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Date post: 02-Oct-2015
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Paraneoplastic Neurological Syndrome: Approach and diagnosis
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Neurological Paraneoplastic Syndrome Abdallah Al-Ahaideb Supervised by Dr. Mona AlKhawajah
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Neurological Paraneoplastic Syndrome

Neurological Paraneoplastic SyndromeAbdallah Al-Ahaideb

Supervised by Dr. Mona AlKhawajahIntroductionHeterogeneous group of disorders caused by mechanisms other than metastases, metabolic, and nutritional deficits, infections coagulopathy or side effects of cancer treatmentMay affect any part of nervous systemCerebral cortex NMJ MuscleDamaging one area (purkinje cell, presynaptic cholinergic synapses)Multiple areas ( encephalomyelitis)

Remote effect of cancer on nervous system

Differ from non metastatic complications:Often precede identification of canceerTime of development, cancer often small and non metastaticNeurological disabilityIrreversiblePathogenesisNot understoodBelieved immunologic because ab and T cell responseDirected against antigens that are ectopically expressed by tumorImmune system identifies these antigen as foreign and mount immune reaction against themT cell response to normal protein in cancer cellSuggest different expression of self antigen protein in cancer cellsAb can be detected in serum and CSF of many neoplastic syndromesSmall cell lung cancer accounts for a disproportionate number of variety of paraneoplasticFeatures:Subacute progression of over weeks to monthsSevere neurologic disabilityCSF often with cells IgG and OCBs

Direct pathogenic effect on target neuronal neuromuscular antigensP/Q type voltage gated calcium channel ab in LEMSACH receptor ab in MGNMDA receptor NR1 ab in anti NMDAR encephalitisAMPA receptor (GluR1/2) ab in subgroup of limbic EncephalitisGanglionic ACH receptor ab in autonomic neuropathyRecoverin ab in carcinoma associated retinopathy

Possible pathogensis:

Diagnostic criteriaDefiniteClassical syndrome and cancer that develops within five yearsNonclassical sx that resovles or significantly improves after cancer RxNonclassical sx with paraneoplastic ab and cancer that develops within five years of diagnosisNeurological syndrome classical or not with well characterized abPossibleClassical, no paraneoplastic ab, no cancer but high risk for a tumorNeurological sx partially characterized by abNonclassical no paraneoplastic abs and cancer present within 2 yrs of dx

Antibody screeningCSF may reveal antibody undetected in serumWell characterized and described in a table previouslyImportant tenents:P/Q type voltage gated ca channel or ACH receptor ab with specific disorders do not differentiate between paraneoplastic and non paraneoplastic cases e.g., stiff person syndrome associated with GAD or amphiphysinSerum of cancer patients without paraneoplastic neurologic sx may contain paraneoplastic ab although titers are usually lowerDifferent ab can be associated with the same paraneoplastic and conversely also that different paraneoplastic with same antibodySeveral paraneoplastic antibodies may co-occur in the same patientsOther diagnosticsCan be difficult when antibodies not detectedAbsence of ab does not exclude paraneoplastic syndromeSeveral diagnostic tests are helpful:MRI: limbic encephalitis because medial temporal lobe show increased FLAIRParaneoplastic cerebellar degeneration may develop atrophy significant on MRIPET: fluorodeoxyglucose will occasionally identify hypermetabolism of medial temporal lobe with limbic encephalopathyLP: detection of AB confirms diagnosis, anti-Tr antibodies and patients with antibodies to antigen expressed in the cell membrane of neurons of the neuropil of hippocampus ANTI NMDA receptor titres in the CSF but not serumElectrophysiology: LEMS, myasthenia gravis, neuromyotonia, dermatomyositisCancer search: Lung with LEMS, thymus with MGOccult malignancyNot uncommon to develop before cancer is identifiedAntibody suggest specific underlying tumorAided with best radiography to diagnose tumorPET scan for small occult neoplasmsHowever negative PET/CT does not R/O cancerWorkup done to R/O tumours is often carriedLEMS screening for two yearsIf found another cancer not related to specific paraneoplastic syndrome then search again till you find it haha!TreatmentTwo approaches:Removal of antigen source by treatment of underlying tumoursSuppression of immune systemLEMS and MG plasma exchange or IVIGAnti-B cell therapy rituximab for Ab mediated such as: stiff man sx, dermatomyositis anti Yo positive paraneoplatic cerebellar degeneration, and anti Hu antibody associated encephalomyelitisOncologic treatment and immunotherapy (immunomodulation, immunosuppression) can be beneficialImmunologic tx adjunct to oncologic should stratified accordinglyCorticosteriods IV IGImmunosuppressive cyclophosphamide, tacrolimus or cycosporine


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