Wegener's Granulomatosis: Neurological Involvement
Wegener's Granulomatosis: Neurological Involvement
Purpose of review Wegener's granulomatosis is a rare autoimmune disease associated with granulomatous inflammation and antineutrophil cytoplasmic antibody-associated vessel vasculitis. Most commonly, upper and lower respiratory tract and kidneys are involved: alveolar hemorrhage and necrotizing glomerulonephritis are hallmarks of full-blown disease; yet, a significant proportion of patients presents with peripheral nervous system (PNS) involvement due to vasculitis or with central nervous system (CNS) involvement due to infiltrating granulomatous manifestations (10–45%). The purpose of this review is to give a systematic overview on Wegener's granulomatosis manifestations of the PNS and CNS and to highlight new findings regarding manifestations, diagnosis and therapy.
Recent findings So far, peripheral neuropathy has been recognized as a severe and frequently occurring organ manifestation in Wegener's granulomatosis which requires early introduction of highly potent immunosuppression to induce remission. Recently, the impact of granulomatous manifestations originating from the ear–nose–throat tract and frequently affecting CNS structures has moved into the focus of attention, first, because they are not uncommon (occurring in 10–45% of patients) and, second, because they are associated with a high frequency of refractory disease courses. For both CNS and PNS involvement, rituximab and infliximab have emerged as potential treatment options for refractory disease.
Summary CNS and PNS manifestation in Wegener's granulomatosis are less frequent than classical manifestations such as lung and kidney involvement in Wegener's granulomatosis; however, neurological manifestations – not only peripheral neuropathy but also granulomatous manifestations affecting CNS structures – necessitate a fast diagnostic work-up and therapeutic intervention in order to prevent or reduce potential damage.
Wegener's granulomatosis is a rare autoimmune disease of unknown origin and characterized by granulomatous inflammation (mainly occurring in the upper and lower respiratory tract) and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis with a predilection for small-size to medium-size vessels in lung (alveolar capillaritis leading to hemorrhage) and kidneys (manifesting as rapid progressive glomerulonephritis). It is assumed that Wegener's granulomatosis starts as localized granulomatous, mucosal inflammation of the upper and/or lower respiratory tract (called localized stage with no evidence of signs of systemic vasculitis) and progresses to a systemic stage with clinical vasculitis manifestations after a variable period (generalized disease stage). Peripheral nervous system (PNS) involvement presents as polyneuropathy or mononeuritis multiplex which is thought to occur due to vasculitis of the vasa nervorum in the generalized disease stage. For central nervous system (CNS) involvement, three different pathogenic patterns have been identified. First, as a manifestation of the generalized disease stage, vasculitis may affect small-size to medium-size vessels of the brain or spinal cord. Second, granulomatous masses originating from the upper respiratory tract perforate neighbouring cartilage and bones and invade CNS structures such as the orbit (e.g. affecting the nervus opticus) or the meninges and brain. These disease manifestations may be associated with an otherwise localized disease stage. Third, granulomatous lesions can develop in intracerebral tissue, for example in the meninges (pachymeningitis) or the brain. Recently, attention has especially been drawn to the granulomatous manifestations because they are frequently resistant to standard therapy. In this review, we will give an overview of the clinical manifestations of the PNS and CNS in Wegener's granulomatosis and highlight new findings regarding neurological manifestations and current therapy strategies.
Abstract and Introduction
Abstract
Purpose of review Wegener's granulomatosis is a rare autoimmune disease associated with granulomatous inflammation and antineutrophil cytoplasmic antibody-associated vessel vasculitis. Most commonly, upper and lower respiratory tract and kidneys are involved: alveolar hemorrhage and necrotizing glomerulonephritis are hallmarks of full-blown disease; yet, a significant proportion of patients presents with peripheral nervous system (PNS) involvement due to vasculitis or with central nervous system (CNS) involvement due to infiltrating granulomatous manifestations (10–45%). The purpose of this review is to give a systematic overview on Wegener's granulomatosis manifestations of the PNS and CNS and to highlight new findings regarding manifestations, diagnosis and therapy.
Recent findings So far, peripheral neuropathy has been recognized as a severe and frequently occurring organ manifestation in Wegener's granulomatosis which requires early introduction of highly potent immunosuppression to induce remission. Recently, the impact of granulomatous manifestations originating from the ear–nose–throat tract and frequently affecting CNS structures has moved into the focus of attention, first, because they are not uncommon (occurring in 10–45% of patients) and, second, because they are associated with a high frequency of refractory disease courses. For both CNS and PNS involvement, rituximab and infliximab have emerged as potential treatment options for refractory disease.
Summary CNS and PNS manifestation in Wegener's granulomatosis are less frequent than classical manifestations such as lung and kidney involvement in Wegener's granulomatosis; however, neurological manifestations – not only peripheral neuropathy but also granulomatous manifestations affecting CNS structures – necessitate a fast diagnostic work-up and therapeutic intervention in order to prevent or reduce potential damage.
Introduction
Wegener's granulomatosis is a rare autoimmune disease of unknown origin and characterized by granulomatous inflammation (mainly occurring in the upper and lower respiratory tract) and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis with a predilection for small-size to medium-size vessels in lung (alveolar capillaritis leading to hemorrhage) and kidneys (manifesting as rapid progressive glomerulonephritis). It is assumed that Wegener's granulomatosis starts as localized granulomatous, mucosal inflammation of the upper and/or lower respiratory tract (called localized stage with no evidence of signs of systemic vasculitis) and progresses to a systemic stage with clinical vasculitis manifestations after a variable period (generalized disease stage). Peripheral nervous system (PNS) involvement presents as polyneuropathy or mononeuritis multiplex which is thought to occur due to vasculitis of the vasa nervorum in the generalized disease stage. For central nervous system (CNS) involvement, three different pathogenic patterns have been identified. First, as a manifestation of the generalized disease stage, vasculitis may affect small-size to medium-size vessels of the brain or spinal cord. Second, granulomatous masses originating from the upper respiratory tract perforate neighbouring cartilage and bones and invade CNS structures such as the orbit (e.g. affecting the nervus opticus) or the meninges and brain. These disease manifestations may be associated with an otherwise localized disease stage. Third, granulomatous lesions can develop in intracerebral tissue, for example in the meninges (pachymeningitis) or the brain. Recently, attention has especially been drawn to the granulomatous manifestations because they are frequently resistant to standard therapy. In this review, we will give an overview of the clinical manifestations of the PNS and CNS in Wegener's granulomatosis and highlight new findings regarding neurological manifestations and current therapy strategies.
