Mesial temporal lobe epilepsy (mTLE), a common adult epilepsy syndrome, is generally acquired. Recent data have demonstrated autoimmune inflammation predominantly affecting the limbic structures of the brain as major cause of adult mTLE development. Patients usually present with mesial temporal lobe seizures with interictal temporal epileptiform activity and slowing, short-term or episodic memory disturbance, and a variety of behavioral, emotional and cognitive changes. Magnetic resonance imaging exhibits volume- and signal-changes of the amygdala and hippocampus, and specific anti-neuronal antibodies binding to either intracellular or plasma membrane neuronal antigens can be detected in sera and cerebrospinal fluid. In addition to their diagnostic value, these antibodies provide some hints on the underlying immunopathogenesis: (i) In limbic encephalitis associated with antibodies to intracellular neuronal antigens (i.e. molecules important in gene expression regulation and signal transduction processes), neuronal antigen-specific CD8+ T cells seemingly account for impairment of neuronal excitability and cell death. However, a pathogenic effect of humoral immune mechanisms is also debated. (ii) In limbic encephalitis associated with antibodies to synaptic and extrasynaptic neuronal cell surface antigens (i.e. ionotropic and metabotropic neurotransmitter receptors and associated molecules), antibody-mediated disturbance of synaptic transmission and plasticity as well as neuronal (network) excitability occurs together with some neurodegenerative effects. However, a pathogenic effect of cellular immune mechanisms is also debated.
Glutamic acid decarboxylase (GAD) and ?-Aminobutyric acid (GABA) receptors have recently been identified as distinct neuronal target antigens in limbic encephalitis. This suggests a critical involvement of disturbed inhibitory GABAergic signaling at presynaptic and postsynaptic sites in the etiology of seizures and neuropsychiatric symptoms characterizing this form of autoimmune epilepsy.
In this Frontiers Research Topic in Neurology, we aim at supplying a survey on what is known on the physiological role of different GABAergic signaling pathway in temporal lobe function, the pathogenesis and functional effects of humoral and cellular immunity on these neuronal circuits and their translation into clinical manifestations of the disorders. Moreover, distinct immunotherapeutic approaches and their preliminary effects will be discussed.
Mesial temporal lobe epilepsy (mTLE), a common adult epilepsy syndrome, is generally acquired. Recent data have demonstrated autoimmune inflammation predominantly affecting the limbic structures of the brain as major cause of adult mTLE development. Patients usually present with mesial temporal lobe seizures with interictal temporal epileptiform activity and slowing, short-term or episodic memory disturbance, and a variety of behavioral, emotional and cognitive changes. Magnetic resonance imaging exhibits volume- and signal-changes of the amygdala and hippocampus, and specific anti-neuronal antibodies binding to either intracellular or plasma membrane neuronal antigens can be detected in sera and cerebrospinal fluid. In addition to their diagnostic value, these antibodies provide some hints on the underlying immunopathogenesis: (i) In limbic encephalitis associated with antibodies to intracellular neuronal antigens (i.e. molecules important in gene expression regulation and signal transduction processes), neuronal antigen-specific CD8+ T cells seemingly account for impairment of neuronal excitability and cell death. However, a pathogenic effect of humoral immune mechanisms is also debated. (ii) In limbic encephalitis associated with antibodies to synaptic and extrasynaptic neuronal cell surface antigens (i.e. ionotropic and metabotropic neurotransmitter receptors and associated molecules), antibody-mediated disturbance of synaptic transmission and plasticity as well as neuronal (network) excitability occurs together with some neurodegenerative effects. However, a pathogenic effect of cellular immune mechanisms is also debated.
Glutamic acid decarboxylase (GAD) and ?-Aminobutyric acid (GABA) receptors have recently been identified as distinct neuronal target antigens in limbic encephalitis. This suggests a critical involvement of disturbed inhibitory GABAergic signaling at presynaptic and postsynaptic sites in the etiology of seizures and neuropsychiatric symptoms characterizing this form of autoimmune epilepsy.
In this Frontiers Research Topic in Neurology, we aim at supplying a survey on what is known on the physiological role of different GABAergic signaling pathway in temporal lobe function, the pathogenesis and functional effects of humoral and cellular immunity on these neuronal circuits and their translation into clinical manifestations of the disorders. Moreover, distinct immunotherapeutic approaches and their preliminary effects will be discussed.