weight) and two subsequent maintenance doses (1 g/kg body weight) with a 3-week interval. The primary outcome was the number of patients with at least moderate improvement on the 2016 ACR/EULAR Total Improvement Score. Secondary outcomes included time to improvement, the number of patients requiring rescue medication and serious adverse events.

Results.
We included patients with DM (n ¼ 9), immune-mediated necrotizing myopathy (n ¼ 6), non-specific myositis/overlap myositis (n ¼ 4) and anti-synthetase syndrome (n ¼ 1). One patient was excluded from analyses because of minimal weakness resulting in a ceiling effect. Eight patients (8/19 ¼ 42.0%; Clopper–Pearson 95% CI: 19.6, 64.6) had at least moderate improvement by 9 weeks. Of these, six reached improvement by 3 weeks. Seven patients required rescue medication due to insufficient efficacy and prematurely ended the study. Three serious adverse events occurred, of which one was pulmonary embolism.

Conclusion.
First-line IVIg monotherapy led to at least moderate improvement in nearly half of patients with a fast clinical response in the majority of responders.