Immunoglobulin light-chain amyloidosis mimicking bulbar amyotrophic lateral sclerosis.

Abstract

A 62-year-old man experienced involuntary weight loss (-36% in the last 6months) followed by dysphagia and dysphonia. He then developed painful and burning paresthaesia in his lower limbs. He also experienced progressive difficulty in walking due to postural dizziness. Clinical examination found an atrophic tongue with profuse fasciculations (Figure 1), few fasciculations in the four limbs, abductor pollicis brevis weakness, distal hypoesthesia in the four limbs, general areflexia, and neurogenic orthostatic hypotension. Nerve conduction studies and needle electromyography showed mixed axonal and demyelinating sensorimotor polyneuropathy, bilateral carpal tunnel syndrome, as well as widespread fasciculations and fibrillations in the bulbar, cervical, thoracic and lumbar regions. IgG lambda monoclonal immunoglobulin (2 g/L), elevated serum lambda/kappa ratio (10.4, N< 1.65) and bone marrow clonal plasma cell infiltration were found, along with tissue amyloid deposition of lambda light chains accessed by immunofluorescence staining of the minor salivary glands. The final diagnosis was immunoglobulin light-chain amyloidosis complicated by lower motor neuron dysfunction. After treatment (melphalan, ixazomib and dexamethasone, followed by daratumumab) all neurological signs/symptoms improved including bulbar signs despite the absence of complete hematological response. To our knowledge the case presented herein is the first of immunoglobulin light-chain amyloidosis with bulbar onset mimicking motor neuron disease at initial presentation. For the two patients with an initial diagnosis of motor neuron disease revealing an immunoglobulin light-chain amyloidosis described in the literature the first symptom was lower limb weakness [1,2]. However, patients with systemic amyloidosis disease are reported to present with bulbar signs but during the course of the disease [3]. Also, motor neuropathy with early-onset severe bulbar involvement has been described for familial amyloid neuropathy (due to mutations in TTR [4,5] or GSN (encodes gelsolin)) [6]. The present report highlights that bulbar signs mimicking bulbar amyotrophic lateral sclerosis could be the first manifestation of immunoglobulin light-chain amyloidosis and underlined that dedicated workup should be performed in all atypical motor neuron diseases associated with sensory abnormalities, neuropathic pain or autonomic dysfunction. Acknowledgments