N Engl J Med

N Engl J Med. of rituximab. His gait began responding after the third rituximab treatment, and he no longer needed a cane by his fifth treatment. His anti-GAD levels initially fluctuated but then steadily decreased to 300C400 nmol/mL by August 2010 (see figure 1). After therapy he continued to have dysarthria, nystagmus, dysmetric saccades, increased tone, dysmetria, and stiff posture, although he was able to walk unassisted. He was lost to follow-up for 3 years, with no maintenance immunotherapy during that time. Open in a separate window Serum anti-GAD antibody titer in relation to immunomodulatory treatment Figure 1. There was no change in antiCglutamic acid decarboxylase (GAD) antibody titers with methylprednisolone (methylpred) or IV immunoglobulin (IVIg), and only a transient change after plasma exchange (PLEX). There was sustained reduction in anti-GAD titer with rituximab treatments. Three years later he presented with labile mood and multiple 1C2 minute episodes of drooling, staring, and difficulty speaking. He continued to display examination findings consistent with SPS and CA. MRI showed increased signal in the mesial temporal structures and insular cortex (figure 2). Video-EEG monitoring revealed frequent electroclinical seizures originating in the right hemisphere. Lumbar puncture was normal. Anti-GAD antibodies in serum and CSF were 148.3 U/mL (radioimmunoassay, Labcorp, RR 0.0C1.5 U/mL) and 10.0 nmol/L (immunoprecipitation assay, Mayo Clinic, RR ? 0.02 nmol/L), respectively. Serum and CSF paraneoplastic panel including voltage-gated potassium channel antibodies was negative. He was treated with divalproex sodium, phenytoin, and levetiracetam, and his seizures stopped. He received 5 sessions of plasmapheresis over 10 days concurrently with high-dose methylprednisolone for 5 doses for a diagnosis of limbic encephalitis (LE). His cognitive and physical function returned to baseline, and 3 weeks later his serum anti-GAD titer was 138.2 U/mL. He was discharged with plans for outpatient rituximab therapy. He deferred formal neuropsychological testing. Open in a separate window MRI brain demonstrating evolution of limbic encephalitis Figure 2. Upper images show axial fluid-attenuated inversion recovery (FLAIR) sequences for this patient at initial presentation (A), 1 week after corticosteroids and plasmapheresis (B), and at 4-month follow-up (C). Lower images show coronal postgadolinium T1 sequences for the same time points. There is FLAIR hyperintensity and contrast enhancement in the mesial temporal lobes and insulae, right-greater-than-left, which resolves with treatment. DISCUSSION Anti-GAD antibodies are implicated in a number of neurologic syndromes, including SPS, CA, and LE. PIK-75 High titers have also been detected in some patients with treatment-resistant PIK-75 localization-related epilepsy.1 Anti-GAD antibody is detected in 80% of patients with newly diagnosed DM1, although at lower titers and against different epitopes from those seen in neurologic disease.2 Patients with neurologic manifestations of elevated anti-GAD levels are more likely to have organ-specific autoantibodies, PIK-75 including anti-TPO (occurring in 50%C60% of patients), anti-gliadin, and others.3,4 Other autoimmune conditions such as pernicious anemia and psoriasis have been reported.3,4 Our patient had both personal and family history of several autoimmune diseases, in keeping with previously described associations. The pathogenic role of anti-GAD antibodies in neurologic disease is unclear.2,4 Titers of anti-GAD antibody do not necessarily correlate with the severity of neurologic manifestations.5 In our patient, there was at least a modest correlation between titers and clinical improvement in response to immunomodulation, both during his initial presentation with SPS and CA and during his episode of LE. Unfortunately, the titers during these Rabbit Polyclonal to MMP17 (Cleaved-Gln129) 2 episodes were reported from.