PET‐positive extralimbic presentation of anti‐glutamic acid decarboxylase antibody‐associated encephalitis

Abstract

Anti-glutamic acid decarboxylase (GAD) antibody-associated autoimmune encephalitis has been reported mostly as limbic encephalitis. Only few cases with extralimbic involvement are reported with limited investigation. Here, we report an extensive investigation with MRI, PET, and pathological examination. A 66-year-old Japanese female with a history of hypothyroidism, colon cancer, pheochromocytoma, and thymoma-associated myasthenia gravis presented with generalised tonic-clonic seizures. MRI showed multiple hyperintense lesions and PET showed hypermetabolic lesions in the brain. Biopsy showed non-specific gliosis, microglial proliferation, and perivascular lymphohistiocytic infiltrates. Various neuronal antibodies were negative, except for anti-GAD antibody. Anti-GAD antibody-associated encephalitis is an increasingly recognised CNS disease. Pathophysiology of this encephalitis is unclear. While PET showed hypermetabolic lesions, the biopsy showed non-specific changes. The treatments may include immunosuppressants, IVIg, and plasma exchange. One should consider to measure this antibody, in addition to others, when autoimmune encephalitis is suspected [Published with video sequences].

Authors' response

“…We agree that there are similarities between our case and recently reported cases of encephalitis with GABA-A receptor antibodies (Petit-Pedrol et al, 2014;Ohkawa et al, 2014). Notably, the MRI findings of extensive multifocal abnormalities on FLAIR and T2 imaging, with cortical and subcortical involvement without contrast enhancement (Petit-Pedrol et al, 2014; figure 4 [Index Patient 1]), are strikingly similar to those of our patient (Kojima et al, 2014). Petit-Pedro et al divides the patients into two groups:…”

“…We thank Dr. Simabukuro for his interest in our case report (Kojima et al, 2014) and appreciate his insightful comment. We agree that the classification of autoim-Letter to the Editor mune encephalopathy associated with antibodies to the cell surface or synaptic proteins is evolving as new antibodies are discovered.…”

“…To the Editor, We refer to the publication of Kojima et al 2014: "PET-positive extralimbic presentation of anti-glutamic acid decarboxylase antibody-associated encephalitis". Neurological disorders associated with antibodies against cell surface and synaptic proteins are fascinating diseases that have changed paradigms in neurological practice, mainly because these disorders were previously unknown and/or mischaracterized (Leypoldt et al, 2014).…”

“…Neurological disorders associated with antibodies against cell surface and synaptic proteins are fascinating diseases that have changed paradigms in neurological practice, mainly because these disorders were previously unknown and/or mischaracterized (Leypoldt et al, 2014). In a recent report, Kojima et al (2014) described a patient with limbic encephalitis and refractory status epilepticus attributed to the presence of low-titer anti-glutamic acid decarboxylase (GAD) antibodies. The authors did not perform comprehensive autoantibody studies, and therefore, the attribution of the patient's syndrome to GAD65 autoimmunity is highly questionable.…”

Autoimmune encephalitis and anti‐GAD/GABA‐A receptor antibodies

“…Brain MRI showed extensive multifocal abnormalities on FLAIR and T2 imaging, with cortical and subcortical involvement without contrast enhancement, which highly resembled the findings for the patient reported by Kojima et al . (). Patients often had coexistent autoantibodies against less relevant or intracellular proteins, including anti‐thyroid peroxidase antibodies (three patients), anti‐GAD65 antibodies (one patient), and anti‐GABA‐B receptor antibodies (one patient).…”