**6. Concluding remarks**

**4.5. LGI**

24 Seizures

or small cell lung carcinoma.

**5. Diagnostic approach**

(**Figure 1(C)–(F)**).

Studies describing treatment of LGI1-antibody associated encephalopathy, LGI1 is a protein secreted by neurons that interact with pre- and postsynaptic receptors. LGI1 mutations have been associated with autosomal dominant temporal lobe epilepsy syndrome [50, 51]. Patients with antibodies against LGI1 develop alterations of memory, confusion, and seizures. The MRI results are typical of limbic encephalitis. Memory and cognitive deficits can be preceded by brief tonic seizures that can be confused for mimic myoclonic movements. Observational studies have provided evidence of a marked improvement with for high-dose steroids, IVIG and PLEX for patients with auto-antibodies to LGI1 and CASPR [37, 50–52]. In a retrospective study of 10 patients with high titers of VGKC-complex antibodies that had seizures and memory disorders, who received IVIG 2 g/kg/day, 100 mg prednisolone on alternate days and PLEX for 5 days, improvement was observed in frequency of seizures and cognition in six patients within 2 weeks to 12 months, correlating with reductions in antibody titers [37]. Earlier treatment, and possibly corticosteroids, appeared to provide greater benefits than before. This disorder had been included previously within the spectrum of antibodies against voltage-dependent potassium channels. Some patients develop hyponatremia and behavior or REM sleep disorders. Only 20% of cases are associated with a neoplasm, usually thymoma

The laboratory diagnosis of AD depends on the identification of the clinical symptoms of the patient, their association with each disease and their correspondence with the detection of AA. For this reason, laboratory tests are of great importance for the evaluation of patients when an AE is suspected. The results can confirm the diagnosis, estimate the severity of the disease, and are useful to follow up its evolution and establish a prognosis. The presence of autoantibodies (AA) alone in a patient does not mean the diagnosis of an AD, the associated signs and symptoms help to achieve the definitive diagnosis and are of crucial importance. Analysis of CSF plays a central part in all diagnostic criteria for encephalitis, including infectious encephalitis, relevant antibodies might be found only in the CSF, because the repertoire of antibodies in the CSF and serum can be different in the same patient (e.g., NMDA receptor in CSF and serum) [52]. By other way, serological tests to detect AA have demonstrated the presence of AA in healthy individuals and in known non-EA patients and approximately half of all autoimmune encephalitis series are Ab-negative cases, so AA is a confirmatory diagnostic test, for this reason the diagnostic tests must be combined. Three basic research techniques are used for this purpose must include: tissue-based assay (TBA), cell-based assay (CBA), and immune-precipitation (IP; in-house). In the TBA, rat or mouse brains are stained with CSF or serum of patients with an indirect immunohistochemistry or immunofluorescence technique or the combination of two fluorophores, one that identifies the autoantibody and the other to the antigen and use of confocal microscopy

Recently, several reports that associate CNS disorders with autoantibodies are directed against cell surface proteins, which are likely to be pathogens. Many of these conditions have seizures as an early and prominent feature, which are commonly refractory to conventional drugs. In contrast, a good response with immunotherapy is often observed. The studies in patients coincide in clinical manifestations, but not in autoantibodies. For this reason, CSF is crucial in the identification of new antigens, including NMDAR, AMPAR, GABABR, GABAARr, mGluR5, DPPX and LGI1, and Caspr2. Serum negativity is more likely with a milder form of the disease, presenting with clinical pictures of psychosis but not requiring intensive care, particularly if the antibodies are generated predominantly in the brain, which makes it necessary to standardize the diagnostic methods in order to be safer and to offer a timely diagnosis. The effects of antibodies on children (the effects of antibodies on hippocampal synapses) are different from that of adults; this may explain some of the differences in clinical pictures between adults and children. For this reason, the selection of patients for the autoimmune evaluation requires a high level of suspicion in the initial consultation. Since there have been currently no universally agreement upon diagnostic criteria for autoimmune epilepsies, the clinical evidence, such as the high frequency of seizures, psychiatric co-morbidity and resistance to AEDs, are important indicators to decide it. More studies are needed to identify early autoantibodies and to perform preventive treatments.
