Nydegger UE (ed): Therapeutic Hemapheresis in the 1990s. Curr Stud Hematol Blood Transf. Basel, Karger, 1990, No 57, pp 167-183
Plasma Exchange in Neurology Pierre-A. Uldry, Andreas-J. Steck
The beneficial effects of plasma exchange (ΡΕ) in neurological disorders were first reported for myasthenia gravis (MG) in 1976 [44] and for GuillainBarré syndrome (GBS) in 1978 [2]. ΡΕ in polyneuropathy associated with monoclonal gammopathies has led to clinical improvement in some patients and was first reported in 1980 [29]. PE has become increasingly popular as a mode of therapy in putative immunological neurological disorders which, in the United States, account for approximately half of the 20,000-30,000 therapeutic ΡΕ performed annually. The potential complications of PE (sepsis, hemorrhage, cardiac or pulmonary failure, viral infections) and its relatively high cost make it necessary to reserve this treatment for neurological situations of expected major benefit. In 1986 in the United States, a consensus development conference convened by the National Institute of Neurological and Communicative Disorders and Stroke, and the National Institutes of Health Office of Medical Applications of Research presented a statement on the utility of therapeutic ΡΕ for neurologic diseases [5]. ΡΕ improves a disease by removing one or several substances that can produce a comparable disorder in passive transfer in animals. It appears logical that ΡΕ should be most effective in disorders that can be effectively passively transferred, and this is the case for GBS and MG. ΡΕ works by removing a pathogenic antibody and is now the treatment of choice in these diseases. A comparable understanding of disease induction has not been achieved in chronic inflammatory demyelinating polyneuropathy or paraproteinemic neuropathy, and ΡΕ seems to be less effective. PE is still experimental in multiple sclerosis and it has also been tried in amyotrophic lateral sclerosis but without benefit. Thus, PE appears to be a rational approach of therapy for some neurologic disorders, and where it is useful, it has strengthened our views on the pathogenesis [52]. In this article, we review
Downloaded by: Université de Paris 193.51.85.197 - 1/10/2020 12:03:17 AM
Department of Neurology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
Uldry/Steck
168
the use and rationale for PE in neurologic disorders, and attempt to summarize current knowledge about plasmapheresis in neurology.
Guillain-Barré Syndrome
Pathogenesis Although the causes of GBS are still imperfectly defined, a growing body of evidence suggests that this disorder is immunologically mediated. There is some evidence that antibodies to peripheral-nerve tissue, demyelinating factors or immune complexes may be involved [ 1 ]. Deposits of IgG and IgM bound to nerve fibers have been found in many patients, and demonstration of serum binding to normal nerve from various species were also reported. Evidence for cell-mediated immunity has been derived from pathologic studies showing that the earliest changes are cellular infiltrates consisting predominantly of lymphocytes, and from the fact that GBS has features remarkably similar to experimental allergic neuritis, an autoimmune disease induced in the animal by injection of peripheral nerve myelin or the P2 basic protein. Recently, Metral et al. [35] analyzed the demyelinating activity of serum of GBS patients after its injection into the sciatic nerve of rat. The demyelinating activity decreased during the time course of the disease earlier in cases receiving PE. Serum from individuals without sequelae and who have recovered from GBS did not produce a conduction block as compared to serum from patients with active GBS. GBS may also occur with lym-
Downloaded by: Université de Paris 193.51.85.197 - 1/10/2020 12:03:17 AM
Clinical Manifestations GBS, or acute inflammatory polyradiculoneuropathy, affects patients of all ages and both sexes. The frequency is 1.7/100,000 population per year. The major clinical manifestation is weakness which evolves over a period of a few days. Proximal as well as distal muscles of the limbs are involved, usually the lower extremities before the upper. The trunk, intercostal, neck and cranial muscles may also be affected. The weakness may progress to total motor paralysis with death from respiratory failure. Hypotonia and absent reflexes are consistent findings. Disturbances of autonomic function are common. The cerebrospinal fluid is usually acellular but the protein level begins to rise several days after the onset of symptoms. While the long-term prognosis is good (85% of cases with complete recovery), a high rate of respiratory failure (16%) and a mortality rate of 2-3% make GBS a very serious condition [57].
Plasma Exchange in Neurology
169
phomatous disease (particularly Hodgkin's disease) or with viral illnesses (AIDS, vaccination). This supports the hypothesis that both humoral and cellular effector mechanisms may contribute to the nerve disorder in GBS.
Prognostic Factors A problem in assessing the efficacy of PE in GBS is the extremely variable course of the disease and range of outcome. McKhann et al. [31] studied 245 patients with GBS, and clinical and laboratory features were estimated to evaluate the beneficial effects of PE. The authors analyzed and compared the age of patients, motor conduction studies, the requirement of ventilatory support and the measure of disability and the time to improve one grade (grade 0 = healthy; 1 = minor symptoms; 2 = able to walk without assistance; 3 = able to walk with assistance; 4 = confined to bed; 5 = assisted ventilation). Only the cases in grades 3-5 were included in this study. The main predictor of a poor outcome was a reduced value for the mean distal motor amplitude (
Plasma Exchange in Neurology Pierre-A. Uldry, Andreas-J. Steck
The beneficial effects of plasma exchange (ΡΕ) in neurological disorders were first reported for myasthenia gravis (MG) in 1976 [44] and for GuillainBarré syndrome (GBS) in 1978 [2]. ΡΕ in polyneuropathy associated with monoclonal gammopathies has led to clinical improvement in some patients and was first reported in 1980 [29]. PE has become increasingly popular as a mode of therapy in putative immunological neurological disorders which, in the United States, account for approximately half of the 20,000-30,000 therapeutic ΡΕ performed annually. The potential complications of PE (sepsis, hemorrhage, cardiac or pulmonary failure, viral infections) and its relatively high cost make it necessary to reserve this treatment for neurological situations of expected major benefit. In 1986 in the United States, a consensus development conference convened by the National Institute of Neurological and Communicative Disorders and Stroke, and the National Institutes of Health Office of Medical Applications of Research presented a statement on the utility of therapeutic ΡΕ for neurologic diseases [5]. ΡΕ improves a disease by removing one or several substances that can produce a comparable disorder in passive transfer in animals. It appears logical that ΡΕ should be most effective in disorders that can be effectively passively transferred, and this is the case for GBS and MG. ΡΕ works by removing a pathogenic antibody and is now the treatment of choice in these diseases. A comparable understanding of disease induction has not been achieved in chronic inflammatory demyelinating polyneuropathy or paraproteinemic neuropathy, and ΡΕ seems to be less effective. PE is still experimental in multiple sclerosis and it has also been tried in amyotrophic lateral sclerosis but without benefit. Thus, PE appears to be a rational approach of therapy for some neurologic disorders, and where it is useful, it has strengthened our views on the pathogenesis [52]. In this article, we review
Downloaded by: Université de Paris 193.51.85.197 - 1/10/2020 12:03:17 AM
Department of Neurology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
Uldry/Steck
168
the use and rationale for PE in neurologic disorders, and attempt to summarize current knowledge about plasmapheresis in neurology.
Guillain-Barré Syndrome
Pathogenesis Although the causes of GBS are still imperfectly defined, a growing body of evidence suggests that this disorder is immunologically mediated. There is some evidence that antibodies to peripheral-nerve tissue, demyelinating factors or immune complexes may be involved [ 1 ]. Deposits of IgG and IgM bound to nerve fibers have been found in many patients, and demonstration of serum binding to normal nerve from various species were also reported. Evidence for cell-mediated immunity has been derived from pathologic studies showing that the earliest changes are cellular infiltrates consisting predominantly of lymphocytes, and from the fact that GBS has features remarkably similar to experimental allergic neuritis, an autoimmune disease induced in the animal by injection of peripheral nerve myelin or the P2 basic protein. Recently, Metral et al. [35] analyzed the demyelinating activity of serum of GBS patients after its injection into the sciatic nerve of rat. The demyelinating activity decreased during the time course of the disease earlier in cases receiving PE. Serum from individuals without sequelae and who have recovered from GBS did not produce a conduction block as compared to serum from patients with active GBS. GBS may also occur with lym-
Downloaded by: Université de Paris 193.51.85.197 - 1/10/2020 12:03:17 AM
Clinical Manifestations GBS, or acute inflammatory polyradiculoneuropathy, affects patients of all ages and both sexes. The frequency is 1.7/100,000 population per year. The major clinical manifestation is weakness which evolves over a period of a few days. Proximal as well as distal muscles of the limbs are involved, usually the lower extremities before the upper. The trunk, intercostal, neck and cranial muscles may also be affected. The weakness may progress to total motor paralysis with death from respiratory failure. Hypotonia and absent reflexes are consistent findings. Disturbances of autonomic function are common. The cerebrospinal fluid is usually acellular but the protein level begins to rise several days after the onset of symptoms. While the long-term prognosis is good (85% of cases with complete recovery), a high rate of respiratory failure (16%) and a mortality rate of 2-3% make GBS a very serious condition [57].
Plasma Exchange in Neurology
169
phomatous disease (particularly Hodgkin's disease) or with viral illnesses (AIDS, vaccination). This supports the hypothesis that both humoral and cellular effector mechanisms may contribute to the nerve disorder in GBS.
Prognostic Factors A problem in assessing the efficacy of PE in GBS is the extremely variable course of the disease and range of outcome. McKhann et al. [31] studied 245 patients with GBS, and clinical and laboratory features were estimated to evaluate the beneficial effects of PE. The authors analyzed and compared the age of patients, motor conduction studies, the requirement of ventilatory support and the measure of disability and the time to improve one grade (grade 0 = healthy; 1 = minor symptoms; 2 = able to walk without assistance; 3 = able to walk with assistance; 4 = confined to bed; 5 = assisted ventilation). Only the cases in grades 3-5 were included in this study. The main predictor of a poor outcome was a reduced value for the mean distal motor amplitude (
