Evaluation of peripheral amyloid neuropathy

Abstract

Symptoms of peripheral nervous system (PNS) damage are common clinical manifestations of systemic amyloidosis. Peripheral amyloid neuropathy is characterized by a progressive course, leading to the disability of patients; however, the current possibilities of pathogenetic therapy make the early diagnosis of amyloid neuropathy particularly urgent.Objective: to evaluate the informative value of laser confocal microscopy (LCM) of the cornea in diagnosing small fiber neuropathy of peripheral nerves in patients with systemic amyloidosis.Patients and methods. The study included nine patients (three men and six women) with morphologically confirmed primary amyloidosis (ALamyloidosis) and 12 patients (three men and nine women) with hereditary transthyretin amyloidosis (TTR-amyloidosis) verified by genetic and morphological methods. At baseline, the mean age of patients with AL-amyloidosis was 60.6±10.7 years, with hereditary TTR-amyloidosis – 57.1±13.1 years. According to the history of the disease in AL-amyloidosis, the mean duration of clinical symptoms was 2.7±1.4 years, with TTR-amyloidosis – 5.5±3.6 years. 20 age- and sex-adjusted healthy volunteers were included in the control group. All patients underwent a clinical neurological examination with an assessment of the severity of neuropathy according to the Neuropathy Impairment Score (NIS); 21 patients with systemic amyloidosis and all volunteers of the control group underwent LCM of the corneal nerve fibers (CNF). The coefficients of anisotropy (КΔL) and orientation symmetry (Ksym) of the CNF were calculated to assess the severity of damage to the corneal nerves.Results and discussion. Clinical neurological examination in patients with AL-amyloidosis revealed polyneuropathic syndrome (45%), tunnel syndrome (22%), their combination (22%), and autonomic dysfunction in the form of orthostatic hypotension and impaired motility of the gastrointestinal tract (GI tract; 56%). Symptoms in patients with TTR-amyloidosis were characterized by a combination of tunnel neuropathy and sensory-motor polyneuropathy (50%), distal symmetric polyneuropathy (42%). Frequent symptoms of PNS damage in systemic amyloidosis include autonomic neuropathy (56% – in AL-amyloidosis, 92% – in TTR-amyloidosis) presenting with orthostatic hypotension, impaired gastrointestinal motility, hypohidrosis, and dysuria. The mean NIS score, which characterizes the severity of somatic neuropathy, was significantly higher in patients with TTR-amyloidosis than AL-amyloidosis (p<0.02). LCM of the cornea showed disturbances in the course and structure of the corneal nerve fibers in all examined patients with systemic amyloidosis. The mean anisotropy coefficient values were lower in patients with systemic amyloidosis than in the control group. There were no significant differences in the AL- and TTR-amyloidosis groups. An inverse correlation of average strength between the values of the anisotropy coefficient and NIS was revealed (r=-0.6; p=0.04) in the group of patients with TTR-amyloidosis.Conclusion. Clinical polymorphism of peripheral somatic and autonomic nervous systems lesions is typical for patients with systemic amyloidosis. LCM of the cornea is informative in the diagnosis of small fibers neuropathy of peripheral nerves in systemic amyloidosis; however, it cannot establish the nosology of neuropathy.

Keywords

• systemic amyloidosis
• peripheral neuropathy
• small fiber neuropathy
• corneal nerve fibers
• laser confocal microscopy