CASE REPORT
A 60-year-old female with no personal or family history of myopathy
started in November/2014 to feel cervical pain in the shoulder girdle
and upper limbs. Over three months, she developed muscle weakness
resulting in proximal myopathy with drop-head and tetraparesis of
proximal predominance. In July/2015, there was worsening of symptoms
with dysphonia (ocular and tongue movements were regular) and
unintentional weight loss (10 kg in 8 months). She also presented a
myopathic gate with hyperlordosis, posterior pelvic tilt and bilateral
winged scapula with hypotrophy of proximal muscles at the limbs without
fasciculations (Figure 1A). Tendon reflexes and sensory perception were
preserved. No respiratory involvement was evident, and her spirometry
was normal. Human immunodeficiency virus and hepatitis serologies,
autoimmune and active neoplastic screenings were negative. Normal levels
of myoglobin, aldolase, creatine phosphokinase, lactate dehydrogenase
and thyroid hormones were found. No abnormalities in echocardiogram or
electrocardiogram were noted. Serum protein electrophoresis revealed an
M-protein IgG lambda spike of 12 g/L with normal immunoglobulin levels,
normal free light chain ratio, negative urinary immunofixation and no
bone marrow plasmacytosis. Anemia, hypercalcemia, renal dysfunction, and
bone attainment were absent. Amyloid substance exploration was negative.
Therefore, a monoclonal gammopathy of undetermined significance (MGUS)
was diagnosed. Needle electromyography (EMG) showed myopathic pattern of
the action potentials of the motor unity in all muscles explored,
especially severe in cervical and the scapular girdle. However, there
were no slow waves and fibrillation at rest. Left biceps brachii muscle
biopsy demonstrated marked variation in fiber size with many atrophic
angulated fibers containing numerous reddish granules representing
positive rods in Gomori trichrome and immunohistochemistry for myotilin.
The atrophic fibers were mainly of type 1; there was no necrosis,
fibrosis or inflammatory infiltrate (Figure 2). The association of SLOMN
and monoclonal gammopathy was assumed as a monoclonal gammopathy of
neurological significance (MGNS) rather than an unknown significance.
In December/2015, collection of peripheral hematopoietic precursors
after mobilization with granulocyte colony-stimulating factor (G-CSF)
was performed obtaining 2.02x10^6 CD34+cells/kg. In January/2016, was
submitted to ASCT after conditioning with melphalan 140 mg/m2.
Neuromuscular deficits got worse in the acute phase after ASCT, with
stabilization at eight months of follow-up. Due to the persistence of
the monoclonal gammopathy at day 100 evaluation after ASCT, treatment
with lenalidomide plus dexamethasone was started in September/2016. The
patient recovered from general status, but after the fourth cycle, this
trend was reversed occurring weight lost. Neuromuscular dysfunction with
kyphotic posture remained stable until May/2017. By that time asthenia
got worse accompanied by weight lost, myopathy aggravation with de novo
hyperreflexia and respiratory insufficiency. With this evolution,
lenalidomide was discontinued on the 9th cycle.
Noninvasive ventilation (NIV) and third-line treatment targeting the
plasma cell clone with cyclophosphamide, bortezomib and dexamethasone
(CyBorDex) were started in July/2017 for a total of eight cycles until
January/2018. For the first time, after four cycles of CyBorDex, serum
immunofixation got negative. Patient strength significantly improved,
regaining the capacity of head elevation (Figure 1B), greater autonomy
in daily life activities at home and a weight recovery of 12 kilograms
over the CyBorDex treatment (Figure 3) again. The patient kept stable
since the start of this treatment, reaching a weight of 54.7 kilograms
and achieved the independence of nocturn NIV. The monoclonal gammopathy
remains in complete remission three years after finishing treatments.