Paraneoplastic neurological syndromes
Upcoming SlideShare
Loading in...5
×
 

Paraneoplastic neurological syndromes

on

  • 502 views

Paraneoplastic Neurological Syndromes, Mechanisms, Molecular Mimicry, Autoantibodies, Treatment, Clinical Assessment

Paraneoplastic Neurological Syndromes, Mechanisms, Molecular Mimicry, Autoantibodies, Treatment, Clinical Assessment

Statistics

Views

Total Views
502
Views on SlideShare
502
Embed Views
0

Actions

Likes
0
Downloads
14
Comments
0

0 Embeds 0

No embeds

Accessibility

Categories

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment
  • Section of Cerebellum with T cell immunostain cd4 and cd8

Paraneoplastic neurological syndromes Paraneoplastic neurological syndromes Presentation Transcript

  • Immunostaining with Anti-Tr antibody 10:41 PM
  • Paraneoplastic Neurological Syndromes A Review. 10:41 PM
  • Objectives • To understand when in the course of malignancy the syndromes occur • To know the antineural antibodies associated with the syndromes • To differentiate efficacy of symptomatic treatment vs. treatment of underlying disease in the different syndromes 10:41 PM
  • Outline for the Session • • • • • • • Introduction History and Evolution of knowledge Pathogenesis – Concept of ―Onconeural‖ Antigen Definition – Terminology Criteria for Diagnosis Individual Syndromes Summary
  • Outline for the Session • • • • • • • Introduction History and Evolution of knowledge Pathogenesis – Concept of ―Onconeural‖ Antigen Definition – Terminology Criteria for Diagnosis Individual Syndromes Summary
  • Background • Heterogeneous group of disorders – Associated with systemic cancers – Mechanisms other than… • • • • • 10:41 PM Metastases Metabolic and nutritional deficits Infections Coagulopathy Side effects of treatment
  • DEFINITION • ―All neurologic abnormalities not caused by the cancer’s spread to the nervous system are paraneoplastic‖ • Seminars Neurol 2004 • ―Remote effects of cancer on the nervous system‖ • NEJM 2004 • ―Distal, non metastatic menifestations of a tumor‖ • OTO 2005 10:41 PM
  • • Most symptomatic paraneoplastic syndromes are rare, affecting perhaps 0.01 percent of patients with cancer • Rudnicki SA, Dalmau J. Paraneoplastic syndromes of the spinal cord, nerve, and muscle. Muscle Nerve 2000;23:1800-18 • Exceptions….. 10:41 PM
  • • Lambert–Eaton myasthenic syndrome, which affects about 3 percent of patients with small-cell lung cancer • Sculier J-P, Feld R, Evans WK, et al. Neurologic disorders in patients with small cell lung cancer. Cancer 1987;60:2275-83 • Myasthenia gravis, which affects about 15 percent of patients with thymoma • Levy Y, Afek A, Sherer Y, et al. Malignant thymoma associated with autoimmune diseases: a retrospective study and review of the literature. Semin Arthritis Rheum 1998;28:73-9. • Demyelinating peripheral neuropathy, which affects about 50 percent of patients with the rare osteosclerotic form of plasmacytoma • Latov N. Pathogenesis and therapy of neuropathies associated with monoclonal gammopathies. Ann Neurol 1995;37:Suppl 1:S32-S42 10:41 PM
  • PARANEOPLASTIC SYNDROMES • Neurologic symptoms of paraneoplastic syndromes usually precede the identification of the cancer – Antoine JC, Cinotti L, Tilikete C, et al. [18F]fluorodeoxyglucose positron emission tomography in the diagnosis of cancer in patients with paraneoplastic neurological syndrome and anti-Hu antibodies. Ann Neurol 2000;48:105-8 10:41 PM
  • PARANEOPLASTIC SYNDROMES • Usually when the paraneoplastic-related cancer is identified, it is small, nonmetastatic, and indolently growing – Graus F, Dalmou J, Reñé R, et al. Anti- Hu antibodies in patients with small-cell lung cancer: association with complete response to therapy and improved survival. J Clin Oncol 1997;15:2866-72 10:41 PM
  • PARANEOPLASTIC SYNDROMES • Paraneoplastic syndromes are generally, but not always, irreversible • Neurologic disability caused by paraneoplastic syndromes is often profound in the absence of any other cancer symptoms – Graus F, Keime-Guibert F, Reñe R, et al. Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients. Brain 2001;124:1138-48 10:41 PM
  • • • • • • • Paraneoplastic Syndromes May Affect Any Portion of the Nervous System Cerebral cortex Brainstem Spinal cord Peripheral nerves Neuromuscular junction Muscle 10:41 PM
  • Background • • • • Occur in < 1% of pts with systemic cancer Heralds diagnosis of cancer in up to 60% Highly specific antineuronal antibodies Most common (presence overlaps) – Paraneoplastic cerebellar degeneration (PCD) – Paraneoplastic encephalomyelitis / sensory neuronopathy (PEM/PSN) – Paraneoplastic opsoclonus myoclonus (POM) – Lambert-Eaton myasthenic syndrome (LEMS) 10:41 PM
  • Diagnosis • Paraneoplastic syndromes occur in patients: – not known to have cancer (most common) – with active cancer – in remission after treatment • exclude other cancer-associated process 10:41 PM
  • Diagnosis with Known Cancer • Search for metastases – MRI of involved site – CSF cytology • Search for nonmetastatic disorders – Vascular, infectious, metabolic disorders, chemotherapy, radiation therapy • Serum/CSF for autoantibodies 10:41 PM
  • Diagnosis without Known Cancer • Exclude other causes of nervous system dysfunction • Search for Cancer – CXR, pelvic examination, – mammograms, examine lymph nodes, serum cancer markers (CEA) – CSF for cells, IgG, OCB, cytology examination – Serum/CSF for autoantibodies – If CSF or autoantibodies positive then follow and search again 10:41 PM
  • Outline for the Session • • • • • • • Introduction History and Evolution of knowledge Pathogenesis – Concept of ―Onconeural‖ Antigen Definition – Terminology Criteria for Diagnosis Individual Syndromes Summary
  • • The concept of immune surveillance of cancer was first formally put forward by Thomas and Burnet in the mid1950s – Burnet, F. M. Cancer: a biological approach. Brit. Med. J. 1, 841-847 (1957). • they proposed that immune mechanisms could act as a natural defence against tumour cells – Thomas, L. Cellular and humoral aspects of the hypersensitivity states. in Discussion to P. B. Medawar's paper. (ed. Lawrence, H. S.) 529-534 (Harper, New York, 1959). • link between the neurological degeneration and cancer in PND is an immunological one – Dunn, G. P., Bruce, A. T., Ikeda, H., Old, L. J. & Schreiber, R. D. Cancer immunoediting: from immunosurveillance to tumor escape. Nature Immunol. 3, 991-998 (2002) 10:41 PM
  • • Symptoms usually develop rapidly in days or a few weeks and then stabilize, leaving the patient severely disabled. • Exceptions do occur, and some patients develop insidious forms of PND that can be misdiagnosed as chronic degenerative disorders – Graus F, Bonaventura I, Uchuya M, et al. Indolent anti-Huassociated paraneoplastic sensory neuropathy. Neurology 1994;44:2258-2261 – Bataller L, Graus F, Saiz A, Vilchez JJ. Clinical outcome in adult onset idiopathic or paraneoplastic opsoclonus-myoclonus. Brain 2001;124:437-443 10:41 PM
  • • Spontaneous neurological improvement, although reported in some syndromes, is rare and should lead to the consideration of a nonparaneoplastic etiology. – Voltz, R. D., Posner, J. B., Dalmau, J. & Graus, F. Paraneoplastic encephalomyelitis: an update of the effects of the anti-Hu immune response on the nervous system and tumour. J. Neurol. Neurosurg. Psychiatr. 63, 133-136 (1997) 10:41 PM
  • Immune Mediated 10:41 PM ANTIGEN !!!!!
  • Outline for the Session • • • • • • • Introduction History and Evolution of knowledge Pathogenesis – Concept of ―Onconeural‖ Antigen Definition – Terminology Criteria for Diagnosis Individual Syndromes Summary
  • Pathogenesis • Onconeuronal Immunity • ―Tumor expression of proteins that normally are restricted to the nervous system triggers an immune response against the tumor that also affects the nervous system‖ • Only a small amount of tumor may trigger response 10:41 PM
  • Pathogenesis continued • Tests for antibodies against the cancerexpressed neuronal proteins • Some disorders caused by antibodies – Myasthenia gravis – LEMS • Other disorders most likely caused by B and T cell mechanisms of neuronal injury 10:41 PM
  • • Darnell, R. B. & Posner, J. B. Observing the invisible: successful tumor immunity in humans. Nat Immunol. 4, 201 (2003). • Darnell, R. B. & Posner, J. B. Paraneoplastic syndromes of the nervous system. N. Engl. J. Med. 349, 1543-1554 (2003) 10:41 PM
  • 10:41 PM
  • 10:41 PM
  • 10:41 PM
  • 10:41 PM
  • Discovery of MHC Role of MHC as APC… 10:41 PM
  • 10:41 PM
  • Target Cell - DC The Problem, However… 10:41 PM
  • 10:41 PM
  • 10:41 PM
  • Are PNS only based on Humoral Immunity ? 10:41 PM
  • 10:41 PM
  • 10:41 PM
  • Outline for the Session • • • • • • • Introduction History and Evolution of knowledge Pathogenesis – Concept of ―Onconeural‖ Antigen Definition – Terminology Criteria for Diagnosis Individual Syndromes Summary
  • “Classic Paraneoplastic Syndromes” • A group of disorders, when present, strongly suggests an underlying cancer – – – – – – 10:41 PM Lambert-Eaton myasthenic syndrome (LEMS) Opsoclonus/myoclonus found in children Subacute cerebellar degeneration Encephalomyelitis Subacute motor neuronopathy Sensory neuronopathy
  • “Non-classic” Paraneoplastic Syndromes • Second group of clinical syndromes ―sometimes‖ associated with cancer • More often appearing in the absence of a neoplasm – Polymyositis – Amyotrophic lateral sclerosis – Sensorimotor polyneuropathy • Extensive search for a neoplasm is generally unwarranted 10:41 PM
  • Outline for the Session • • • • • • • Introduction History and Evolution of knowledge Pathogenesis – Concept of ―Onconeural‖ Antigen Definition – Terminology Criteria for Diagnosis Individual Syndromes Summary
  • 10:41 PM
  • Outline for the Session • • • • • • • Introduction History and Evolution of knowledge Pathogenesis – Concept of ―Onconeural‖ Antigen Definition – Terminology Criteria for Diagnosis Individual Syndromes Summary
  • 10:41 PM
  • Some generalizations … 10:41 PM
  • Frequency of Paraneoplastic Syndromes • ―Clinically significant paraneoplastic syndromes probably occur in fewer than 0.1% of patients with cancer‖ – Robert B. Darnell, M.D., Ph.D., and Jerome B. Posner, M.D, N Engl J Med 2003;349:1543-54. • If a patient without a known cancer presents with one of the ―classic‖ paraneoplastic syndromes the likelihood he/she has cancer is considerable – i.e., LEMS 60% paraneoplastic – Subacute cerebellar degeneration 50% – Robert B. Darnell, M.D., Ph.D., and Jerome B. Posner, M.D, N Engl J Med 2003;349:1543-54. 10:41 PM
  • Diagnosis • Suggestive clinical features: – Acute or Subacute onset, may progress over commonly days, sometimes weeks to months – Severe neurologic disability – One portion of nervous system more than widespread involvement – Some syndromes present stereotypically 10:41 PM
  • Diagnosis Autoantibodies • Presence of autoantibodies: – helps to confirm the clinical diagnosis – focus the search for an underlying malignancy – Anti-Hu, Anti-Yo, Anti-Ri, Anti-Tr, Anti-CV2, etc. 10:41 PM
  • Treatment • Unrewarding in general • Most patient left with severe neurologic disability • Immunosuppression ineffective in most, except LEMS and MG • Exceptions … • LEMS, MG, Neuropathy with Myeloma • Adult OMS – may respond 10:41 PM
  • “Classic Paraneoplastic Syndromes” Specific Syndromes • • • • Paraneoplastic cerebellar degeneration Most common Best characterized Rare disorder – 780 cases report by 2005 • A group of related disorders that differ in clinical features, prognosis, and types of malignancies – Peterson K, Rosenblum MK, Kotanides H, Posner JB. Paraneoplastic cerebellar degeneration. I. A clinical analysis of 55 anti-Yo antibody positive patients. Neurology 2002; 42:1931-7 10:41 PM
  • Paraneoplastic Cerebellar Degeneration • Disorders can be separated by characteristic antibodies to particular tumor-associated antibodies • PCD can be associated with any cancer, but most common: – – – – 10:41 PM lung cancer (small-cell) ovarian uterine lymphomas
  • Paraneoplastic Cerebellar Degeneration • Neurologic symptoms prompt patient to see doctor before cancer is symptomatic • Cancer is usually found months to 2-4 years after onset of neurologic symptoms • Sometimes only at autopsy 10:41 PM
  • Paraneoplastic Cerebellar Degeneration • Clinical features: – slight incoordination in walking – rapidly evolving over weeks to months with progressive gait ataxia – incoordination in arms, legs and trunk – dysarthria – nystagmus with oscillopsia 10:41 PM
  • Paraneoplastic Cerebellar Degeneration • Within a few months it reaches its peak and then stabilizes – – – – – – – 10:41 PM most cannot walk without support cannot sit unsupported handwriting is impossible eating independently difficult speech very difficult to understand oscillopsia may prevent reading diplopia & vertigo
  • Paraneoplastic Cerebellar Degeneration • Neurologic signs always bilateral, usually symmetric • Deficits frequently limited to cerebellar dysfunction • Other neurologic deficits (mild) – – – – – – 10:41 PM sensorineural hearing loss dysphagia hyperreflexia extrapyramidal signs peripheral neuropathy dementia
  • Paraneoplastic Cerebellar Degeneration • Laboratory evaluation – diffuse cerebellar atrophy months to years after onset on head imaging – CSF (early) • increased lymphocytes • slightly elevated protein and IgG concentrations • Pleocytosis resolves with time 10:41 PM
  • Paraneoplastic Cerebellar Degeneration • Autoantibodies in serum and CSF – found in a subset of patients • number is unknown – react with Purkinje cells of cerebellum & tumor – well characterized • anti-Yo, anti-Hu, anti-Ri, anti-Tr, anti-CV2, anti-Ma proteins, 10:41 PM
  • Paraneoplastic Cerebellar Degeneration • Autoantibodies in serum and CSF/cancer – – – – – – 10:41 PM anti-Yo ovary, breast anti-Hu SCLC anti-Ri Breast, SCLC, anti-Tr Hodgkin’s lymphoma anti-CV2 SCLC anti-Ma proteins Testicular
  • Paraneoplastic Cerebellar Degeneration • Pathology – CNS may be normal at autopsy – usually the cerebellum is atrophic with abnormally widened sulci and small gyri – microscopic • extensive/complete loss of Purkinje cells of the cerebellar cortex – pathologic changes sometimes involving other parts of nervous system 10:41 PM
  • Paraneoplastic Cerebellar Degeneration • Diagnosis – recognize characteristic clinical syndrome – exclude other causes of late-onset cerebellopathy • • • • • • • • 10:41 PM Leptomeningeal metastasis infections toxicity of chemotherapies viral brainstem encephalitis demyelinating disease Creutzfeld-Jakob disease infarction, hypothyroidism alcoholic and hereditary cerebellar degenerations
  • Paraneoplastic Cerebellar Degeneration • Once the disease peaks it doesn’t usually change • Treatment or cure of underlying cancer usually doesn’t help • Immune suppression (steroids) or plasmapheresis is not effective • ? clonazepam for ataxia 10:41 PM
  • 10:41 PM
  • More “Classic” Syndromes Sensory Neuronopathy (SN) • <20% paraneoplastic • Also occurs in patients with autoimmune disorders, Sjogren’s syndrome • 2/3 of paraneoplastic SN have small-cell lung cancer • Neurologic syndrome usually precedes diagnosis of cancer • • • • 10:41 PM dysesthetic pain and numbness of face, trunk, extremities severe sensory ataxia all sensory modalities affected, loss of DTRs motor nerve action potentials are normal
  • Subacute Motor Neuronopathy (Spinal Muscular Atrophy, ALS like diseases) • Rare complication of Hodgkin’s and other lymphomas • <3% of cases are paraneoplastic • Subacute, progressive, painless, patchy lower motor neuron weakness • Affects legs more than arms • Profound weakness • Degeneration of neurons in the anterior horns of the spinal cord • Sometimes can have associated UMN signs 10:41 PM
  • Encephalomyelitis • Cancer patients with clinical signs of damage to more than one area of the nervous system • Limbic encephalitis • • • • rare complication of small-cell lung cancer personality/mood changes develop over days or weeks severe impairment of recent memory sometimes with agitation, confusion, hallucinations, & seizures • brain MRI: normal or signal changes in the medial temporal lobe(s) • may improve with treatment of underlying tumor 10:41 PM
  • 10:41 PM
  • Opsoclonus/Myoclonus Found in Children • Opsoclonus – involuntary, arrhythmic, multidirectional, highamplitude conjugate saccades – associated with myoclonus – may have cerebellar signs • 50% of children harbor a neuroblastoma • Neurologic signs precede discovery of tumor in 50% • Anti-Ri antibody associated with opsoclonus 10:41 PM
  • POM • In adults, most commonly associated with… – Small cell lung cancer – Breast cancer • Develops prior to diagnosis of cancer • Manifestations – Rapidly progressive cerebellar ataxia – Opsoclonus – Myoclonus • Treatment of cancer > immunosuppressive tx 10:41 PM
  • Photoreceptor Degeneration • Cancer-associated retinopathy (CAR) • Rare syndrome • Small-cell lung cancer, melanoma, gynecologic tumors • Episodic visual obscurations, night blindness, light-induced glare, photosensitivity, impaired color vision progressing to painless vision loss • Typically precedes diagnosis of cancer • ? prednisone 10:41 PM
  • Lambert-Eaton Myasthenic Syndrome (LEMS) • Presynaptic disorder of neuromuscular transmission • Proximal weakness, areflexia or hyporeflexia, autonomic dysfunction • 45% to 60% associated with SCLC, reported also with renal cell carcinoma, lymphoma and breast • Syndrome precedes tumor diagnosis by several months to years 10:41 PM
  • Lambert-Eaton Myasthenic Syndrome (LEMS) • • • • Onset with proximal lower extremity weakness Later proximal upper extremity weakness Respiratory and craniobulbar involvement uncommon Autonomic dysfunction prominent – dry mouth, dry eyes, impotence, orthostatic hypotension, hyperhidrosis • Facilitation with sustained contraction • >100% CMAP increase with repetitive stimulation 10:41 PM
  • Lambert-Eaton Myasthenic Syndrome (LEMS) • >92% with antibodies against P/Q-type voltage-gated calcium channels (presynaptic) • Impaired influx of calcium into nerve terminal with reduced neuromuscular junction transmission • A LEMS diagnosis warrants a thorough investigation for underlying carcinoma, SCLC • Careful observation and serial evaluations until tumor found 10:41 PM
  • Lambert-Eaton Myasthenic Syndrome (LEMS) • Unlike most paraneoplastic syndromes LEMS usually responds to: – – – – plasmapheresis corticosteroids azathioprine intravenous immunoglobin • Long-term treatment often needed 10:41 PM
  • 10:41 PM
  • Are PNS’s because of abberencies within the immune system ?? 10:41 PM
  • • “Specifically, an immune response to neuronal proteins that are expressed by the tumour cells (termed onconeural antigens) recognize and suppress the growth of the malignancy” » Darnell, R. B. & Posner, J. B. Observing the invisible: successful tumor immunity in humans. Nat Immunol. 4, 201 (2003). » Darnell, R. B. & Posner, J. B. Paraneoplastic syndromes of the nervous system. N. Engl. J. Med. 349, 1543-1554 (2003) 10:41 PM
  • 10:41 PM
  • • The tumor is often occult, and the neurologic disorder typically precedes the diagnosis of the tumor.8,22 • patients with the Hu paraneoplastic syndrome typically harbor small-cell lung cancers that are limited to single nodules (53 of 55 patients in one study) – Dalmau J, Graus F, Rosenblum MK, Posner JB. Anti-Hu–associated paraneoplastic encephalomyelitis/sensory neuropathy: a clinical study of 71 patients. Medicine (Baltimore) 1992;71:59-72. • This was despite the fact that most small-cell lung cancers (over 60 percent) are widely metastatic at diagnosis. 10:41 PM
  • • The histologic features of tumors in paraneoplastic neurologic disorders do not differ from those of other tumors, except that the tumors may be heavily infiltrated with inflammatory cells. » Cooper R, Khakoo Y, Matthay KK, et al. Opsoclonusmyoclonus-ataxia syndrome in neuroblastoma: histopathologic features — a report from the Children’s Cancer Group. Med Pediatr Oncol 2001;36:623-9. » Rosenblum MK. Paraneoplasia and autoimmunologic » injury of the nervous system: the anti-Hu syndrome. Brain Pathol 1993;3:199-212. 10:41 PM
  • • Many reports suggest that patients with paraneoplastic neurologic disorders have a better prognosis than patients with histologically identical tumors that are not associated with paraneoplastic neurologic disorders. » Altman AJ, Baehner RL. Favorable prognosis for survival in children with coincident opso-myoclonus and neuroblastoma. Cancer 1976;37:846-52. » Maddison P, Newsom-Davis J, Mills KR, Souhami RL. Favourable prognosis in Lambert- Eaton myasthenic syndrome and smallcell lung carcinoma. Lancet 1999;353:117- 8. 10:41 PM
  • Treatment • two treatment approaches • removal of the source of the antigen by treatment of the underlying tumor, and, • suppression of the immune response • Overall results disappointing in majority. 10:41 PM
  • Immunotherapy • Predominantly Ab mediated – Plasma exchange, IvIg, Corticosteroids • Example – MG, LEMS 10:41 PM
  • Immunotherapy • Predominantly T cell mediated • drugs such as tacrolimus or mycophenolate Mofetil » Albert ML, Austin LM, Darnell RB. Detection and treatment of activated T cells in the cerebrospinal fluid of patients with paraneoplastic cerebellar degeneration. Ann Neurol 2000;47:9-17 » Schneider C, Gold R, Reiners K, Toyka KV. Mycophenolate mofetil in the therapy of severe myasthenia gravis. Eur Neurol 2001; 46:7982. • Examples - paraneoplastic cerebellar degeneration with anti-Yo antibodies or encephalomyelitis with anti-Hu antibodies 10:41 PM
  • Recommended Regime • IVIG @ 0.5 gm/kg/day x 5 days • IV methylprednisolone @ 1 gm/day x 3days, • IV cyclophosphamide @ 600 mg/m-2 BSA X 1 day • Keime-Guibert F, Graus F, Fleury A, et al. Treatment of paraneoplastic neurological syndromes with antineuronal antibodies (Anti-Hu, Anti-Yo) with a combination of immunoglobulins, cyclophosphamide, and methylprednisolone. J Neurol Neurosurg Psychiatry 2000;68:479-82. 10:41 PM
  • • If there is evidence of improvement or stability, the treatment can be repeated three times at three-week intervals. • If the patient improves after the third treatment, maintenance treatment with – IVIG @ 0.5 gm/kg/day x 5 days – IV methylprednisolone @ 1 gm/day x 3days, – IV cyclophosphamide @ 600 mg/m-2 BSA X 1 day • Keime-Guibert F, Graus F, Fleury A, et al. Treatment of paraneoplastic neurological syndromes with antineuronal antibodies (Anti-Hu, Anti-Yo) with a combination of immunoglobulins, cyclophosphamide, and methylprednisolone. J Neurol Neurosurg Psychiatry 2000;68:479-82. 10:41 PM
  • • Tacrolimus @ 0.15 mg/kg/per day for 14 days, followed by 0.3 mg/kg/day for 7 days. • This regimen decreased the number of activated T cells in the spinal fluid but had no substantial effect on the clinical course. » Albert ML, Austin LM, Darnell RB. Detection and treatment of activated T cells in the cerebrospinal fluid of patients with paraneoplastic cerebellar degeneration. Ann Neurol 2000;47:9-17. 10:41 PM
  • • Most of the syndromes may have both arms, therefore preferable to block both. 10:41 PM
  • Outline for the Session • • • • • • • Introduction History and Evolution of knowledge Pathogenesis – Concept of ―Onconeural‖ Antigen Definition – Terminology Criteria for Diagnosis Individual Syndromes Summary
  • 10:41 PM
  • Summary, take home points • Paraneoplastic syndromes are rare • Often precede the diagnosis of cancer • Thought to result from cross-reactivity of antibodies to a common antigen within tumor and nervous tumor • Disability persists despite treatment of underlying tumor 10:41 PM
  • 10:41 PM