Table 1 Antibody-related movement disorders: Clinical features and tumor association
Syndrome | Antigenic targets of associated antibodies | Specific movement disorder features | Other possible clinical features | Tumor association |
|---|---|---|---|---|
Ataxia | GAD | Mostly 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 patients | Often associated with further autoimmune diseases e.g. diabetes type 1, thyroiditis. Overlap with stiff-person syndrome, limbic encephalitis temporal-lobe epilepsy | < 5% |
CASPR2 | Rarely 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) | |
DPPX | Combined ataxia with→ | Dysautonomia, pyramidal signs, sensory symptoms, cognitive problems. Red flags: Prolonged diarrhea, weight loss | < 10%, lymphoma | |
NMDAR | Combined ataxia with→ Ataxia is more frequent in children | Behavioral changes, psychiatric disorders, cognitive impairment, seizures, mutism, dysautonomia | 25–50% of woman have ovarian teratomas. In children very rare. In patients > 45 yrs. Other tumors possible, e.g. SCLC, breast cancer, etc | |
IgLON5 | Combined ataxia with→ | Sleep disorder, bulbar dysfunction, gait abnormalities, cognitive decline, eye movement abnormalities | < 5% | |
mGluR1 | Isolated acute cerebellar ataxia | In 50% of patients dysgeusia | Unknown, possibly ∼50% lymphoma | |
VGCC | Isolated paraneoplastic cerebellar ataxia or combined with→ | Lambert-Eaton syndrome or limbic encephalitis | Highly associated with SCLC especially if associated with SOX1 abs | |
GQ1b | Combined ataxia with→ | areflexia, ophthalmoplegia and further signs for brainstem involvement (Miller-Fisher Syndrome/ Bickerstaff encephalitis) | < 5% | |
Yo/CDR2 | Isolated or combined paraneoplastic cerebellar ataxia with→ | brainstem encephalitis, neuropathy | > 95%, highly associated with breast and ovarian cancer | |
Hu/ANNA1 | Combined paraneoplastic cerebellar ataxia with→ | encephalomyelitis, limbic encephalitis, peripheral sensory neuropathy | > 95%, highly associated with SCLC and other neuroendocrine tumors. | |
Ri/ANNA2 | Combined paraneoplastic cerebellar ataxia with→ | limbic or brainstem encephalitis, myelitis and opsoclonus | 95%, highly associated with breast and ovarian cancer | |
Tr/DNER | Isolated paraneoplastic cerebellar ataxia or combined with→ | encephalopathy or neuropathy | 95%, highly associated with lymphoma | |
PCA2 | Combined paraneoplastic cerebellar ataxia with→ | limbic or brainstem encephalitis, myelitis, neuropathy, Lambert-Eaton Syndrome | Not definitely known; probably highly associated with SCLC and other neuroendocrine tumors. | |
ANNA3 | Combined paraneoplastic cerebellar ataxia with→ | limbic or brainstem encephalitis, myelitis, neuropathy | Not definitely known; probably highly associated with SCLC and other neuroendocrine tumors. | |
Zic4 | In patients with isolated Zic4 abs, mostly paraneoplastic cerebellar ataxia | Associated with various paraneoplastic neurologic syndromes especially if cooccurring with CRMP5 or Hu abs. | > 90%, usually SCLC | |
GABABR | Isolated or combined ataxia with→ | brainstem encephalitis/ encephalitis with opsoclonus, chorea and seizures | > 50%, often SCLC especially if combined with antibodies against intracellular antigens | |
CV2/CRMP5 | Combined 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 dyskinesias | NMDAR | Coexistence of chorea, dystonia and stereotypies; often characteristic orofacial and limb dyskinesias | Behavioral changes, psychiatric disorders, cognitive impairment, seizures, mutism, dysautonomia | 25–50% of woman have ovarian teratomas. In children very rare. In patients > 45 yrs. Other tumors possible, e.g. SCLC, breast cancer, etc |
Neurexin-3a | Orofacial dyskinesias combined with other clinical features like→ | Encephalopathy, seizures, altered consciousness, memory deficits, agitation | unkown | |
CASPR2 | Chorea or hemichorea preceding or combined with behavioral changes | Ataxia, pain, sleep dysfunction, autonomic dysfunction, weight loss, limbic encephalitis; male predominance (85%); age > 65 yrs. | 20% (mostly thymoma) | |
LGI1 | Chorea or hemichorea preceding or combined with cognitive impairment and encephalopathy | Limbic encephalitis, often subacute > 3 months. Bradycardia, hyponatremia | < 5% | |
IgLON5 | Combined chorea/orofacial dyskinesias with other clinical features like→ | Sleep disorder, bulbar dysfunction, gait abnormalities, cognitive decline, eye movement abnormalities | Rare, < 5% | |
CV2/CRMP5 | Combined chorea with other clinical features like→ | Cognitive decline, neuropathy, optic neuritis, myelitis, ataxia | > 90% highly associated with SCLC and thymoma | |
Hu | Combined chorea with other clinical features like→ | Gastrointestinal pseudoobstruction, sensorineuronal hearing loss | > 95%, Highly associated with SCLC and other neuroendocrine tumors | |
D2R | Combined chorea in children with→ | basal ganglia encephalitis, “Sydenham’s chorea” or in relapses after HSVE | Unknown, very rare in children | |
Dystonia | NMDAR | Combined dystonia with chorea and stereotypies and signs of encephalopathy; hemidystonia and craniocervical dystonia are rarely main symptoms in children and young adults | Behavioral changes, psychiatric disorders, cognitive impairment, seizures, mutism, dysautonomia | 25–50% of woman have ovarian teratomas. In children very rare. In patients > 45 yrs. Other tumors possible, e.g. SCLC, breast cancer, etc |
Ri | Severe jaw-closing dystonia combined with larnygospasm | Limbic/brainstem encephalitis | > 90%, mostly female patients with breast or ovarian cancer | |
IgLON5 | Rarely combined dystonia (jaw or/and cervical dystonia) with other clinical features like→ | Sleep disorder, bulbar dysfunction, gait abnormalities, cognitive decline, eye movement abnormalities | Rare, < 5% | |
Myoclonus | CASPR2 | Paroxysmal 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) |
LGI1 | Usually no myoclonus but facial-brachial dystonic seizures (FBDS); FBDS can be misdiagnosed as myoclonus | Limbic encephalitis, often subacute > 3 months. Bradycardia, hyponatremia | < 5% | |
GlyR | Myoclonus typically as part of PERM/ SPSD | Hyperekplexia, opisthotonus, autonomic dysfunction, encephalopathy, eye movement abnormalities, brainstem encephalitis | < 10% thymoma, lymphoma, SCLC, breast cancer | |
DPPX | Myoclonus with or without hyperekplexia; mostly combined with other clinical features like→ | Limbic encephalitis, brainstem disorders, prolonged diarrhea, weight loss, dysautonomia | < 10%, lymphoma | |
IgLON5 | Combined myoclonus with other clinical features like→ | Sleep disorder, bulbar dysfunction, gait abnormalities, cognitive decline, eye movement abnormalities | Rare, < 5% | |
GFAP | Combined myoclonus with other clinical features like→ | Meningoencephalomyelitis with headache and subacute encephalopathy | 20–40%; diverse neoplasms | |
Parkinsonism | D2R | Very rare; in children parkinsonism combined with→ | Encephalopathy | Unknown, very rare in children |
NMDAR | Combined parkinsonism with other clinical features like→ | Behavioral changes, psychiatric disorders, cognitive impairment, seizures, mutism, dysautonomia | 25–50% of woman have ovarian teratomas. In children very rare. In patients > 45 yrs. other tumors possible, e.g. SCLC, breast cancer, etc. | |
Ma2 | Combined paraneoplastic parkinsonism with other clinical features like→ generally subacute and rapid progressive course | Hypothalamic-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/CRMP5 | Combined paraneoplastic parkinsonism with other clinical features like→ generally subacute and rapid progressive course | Encephalopathy, myelitis, optic neuritis, peripheral neuropathy | > 90%, SCLC, other neuroendocrine tumors, breast cancer, lymphoma, thymoma | |
IgLON5 | Combined parkinsonism with other clinical features like→ PSP-like picture (vertical gaze palsy) | Sleep disorder, bulbar dysfunction, gait abnormalities, cognitive decline, eye movement abnormalities | Rare, < 5% | |
CASPR2 | Combined 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) | |
LGI1 | Combined parkinsonism with other clinical features like→ | Limbic encephalitis, often subacute > 3 months. Bradycardia, hyponatremia | < 5% | |
DPPX | Combined parkinsonism with other clinical features like→ | Limbic encephalitis, brainstem disorders, prolonged diarrhea, weight loss, dysautonomia | < 10%, lymphoma | |
Paroxysmal movement disorders | LGI1 | Characteristic facial-brachial dystonic seizures (FBDS) | Limbic encephalitis, often subacute > 3 months. Bradycardia, hyponatremia | < 5% |
CASPR2 | Paroxysmal episodic ataxia and myoclonus often triggered by orthostatism and walking | Ataxia, pain, sleep dysfunction, autonomic dysfunction, weight loss, limbic encephalitis; male predominance (85%); age > 65 yrs. | ∼20% (mostly thymoma) | |
NMDAR | Paroxysmal dystonic posturing preceding encephalitis | Behavioral changes, psychiatric disorders, cognitive impairment, seizures, mutism, dysautonomia | 25–50% of woman have ovarian teratomas. In children very rare. In patients > 45 yrs. Other tumors possible, e.g. SCLC, breast cancer, etc | |
AQP4 | Painful tonic spasms | Typically occurring in demyelinating diseases, in particular in NMOSD | < 5% | |
Stiff person spectrum disorders | GAD | Isolated or combined SPS | Encephalopathy, ataxia, sensory symptoms, pyramidal signs, dysautonomia, epilepsy; often coexistence with autoimmune diseases like type 1 diabetes, vitiligo etc. | < 5% |
GlyR | Isolated or combined SPS, PERM | Oculomotor disturbance, bulbar symptoms, dysautonomia, pyramidal signs, sensory symptoms, encephalopathy; rarely associated with limbic encephalitis | < 10% thymoma, lymphoma, SCLC, breast cancer | |
Amphiphysin | Isolated or combined SPS | Ataxia, sensory ganglionopathy and myelopathy | > 90%, SCLC, other neuroendocrine tumors, breast cancer, lymphoma, thymoma | |
DPPX | Combined 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 | |
GABAAR | Isolated or combined SPS with → | Epilepsy | unknown but probably rare especially in children | |
Ri | Combined SPS as part of → | Brainstem encephalitis | > 90%, mostly female patients with breast or ovarian cancer | |
Tremor | AMPAR, CASPR2, LGI1, DPPX, GABABR, GlyR, mGluR1, NMDAR | Combined tremor syndrome in the context of→ | Limbic encephalitis/encephalitis | AMPAR and GABAR-B > 50% SCLC; mGluR1 lymphoma; for other antibodies see above |
GFAP | Combined tremor syndrome often with ataxia and myoclonus in patient with→ | Meningoencephalomyelitis with encephalopathy with epilepsy, cognitive or psychiatric problems, myelopathy, or ataxia | 20–40%; diverse neoplasms | |
Paranodal antigens (CNTN1, NF155, NF140/186, Caspr1) | Disabling limb tremor in the context of→ | CIDP | Rare, < 5% |