Click here to load reader

Chronic inflammatory demyelinating polyradiculoneuropathy associated with pregnancy

  • View

  • Download

Embed Size (px)

Text of Chronic inflammatory demyelinating polyradiculoneuropathy associated with pregnancy

  • Chronic Inflammatory Dem y elinating Pol yradiculoneuropath y Associated with Pregnancy P. A. McCombe, MB, BS, P. G. McManis, MB, RS, J. A. Frith, MB, BS, J. D. Pollard, PhD, and J. G. McLeod, DPhil(0xon)

    In a series of 61 patients with the relapsing variety of chronic inflammatory demyelinating polyneuropathy, there were 16 women of childbearing age, 9 of whom became pregnant. In 4 of these women, the onset of neuropathy occurred in pregnancy and in the other 5 relapses occurred during pregnancy. There was a sig- nificant increase in the number of relapses during the year of pregnancy, and a tendency for symptoms to worsen during the third trimester or immediate postpar- tum period. It is concluded that there is an increased risk of relapse of chronic inflammatory demyelinating polyneuropathy in pregnancy.

    McCombe PA, McManis PG, Frith JA, Pollard JD, McLeod JG: Chronic inflammatory demyelinating

    polyradiculoneuropathy associated with pregnancy. Ann Neurol 21:102-104, 1987

    Although the onset and relapses of chronic inflamma- tory demyelinating polyradiculoneuropathy (CIDP) have been described in pregnancy in isolated case re- ports 12, 4, 5, 8, 111, there has been no study of the association in a large series of cases. We have therefore reviewed 93 patients with the clinical, electrophysio- logical, and pathological features of CIDP, in 9 of whom the onset or relapse of polyneuropathy was as- sociated with pregnancy, in order to evaluate the effect of pregnancy on the course of the illness.

    Methods Patients Ninety-three patients (57 males, 36 females) with CIDP were referred to OUT department for investigation; sural nerve biopsy was performed on 87. All patients fulfilled the established criteria for the diagnosis of CIDP [6, 12). Sixty- one patients had a relapsing course and 32 had a subacute progressive course.

    Statistical Analysis For the purposes of statistical analysis, a. relapse of CIDP was defined as a worsening of symptoms or signs, resulting in an

    From the Department of Medicine, University of Sydney, N.S.W. 2006, Australia. Received Mar 12, 1986, and in revised form June 9. Accepted for publication June 10, 1986. Address reprint requests to Dr McLeod.

    increase in disability by one or more grades on the disability scale [12) with subsequent improvement. The onset of re- lapses was not related to change in therapy. The number of relapses of CIDP for a patient is defined as the total number of episodes of disease, excluding the initial episode. The pregnancy year is the 9 months of pregnancy and the 3 months immediately post partum. No patient had more than one relapse during pregnancy.

    The relapse rate was defined as the number of relapses divided by the number of years of observation. Relapse rates were compared between groups by using an exact test based on the binomial distribution. The chi-squared test, with a correction factor for continuity, was also used but was of limited value as the expected value in some cases was less than 5. For the comparison of pregnant and nonpregnant periods in childbearing women, the variability among women was allowed for using the Mantel-Haenszel test.

    Results Of the 61 patients with the relapsing form of CIDP, 10 had insufficient information to determine the duration of their illness and relapse rate. The relapse rate for the remaining 51 patients of both sexes (31 males, 20 fe- males) was 0.33 per year. Four of the 20 females were outside the childbearing age (arbitrarily defined as 17 to 50 years) during their illness. Of the remaining 16 premenopausal females, 9 had pregnancies. The course in one patient (PO) with pregnancy-associated relapses is shown in the Figure. The obstetric and relapse his- tories of these 9 women are summarized in Table 1. Their ages at onset ranged from 18 to 32 years (mean, 23.9 years; SD, 5.8). They all displayed the clinical features of CIDP during relapse, with paresthesias, weakness, hyporeflexia or areflexia, and sensory im- pairment. One patient (SF) had diplopia as an addi- tional symptom. Lumbar puncture was performed on all patients. The cerebrospinal fluid protein concentra- tion ranged from 0.15 to 2.12 &liter (mean, 0.93; SD, 0.57).

    The 9 childbearing women had a total of 30 preg- nancies. Eleven pregnancies occurred before the onset of CIDP; the disease onset occurred during 4 pregnan- cies, and as these initial episodes were not defined as relapses, they were excluded from analysis; the re- maining 15 pregnancies occurred after the disease on- set and were analyzed statistically for an association with relapses. Table 2 shows the relapse rate for the women of childbearing age who had never had a preg- nancy, compared with those women who became preg- nant after the disease onset. The relapse rate for the parous women was further analyzed to compare the relapse rate during the pregnancy years with those when they were not pregnant. The difference is significant (exact test, p = 0.02; x2 = 6.49; p < 0.02). As women vary in their relapse rates, the Mantel- Haenszel test was also applied to compare pregnant and nonpregnant periods in these 9 childbearing women (x2 = 4.60; p < 0.05). There is also a


  • P i

    1 2 3 4 5 6 7

    Y E A R S

    Course of chronic infEammutory demyelinating polyradiculo- neuropathy in Patient PO. Onset and two relapses were related to pregnancy. Filled horizontal bars indicate time of pregnancy. D3, Dq, and Ds indicate time ofaklivery of third,fourth, and fifth children. Worsening of symptoms occurred post partum fol- lowing each delivery. Open horizontal bars indicate duration of corticosteroid therapy. P indicates commencement of a course of plusmapheresis. Disability scores are those as described by Prineas and McLeod {12}.

    significant difference between the number of relapses experienced by nonparous women with CIDP and those experienced by parous women during their preg- nancy years (exact test, p = 0.01).

    Five of the 8 relapses (62.5%) associated with preg- nancy occurred in the third trimester or 3 months post parturn, and in 1 patient (PO, Figure) there was sig- nificant worsening of symptoms post parturn.

    Table I. Obstetric Details of Patients with CIDP

    Discussion All patients had a subacute or chronic polyneuropathy with the electrophysiological and pathological features of CIDP [6, 12). There was no family history of poly- neuropathy and no clinical or laboratory evidence of metabolic, neoplastic, or other causes; no patient had a paraproteinemia. The possibilities were considered, and are difficult to exclude, that pregnant patients may have been observed more closely or that they may have reported symptoms more frequently than did nonpregnant patients. However, these potential sources of bias seem unlikely, as in our experience most patients with CIDP will report worsening of symptoms of one or more grades of disability.

    The statistical approach used for this study is similar to that used by Korn-Lubetzki and colleagues 193 for multiple sclerosis; these authors demonstrated a statis- tically significant decrease in the number of relapses in the third trimester but an increase post partum.

    When the relapse rate for the parous women when pregnant was compared to that when not pregnant, the difference was significant. The difference was also significant when the number of relapses of women with CIDP who had never been pregnant was com- pared to that of women during their pregnancy years. There appeared to be a tendency for relapses, or a worsening of symptoms during relapse, during the third trimester or post partum.

    Number of Number of Pregnancies At Risk Relapses Not

    Total after Onset Pregnancies Associated Number of Number of of CIDP (at Associated with with

    Patient Pregnancies risk pregnancies) Relapse Pregnancy Observation

    AD 4 4 1 1 11 JH 3 1 0 4 9 PO 5 2 2 1 6 PC 3 0 0 0 7 EA 4 0 0 0 2 PK 2 2 1 0 32 SF 2 2 1 6 15 AB 5 3 2 2 42 DH 2 1 1 7 12

    Total 30 15 8 21 136

    Years of

    CIDP = chronic inflammatory demyelinating polyradiculoneuropathy.

    Table 2. Relapse Rate

    Number of Relapse Number Number Years of Rate of Women of Relapses Observation (relapsedyr)

    Nonparous women 7 10 75 0.13 Parous women

    During pregnancy years 9 8 15 0.53 At other times 9 21 12 1 0.17

    Brief Communication: McCombe et al: CIDP and Pregnancy 103

  • There have been previous isolated case reports of subacute and relapsing neuropathy occurring in preg- nancy, frequently during its later stages. Castaigne and colleagues [ 3 ] referred briefly to 2 patients who had relapses during pregnancy at 3 and 6 months, respec- tively. Calderon-Gonzalez and associates 121 described a patient in whom relapses of a symmetrical poly- neuropathy occurred during the second and third trimesters in three successive pregnancies, and subse- quently while taking oral contraceptives. Novak and Johnson [ll] reported a patient who had a subacute onset of peripheral neuropathy in the third trimester of her first pregnancy and in the second trimester of her second pregnancy. Jones and Berry IS] descrihed a patient who had the onset of CIDP in her first preg- nancy and relapses in the subsequent two pregnancies. Dalakas and Engel 141 studied one patient in whom the onset occurred in the later months of pregnancy. DAmbrosio and de Angelis 153 described a patient who had the onset of relapsing polyneuritis during the third trimester of her first pregnancy, a relapse late in the third trimester of the second pregnancy, and a further relapse six months after commencement of an oral contraceptive.

    Guillain-Bar& syndrome may occur in pregnancy but it does not appear to be more commcm in pregnant women than in the general population, and pregnancy does not seem to influence the course or severity of the disease [I, 5 , 10, 131.

    The mechanism of relapses of CIDP in pregnancy is uncertain. Studies of the immune system in pregnancy have been directed mainly toward the mechanism of protection of the fetus from rejection by the mother [71. It is not known how immunological responses in pregnancy could cause or exacerbate CIDP. PossibIe mechanisms may be the existence of a cross-reactivity between fetal and maternal neural antigens or an im- mune response in pregnancy that provokes an anam- nestic response to neural antigen.

    - P. A. McCombe was a National Health and Medical Research Coun- cil Postgraduate Medical Scholar and P. G. McManis was a Bushell Research Fellow. The statistical advice of Professor G. Berry, School of Public Health and Tropical Medicine, and Dr J . Simes, Royal Prince Alfred Hospital, and the skilled technical assistance of Miss P. Martin are gratefully acknowledged. -

    References 1. Ahlberg G, Ahlmark G. The Landry-Guillain-Barre syndrome

    and pregnancy. Acta Obstet Gynecol Scand 57:377-380, 19.78 2. Calderon-Gonzalez R, Gonzalez-Cantu N, Rizzi-Hernandez H:

    Recurrent polyneuropathy with pregnancy and oral contracep- tives. N Engl J Med 282:1307-1308, 1970

    3. Castaigne P, Brunet P, Nouailhat F: Enquete cilinique sur les polyradiculonCvrites inflammatoires en France. Rev Neurol (Paris) 115:849-872, 1966

    4. Dalakas MC, Engel W K Chronic relapsing (dysimmune) poly-










    neuropathy: pathogenesis and treatment. Ann Neurol

    DAmbrosio G, de Angelis G: Syndrome de Guillain-Barre au cours de la grossesse. Rev Neurol (Paris) 141:33-36, 1985 Dyck PJ, Lais AC, Ohta M, et al: Chronic inflammatory poly- radiculoneuropathy. Mayo Clin Proc 50:62 1-637, 1975 Jacoby DR, Olding LB, Oldstone MBA: Immunological regula- tion of fetal-maternal balance. Adv Immunol35:157-208, 1984 Jones MW, Berry K Chronic relapsing polyneuritis associated with pregnancy. Ann Neucol9:413, 1981 Korn-Lubetzki I, Kahana E, Cooper G, Abramsky 0: Activity of multiple sclerosis during pregnancy and puerperium. Ann Neurol 16229-231, 1984; (reply to letter) 18:101, 1985 McFarland HR, Heller G L Guillain-Barr6 disease complex: a statement of diagnostic criteria and analysis of 100 cases. Arch Neurol 14:196-201, 1966 Novak DJ, Johnson KF: Relapsing idiopathic polyneuritis dur- ing pregnancy. Arch Neurol 28:219-223, 1977 Prineas JW, McLeod JG: Chronic relapsing polyneuritis. J Neurol Sci 27:427-458, 1976 Ravn H: The Landry-Guillain-Barre syndrome. Acta Neurol

    ~ ( suPP~) : 134- 135, 1981

    Stand 43:l-64, 1967

    Whipples Disease Confined to the Central Nervous System Melanie Adams, MD, Patricia A. Rhyner, MD,t John Day, MD,S Stephen DeArmond, MD, PhD,+ and Edward A. Smuckler, MD, PhD

    Progressive hypersomnia, memory disturbance, and vertical ophthalmoplegia developed in a 63-year-old woman. The diagnosis of Whipples disease of the cen- tral nervous system was suggested by her presentation and results of studies using magnetic resonance imag- ing. Despite a one-month course of antibiotics, active Whipples disease, localized to the central nervous sys- tem, was found at autopsy.

    Adams M, Rhyner PA, Day J, DeArmond S, Smuckler EA: Whipples disease confined

    to the central nervous system. Ann Neurol 21:104-108, 1987

    Whipples disease is a rare multisystem disorder pre- senting most often with symptoms of gastrointestinal malabsorption, fevers, arthralgias, and lymphadenopa-

    From the Departments of Pathology, t Radiology, and $Neurology, School of Medicine, University of California, San Francisco, San Francisco, CA 94143. Received Feb 18, 1986, and in revised form June 9, 1986. Accepted for publication June 9, 1986. Address reprint requests to Dr Adams, Department of Pathology, HSW-501, School of Medicine, University of California, San Fran- cisco, CA 94143.