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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

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%