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  • Updated 02.01.2022
  • Released 05.13.1996
  • Expires For CME 02.01.2025

Immunoglobulin light chain amyloidosis: neurologic complications

Introduction

Overview

Amyloidosis is a generic term and refers to the extracellular deposition of fibrils composed of low weight chain of a variety of proteins. Immunoglobulin light chain (AL) amyloidosis is one of the major causes of amyloid neuropathy, which remains a serious, usually rapidly fatal disease. However, in this updated article, the authors discuss evidence indicating that peripheral blood stem cell transplantation has proven to be effective treatment in carefully chosen patients. Patients with limited organ involvement have shown a good response to autologous hematopoietic cell transplantation with prolongation of survival. Early hematopoietic cell transplantation in well-selected patients is the current treatment of choice for amyloid neuropathy. Thus, early diagnosis and referral for treatment is essential before the disease spreads to multiple organs. Prognosis has improved with the use of early mortality risk scores to recognize those patients most at risk for early death. Diagnosis is still based on discovery of amyloid deposits in tissue biopsy identified by immunohistochemistry, but new techniques, such as mass spectrometry, show promise in determining amyloid types. Neurologists, who are most likely to see patients with neuropathy only, are in a favorable position to make an early diagnosis. The discussion of the clinical presentation and laboratory findings in this article can aid in early recognition of this disease. Review of neurologic manifestations of primary systemic amyloidosis, early recognition of the disease by new methods, and considering early treatment (especially autologous hematopoietic cell transplantation) with prolongation of survival are all covered.

Key points

• Immunoglobulin light chain (AL) amyloidosis is one of the major causes of amyloid neuropathy.

• Peripheral neuropathy is the presenting sign of immunoglobulin light chain amyloidosis in about 15% of patients.

• Diagnosis is based on discovery of amyloid deposits in tissue biopsy and immunohistochemical tests of amyloid for light chains.

• Early hematopoietic cell transplantation in well-selected patients is the current treatment of choice for amyloid neuropathy.

• Prognosis has improved with the use of early mortality risk scores to recognize those patients most at risk for early death.

Historical note and terminology

The term "amyloid" denotes a waxy, amorphous, eosinophilic material named by botanist Mathias Schlieden in 1838 for the waxy components of plants and later used by Virchow in 1853 to describe similar pathological findings in humans. Virchow believed that it was composed of polysaccharides. All varieties of amyloid have similar physical properties such as staining red with Congo red dye and showing a distinctive apple-green birefringence under polarized light.

Initially, the classification of amyloidosis was based on the clinical and pathological presentation and familial attributes (44; 45). Most current classifications are based on the recommendations by the International Society of Amyloidosis Nomenclature Committee (06), as determined by immunohistochemical testing, direct gene studies, or mass spectrometry analyses (Table 1). More than 30 causative protein of amyloidosis have been reported and some of them, such as amyloid β precursor protein (APP) in Alzheimer disease, prion protein in prion diseases, immunoglobulin light chain amyloidosis, transthyretin (TTR) in ATTR amyloidosis, and serum amyloid A in amyloid A amyloidosis, cause fatal outcomes (06; 103; 66). The deposition of amyloid is localized to the central nervous system in Alzheimer disease and most prion diseases (06), whereas systemic deposition occurs in AL, ATTR, and AA amyloidoses (67; 103). This review will focus on immunoglobulin light chain amyloidosis and associated neurologic and medical manifestations, but it will also discuss ATTR amyloidosis because it often enters into the differential diagnosis of immunoglobulin light chain amyloidosis.

Immunoglobulin light chain (AL) amyloidosis is caused by the secretion of a monoclonal serum protein (M-protein) by a plasma cell dyscrasia. The light chain of immunoglobulin deposits in extracellular spaces of organs and aggregates as amyloid fibrils that are insoluble, resulting in organ damage. It is treated with autologous hematopoietic cell transplantation or chemotherapy to eradicate the underlying clone and should be differentiated from other forms of amyloidosis (eg, AA amyloidosis and ATTR amyloidosis) as they are nonneoplastic and will not benefit from chemotherapy.

Table 1. Classification of Major Systemic Amyloidosis

Type

Precursor protein

AL amyloidosis

Immunoglobulin light chain

AA amyloidosis

Serum amyloid A

ATTR amyloidosis

Transthyretin

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