Table 2.
Antibody target | Relative frequency in clinical practice | Tumour association | Movement disorder presentation | Other clinical features | |
---|---|---|---|---|---|
Neuronal surface antibodies | |||||
AQP4 | ++ | (+)/− | Painful tonic spasms | Neuromyelitis optica spectrum disorders, typically with optic neuritis, pyramidal weakness, sensory symptoms, bladder disturbance | |
Rarely; lung or breast cancer, teratoma | |||||
ATP1A3 | Not yet clear (single case report in 2015) | + | Cerebellar ataxia | Vertical gaze palsy, spastic tetraparesis, deterioration of visual acuity | |
Colon adenocarcinoma | |||||
CASPR2 | ++ | +/− | Cerebellar ataxia, chorea, neuromyotonia, myokymia | Morvan syndrome, limbic encephalitis, neuropathy (rarely Guillain-Barré-like syndrome), neuropathic pain | |
In ∼20%: thymoma ≫ lung, prostate, sigmoid or thyroid cancer, myeloma | |||||
DNER | + | +++ | Cerebellar ataxia | Encephalitis, neuropathy | |
In∼ 90%: Hodgkin lymphoma ≫ lung carcinoma | |||||
DPPX | ++ | +/− | SPSD, myoclonus, startle, ataxia, tremor, parkinsonism, opsoclonus myoclonus | Multifocal encephalitis or brainstem encephalitis with prominent gastrointestinal symptoms (prolonged diarrhoea, constipation), other dysautonomic signs (urinary or erectile dysfunction, cardiac arrhythmia, thermodysregulation, Raynaud’s phenomenon), sensory disturbance (allodynia, paraesthesia) | |
In ∼7%: B-cell neoplasms | |||||
D2R | Very rare | − | Basal ganglia encephalitis in children with dystonia, chorea or parkinsonism; Sydenham’s chorea | Psychiatric and sleep disturbance | |
GABAAR | ++ | +/− | Chorea, dystonia or ataxia (as part of a more widespread encephalopathy), opsoclonus myoclonus syndrome; possible association with SPSD | Encephalopathy with epilepsy, behavioural or cognitive problems or reduced consciousness; frequent multifocal T2 hyperintensities on MRI; tendency to autoimmune predisposition (coexisting antibodies, e.g. GAD or NMDAR antibodies, thyroid autoimmunity, idiopathic thrombocytopenic purpura, gluten sensitivity or myasthenia) | |
In ∼40%: thymoma, lung carcinoma, rectal cancer, myeloma | |||||
GABABR | ++ | +/− | Opsoclonus myoclonus ataxia syndrome, cerebellar ataxia | Limbic encephalitis with prominent seizures | |
In ∼60%: small cell lung cancer ≫ breast cancer multiple myeloma, rectal carcinoma, oesophageal carcinoma | |||||
GluRδ2 | Very rare; case reports from Japan only | Para/post-infectious | Cerebellar ataxia | (Limbic) encephalitis, epilepsy | |
GlyR | +++ | +/− | SPSD, myoclonus, hyperekplexia, ataxia | Brainstem encephalitis; reported also in: optic neuritis; limbic / epileptic encephalopathy, epilepsy, steroid-responsive deafness (clinical relevance less clear) | |
In ∼9%: thymoma > small cell lung cancer, breast cancer, Hodgkin lymphoma, chronic lymphocytic leukaemia | |||||
GlyT2 | Not yet clear; preliminary report of two patients | SPSD | Co-occurring with → GAD antibodies | ||
IgLON5 | + | Gait instability, cerebellar ataxia, chorea in patients with tau brain pathology | REM and Non-REM sleep behaviour disorder; sleep apnoea, stridor, dysphagia, oculomotor disturbance, cognitive decline, dysautonomia | ||
LGI1 | +++ | (+)/− In ∼ 7%: liver carcinoid, neuroendocrine pancreas tumour, mesothelioma, rectal carcinoma | Faciobrachial dystonic seizures, chorea, parkinsonism | Limbic encephalitis; hyponatraemia, bradycardia | |
mGluR1 | + | +/− | Cerebellar ataxia | Memory or attention deficits, dysgeusia, psychiatric problems (auditory hallucinations, paranoia) | |
In ∼ 43%: Hodgkin lymphoma ≫ prostate adenocarcinoma | |||||
NMDAR | ++++ | +/− | Orofacial and limb dyskinesia, chorea, dystonia, myoclonus, ataxia, parkinsonism, paroxysmal dyskinesias | Prodromal infectious-like symptoms, neuropsychiatric disturbance, encephalopathy with epilepsy, cognitive deficits, reduced consciousness, dysautonomia, central hypoventilation | |
In ∼40%: ovarian teratoma ≫ extraovarian teratomas, ovarian carcinomas; lung, breast, testicular and pancreatic tumours | |||||
Neurexin-3α | + | Mild orofacial dyskinesias | Encephalopathy with epilepsy, reduced consciousness, memory deficits, psychomotor agitation | ||
VGCC | ++ | ++ | Cerebellar ataxia | Lambert-Eaton myasthenic syndrome, encephalopathy, neuropathy | |
Tumour association varies in different studies between 20 and 90%, mostly small cell lung cancer | |||||
VGKCcomplexa; | N/A | N/A | N/A | N/A | |
Antibodies targeting intracellular, synaptic proteins | |||||
Amphiphysin | ++ | +++ | SPSD | Sensory ganglionopathy, myeolpathy | |
Breast cancer, small cell lung cancer | |||||
GAD | ++++ | +/− | SPSD, cerebellar ataxia | Limbic encephalitis; focal epilepsy; often concomitant autoimmunity (e.g. diabetes type 1, thyroid disease, vitiligo, pernicious anaemia) | |
(rarely, various tumours) | |||||
Gephyrin | Single case | (+) | SPSD | – | |
Mediastinal carcinoma | |||||
GABARAP | + | − | SPSD | Only in association with → GAD antibodies | |
Antibodies targeting cytoplasmic and nuclear antigens | |||||
ANNA3b | + | +++ | Cerebellar ataxia | Sensory/sensorimotor neuropathy, myelopathy, brainstem or limbic encephalitis | |
Small cell lung cancer, lung or oesophageal adenocarcinoma | |||||
AP3B2/Nb | Single case | − | Cerebellar ataxia | Pyramidal tract involvement | |
ARHGAP26/ Ca | Very rare; six cases | +/− | Cerebellar ataxia | Limbic encephalitis | |
Ovarian carcinoma | |||||
CARP VIII | Very rare; two cases | ++ | Cerebellar ataxia | − | |
Ovarian carcinoma, melanoma | |||||
CRMP5/CV2 | ++ | +++ | Chorea | Optic neuritis, myelitis (can mimic neuromyelitis optica), cognitive decline, neuropathy | |
Small cell lung cancer, thymoma | |||||
GFAP | + | +/− In ∼34%: prostate and gastroesophageal adenocarcinomas, myeloma, melanoma, colonic carcinoid, parotid pleomorphic adenoma, teratoma | Cerbebellar ataxia, tremor, undefined movement disorders | Menigeoencephalomyelitis or limited forms, with headache, cognitive problems, optic papillitis, sensory disturbance, gastrointestinal and urogenital dysautonomia, neuropathy; often concomitant autoimmunity (e.g. diabetes type 1, thyroid disease, myasthenia, rheumatoid arthritis, alopecia) | |
Homer-3 | Very rare; four cases | − | Cerebellar ataxia | Epilepsy, confusion | |
Hu / ANNA-1 | +++ | +++ | Chorea, cerebellar ataxia, opsoclonus myoclonus ataxia syndrome | Encephalomyelitis, limbic encephalitis, brainstem encephalitis, sensory neuropathy, gastrointestinal pseudoobstruction | |
Small cell lung cancer ≫ neuroblastoma or intestinal, prostate, breast, bladder, and ovary carcinoma | |||||
ITPR1 | + | +++ | Cerebellar ataxia | Peripheral neuropathy | |
Breast cancer associated with BRCA1 | |||||
Ma2/Ta | ++ | +++ | Parkinsonism | Limbic, diencephalic or brainstem encephalitis, myelopathy or radiculoplexopathy, with encephalopathy, hypothalamic-pituitary endocrine dysfunction, weight gain, prominent sleep disorders, eye movement abnormalities (opsoclonus, supranuclear gaze palsy), dysphagia, muscular atrophy, fasciculations | |
Testis ≫ lung cancer; rarely no neoplasia | |||||
Ri / ANNA-2 | ++ | +++ | Dystonia (jaw closing dystonia, laryngospasms), opsoclonus myoclonus ataxia syndrome, oculopalatal myoclonus, cerebellar ataxia, SPSD | Brainstem encephalitis with cranial nerve palsies, nystagmus, dysarthria, ataxia, rigidity, trismus, pyramidal signs | |
Gynaecological tumours, mainly breast cancer, and lung cancer | |||||
Sox1 | ++ | +++ | Cerebellar ataxia | Lambert-Eaton myasthenic syndrome, sensory/sensorimotor neuropathy, brainstem encephalitis | |
Lung cancer | |||||
Yo/PCA1 | +++ | +++ | Cerebellar ataxia | Rhombencephalitis, peripheral neuropathy | |
Gynaecological tumours | |||||
PKCγ | Very rare; two cases | ++ | Cerebellar ataxia | – | |
Non-small cell lung cancer, hepatobiliary adenocarcinoma | |||||
Zic4 | +++ | +++ | Cerebellar ataxia | – | |
Small cell lung cancer ≫ ovarian adenocarcinoma |
Of note, exact prevalences are unknown, and relative frequencies are based on the literature and own experience only, but given to indicate their relevance in clinical practice.
aAntibodies against the voltage gated potassium channel complex (VGKCcomplex) were previously detected by radioimmunoassay (RIA), which does not allow distinction of the later identified, specific targets (LGI1, CASPR2, or very rarely contactin-2, or possibly some yet uncharacterized antigens). To test specifically for CASPR2 or LGI1 antibodies, cell-based assays are applied, and this may yield positive results even if the VGKCcomplex-RIA has been negative. Conversely, there is a proportion of sera positive in the VGKCcomplex-RIA that do not harbour antibodies that recognize LGI1 and/or CASPR2, and it has been argued this is unlikely to indicate true autoimmune disease.
bAntigen unknown.
+ = rare; ++ = occasional; +++ = frequent; ++++ = very frequent; CARP VIII = carbonic anhydrase VIII; CASPR2 = contactin-associated protein 2; CRMP5/CV2 = collapsin response mediator protein 5; D2R = dopamine 2 receptor; DPPX = dipeptidyl peptidase-like protein 6; GABAAR = γ-aminobutyric acid A receptor; GABABR = γ-aminobutyric acid B receptor; GAD = glutamic acid decarboxylase; GluRδ2 = glutamate receptor delta 2; GlyR = glycine receptor; GlyT2 = glycine transporter 2; Hu/ANNA-1 = Hu proteins (HuD, HuC)/anti-neuronal nuclear autoantibody 1; IgLON5 = IgLON family member 5; Ma2/Ta = PNMA2; mGluR1 = metabotropic glutamate receptor 1; NMDAR = N-methyl-d-aspartate receptor; PKCγ = protein kinase C gamma; Ri/ANNA-2 = Nova-1, Nova-2/anti-neuronal nuclear autoantibody 2; Sox1 = Sry-like high mobility group box protein 1; SPSD = stiff person spectrum disorders; VGCC = P/Q-type voltage gated calcium channel; VGKCcomplex = voltage gated potassium channel complex a; Yo/PCA1 = CDR62/ CDR2, CDR34/ CDR1; Zic4 = Zinc finger protein 4.