Encephalomyelitis (EM) |
Clinical dysfunction of multiple levels of nervous system, including peripheral involvement, for example EM with peripheral neuropathy, EM with sensory neuronopathy (SNN) |
Hu (also called antineuronal nuclear antibody 1, ANNA-1) or CV2/collapsin response-mediator protein 5 (CRMP5) antibodies |
SCLC >> NSCLC, other neuroendocrine tumors, and neuroblastoma |
Meningeal carcinomatosis (meningeal enhancement, low glucose or presence of tumoral cells in CSF), Neurosarcoidosis (systemic involvement may be shown by FDG-PET, biopsy showing non-caseating granulomas) |
Limbic encephalitis |
Diagnostic Criteria (Graus 201626. Graus F, Dalmau J. Role of 18F-FDG-PET imaging in the diagnosis of autoimmune encephalitis - Authors’ reply. Lancet Neurol . 2016 Sep 1;15(10):1010. https://doi.org/10.1016/S1474-4422(16)30130-2 https://doi.org/10.1016/S1474-4422(16)30...
) Diagnosis can be made when all four* of the following criteria have been met: 1 Subacute onset (rapid progression of less than 3 months) of working memory deficits, seizures, or psychiatric symptoms suggesting involvement of the limbic system 2 Bilateral brain abnormalities on T2-weighted fluid-attenuated inversion recovery MRI highly restricted to the medial temporal lobes† 3 At least one of the following: • CSF pleocytosis (white blood cell count of more than five cells per mm3) • EEG with epileptic or slow-wave activity involving the temporal lobes 4 Reasonable exclusion of alternative causes *If one of the first three criteria is not met, a diagnosis of definite limbic encephalitis can be made only with the detection of antibodies against cell-surface, synaptic, or onconeural proteins. |
High risk antibodies (frequency of cancer>70%) |
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Infections (Herpes simplex, Human herpesvirus-6, Neurossyphilis, Whipple) Autoimmune systemic diseases (System Lupus Erythematosus, Sj:ogren, Behçet, Relapsing Polychondritis) Gliomas Lymphoma Status epilepticus Chronic temporal lobe epilepsy |
Hu |
SCLC >> NSCLC, other neuroendocrine tumors, and neuroblastoma |
Ma2 |
Testicular cancer (young men) and NSCLC in older patient (with both Ma1 and Ma2 positivity) |
High-Risk Antibodies (30-70% of association with cancer) |
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AMPAR |
SCLC and malignant thymoma |
GABABR |
SCLC (Paraneoplastic cases are more commonly observed in elderly men and smokers with associated anti-KCTD16 antibodies. Most young patients are not paraneoplastic) |
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Lower-Risk antibodies (<30%) |
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Caspr2 |
When phenotype os CASOR2 in LE, almost always non paraneoplastic, but if phenotype is Morvan Syndrome, half is associated with tumor |
LGI1 |
Thymoma and neuroendocrine |
GLYR |
Malignant thymoma and Hodgkin lymphoma |
GAD |
SCLC, other neuroendocrine tumors, and malignant thymoma |
AK5 |
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Rapidly progressive cerebellar syndrome |
Previously known as subacute cerebellar degeneration Rapidly progressive, severe, bilateral, cerebellar symptoms. Sometimes extra cerebellar dysfunction maybe present, including brainstem |
Anti-Yo (also known as Purkinje cell antibody -1, PCA-1) |
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Autoimmune cerebellar ataxia antibodies against GAD (glutamic acid decarboxylase), mGLUR1, GLUK2, antibodies gluten ataxia Cerebellar multiple system atrophy Creutzfeldt-Jakob Disease |
Anti-Ri (ANNA-2, ANNA = antineuronal nuclear antibody) |
Breast > lung (SCLC and NSCLC) Breast Cancer in Women and lung cancer in men |
Tr (DNER - elta/notch-like epidermal growth factor related receptor) |
Hodgkin lymphoma |
Ma2 and/or Ma |
Testicular cancer (young men) and NSCLC in older patient (with both Ma1 and Ma2 positivity) |
KLHL11 (Kelch-like protein 11) |
Testicular cancer in young men |
Opsoclonus-myoclonus |
Involuntary high frequence chaotic multidirectional saccadic movements + nonrhythmic action myoclonus on trunk, limbs and head. Additional features eg. Cerebellar signs and or encephalopathy may be present |
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50% of OMS in children are paraneoplastic and closely associated with neuroblastoma in adults paraneoplastic etiology accounts for 40% of cases. In adults Patients with breast cancer and OMS usually have Ri (ANNA-2 antibodies) |
Idiopathic OMS (younger, prodromal symptoms of viral infection/vaccination, less frequently encephalopathy), drugs (lithium, amiytityline, cocaine, phenytoin with diazepam, phenelzine with imipramine, cyclosporin) Neonatal - transient Celiac disease Stem cell transplant HIV Multiple sclerosis Thalamic hemorrhage |
Sensory neuropathy |
the diagnosis of classical sensory neuronopathy should be considered if all the following criteria are present: - subacute onset with a Rankin score of at least 3 before 12 weeks of evolution, - onset of numbness, and often pain, - marked asymmetry of symptoms at onset, - involvement of the arms, proprioceptive loss in the areas affected, - and electrophysiological studies that show marked, but not restricted, involvement of the sensory fibers with absent sensory nerve action potentials in at least one of the nerves studied. |
Hu |
SCLC >> NSCLC, other neuroendocrine tumors, and neuroblastoma |
Idiopathic (most frequent etiology, painless, onset on lower limbs) Sjögren ́s syndrome Cisplatin/oxaliplatin treatment (usually 1 month after therapy, “coasting phenomenon - progression of sensory loss even after cessation of chemotherapy |
CV2/CRMP5 |
SCLC and thymoma |
amphiphysin antibodies |
SCLC and breast cancer |
Gastrointestinal pseudo-obstruction |
Recurrent episodes of abdominal pain, distension, constipation without evidence of mechanical obstruction Due to myenteric plexus dysfunction and may be accompanied by other signs of autonomic dysfunction, Sensory neuropathy or encephalomyelitis |
Hu |
SCLC >> NSCLC, other neuroendocrine tumors, and neuroblastoma |
Chagas, Diabetes, Parkinson’s Disease, Scleroderma Mechanical obstruction |
Lambert-Eaton Myasthenic Syndrome |
Progressive proximal lower limb weakness, progressing to upper limbs, distal muscles and finally ocular and bulbar muscles, majority of patients develop autonomic dysfunction (dry mouth, erectile dysfunction, constipation). Absent muscles reflex, which improve after repeat exercise or maximal voluntary contraction (facilitation). EMG shows incremental response after high-frequency nerve stimulation. |
antibodies against P/Q type voltage-gated calcium channels (VGCCs) are present in nearly 90% - not necessary for diagnosis. |
Present in paraneoplastic and non paraneoplastic LEMS. DELTA-P score for predicting tumor association 1 point for the presence of each of the following items at or within 3 months from onset: age at onset ≥ 50 years, smoking at diagnosis, weight loss ≥ 5%, bulbar involvement, erectile dysfunction, and Karnofsky performance status lower than 70 (Delta P of 4 or more points correspond to >90% of presence of SCLC. |
Idiopathic LEMS Myasthenia gravis |
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SOX-1 |
Strongly associates with SCLC or paraneoplastic syndromes associated with SCLC |
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