Letters to the Editor Antiparkinsonian Treatment in Pregnancy

We read with interest the article by Shulman and colleagues in a 2000 issue of Movement Disorders. In that article, one case of pregnancy in a patient with Parkinson’s disease (PD) on levodopa therapy was reported. After prospective and quantitative neurological examination of the patient, the authors concluded that pregnancy exacerbates PD and could have a longterm negative impact on the course of the illness. A few cases of pregnancy in parkinsonian women have been described; all of these patients were treated with levodopa but none demonstrated major drug teratogenity. Moreover, dopamine agonist treatment during pregnancy of PD patients has been reported by Benito-Leon and associates as a bromocriptine monotherapy; another patient described by Hagell and coworkers discontinued bromocriptine after 2 months of pregnancy. In neither case did bromocriptine treatment result in any teratogenity. Pergolide administration in parkinsonian women during pregnancy has not been reported previously. We describe a woman with PD treated with combined pergolide and levodopa therapy during pregnancy. A 36-year-old woman developed PD with progressive motor slowness in the left limbs at age 32 years in 1996. At the first examination, she presented a slight rigidity and bradykinesia to the left arm and leg and a mild hypomimia. There was no evidence of resting tremor. Hoehn and Yahr rating was 2. Evaluation for other causes of parkinsonism revealed no significant abnormalities. Family history for PD was not reported. Treatment with pergolide up to a dose of 1 mg three times daily resulted in partial improvement, and after 6 months levodopa was added at a dose of 200 mg per day, resulting in optimal control of her symptoms. After 2 years the patient complained of a predictable wearing-off period in the afternoon, demonstrated as slight bradykinesia, mild rigidity in lower limbs, and gait disturbances such as short steps and shuffling, mainly in her left leg. When the patient became pregnant at age 35 years, the dosage of pergolide and levodopa was continued throughout the pregnancy. During the pregnancy, all wearing-off phenomena disappeared and she had optimal control of motor symptoms throughout the day. She gave birth to a normal-term infant in July 2000 with Apgar scores of 9, by cesarean section, because of a podalic presentation. The child shows no evidence of congenital malformation and remains healthy at this time, 13 months of age, with normal development. During the puerperal period the end-of-dose wearing-off symptom reappeared and reached the same level as before pregnancy. To our knowledge, this is the first description of combined pergolide and levodopa treatment during pregnancy in a woman with PD. Except for one case of osteomalacia and another of spontaneous abortion, for which the cause is not well established, no major complications of pregnancy, nor any adverse effects on the fetus that could primarily be related to levodopa plus carbidopa or benserazide have been reported in the literature. Studies of carbidopa–levodopa in laboratory animals demonstrated some increase in skeletal malformation but only with high doses, greater than 500 mg/kg/day. Among antiparkinsonian treatment, amantadine has shown teratogenicity in a case of cardiovascular maldevelopment, associated with maternal exposure, during the first trimester of pregnancy. The use of amantadine as an antiviral treatment or prophylaxis has been discouraged in pregnant women. Hagell and associates held that treatment with the dopamine agonists bromocriptine and lisuride was safe during pregnancy. Furthermore, in premarketing studies of pergolide for endocrine disorders, two major and three minor congenital abnormalities were described among 38 pregnancies, but a causal relationship has not been established. Pergolide has not shown evidence of harm to fetuses in mice or rabbits in animal studies. There is no information regarding pregnancy and pramipexole or ropinirole therapy. Although levodopa and some dopamine agonist treatments are reported not to cause pregnancy complication, the effects of pregnancy on the symptoms of PD seem to be controversial. In the review by Hagell and colleagues, it was reported that in 46% of pregnancies PD symptoms worsened or new symptoms occurred during or shortly after pregnancy. Few reports have observed that a patient’s symptomatology remained stable or without any complication throughout pregnancy. The patient described by Shulman and coworkers experienced marked worsening of motor symptoms and a need for progressively higher levodopa dosages throughout the pregnancy, reaching a peak dose in the postpartum period. The author’s impression was that pregnancy may have worsened PD symptoms, both during the last period of pregnancy and in the postpartum period, suggesting a role for estrogens on the dopaminergic system. When analyzing this case, the worsening of parkinsonian symptoms in this particular patient occurred in the last period of the pregnancy and in the postpartum period, at a time when estrogen levels are low. The high estrogen levels during pregnancy could play a beneficial role, improving parkinsonian symptoms, considering the dopaminergic-sparing properties of this hormone resulting from interaction with catechol-O-methyltransferase enzyme. Furthermore, a recent study described a beneficial effect in PD from estrogen replacement therapy. Other authors have suggested that the changes in parkinsonian symptoms of PD women treated with antiparkinsonian drugs during pregnancy could be the result of a natural disease progression, or that pregnancy induced pharmacokinetic modification. Moreover, as suggested by Shulman and colleagues, physical and psychosocial stressors could play an additional role, ex*Correspondence to: Dr. Paolo Lamberti, Clinica Neurologica II – Policlinico, Piazza Giulio Cesare 11, 70124 Bari, Italy. E-mail: [email protected] Received 10 May 2001; Accepted 28 August 2001 Published online 21 February 2002 in Wiley InterScience (www. interscience.wiley.com). DOI 10.1002/mds.10040 Movement Disorders Vol. 17, No. 2, 2002, pp. 428–432 © 2002 Movement Disorder Society