Sporadic late-onset nemaline myopathy: clinical, pathology and imaging findings in a single center cohort

Abstract

Sporadic late-onset nemaline myopathy (SLONM) is a rare acquired myopathy characterized by rapid-onset proximal weakness in late adulthood, and the presence of nemaline bodies on muscle biopsy. In recent years, several therapeutic interventions, including immunomodulating agents and autologous stem cell transplantation, have shown variable degrees of efficacy in different patients, but no consensus has been reached to allow an effective tailoring of treatments in this severe disease. We performed a retrospective evaluation of clinical, pathological, laboratory, muscle MRI, and follow-up data of SLONM patients diagnosed in the period 2010-2015 in our neuromuscular center. Six patients (three males and three females) were identified. Average time elapsed from the onset of symptoms to referral to the neuromuscular specialist was 23.7 months. Monoclonal gammopathy was detectable in five patients. Nemaline bodies were detected in all the patients, and their abundance correlated with clinical severity. Signs of cardiac involvement were present in all the patients to different extents. Muscle MRI showed a preferential involvement of neck extensors, paraspinal, gluteal, hamstring and soleus muscles. All patients were treated with prednisone and repeated courses of intravenous immunoglobulins, and a favorable outcome was reached in five patients. Our experience confirms that SLONM is clinically characterized by subacute proximal and axial muscle weakness. Time to referral was relatively long and should be reduced with increasing awareness of the disease. Muscle MRI could be of help as a diagnostic tool to identify this potentially treatable myopathy. Cardiac evaluation should be warranted in all SLONM patients to detect subclinical heart involvement.

Impact of hematologic complete response in the treatment of sporadic late-onset nemaline myopathy associated with monoclonal gammopathy

“…Monoclonal gammopathy of undetermined significance (MGUS) may be associated with pathologies with severe neuromuscular manifestations, namely POEMS Syndrome and AL Amyloidosis [1][2][3][4]. Another lessknown association is with a rare disorder named sporadic late-onset nemaline myopathy (SLONM) [5][6][7][8][9][10] and happens in more than half of these patients [11,12]. Diagnosis is confirmed by muscle biopsy with detection of intracytoplasmic nemaline rod bodies, representing Z-disc disorganization products that immunoreact with alfa-actinin and myotilin, accompanied by progressive atrophy of the muscle fiber [5,11].…”

“…Another lessknown association is with a rare disorder named sporadic late-onset nemaline myopathy (SLONM) [5][6][7][8][9][10] and happens in more than half of these patients [11,12]. Diagnosis is confirmed by muscle biopsy with detection of intracytoplasmic nemaline rod bodies, representing Z-disc disorganization products that immunoreact with alfa-actinin and myotilin, accompanied by progressive atrophy of the muscle fiber [5,11]. Necrotic or regenerating fibers and inflammatory infiltration are usually absent [13].…”

“…Necrotic or regenerating fibers and inflammatory infiltration are usually absent [13]. Clinically, SLONM appears mostly after the fourth decade of life as a rapidly progressing tetraparesis, mostly by proximal/axial muscle weakness with features such as dropped head syndrome, facial, bulbar involvement (dysphagia) and respiratory insufficiency leading to severe disability or death [5,11,12]. Head drop, neck muscle weakness, or neck muscle pain are features described in more than half of the patients with SLONM associated with MGUS (SLONM-MGUS) [13].…”

“…Head drop, neck muscle weakness, or neck muscle pain are features described in more than half of the patients with SLONM associated with MGUS (SLONM-MGUS) [13]. Cardiac involvement is less common, but there are echocardiographic and electric conduction cardiac abnormalities in some patients [3,[11][12][13][14][15][16]. The first cases published suggested an autoimmune etiology, and it was uncertain whether monoclonal gammopathy was associated or coincidental [6].…”

“…The first cases published suggested an autoimmune etiology, and it was uncertain whether monoclonal gammopathy was associated or coincidental [6]. Treatment of first cases using immunosuppressive strategies showed better results with intravenous immunoglobulin [11,17], mostly on non-MGUS associated cases [12]. Nonetheless, other immunosuppressive treatments (prednisone, cyclophosphamide, rituximab) or even plasmapheresis showed disappointing and inconstant outcomes which led the autoimmune etiology to be questioned, at least for some patients [3,5,6,10,14,18,19].…”