Response to IVIG Leads to Diagnosis of Stiff Person Syndrome in a Patient with Limbic Encephalitis and GAD65 Autoantibodies (Ab) without Diabetes

Presentation Number: SAT 636
Date of Presentation: April 1st, 2017

Mohammad Saud Khan*1, Jennifer B Hao2, Foiqa Chaudhry3, Abhinav Tiwari4, Himani Sharma4 and Juan Carlos Jaume2
1University of Toledo Medical Center, Toledo, OH, 2University of Toledo, College of Medicine and Life Sciences, Toledo, OH, 3University of Toledo Medical Center, Sylvania, OH, 4University of Toledo Medical Center, Toledo

Abstract

Introduction: Stiff-person syndrome (SPS) is a rare neurological disorder characterized by progressive muscle rigidity and stiffness superimposed on painful muscle spasms predominantly affecting the muscles of trunk and proximal limbs. GAD 65 Ab are found in high titers in these patients and have been linked to its pathogenesis. GAD65 Ab are also elevated in other neurological conditions such as cerebellar ataxia, epilepsy, palatal tremor, and autoimmune limbic encephalitis (LE).

Case presentation: A 48 year old right handed Caucasian female presented with a 2 month history of recurrent severe headaches, cognitive impairment with decreased memory, behavioral symptoms in the form of agitation, hallucinations and paranoia with episodes of disorientation, confusion and visual blurring. She complained of stiffness and rigidity involving neck and back muscles with muscle spasms and difficulty ambulating with frequent falls. Motor system examination revealed generalized rigidity, muscle strength was 5/5 in all four limbs, deep tendon reflexes were normal, and down going planters bilaterally. Sensory examination was normal with intact cerebellar signs. Neuropsychological testing showed cognitive decline in the form of impairment of short-term memory. MRI of the brain with contrast did not show any significant abnormality. Lumbar puncture and CSF analysis done revealed lymphocytic pleocytosis, with elevated white cell count and lymphocytes. EEG monitoring showed background slowing. Given the patient’s clinical presentation and investigational workup, a diagnosis of LE was considered. Patient received treatment with intravenous immunoglobulin (IVIG) 60 gm x 1 infusion and unexpectedly had improvement of her muscle stiffness, which raised a suspicion for SPS. Prior to IVIG, GAD65 Ab initially measured 6.7 IU/ml (0-5 IU/ml), and two months later 148 IU/ml (0-5IU/ml).

TSH was 0.98 micro IU/ml (0.1-5 micro IU/ml) and free T4 was low at 0.66 ng/dl (0.71-1.85 ng/dl). TPO Ab were elevated at 45 IU/ml (0-35 IU/ml), as well as thyroglobulin Ab at 42.4 IU/ml (0-40 IU/ml). Levothyroxine 125 mcg/day was started for her autoimmune hypothyroidism. A1C was normal at 5.3% without evidence for diabetes. Diazepam 5 mg four times a day was initiated and increased to 10 mg four times per day. At follow up, she reported improvement in muscle stiffness/spasms, cognitive, and behavioral symptoms.

Conclusion: Although GAD65 Ab are implicated in the pathogenesis of both SPS and LE, their association is quite rare. Here we present a case of LE with inadvertent diagnosis of GAD65-positive SPS determined after successful treatment with IVIG therapy.

 

Nothing to Disclose: MSK, JBH, FC, AT, HS, JCJ