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The progressive encephalomyelitis with rigidity syndrome (PEMRS) is a rare neurological disorder that can be considered as the most severe form of the “stiff person” syndrome1 2although other authors suggest that it may be a distinct entity.3 Pathogenesis is far from being clearly defined, but some studies point to humoral immunity as having an important role. Antiglutamic acid decarboxylase (anti-GAD) antibodies have been found to be present in about 40% of patients with stiff person syndrome.4 Treatment is very difficult and in the only case reported so far in which intravenous immunoglobulin has been used the response was poor.2 We report a case of PEMRS with anti-GAD antibodies that had an excellent response to intravenous immunoglobulin.
A 67 year old woman was admitted to our hospital with a 9 month history of progressive gait disturbance and painful leg contractions. Family history was negative for neurological disorders. General examination was unremarkable. On neurological examination she showed marked stiffness in her legs and painful spasms; these appeared spontaneously but could also be elicited by external events such as touch, noise, and frightening. The examination was otherwise normal.
Brain and spinal MRI did not show any abnormality. Both needle EMG and nerve conduction were normal except for spontaneous firing of motor units. Blood tests including vitamin B12 and folic acid, C3, C4, thyroid hormones, antithyroglobulin antibodies, syphilis serology, and CSF examination were all within normal limits. Anti-GAD autoantibodies were positive, both in serum (1/16000 IU with histochemistry and 1/30325 IU/ml with radioimmunoassay (RIA) and in the CSF (1/40 IU with histochemistry).
For unknown reasons, a week after admission the clinical course changed: the patient seemed to be confused, became disoriented, and her consciousness was clearly impaired. The spasms were more severe and neurological examination showed bilateral pyramidalism with Babinski's sign. The clinical picture corresponded to a progressive encephalopathy, This was confirmed by EEG (generalised slow waves). We started treatment with valproate, gabapentin, and diazepam but lack of improvement led us to try intravenous immunoglobulin (0.4 g/kg/24 hours for 5 days and then the same dosage every 2 days) together with intravenous methylprednisolone (80 mg/24 hours). A positive response appeared at the 5th day. After 7 days of treatment she regained normal consciousness and did not show any spasms.
However, 6 weeks later the patient presented with gait disturbances again. Anti-GAD autoantibodies were again positive in serum (1/8000 IU with histochemistry and 1/36250 IU/ml with RIA) and in the CSF (1/20 IU with histochemistry). For this reason, immunoglobulin (0.4 g/24 hours for 5 days) was used again with prednisone (60 mg/24 hours orally (the previous dose had been reduced to 40 mg/48 hours)). Six months after admission she continued free of spasms, with a total independence for daily life activities, but on examination she had a mild loss of memory and a mild loss of strength in both hands.
The aetiology of both stiff person syndrome and PEMRS remains unknown although an autoimmune mechanism has been suggested. Therefore, plasmapheresis, intravenous immunoglobulin, and diazepam have been empirically proposed as treatments of stiff man syndrome.2 5 6 PEMRS could be responsive to plasmapheresis and immunosupression,7 but to our knowledge, this is the first case of PEMRS reported in which intravenous immunoglobulin has been successfully used. It seems possible that the successful outcome should be due to the association of prednisone with intravenous immunoglobulin.
The initial clinical picture of this case resembled closely the stiff person syndrome, even with a positive determination of anti-GAD autoantibodies in CSF. PEMRS features appeared some days later. The patient was treated with diazepam, gabapentin, and valproate without any response; moreover, she developed severe muscle spasms and a confusional state. Five days after starting treatment with intravenous immunoglobulin and steroids, the patient reached a normal level of consciousness and the leg cramps disappeared, although she had a moderate loss of strength in her hands and a mild memory loss. When she was discharged 4 weeks later on prednisone (80 mg/day) these were her only symptoms. However, when prednisone was decreased some cramps reappeared and prednisone had to be increased again to the previous dose and an immunoglobulin cycle was needed, obtaining a positive response. She has been free of cramps since then.
We think that intravenous immunoglobulin associated with prednisone could be a useful and life saving treatment for patients with PEMRS.
We thank Dr F Graus (Hospital Clinic i Provincial, Barcelona) for the determination of GAD antibodies.
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