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Table 1 Antibody-related movement disorders: Clinical features and tumor association

From: Antibody-related movement disorders – a comprehensive review of phenotype-autoantibody correlations and a guide to testing

SyndromeAntigenic targets of associated antibodiesSpecific movement disorder featuresOther possible clinical featuresTumor association
AtaxiaGADMostly truncal ataxia, nystagmus and dysarthria typically in woman over 60; preceding episodes of brainstem and cerebellar dysfunction or persistent vertigo before onset of permanent ataxia in some patientsOften associated with further autoimmune diseases e.g. diabetes type 1, thyroiditis.
Overlap with stiff-person syndrome, limbic encephalitis temporal-lobe epilepsy
< 5%
CASPR2Rarely isolated ataxia, generally combined ataxia with→
Rarely presentation of paroxysmal episodic ataxia (generally in the setting of limbic encephalitis)
Ataxia, pain, sleep dysfunction, autonomic dysfunction, weight loss, limbic encephalitis; male predominance (85%); age > 65 yrs.20% (mostly thymoma)
DPPXCombined ataxia with→Dysautonomia, pyramidal signs, sensory symptoms, cognitive problems.
Red flags: Prolonged diarrhea, weight loss
< 10%, lymphoma
NMDARCombined ataxia with→
Ataxia is more frequent in children
Behavioral changes, psychiatric disorders, cognitive impairment, seizures, mutism, dysautonomia25–50% of woman have ovarian teratomas. In children very rare. In patients > 45 yrs. Other tumors possible, e.g. SCLC, breast cancer, etc
IgLON5Combined ataxia with→Sleep disorder, bulbar dysfunction, gait abnormalities, cognitive decline, eye movement abnormalities< 5%
mGluR1Isolated acute cerebellar ataxiaIn 50% of patients dysgeusiaUnknown, possibly 50% lymphoma
VGCCIsolated paraneoplastic cerebellar ataxia or combined with→Lambert-Eaton syndrome or limbic encephalitisHighly associated with SCLC especially if associated with SOX1 abs
GQ1bCombined ataxia with→areflexia, ophthalmoplegia and further signs for brainstem involvement (Miller-Fisher Syndrome/ Bickerstaff encephalitis)< 5%
Yo/CDR2Isolated or combined paraneoplastic cerebellar ataxia with→brainstem encephalitis, neuropathy> 95%, highly associated with breast and ovarian cancer
Hu/ANNA1Combined paraneoplastic cerebellar ataxia with→encephalomyelitis, limbic encephalitis, peripheral sensory neuropathy> 95%, highly associated with SCLC and other neuroendocrine tumors.
Ri/ANNA2Combined paraneoplastic cerebellar ataxia with→limbic or brainstem encephalitis, myelitis and opsoclonus95%, highly associated with breast and ovarian cancer
Tr/DNERIsolated paraneoplastic cerebellar ataxia or combined with→encephalopathy or neuropathy95%, highly associated with lymphoma
PCA2Combined paraneoplastic cerebellar ataxia with→limbic or brainstem encephalitis, myelitis, neuropathy, Lambert-Eaton SyndromeNot definitely known; probably highly associated with SCLC and other neuroendocrine tumors.
ANNA3Combined paraneoplastic cerebellar ataxia with→limbic or brainstem encephalitis, myelitis, neuropathyNot definitely known; probably highly associated with SCLC and other neuroendocrine tumors.
Zic4In patients with isolated Zic4 abs, mostly paraneoplastic cerebellar ataxiaAssociated with various paraneoplastic neurologic syndromes especially if cooccurring with CRMP5 or Hu abs.> 90%, usually SCLC
GABABRIsolated or combined ataxia with→brainstem encephalitis/ encephalitis with opsoclonus, chorea and seizures> 50%, often SCLC especially if combined with antibodies against intracellular antigens
CV2/CRMP5Combined paraneoplastic cerebellar ataxia with chorea and other clinical features like →Cognitive decline, neuropathy, optic neuritis, myelitis,> 90%, SCLC, other neuroendocrine tumors, breast cancer, lymphoma, thymoma.
Chorea and dyskinesiasNMDARCoexistence of chorea, dystonia and stereotypies; often characteristic orofacial and limb dyskinesiasBehavioral changes, psychiatric disorders, cognitive impairment, seizures, mutism, dysautonomia25–50% of woman have ovarian teratomas. In children very rare. In patients > 45 yrs. Other tumors possible, e.g. SCLC, breast cancer, etc
Neurexin-3aOrofacial dyskinesias combined with other clinical features like→Encephalopathy, seizures, altered consciousness, memory deficits, agitationunkown
CASPR2Chorea or hemichorea preceding or combined with behavioral changesAtaxia, pain, sleep dysfunction, autonomic dysfunction, weight loss, limbic encephalitis; male predominance (85%); age > 65 yrs.20% (mostly thymoma)
LGI1Chorea or hemichorea preceding or combined with cognitive impairment and encephalopathyLimbic encephalitis, often subacute > 3 months. Bradycardia, hyponatremia< 5%
IgLON5Combined chorea/orofacial dyskinesias with other clinical features like→Sleep disorder, bulbar dysfunction, gait abnormalities, cognitive decline, eye movement abnormalitiesRare, < 5%
CV2/CRMP5Combined chorea with other clinical features like→Cognitive decline, neuropathy, optic neuritis, myelitis, ataxia> 90% highly associated with SCLC and thymoma
HuCombined chorea with other clinical features like→Gastrointestinal pseudoobstruction, sensorineuronal hearing loss> 95%, Highly associated with SCLC and other neuroendocrine tumors
D2RCombined chorea in children with→basal ganglia encephalitis, “Sydenham’s chorea” or in relapses after HSVEUnknown, very rare in children
DystoniaNMDARCombined dystonia with chorea and stereotypies and signs of encephalopathy; hemidystonia and craniocervical dystonia are rarely main symptoms in children and young adultsBehavioral changes, psychiatric disorders, cognitive impairment, seizures, mutism, dysautonomia25–50% of woman have ovarian teratomas. In children very rare. In patients > 45 yrs. Other tumors possible, e.g. SCLC, breast cancer, etc
RiSevere jaw-closing dystonia combined with larnygospasmLimbic/brainstem encephalitis> 90%, mostly female patients with breast or ovarian cancer
IgLON5Rarely combined dystonia (jaw or/and cervical dystonia) with other clinical features like→Sleep disorder, bulbar dysfunction, gait abnormalities, cognitive decline, eye movement abnormalitiesRare, < 5%
MyoclonusCASPR2Paroxysmal myoclonus triggered by walking or orthostatism, spinal segmental myoclonus, generalized myoclonus> mostly combined with other clinical features ->Ataxia, pain, sleep dysfunction, autonomic dysfunction, weight loss, limbic encephalitis; male predominance (85%); age > 65 yrs.20% (mostly thymoma)
LGI1Usually no myoclonus but facial-brachial dystonic seizures (FBDS); FBDS can be misdiagnosed as myoclonusLimbic encephalitis, often subacute > 3 months. Bradycardia, hyponatremia< 5%
GlyRMyoclonus typically as part of PERM/ SPSDHyperekplexia, opisthotonus, autonomic dysfunction, encephalopathy, eye movement abnormalities, brainstem encephalitis< 10% thymoma, lymphoma, SCLC, breast cancer
DPPXMyoclonus with or without hyperekplexia; mostly combined with other clinical features like→Limbic encephalitis, brainstem disorders, prolonged diarrhea, weight loss, dysautonomia< 10%, lymphoma
IgLON5Combined myoclonus with other clinical features like→Sleep disorder, bulbar dysfunction, gait abnormalities, cognitive decline, eye movement abnormalitiesRare, < 5%
GFAPCombined myoclonus with other clinical features like→Meningoencephalomyelitis with headache and subacute encephalopathy20–40%; diverse neoplasms
ParkinsonismD2RVery rare; in children parkinsonism combined with→EncephalopathyUnknown, very rare in children
NMDARCombined parkinsonism with other clinical features like→Behavioral changes, psychiatric disorders, cognitive impairment, seizures, mutism, dysautonomia25–50% of woman have ovarian teratomas. In children very rare. In patients > 45 yrs. other tumors possible, e.g. SCLC, breast cancer, etc.
Ma2Combined paraneoplastic parkinsonism with other clinical features like→ generally subacute and rapid progressive courseHypothalamic-pituitary dysfunction, weight gain, prominent sleep disorders including excessive daytime sleepiness, rapid eye movement (REM) sleep behavior disorder (RBD), narcolepsy cataplexy, and eye movement abnormalities> 90% testis tumors
CV2/CRMP5Combined paraneoplastic parkinsonism with other clinical features like→ generally subacute and rapid progressive courseEncephalopathy, myelitis, optic neuritis, peripheral neuropathy> 90%, SCLC, other neuroendocrine tumors, breast cancer, lymphoma, thymoma
IgLON5Combined parkinsonism with other clinical features like→ PSP-like picture (vertical gaze palsy)Sleep disorder, bulbar dysfunction, gait abnormalities, cognitive decline, eye movement abnormalitiesRare, < 5%
CASPR2Combined parkinsonism with other clinical features like→Ataxia, pain, sleep dysfunction, autonomic dysfunction, weight loss, limbic encephalitis; male predominance (85%); age > 65 yrs.20% (mostly thymoma)
LGI1Combined parkinsonism with other clinical features like→Limbic encephalitis, often subacute > 3 months. Bradycardia, hyponatremia< 5%
DPPXCombined parkinsonism with other clinical features like→Limbic encephalitis, brainstem disorders, prolonged diarrhea, weight loss, dysautonomia< 10%, lymphoma
Paroxysmal movement disordersLGI1Characteristic facial-brachial dystonic seizures (FBDS)Limbic encephalitis, often subacute > 3 months. Bradycardia, hyponatremia< 5%
CASPR2Paroxysmal episodic ataxia and myoclonus often triggered by orthostatism and walkingAtaxia, pain, sleep dysfunction, autonomic dysfunction, weight loss, limbic encephalitis; male predominance (85%); age > 65 yrs.20% (mostly thymoma)
NMDARParoxysmal dystonic posturing preceding encephalitisBehavioral changes, psychiatric disorders, cognitive impairment, seizures, mutism, dysautonomia25–50% of woman have ovarian teratomas. In children very rare. In patients > 45 yrs. Other tumors possible, e.g. SCLC, breast cancer, etc
AQP4Painful tonic spasmsTypically occurring in demyelinating diseases, in particular in NMOSD< 5%
Stiff person spectrum disordersGADIsolated or combined SPSEncephalopathy, ataxia, sensory symptoms, pyramidal signs, dysautonomia, epilepsy; often coexistence with autoimmune diseases like type 1 diabetes, vitiligo etc.< 5%
GlyRIsolated or combined SPS, PERMOculomotor disturbance, bulbar symptoms, dysautonomia, pyramidal signs, sensory symptoms, encephalopathy; rarely associated with limbic encephalitis< 10% thymoma, lymphoma, SCLC, breast cancer
AmphiphysinIsolated or combined SPSAtaxia, sensory ganglionopathy and myelopathy> 90%, SCLC, other neuroendocrine tumors, breast cancer, lymphoma, thymoma
DPPXCombined SPS with prominent hyperekplexia, myoclonus, ataxia and further clinical signs like→Dysautonomia, pyramidal signs, sensory symptoms, cognitive problems. Red flags: Prolonged diarrhoea, weight loss< 10%, lymphoma
GABAARIsolated or combined SPS with →Epilepsyunknown but probably rare especially in children
RiCombined SPS as part of →Brainstem encephalitis> 90%, mostly female patients with breast or ovarian cancer
TremorAMPAR, CASPR2, LGI1, DPPX, GABABR, GlyR, mGluR1, NMDARCombined tremor syndrome in the context of→Limbic encephalitis/encephalitisAMPAR and GABAR-B > 50% SCLC; mGluR1 lymphoma; for other antibodies see above
GFAPCombined tremor syndrome often with ataxia and myoclonus in patient with→Meningoencephalomyelitis with encephalopathy with epilepsy, cognitive or psychiatric problems, myelopathy, or ataxia20–40%; diverse neoplasms
Paranodal antigens (CNTN1, NF155, NF140/186, Caspr1)Disabling limb tremor in the context of→CIDPRare, < 5%