Amyotrophic lateral sclerosis presenting during pregnancy : report of clinical and genetic features of three cases

Objectives: A few previous reports have described patients with ALS presenting during pregnancy, but the association is rare and pathogenic relationship is still to be demonstrated. In this study we wished to evaluate the frequency, clinical and genetic aspects of ALS cases, associated with pregnancy, in a cohort of patients attending our neuromuscular centre. Methods: We retrospectively analysed charts from female patients with a diagnosis of ALS attending the Muscle Clinics at Nemo Center and at IRCCS Policlinico San Donato during the year 2008. Of 76 female patients, 3 had the diagnosis of ALS during the first pregnancy (4%). Results: Case 1: a previously healthy 33-year-old woman presented with subacute, severe, left lower limb pain after delivery, followed by progressive weakness and wasting of the left leg, mimicking a lumbo-sacral radiculopathy. Electrophysiological studies showed widespread denervation involving more than one district. Genetic studies demonstrated an aspartate for glycine substitution at position 93 (G93D) in the Cu/Zn superoxide dismutase 1 (SOD1). Case 2: A 43-year-old woman started complaining of diffuse fasciculations in the right leg, followed by progressive weakness and wasting, immediately after delivery. Family history and electrophysiological studies confirmed the diagnosis of ALS. Genetic studies demonstrated a phenilalanine for leucine substitution at position 84 (L84F) in the SOD1. Case 3: A 32-year-old pregnant woman presented with progressive weakness and oedema of the left hand during her first pregnancy (at 6- months). A cesarean delivery at week 43 was performed because of gestosis. Weakness rapidly got worse and progressed to the 4 limbs. Severe muscle atrophy and widespread fasciculations became evident in the months following delivery. Electrophysiological studies showed fasciculation and denervation in several districts. Genetic studies ruled out mutations in the SOD1 gene. Conclusion: Our data confirm that, although rare, pregnancy may reveal an already present but not yet clinically overt ALS through pathological mechanisms yet to be determined. Further studies are needed to explore the possibility that, amongst others, hormonal modifications during pregnancy may increase the susceptibility to oxidative stress related, for instance, to mutations in SOD1.