Carol Lee Koski

European federation of neurological societies/peripheral nerve society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society - First Revision

Background:  Consensus guidelines on the definition, investigation, and treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have been previously published in European Journal of Neurology and Journal of the Peripheral Nervous System.

The Guillain–Barré Syndrome and the 1992–1993 and 1993–1994 Influenza Vaccines

BACKGROUND The number of reports of influenza-vaccine-associated Guillain-Barré syndrome to the national Vaccine Adverse Event Reporting System increased from 37 in 1992-1993 to 74 in 1993-1994, arousing concern about a possible increase in vaccine-associated risk. METHODS Patients given a diagnosis of the Guillain-Barré syndrome in the 1992-1993 and 1993-1994 influenza-vaccination seasons were identified in the hospital-discharge data bases of four states. Vaccination histories were obtained by telephone interviews during 1995-1996 and were confirmed by the vaccine providers. Disease with an onset within six weeks after vaccination was defined as vaccine-associated. Vaccine coverage in the population was measured through a random-digit-dialing telephone survey. RESULTS We interviewed 180 of 273 adults with the Guillain-Barré syndrome; 15 declined to participate, and the remaining 78 could not be contacted. The vaccine providers confirmed influenza vaccination in the six weeks before the onset of Guillain-Barré syndrome for 19 patients. The relative risk of the Guillain-Barré syndrome associated with vaccination, adjusted for age, sex, and vaccine season, was 1.7 (95 percent confidence interval, 1.0 to 2.8; P=0.04). The adjusted relative risks were 2.0 for the 1992-1993 season (95 percent confidence interval, 1.0 to 4.3) and 1.5 for the 1993-1994 season (95 percent confidence interval, 0.8 to 2.9). In 9 of the 19 vaccine-associated cases, the onset was in the second week after vaccination, all between day 9 and day 12. CONCLUSIONS There was no increase in the risk of vaccine-associated Guillain-Barré syndrome from 1992-1993 to 1993-1994. For the two seasons combined, the adjusted relative risk of 1.7 suggests slightly more than one additional case of Guillain-Barré syndrome per million persons vaccinated against influenza.

European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of multifocal motor neuropathy. Report of a Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society - first revision

A European Federation of Neurological Societies/Peripheral Nerve Society consensus guideline on the definition, investigation, and treatment of multifocal motor neuropathy (MMN) was published in 2006. The aim is to revise this guideline. Disease experts considered references retrieved from MEDLINE and Cochrane Systematic Reviews published between August 2004 and July 2009 and prepared statements that were agreed to in an iterative fashion. The Task Force agreed on Good Practice Points to define clinical and electrophysiological diagnostic criteria for MMN, investigations to be considered, and principal recommendations for treatment.

European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society - First Revision

Background: Consensus guidelines on the definition, investigation, and treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have been published (J Peripher Nerv Syst 2005; 10: 220–228, Eur J Neurol 2006; 13: 326–332). Objectives: To revise these guidelines. Methods: Disease experts, including a representative of patients, considered references retrieved from MEDLINE and Cochrane Systematic Reviews published between August 2004 and July 2009 and prepared statements that were agreed in an iterative fashion.

European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society

Numerous sets of diagnostic criteria have sought to define chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and randomized trials and systematic reviews of treatment have been published. The objective is to prepare consensus guidelines on the definition, investigation and treatment of CIDP. Disease experts and a patient representative considered references retrieved from MEDLINE and Cochrane Systematic Reviews in May 2004 and prepared statements which were agreed in an iterative fashion. The Task Force agreed on good practice points to define clinical and electrophysiological diagnostic criteria for CIDP with or without concomitant diseases and investigations to be considered. The principal treatment recommendations were: (1) intravenous immunoglobulin (IVIg) or corticosteroids should be considered in sensory and motor CIDP (level B recommendation); (2) IVIg should be considered as the initial treatment in pure motor CIDP (Good Practice Point); (3) if IVIg and corticosteroids are ineffective plasma exchange (PE) should be considered (level A recommendation); (4) If the response is inadequate or the maintenance doses of the initial treatment are high, combination treatments or adding an immunosuppressant or immunomodulatory drug should be considered (Good Practice Point); (5) Symptomatic treatment and multidisciplinary management should be considered (Good Practice Point).

Serologic evidence of previous Campylobacter jejuni infection in patients with the Guillain-Barré syndrome

The Guillain-Barre syndrome, sometimes called acute inflammatory polyneuropathy, is an inflammatory demyelinating disease of peripheral nerves characterized by various degrees of weakness, sensory abnormalities, and autonomic dysfunction [1, 2]. Since the marked decline in poliomyelitis, the Guillain-Barre syndrome has become the most common cause of acute neuromuscular paralysis in adults and children in the United States and has an annual incidence of 1.7 per 100 000 people [3, 4]. Epidemiologic studies in all parts of the world have confirmed the association between the Guillain-Barre syndrome and previous acute infection, especially of the respiratory or gastrointestinal tracts [4-8]. Most report that between 50% and 75% of patients have an infectious illness 1 to 3 weeks before onset of neurologic symptoms; previous diarrheal illness occurs in 10% to 30% of patients [4-6]. Bacteria of the genus Campylobacter are important human pathogens and are common causes of gastrointestinal illness in both developed and developing countries [9]. Extraintestinal complications of Campylobacter jejuni infection such as reactive arthritis, pancreatitis, and carditis are well described [10], and in the last decade, clinical and epidemiologic evidence has suggested that infection with C. jejuni may be a precipitating factor for development of the Guillain-Barre syndrome. In small serologic studies of patients with the Guillain-Barre syndrome, as many as one third to one half of patients had increased levels of C. jejuni antibodies at the time of onset of neurologic symptoms [11-13]. Routine stool cultures of eight patients with the Guillain-Barre syndrome in Japan yielded C. jejuni in seven (88%) patients [14]. In an important U.S. investigation of 106 patients with the Guillain-Barre syndrome, C. jejuni was isolated from 4 (44%) of 9 patients who had antecedent clear-cut diarrheal illness; however, cultures had not been obtained from 97 other patients [15]. To assess the extent to which the Guillain-Barre syndrome is associated with recent C. jejuni infection, we did serologic screening with defined assays to determine the frequency of C. jejuni antibodies in a large group of patients with the syndrome and in two control groups. Methods Study Population Case Patients Case patients included 126 persons with the Guillain-Barre syndrome admitted to the University of Maryland Medical Center, the University of Medicine and Dentistry of New Jersey, or to one of several hospitals in St. Louis between 1983 and 1990. A consecutive sample was used. All patients met the National Institute of Neurologic and Communicative Disorders and Stroke [16] criteria for diagnosis of the Guillain-Barre syndrome; none had any exclusion criteria. Most of the patients had demyelinating polyneuropathy, although some had axonal damage. All had a monophasic illness that progressed during 1 to 4 weeks, plateaued, and almost all patients recovered to some extent; one patient died. Blood samples were collected within 3 weeks after the onset of neurologic symptoms from 118 of the patients; 8 patients had blood samples collected from 24 days to more than 3 months after onset of neurologic symptoms (median, 10 weeks). Because antibody response to C. jejuni infection is usually transient [17], specimens from these eight patients are not included in the analysis. Histories of symptoms of gastrointestinal or respiratory infections before onset of the Guillain-Barre syndrome were not available. Controls Two groups of controls were studied. One control group, a convenience sample, consisted of 56 patients with neurologic diseases other than the Guillain-Barre syndrome who were admitted to the neurology services at the University of Maryland, the University of Medicine and Dentistry of New Jersey, or one of the St. Louis hospitals. Diagnoses of these patients included optic neuritis, multiple sclerosis, amyotrophic lateral sclerosis, polyneuropathy associated with IgM paraproteinemia, chronic inflammatory demyelinating polyneuropathy, Charcot-Marie-Tooth disease, unexplained peripheral neuropathy, ischemic neuropathy, neuropathy associated with diabetes, and drug-induced neuropathy. The second control group, a voluntary sample, included 18 healthy employees of the neurology departments of the three universities and 29 healthy family members of case patients and of disease controls. Medical histories of healthy controls were not obtained. Sera and Data Collection Sera from case patients and controls was stored frozen at the collection sites until the serologic assays were done. Data collected included disease severity of case patients, sex, age, and date of sera collection. Information about race was available only from the patients at the University of Medicine and Dentistry of New Jersey. Serologic Methods Presence of serum IgA, IgG, and IgM antibodies specific for C. jejuni was determined by enzyme-linked immunosorbent assay (ELISA) as previously described [17]. Antigens from three C. jejuni strains of Penner (O-) types 1, 2, and 3, which are commonly isolated from humans, were prepared as described by McCoy and colleagues [18]; they contained a mixture of acid-extracted proteins common to C. jejuni strains [17, 19, 20]. The serum dilutions used were as follows: 1:50 for IgA, 1:200 for IgG, and 1:400 for IgM. The class-specific second antibody used (and the use dilution) was peroxidase-conjugated goat anti-human IgA (1:2000), IgG (1:2500), or IgM (1:1000) (Tago Inc; Burlingame, California). The plates were read at 414 nm on a Dynatech ELISA reader (Alexandria, Virginia), and results were expressed as an optical density value for each well. All sera had been coded and were assayed blindly three times on different days in duplicate wells for each run. Calculation of Optical Density Ratios The assays were standardized using sera from a patient with the Guillain-Barre syndrome and culture-proven C. jejuni infection (positive control) and sera from 38 healthy children in New York who had had no recent history of diarrheal illness (negative controls). Optical density values were determined serially for plates containing these sera, and the mean optical density of the positive control was plotted versus the mean optical density + 1 SD of the negative controls. For each immunoglobulin class, a regression line was calculated and then used each day the assay was done (using the same positive control serum) to generate a threshold value for determination of the optical density ratio. (Regression analysis for IgA assay, r = 0.973, P < 0.001; regression analysis for the IgG assay, r = 0.998, P < 0.001; regression analysis for the IgM assay, r = 0.981, P < 0.001.) To control for day-to-day assay variation, the optical density ratio was defined as the ratio of the optical density of each unknown serum sample to the observed threshold on that day. A similar method has been used to standardize Helicobacter ELISA determination [21]. Case Definitions and Statistical Methods A positive serologic response was defined as an optical density ratio greater than or equal to a specified threshold in one or more immunoglobulin classes. Differences in the proportion of positive responses among case patients and controls were ascertained using an optical density ratio 1, 2, or 3 as the threshold. Statistical analyses were done in a univariate manner using the Mantel Haenszel Chi-squared analysis or the Fisher exact test when indicated and by the calculation of odds ratios. The sensitivity and specificity of the assays were determined as follows. Optical density ratios were determined as described above for 17 patients in the convalescent phase of culture-proven C. jejuni infection. These were U.S. soldiers who had become infected while on military exercise in Thailand in 1988; convalescent sera were obtained 4 weeks after onset of diarrhea. The comparison group comprised 19 healthy adults who were employees of or visitors to the Infectious Diseases Division of Vanderbilt University and included 20 healthy children in Nashville who had no recent history of diarrheal illness. Results Patients Demographic characteristics of the 118 case patients and 103 controls are shown in (Table 1). Age was known for 112 (95%) case patients and 93 (90%) controls; gender was known for 116 (98%) case patients and for 99 (96%) controls. Information about the month blood was drawn was available for 116 (98%) case patients and 80 (78%) controls. The groups were similar except that controls were somewhat younger (median age, 33 years compared with 41 years for case patients) and were more likely to have had their blood drawn during the summer months. Race of patients and controls (from the University of Medicine and Dentistry of New Jersey only) also was similar in the two groups. In both groups there were more male patients. Table 1. Demographic Characteristics of 118 Patients with the Guillain-Barre Syndrome and of 103 Controls, Including 56 Controls with Disease and 47 Healthy Controls Serologic Assays in Persons with Campylobacter jejuni Infection and in Controls Among 17 persons with culture-proven C. jejuni infections, in the IgA assay, 15 (88%) had an optical density ratio 1. Increasing the threshold for defining a positive serologic response to an optical density ratio 2 and 3 decreased the sensitivity of the test (Table 2). The specificity of the test was evaluated by the serologic responses in the control group. Defining a positive serologic response as an optical density ratio 1, the IgA assay was 85% specific (specificity determined by subtracting the percentage of controls exceeding threshold from 100%) (Table 2). Increasing the threshold to an optical density ratio 2 or 3 improved the specificity of the test. The sensitivity and specificity of the IgG and IgM assays are also shown in Table 2. As expected, raising the stringency by increasing the optical density ratios or numbers of positive classes

European Federation of Neurological Societies/Peripheral Nerve Society Guideline* on management of chronic inflammatory demyelinating polyradiculoneuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society

Abstract  Background: Numerous sets of diagnostic criteria have sought to define chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and randomized trials and systematic reviews of treatment have been published. Objectives: The aim of this guideline was to prepare consensus guidelines on the definition, investigation, and treatment of CIDP. Methods: Disease experts and a representative of patients considered references retrieved from MEDLINE and Cochrane Systematic Reviews in May 2004 and prepared statements that were agreed in an iterative fashion. Recommendations: The Task Force agreed on good practice points to define clinical and electrophysiological diagnostic criteria for CIDP with or without concomitant diseases and investigations to be considered. The principal treatment recommendations were as follows: (1) intravenous immunoglobulin (IVIg) or corticosteroids should be considered in sensory and motor CIDP (level B recommendation); (2) IVIg should be considered as the initial treatment in pure motor CIDP (good practice point); (3) if IVIg and corticosteroids are ineffective, plasma exchange should be considered (level A recommendation); (4) if the response is inadequate or the maintenance doses of the initial treatment are high, combination treatments or adding an immunosuppressant or immunomodulatory drug should be considered (good practice point); and (5) symptomatic treatment and multidisciplinary management should be considered (good practice point).

European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy

Several diagnostic criteria for multifocal motor neuropathy have been proposed in recent years and a beneficial effect of intravenous immunoglobulin (IVIg) and various other immunomodulatory drugs has been suggested in several trials and uncontrolled studies. The objectives were to prepare consensus guidelines on the definition, investigation and treatment of multifocal motor neuropathy. Disease experts and a patient representative considered references retrieved from MEDLINE and the Cochrane Library in July 2004 and prepared statements which were agreed in an iterative fashion. The Task Force agreed good practice points to define clinical and electrophysiological diagnostic criteria for multifocal motor neuropathy and investigations to be considered. The principal recommendations and good practice points were: (i) IVIg (2 g/kg given over 2–5 days) should be considered as the first line treatment (level A recommendation) when disability is sufficiently severe to warrant treatment. (ii) Corticosteroids are not recommended (good practice point). (iii) If initial treatment with IVIg is effective, repeated IVIg treatment should be considered (level C recommendation). The frequency of IVIg maintenance therapy should be guided by the individual response (good practice point). Typical treatment regimens are 1 g/kg every 2–4 weeks or 2 g/kg every 4–8 weeks (good practice point). (iv) If IVIg is not or not sufficiently effective then immunosuppressive treatment may be considered. Cyclophosphamide, ciclosporin, azathioprine, interferon beta1a, or rituximab are possible agents (good practice point). (v) Toxicity makes cyclophosphamide a less desirable option (good practice point).

Pulse cyclophosphamide therapy in chronic inflammatory demyelinating polyneuropathy

Fifteen patients with chronic inflammatory demyelinating neuropathy (CIDP) were treated with pulse intravenous cyclophosphamide (IVCY) monthly for up to 6 months. Eleven patients reached a complete remission; only one patient worsened. Complications included nausea, vomiting, anemia, and hair loss. This case series suggests that monthly IVCY is beneficial in the treatment of CIDP and warrants a controlled study.

Complement regulatory molecules on human myelin and glial cells : differential expression affects the deposition of activated complement proteins

Abstract: The expression of decay‐accelerating factor CD55, membrane cofactor protein CD46, and CD59 was studied on Schwann cells cultured from human sural nerve and myelin membranes prepared from human cauda equina and spinal cord. These proteins are regulatory membrane molecules of the complement system. CD55 and CD46 are inhibitors of C3 and C5 convertases and CD59 inhibits C8 and C9 incorporation into C5b‐9 complex and C9‐C9 polymerization. The presence of these proteins was assessed by using antibodies to each of the proteins by fluorescent microscopy, fluorescence‐activated cell sorter analysis, and also sodium dodecyl sulfate‐polyacrylamide gel electrophoresis and western blot analysis. Schwann cells in culture expressed CD55, CD46, and CD59. It is interesting that only CD59 was detected on myelin from both central and peripheral nerve tissue. The ability of these proteins to limit C3 peptide deposition and C9 polymerization in myelin was studied by western blot analysis. C3b deposition was readily detected on antibody‐sensitized myelin incubated with normal human serum used as a source of complement but not with EDTA‐treated or heat‐inactivated serum. C3b deposition was not affected by anti‐CD55 antibody. On the other hand, poly‐C9 formation in myelin, which was maximum when 50% normal human serum was used, was increased four‐ to fivefold when myelin was preincubated with anti‐CD59. Our data suggest that complement activation on myelin is down‐regulated at the step of the assembly of terminal complement complexes, including C5b‐9, due to the presence of CD59.