Anti-GAD encephalitis in a child with beta-thalassemia after allogeneic hematopoietic stem cell transplantation

Abstract

Glutamic acid decarboxylase (GAD) is an intracellular enzyme expressed in brain neurons and insulin-secreting β-cells of the pancreas. Anti-GAD-anitibodies are associated with type 1 diabetes mellitus, limbic encephalitis, cerebellar ataxia, temporal autoimmune epilepsy, and rigid man syndrome. We present a rare clinical case of anti-GAD-anitibodies- associated immune encephalitis in a child with beta-thalassemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT).A 3-year-old boy diagnosed with beta-thalassemia underwent allo-HSCT from a 9/10 compatible unrelated donor. The macrophage activation syndrome occurred during the early post-transplantation period. The seizure with a focal onset happened on day +65. The cytotoxic edema in the region of the left hippocampus without signs of accumulation of a contrast agent was revealed at the magnetic resonance imaging of the brain. Pleocytosis, increase in protein levels, infection and antibodies to receptors and synaptic proteins of neurons were not detected at the analysis of cerebrospinal fluid. A positive titer to anti-GAD-anitibodies was detected in the blood – 315.82 IU/ml (the norm is up to 10 IU/ml). The child was treated with cyclophosphamide 750 mg/m2, rituximab 375 mg/m2, and tocilizumab 8 mg/kg. The cytotoxic edema in the left hippocampus regressed at the control magnetic resonance imaging on day +117.Infectious, immune and toxic agents can cause the damage of central nervous system in patients after allo-HSCT. The mechanism of immune damage to the central nervous system S in such patients is still being studied and may be different: expansion of autoreactive lymphocytes due to failure of T-cell regulation due to chemo- or immunosuppressive therapy, “passenger lymphocyte” syndrome, violation of T-cell regulation due to the course of infectious complications and acute graft versus host disease.In a series of diagnostic searches in patients with central nervous system lesions after allo-HSCT, it is necessary to include immune damage to the nervous system. Diagnosis of such conditions is a difficult task due to comorbidity and multicomponent accompanying therapy, including immunosuppressive therapy, administered to patients.

Keywords

• autoimmune encephalitis
• acute symptomatic seizures
• hematopoietic stem cell transplantation