INTRODUCTION
Monoclonal gammopathy of undetermined significance (MGUS) may be
associated with pathologies with severe neuromuscular manifestations,
namely POEMS Syndrome and AL Amyloidosis[1-4]. Another less-known
association is with a rare disorder named sporadic late-onset nemaline
myopathy (SLONM)[5-10] 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]. 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]. Cardiac involvement is less common, but there are
echocardiographic and electric conduction cardiac abnormalities in some
patients[3, 11-16]. 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]. The
hypothesis that SLONM-MGUS is a continuum of light-chain deposition
disease (LCDD) is corroborated by the presence of light chain deposition
in skeletal muscles observed in some cases described [20]. However,
LCDD is a multiple organ disease while SLONM attainment is restricted to
muscles, which could be an argument in favor of autoimmune abnormalities
in its pathogenesis[13]. AL amyloidosis and POEMS are usually
treated targeting the plasma cell clone with clinical improvement, as
any manifestation associated with a plasma cell dyscrasia as postulated
to SLONM-MGUS. [21-24]. The fast progression and severity of
SLONM-MGUS (mortality of 70% in 1-5 years) led clinicians to use the AL
Amyloidosis treatment approach by using the autologous stem cell
transplant (ASCT) with good results and low mortality rate (2-3%) [5,
12, 25]. There are successful cases with clinical and histological
improvement, as well as an increment in survival after conditioning with
melphalan and ASCT, suggesting a possible toxic action of monoclonal
protein as a degenerative mechanism for neurologic symptoms[14, 19,
20, 26-28]. Some propose light and heavy chains, rather than nemaline
bodies, as responsible for myotoxic effects, and there is a report of
coexistence of nemaline myopathy and amyloid myopathy[20, 29].
Furthermore, the evidence is growing about the association between
disease severity and the size of the monoclonal protein supporting the
rationale to use therapeutics targeting the clonal plasma cells[11,
12, 14, 28]. Other effective treatment options beyond ASCT, used in
plasma cell dyscrasias can also be efficient, such as bortezomib[3,
14, 20, 30], lenalidomide[28, 31], cyclophosphamide or
thalidomide[32]. Hematologic therapy seems to be the one that allows
a lower risk of progression of the disease 24 months after
treatment[15].