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More and more pathogenic neuronal autoantibodies are recognized.
These antibodies can cause different clinically recognizable encephalitis syndromes, and most autoimmune encephalitis have cognitive dysfunction.
This review summarizes the cognitive characteristics of each type of autoantibody encephalitis and the impact of autoantibodies on cognition.
Yimaitong compiles and compiles, please do not reprint without authorization.
NMDAR encephalitis 1.
Acute NMDAR encephalitis is the most common autoimmune encephalitis.
Usually flu-like prodromal symptoms are followed by symptoms of psychosis and cognitive impairment, seizures, movement disorders, autonomic instability, and loss of consciousness.
Cognitive dysfunction is often severe, and usually extends to all areas in the acute phase.
Executive function and memory impairment are the most significant, but attention, language, visual space processing and social cognition are also affected to varying degrees.
A study reported that a patient with memory loss, cognitive fluctuations, visual hallucinations, and sleep disorders was misdiagnosed as Lewy body dementia before the NMDAR antibody was tested.
2.
Long-term follow-up Although cognitive dysfunction is more extensive in the acute phase, it may last for several years after the initial onset.
As with the acute phase, episodic memory and executive function are most commonly affected one year after the first onset.
A recent systematic review showed that as many as three-quarters of patients have chronic cognitive impairment, and timely immunotherapy is particularly important for prognosis.
3.
The mechanism of cognitive impairment NMDA receptor is a tetrameric ligand-gated ion channel that mediates excitatory transmission in the central nervous system and is critical for long-term potentiation (LTP) of neural substrates for learning and memory important. In NMDAR encephalitis, a large number of IgG NMDAR antibodies against the receptor NR1 subunit are produced in the sheath, leading to reversible and titer-dependent internalization of the NMDA receptor, followed by a decrease in receptor density and a decrease in NMDAR-mediated current.
The antibody-mediated disruption of the interaction between NMDA and ephrin-B2 receptor is the key, leading to NMDA translocation, allowing subsequent internalization.
In fact, animal studies have shown that if ephrin-B2 is used in combination, the pathogenic effect of antibodies will be blocked, and downstream effects will not appear.
Infusion of NMDAR antibody in vivo can reduce the excitatory postsynaptic current of hippocampal neurons in rats, and at the same time impair learning and spatial working memory.
The infusion of inflammatory cytokines also reduced excitatory postsynaptic currents and further impaired academic performance, indicating that there may be other factors affecting cognitive dysfunction.
Recently, there is a study that after injection of NMDAR antibody into the rat hippocampus, the object recognition function is impaired, which expands the spectrum of cognitive dysfunction mediated by NMDAR antibody.
NMDAR is highly concentrated in the hippocampus and frontal cortex, which may be the basis of the pathological changes dominated by episodic memory and executive dysfunction.
In fact, in patients with NMDAR encephalitis, decreased functional connections between the hippocampus and the medial prefrontal cortex, as well as impaired connections within the medial temporal lobe (MTL) network, can predict the severity of memory impairment.
In addition, although the disease is not a typical limbic encephalitis, after the acute phase, a reduction in bilateral hippocampal volume and microstructural integrity can be observed, which is also related to memory impairment.
Extensive damage to the superficial white matter-including short-range contact fibers and cortical inner myelin sheath, is also associated with attention and memory impairment.
Extensive changes in the integrity of deep white matter are related to the severity of the disease.
This structural damage to the hippocampus and white matter indicates that the pathological mechanism has other mechanisms besides the reversible internalization of NMDAR, such as T cell-mediated processes.
LGI1 encephalitis 1.
Acute LGI1 encephalitis is most common in middle-aged men.
The typical symptom is limbic encephalitis, which can manifest as cognitive impairment, behavioral changes, and focal seizures. Seizures usually precede the onset of cognitive impairment, and progressive amnesia usually occurs when it gradually worsens.
Although the phenotype of LGI1 encephalitis is similar to other paraneoplastic and non-paraneoplastic limbic encephalitis, facial-brachial dystonia Sexual seizures (FBDS) are unique to LGI1 encephalitis.
Significant amnesia is a characteristic of LGI1 encephalitis, especially autobiographical memory impairment, usually accompanied by obvious confusion and disorientation.
Isolated amnestic syndrome can occur in up to 10% of LGI1 encephalitis cases.
In the absence of seizures and insidious onset, LGI1 encephalitis can mimic other cognitive impairment syndromes, such as neurodegenerative dementia.
2.
Long-term follow-up In LGI1 encephalitis, most patients have chronic cognitive impairment, which mainly affects memory, but also has deficits in attention and executive function.
In fact, early treatment of isolated FBD can significantly reduce the risk of cognitive impairment, suggesting the importance of early identification of FBD.
3.
The mechanism of cognitive impairment is different from the NMDAR antibody.
The LGI1 antibody is mainly IgG4, and some of it is IgG1.
LGI1 is a trans-synaptic protein that forms a complex with pre-synaptic ADAM23 and post-synaptic ADAM22.
The LGI1 antibody directly destroys this binding, thereby reducing the density of synaptic AMPAR.
However, in view of the significant difference in clinical manifestations between AMPAR encephalitis and LGI1 encephalitis, LGI1 antibodies may have other downstream effects besides regulating AMPARs.
A recent study suggested the possibility of synergy.
Monoclonal antibodies from patients with LGI1 mediated diseases have been found to target multiple epitopes and have obvious specificity for the LRR and EPTP domains of the protein.
In this study, the LGI1 antibody combined with LRR and EPTP seems to mediate different functional effects.
Antibodies that target LRR bind to and internalize the LGI1-ADAM22/23 complex; while EPTP-bound antibodies mainly disrupt the interaction between LGI1 and its receptor.
In rodents, LGI1 is usually expressed in the CA3 and CA1 regions of the hippocampus.
Correspondingly, MR imaging in the acute phase of LGI1 encephalitis is usually abnormal, typically manifested as MTL inflammation.
During follow-up, almost all patients showed some degree of hippocampal atrophy, usually bilateral, especially in the CA3 subregion.
CASPR2 encephalitis and Morvan syndrome 1.
The acute phase of CASPR2 antibody is associated with a wide range of neurological syndromes, with clinical manifestations including peripheral nerve hyperexcitability (commonly called neuromuscular rigidity), neuropathic pain, paroxysmal dyskinesia, and margins encephalitis.
Among the different CASPR2-related syndromes, limbic encephalitis and Morvan syndrome have special effects on cognitive function.
CASPR2 encephalitis is similar to LGI1 encephalitis and is characterized by limbic dysfunction, accompanied by transient seizures, memory impairment, and frontal lobe dysfunction.
Morvan syndrome is a rare disease.
In addition to sleep disorders, hallucinations, autonomic dysfunction and pain, it also manifests as peripheral nerve hyperexcitability and encephalopathy.
Borderline dysfunctions, such as temporal lobe seizures, antegrade amnesia, or MRI hyperintensity, are not common in Morvan syndrome, except for patients with positive CASPR2 and LGI1 antibodies.
CASPR2 limbic encephalitis and Morvan syndrome are more common in elderly men, but Morvan syndrome is more associated with thymoma and other autoimmune diseases.
2.
Long-term follow-up There are very limited data on the long-term prognosis of CASPR2 encephalitis and Morvan syndrome.
Non-paraneoplastic CASPR2 encephalitis or Morvan syndrome recovers partially or completely after immunosuppression.
However, recurrence is very common, manifests as epilepsy, and usually responds well to steroids.
3.
The mechanism of cognitive impairment CASPR2 is a member of the neurofilament protein family, a cell adhesion transmembrane protein, CASPR2 stabilizes VGKCs, and antibody-mediated protein destruction causes peripheral hyperexcitability syndrome. CASPR2 is involved in the transport of AMPA receptors to the synaptic membrane, indicating that glutamate transmission dysfunction may be the basis of cognitive dysfunction in CASPR2-mediated central nervous system diseases.
Another study believes that CASPR2 plays a role in inhibitory hippocampal synapses, and the intervention of antibody-mediated inhibitory interneuron activity may lead to increased neuronal excitability and eventually cause seizures.
Like the LGI1 antibody, the CASPR2 antibody is mainly IgG4.
However, the mechanism by which these antibodies cause disease is still not fully understood, and there are conflicting results in the literature.
Some studies believe that antibodies mediate the internalization of CASPR2, but some believe that there is no internalization.
Those studies that have not found evidence of antibody-mediated internalization indicate that CASPR2 antibody exerts its function by interfering with the interaction between CASPR2 and TAG-163.
Finally, the CASPR2 antibody may also exert its pathogenicity by changing the protein's known function in AMPAR synaptic transport.
These results indicate that CASPR2 may have different functions in different synapses, which means that CASPR2 antibodies have different but synergistic effects in the pathophysiology of encephalitis or Morvan syndrome.
AMPAR encephalitis 1.
Acute AMPAR encephalitis is relatively rare, and most studies describe limbic dysfunction characterized by anterograde and retrograde amnesia, confusion, mental symptoms, and epilepsy.
A recent systematic review found 55 patients with AMPAR encephalitis; different phenotypes were observed, but amnesia is considered the most common clinical symptom.
2.
Long-term follow-up data on the neuropsychological results of patients with AMPAR encephalitis are limited.
In one case report, significant memory impairment still exists 1 year after the onset, accompanied by hippocampal atrophy, sustained high hippocampal metabolism on 18FDG PET imaging, and sustained epileptic activity on EEG.
3.
The mechanism of cognitive impairment AMPAR is a glutamate-gated ion channel composed of a combination of tetrameric subunits GluA1-4. AMPAR mediates many rapid excitatory neurotransmissions in the brain and is a component of LTP.
Typical AMPAR antibodies target the GluA1 and GluA2 subunits.
AMPAR antibody leads to a decrease in AMPAR expression and changes its synaptic localization through receptor internalization and degradation.
The reduction of extra-synaptic AMPAR can lead to LTP damage.
In addition to LTP changes, there are also learning and memory impairments.
GluA1/2 and GluA2/3 are mainly expressed in the hippocampus and marginal regions, so these regions are special targets for AMPAR antibodies.
In fact, most brain MRIs are abnormal in the acute phase, usually showing bilateral temporal lobes enhancement, reflecting the area with the highest AMPAR density.
Given that AMPAR is found throughout the brain, although its concentration is lower than that of the marginal regions, autoantibody binding in other regions can explain the obvious heterogeneity in clinical manifestations.
The wider distribution also supports the reports of some AMPAR encephalitis cases.
Overall atrophy and low metabolism.
GABAAR encephalitis 1.
Acute GABAAR antibody-mediated encephalitis has a wide range of clinical phenotypes, affecting men and women of all ages.
The largest case series to date confirmed that two-thirds of patients had seizures with cognitive changes.
2.
The mechanism of cognitive impairment GABA receptors are the main mediators of inhibitory synaptic transmission in the central nervous system.
GABAA receptors are ligand-gated chloride channels that support rapid synaptic inhibition, while GABAB receptors are G protein-coupled receptors that regulate slower inhibition transmission.
GABAAR autoantibodies are usually IgG1, and antibodies targeting the extracellular epitopes of the γ2, α1, and β3 subunits result in a decrease in synaptic and extrasynaptic GABAAR, which leads to a decrease in inhibitory postsynaptic current.
In the acute phase, MRI of the head is usually abnormal; 77% show multifocal, asynchronous gray and white matter changes, most commonly in the temporal and frontal lobes.
These extensive changes reflect the wide distribution of GABAAR, and the possible presence of additional anti-neuronal antibodies may support the heterogeneity of GABAAR encephalitis.
GABABR encephalitis 1.
Acute GABABR encephalitis was first described in a group of 15 patients, and it was characterized by seizures and memory impairment.
The elderly are the most vulnerable and are closely related to small cell lung cancer.
Up to 50% of patients develop small cell lung cancer, and the prognosis is poor.
Although recent clinical descriptions have expanded the clinical phenotype, cognitive impairment and epilepsy are still the central symptoms, almost universally affecting patients in the acute phase; and some patients with GABABR encephalitis are manifested as "rapidly progressive dementia" without seizures.
The case is accompanied by subacute cognitive impairment.
The prognosis is usually very poor.
The median survival time is 17 months.
The long-term prognosis of GABABR encephalitis remains to be studied.
2.
The mechanism of cognitive impairment The antibodies related to GABABR encephalitis are mainly directed against the IgG1 subclass of the extracellular domain of the B1 subunit.
The role of GABABR autoantibodies is to inhibit channel function, rather than internalizing or depleting cell surface receptor levels.
Consistent with the clinical phenotype, knockout GABAB1R mice showed spontaneous seizures and obvious memory impairment.
GABAB receptors are mainly expressed in the hippocampus, amygdala, thalamus and cerebellum, reflecting the common MTL abnormalities in imaging of acute encephalitis.
Summary Each neuron antibody has a different mechanism.
Although the downstream effects include cognitive dysfunction, the affected area varies by subtype.
However, it is still a comprehensive description of the acute and chronic damage of encephalitis syndrome.
A long way to go.
Original index: LL Gibson, A McKeever, E Coutinho, et al.
Cognitive impact of neuronal antibodies: encephalitis and beyond.
Transl Psychiatry.
2020 Sep 1;10(1):304.
These antibodies can cause different clinically recognizable encephalitis syndromes, and most autoimmune encephalitis have cognitive dysfunction.
This review summarizes the cognitive characteristics of each type of autoantibody encephalitis and the impact of autoantibodies on cognition.
Yimaitong compiles and compiles, please do not reprint without authorization.
NMDAR encephalitis 1.
Acute NMDAR encephalitis is the most common autoimmune encephalitis.
Usually flu-like prodromal symptoms are followed by symptoms of psychosis and cognitive impairment, seizures, movement disorders, autonomic instability, and loss of consciousness.
Cognitive dysfunction is often severe, and usually extends to all areas in the acute phase.
Executive function and memory impairment are the most significant, but attention, language, visual space processing and social cognition are also affected to varying degrees.
A study reported that a patient with memory loss, cognitive fluctuations, visual hallucinations, and sleep disorders was misdiagnosed as Lewy body dementia before the NMDAR antibody was tested.
2.
Long-term follow-up Although cognitive dysfunction is more extensive in the acute phase, it may last for several years after the initial onset.
As with the acute phase, episodic memory and executive function are most commonly affected one year after the first onset.
A recent systematic review showed that as many as three-quarters of patients have chronic cognitive impairment, and timely immunotherapy is particularly important for prognosis.
3.
The mechanism of cognitive impairment NMDA receptor is a tetrameric ligand-gated ion channel that mediates excitatory transmission in the central nervous system and is critical for long-term potentiation (LTP) of neural substrates for learning and memory important. In NMDAR encephalitis, a large number of IgG NMDAR antibodies against the receptor NR1 subunit are produced in the sheath, leading to reversible and titer-dependent internalization of the NMDA receptor, followed by a decrease in receptor density and a decrease in NMDAR-mediated current.
The antibody-mediated disruption of the interaction between NMDA and ephrin-B2 receptor is the key, leading to NMDA translocation, allowing subsequent internalization.
In fact, animal studies have shown that if ephrin-B2 is used in combination, the pathogenic effect of antibodies will be blocked, and downstream effects will not appear.
Infusion of NMDAR antibody in vivo can reduce the excitatory postsynaptic current of hippocampal neurons in rats, and at the same time impair learning and spatial working memory.
The infusion of inflammatory cytokines also reduced excitatory postsynaptic currents and further impaired academic performance, indicating that there may be other factors affecting cognitive dysfunction.
Recently, there is a study that after injection of NMDAR antibody into the rat hippocampus, the object recognition function is impaired, which expands the spectrum of cognitive dysfunction mediated by NMDAR antibody.
NMDAR is highly concentrated in the hippocampus and frontal cortex, which may be the basis of the pathological changes dominated by episodic memory and executive dysfunction.
In fact, in patients with NMDAR encephalitis, decreased functional connections between the hippocampus and the medial prefrontal cortex, as well as impaired connections within the medial temporal lobe (MTL) network, can predict the severity of memory impairment.
In addition, although the disease is not a typical limbic encephalitis, after the acute phase, a reduction in bilateral hippocampal volume and microstructural integrity can be observed, which is also related to memory impairment.
Extensive damage to the superficial white matter-including short-range contact fibers and cortical inner myelin sheath, is also associated with attention and memory impairment.
Extensive changes in the integrity of deep white matter are related to the severity of the disease.
This structural damage to the hippocampus and white matter indicates that the pathological mechanism has other mechanisms besides the reversible internalization of NMDAR, such as T cell-mediated processes.
LGI1 encephalitis 1.
Acute LGI1 encephalitis is most common in middle-aged men.
The typical symptom is limbic encephalitis, which can manifest as cognitive impairment, behavioral changes, and focal seizures. Seizures usually precede the onset of cognitive impairment, and progressive amnesia usually occurs when it gradually worsens.
Although the phenotype of LGI1 encephalitis is similar to other paraneoplastic and non-paraneoplastic limbic encephalitis, facial-brachial dystonia Sexual seizures (FBDS) are unique to LGI1 encephalitis.
Significant amnesia is a characteristic of LGI1 encephalitis, especially autobiographical memory impairment, usually accompanied by obvious confusion and disorientation.
Isolated amnestic syndrome can occur in up to 10% of LGI1 encephalitis cases.
In the absence of seizures and insidious onset, LGI1 encephalitis can mimic other cognitive impairment syndromes, such as neurodegenerative dementia.
2.
Long-term follow-up In LGI1 encephalitis, most patients have chronic cognitive impairment, which mainly affects memory, but also has deficits in attention and executive function.
In fact, early treatment of isolated FBD can significantly reduce the risk of cognitive impairment, suggesting the importance of early identification of FBD.
3.
The mechanism of cognitive impairment is different from the NMDAR antibody.
The LGI1 antibody is mainly IgG4, and some of it is IgG1.
LGI1 is a trans-synaptic protein that forms a complex with pre-synaptic ADAM23 and post-synaptic ADAM22.
The LGI1 antibody directly destroys this binding, thereby reducing the density of synaptic AMPAR.
However, in view of the significant difference in clinical manifestations between AMPAR encephalitis and LGI1 encephalitis, LGI1 antibodies may have other downstream effects besides regulating AMPARs.
A recent study suggested the possibility of synergy.
Monoclonal antibodies from patients with LGI1 mediated diseases have been found to target multiple epitopes and have obvious specificity for the LRR and EPTP domains of the protein.
In this study, the LGI1 antibody combined with LRR and EPTP seems to mediate different functional effects.
Antibodies that target LRR bind to and internalize the LGI1-ADAM22/23 complex; while EPTP-bound antibodies mainly disrupt the interaction between LGI1 and its receptor.
In rodents, LGI1 is usually expressed in the CA3 and CA1 regions of the hippocampus.
Correspondingly, MR imaging in the acute phase of LGI1 encephalitis is usually abnormal, typically manifested as MTL inflammation.
During follow-up, almost all patients showed some degree of hippocampal atrophy, usually bilateral, especially in the CA3 subregion.
CASPR2 encephalitis and Morvan syndrome 1.
The acute phase of CASPR2 antibody is associated with a wide range of neurological syndromes, with clinical manifestations including peripheral nerve hyperexcitability (commonly called neuromuscular rigidity), neuropathic pain, paroxysmal dyskinesia, and margins encephalitis.
Among the different CASPR2-related syndromes, limbic encephalitis and Morvan syndrome have special effects on cognitive function.
CASPR2 encephalitis is similar to LGI1 encephalitis and is characterized by limbic dysfunction, accompanied by transient seizures, memory impairment, and frontal lobe dysfunction.
Morvan syndrome is a rare disease.
In addition to sleep disorders, hallucinations, autonomic dysfunction and pain, it also manifests as peripheral nerve hyperexcitability and encephalopathy.
Borderline dysfunctions, such as temporal lobe seizures, antegrade amnesia, or MRI hyperintensity, are not common in Morvan syndrome, except for patients with positive CASPR2 and LGI1 antibodies.
CASPR2 limbic encephalitis and Morvan syndrome are more common in elderly men, but Morvan syndrome is more associated with thymoma and other autoimmune diseases.
2.
Long-term follow-up There are very limited data on the long-term prognosis of CASPR2 encephalitis and Morvan syndrome.
Non-paraneoplastic CASPR2 encephalitis or Morvan syndrome recovers partially or completely after immunosuppression.
However, recurrence is very common, manifests as epilepsy, and usually responds well to steroids.
3.
The mechanism of cognitive impairment CASPR2 is a member of the neurofilament protein family, a cell adhesion transmembrane protein, CASPR2 stabilizes VGKCs, and antibody-mediated protein destruction causes peripheral hyperexcitability syndrome. CASPR2 is involved in the transport of AMPA receptors to the synaptic membrane, indicating that glutamate transmission dysfunction may be the basis of cognitive dysfunction in CASPR2-mediated central nervous system diseases.
Another study believes that CASPR2 plays a role in inhibitory hippocampal synapses, and the intervention of antibody-mediated inhibitory interneuron activity may lead to increased neuronal excitability and eventually cause seizures.
Like the LGI1 antibody, the CASPR2 antibody is mainly IgG4.
However, the mechanism by which these antibodies cause disease is still not fully understood, and there are conflicting results in the literature.
Some studies believe that antibodies mediate the internalization of CASPR2, but some believe that there is no internalization.
Those studies that have not found evidence of antibody-mediated internalization indicate that CASPR2 antibody exerts its function by interfering with the interaction between CASPR2 and TAG-163.
Finally, the CASPR2 antibody may also exert its pathogenicity by changing the protein's known function in AMPAR synaptic transport.
These results indicate that CASPR2 may have different functions in different synapses, which means that CASPR2 antibodies have different but synergistic effects in the pathophysiology of encephalitis or Morvan syndrome.
AMPAR encephalitis 1.
Acute AMPAR encephalitis is relatively rare, and most studies describe limbic dysfunction characterized by anterograde and retrograde amnesia, confusion, mental symptoms, and epilepsy.
A recent systematic review found 55 patients with AMPAR encephalitis; different phenotypes were observed, but amnesia is considered the most common clinical symptom.
2.
Long-term follow-up data on the neuropsychological results of patients with AMPAR encephalitis are limited.
In one case report, significant memory impairment still exists 1 year after the onset, accompanied by hippocampal atrophy, sustained high hippocampal metabolism on 18FDG PET imaging, and sustained epileptic activity on EEG.
3.
The mechanism of cognitive impairment AMPAR is a glutamate-gated ion channel composed of a combination of tetrameric subunits GluA1-4. AMPAR mediates many rapid excitatory neurotransmissions in the brain and is a component of LTP.
Typical AMPAR antibodies target the GluA1 and GluA2 subunits.
AMPAR antibody leads to a decrease in AMPAR expression and changes its synaptic localization through receptor internalization and degradation.
The reduction of extra-synaptic AMPAR can lead to LTP damage.
In addition to LTP changes, there are also learning and memory impairments.
GluA1/2 and GluA2/3 are mainly expressed in the hippocampus and marginal regions, so these regions are special targets for AMPAR antibodies.
In fact, most brain MRIs are abnormal in the acute phase, usually showing bilateral temporal lobes enhancement, reflecting the area with the highest AMPAR density.
Given that AMPAR is found throughout the brain, although its concentration is lower than that of the marginal regions, autoantibody binding in other regions can explain the obvious heterogeneity in clinical manifestations.
The wider distribution also supports the reports of some AMPAR encephalitis cases.
Overall atrophy and low metabolism.
GABAAR encephalitis 1.
Acute GABAAR antibody-mediated encephalitis has a wide range of clinical phenotypes, affecting men and women of all ages.
The largest case series to date confirmed that two-thirds of patients had seizures with cognitive changes.
2.
The mechanism of cognitive impairment GABA receptors are the main mediators of inhibitory synaptic transmission in the central nervous system.
GABAA receptors are ligand-gated chloride channels that support rapid synaptic inhibition, while GABAB receptors are G protein-coupled receptors that regulate slower inhibition transmission.
GABAAR autoantibodies are usually IgG1, and antibodies targeting the extracellular epitopes of the γ2, α1, and β3 subunits result in a decrease in synaptic and extrasynaptic GABAAR, which leads to a decrease in inhibitory postsynaptic current.
In the acute phase, MRI of the head is usually abnormal; 77% show multifocal, asynchronous gray and white matter changes, most commonly in the temporal and frontal lobes.
These extensive changes reflect the wide distribution of GABAAR, and the possible presence of additional anti-neuronal antibodies may support the heterogeneity of GABAAR encephalitis.
GABABR encephalitis 1.
Acute GABABR encephalitis was first described in a group of 15 patients, and it was characterized by seizures and memory impairment.
The elderly are the most vulnerable and are closely related to small cell lung cancer.
Up to 50% of patients develop small cell lung cancer, and the prognosis is poor.
Although recent clinical descriptions have expanded the clinical phenotype, cognitive impairment and epilepsy are still the central symptoms, almost universally affecting patients in the acute phase; and some patients with GABABR encephalitis are manifested as "rapidly progressive dementia" without seizures.
The case is accompanied by subacute cognitive impairment.
The prognosis is usually very poor.
The median survival time is 17 months.
The long-term prognosis of GABABR encephalitis remains to be studied.
2.
The mechanism of cognitive impairment The antibodies related to GABABR encephalitis are mainly directed against the IgG1 subclass of the extracellular domain of the B1 subunit.
The role of GABABR autoantibodies is to inhibit channel function, rather than internalizing or depleting cell surface receptor levels.
Consistent with the clinical phenotype, knockout GABAB1R mice showed spontaneous seizures and obvious memory impairment.
GABAB receptors are mainly expressed in the hippocampus, amygdala, thalamus and cerebellum, reflecting the common MTL abnormalities in imaging of acute encephalitis.
Summary Each neuron antibody has a different mechanism.
Although the downstream effects include cognitive dysfunction, the affected area varies by subtype.
However, it is still a comprehensive description of the acute and chronic damage of encephalitis syndrome.
A long way to go.
Original index: LL Gibson, A McKeever, E Coutinho, et al.
Cognitive impact of neuronal antibodies: encephalitis and beyond.
Transl Psychiatry.
2020 Sep 1;10(1):304.