Table 1.
Comparison between anti-AK5 encephalitis and other antibody-positive CNS diseases commonly involving limbic system.
| Disease | Diagnostic biomarkers | Median age, year (range); female: male ratio | Common clinical features | Frequency of tumor (%); associated tumor types (%) | MRI findings | Preferred sample types; detection methodology |
|---|---|---|---|---|---|---|
| Anti-AK5 encephalitis [9,30] | Serum/CSF: AK5 antibody | 64 (48–94); 1:2.3 |
Cognitive impairment (100 %), psychiatric-behavioral disturbances (90 %), prosopagnosia (16.7 %), speech disorder (16.7 %) and seizure (13.3 %) | 0 | 90 % temporal T2/FLAIR hyperintensity | CSF; TBA (IFA) and CBA |
| Anti-LGI1 encephalitis [31,32] | Serum/CSF: LGI1 antibody | 54 (18–85); 1:2 |
Cognitive impairment 97 %), seizure (90 %) and behavioral disturbance (90 %) | <10 %; thymoma, SCLC | 75 % mesial temporal lobe T2/FLAIR hyperintensity | Serum; TBA (IFA) and CBA |
| Anti-CASPR2 Encephalitis [31,33] |
Serum/CSF: CASPR2 antibody | 65 (60–70);m ale predominance |
Cognitive impairment (80 %), seizure (50 %), CA (35 %), neuropathic pain (60 %), peripheral nerve hyperexcitability (55 %), insomnia (55 %) and autonomic dysfunction (45 %) | ∼20 %; mostly thymoma | 70 % normal, and 24 % bilateral medial temporal lobes T2/FLAIR hyperintensity | Serum; TBA (IFA) and CBA |
| Anti-AMPAR encephalitis [34] | Serum/CSF: AMPAR antibody | 57 (3–92); 1:2 | Cognitive impairment (82 %), psychiatric symptoms (80 %), altered state of consciousness (77 %), dyskinesia (38 %) and seizure (29 %) | ∼60 %; SCLC, thymoma and breast cancer |
60 % temporal lobe T2/FLAIR hyperintensity | CSF; TBA (IFA) and CBA |
| Anti-GABABR encephalitis [32] | Serum/CSF: GABABR Antibody |
55 (18–76); 1:2 | Seizure (93 %), cognitive impairment (82 %), psychiatric symptoms (77 %) and altered state of consciousness (51 %) | ∼50 %; SCLC | 30 % temporal lobe T2/FLAIR hyperintensity | CSF; TBA (IFA) and CBA |
| Anti-NMDAR encephalitis [35] | Serum/CSF: NMDAR antibody | 21 (<1–85); 4:1 | Psychiatric disorders (90 %), seizure (82 %), memory loss, motor disorders (75 % adults and 95 % children), speech disorders and central hypoventilation | ∼40 %; ovarian teratoma | 70 % normal and non-specific changes | CSF; TBA (IFA) and CBA |
| KLHL11-PNS [[36], [37], [38]] | Serum/CSF: KLHL11 antibody | 46 (9–79); predominantly males | Rhombencephalitis (70 %), cochleovestibulopathy (30 %; vertigo, sensorineural hearing loss and tinnitus) and LE (23 %) | >70 %; testicular germ cell tumor (78.7 %), teratoma (14.8 %) | T2/FLAIR hyperintensities in the temporal lobe, brainstem and cerebellum | Serum or CSF; TBA (IFA) and CBA |
| Ma2-PNS [20,30,36,[39], [40], [41]] | Serum/CSF: Ma and/or Ma2 antibody | Female: 64 (53–82); Male: 34 (22–70); 1:2 |
Diencephalitis, LE andbrainstem encephalitis | >90 %; testicular cancer (47 %), lung cancer (17 %), other cancers (36 %; mainly gastrointestinal tumors) | T2/FLAIR hyperintensities in the diencephalon, temporal lobe and brainstem | Serum; TBA (IFA) and western blot |
| Hu/ANNA-1-PNS [30,[40], [41], [42], [43]] | Serum/CSF: Hu/ANNA-1 antibody | 69 (36–76); slight female predominance | Rapid progressive cerebellar syndrome, brainstem encephalitis, LE and encephalomyelitis | >90 %; SCLC (75 %), NSCLC (10 %), extra-thoracic cancers (15 %) | T2/FLAIR Hyperintensities in temporal lobe and cerebellum | Serum; TBA (IFA) and western blot |
| Anti-mGluR5 encephalitis [44] | Serum/CSF: mGluR5 antibody | 29 (6–75); no predominance | Cognitive impairment (91 %), psychiatric and behavior disorder (91 %), sleep disturbance (64 %), seizure (55 %), decreased level of consciousness (55 %) and movement disorders (45 %) | ∼55 %; mostly Hodgkin lymphoma | 18 % temporal lobe T2/FLAIR hyperintensities | CSF; TBA (IFA) and CBA |
| GAD antibody-spectrum diseases [25,30,41,[45], [46], [47], [48]] | Serum: high titre of GAD65 antibody; CSF: GAD65 antibody |
60 (29–80); strong female predominance (>80 %) | Stiff-person syndrome spectrum, cerebellar syndrome, LE, and epilepsy | <10 %; SCLC, neuroendocrine tumor, thymoma, breast cancer, non-Hodgkin's lymphoma | Temporal lobe T2/FLAIR hyperintensities | Serum and CSF; radioimmunoassay and CBA |
Abbreviations: AK5, anti-adenylate kinase 5; AMPAR, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; ANNA-1, antineuronal nuclear antibody type 1; CA, cerebellar ataxia; CASPR2, contactin-associated protein-like 2; CBA, cell-based assay; CLL, chronic lymphocytic leukemia; CNS, central nervous system; CSF, cerebrospinal fluid; DWI, diffusion-weighted imaging; ELISA, enzyme-linked immunosorbent assay; FLAIR, fluid-attenuated inversion recovery; GABABR, gamma aminobutyric acid-B receptor; GAD, glutamic acid decarboxylase; IFA, indirect immunofluorescence assay; KLHL11, kelch-like protein 11; LE, limbic encephalitis; LGI1, leucine-rich glioma-inactivated 1; mGluR5, metabotropic glutamate receptor type 5; MRI, magnetic resonance imaging; NMDAR, N-methyl-d-aspartate receptor; NSCLC, non-small cell lung cancer; PCR, polymerase chain reaction; PNS, paraneoplastic neurological syndrome; SCLC, small cell lung cancer; TBA, tissue-based assay.