1 1 Paraneoplastic Paraneoplastic Antibodies Antibodies in Clinical Practice in Clinical Practice Mohammed El Mohammed El lahawi lahawi New Cross Hospital New Cross Hospital Wolverhampton Wolverhampton
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ParaneoplasticParaneoplastic Antibodies Antibodies in Clinical Practicein Clinical Practice
Mohammed El Mohammed El lahawilahawiNew Cross HospitalNew Cross Hospital
WolverhamptonWolverhampton
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Effects of NeoplasmEffects of Neoplasm
• Direct mass ( pressure ) effect
• Metastasis effect
• Remote effect
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The Nervous SystemThe Nervous System
1- Central NS :- Brain - Cranial Nerves- Cerebellum- Spinal Cord
2- Peripheral NS :- Peripheral nerves- Neuromuscular junctions
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The Nervous SystemThe Nervous System
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The BrainThe Brain
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The BrainThe Brain
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Tumours presentationsTumours presentations
• Directly from the tumour
• Remote effect from the tumour
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Tumours of the Nervous SystemTumours of the Nervous System
• Primary tumours
• Secondary tumours ( metastatic )
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Spinal cord tumourSpinal cord tumour
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ParaneoplasticParaneoplastic Syndromes Syndromes --DefinitionDefinition
(…….. Are a group of a rare degenerative disorders that are triggered by a person’s immune system response to a neoplasm ….. )
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PNS PNS -- DefinitionDefinition
(..….Clinical manifestations or “remote effect “ produced by a tumour at a site different from the tumour itself or its metastasis ……. )
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Neurological Neurological -- PNSsPNSs
( These occur when cancer fighting antibodies or white blood cells – T cells –mistakenly attack normal cells in the nervous system …… )
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PNSPNS
• First paraneoplastic anti-neural antibody was reported in 1965
• Typically affect middle-aged to elderly people
• Neurological symptoms develop over a period of days to weeks
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PNS : when it happens ?PNS : when it happens ?
• Many months or years before the appearance of the symptoms or signs of the underlying cancer
• At the same time of the cancer• During the course of the cancer• When the cancer relapse• Rarely after treatment
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PNS PNS -- pathophysiologypathophysiology
( The tumour produce antibodies that create an immune reaction or an immune response in certain parts of the nervous system , leading to tissue damage and hence the clinical manifestation … )
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PNS PNS –– Which Tumours ??Which Tumours ??
• All tumours• Commonest tumours are :
~ lung~ Ovarian~ Lymphatic ~ Breast
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PNS PNS –– Which parts of NS Which parts of NS
# The brain# The Cerebellum# The peripheral nerves# The Neuromuscular junction# The eyes
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Neurological Neurological paraneoplasticparaneoplasticdiseasesdiseases
• Cerebellar ataxia and C degeneration• Lambert-Eaton myasthenic syndrome• Stiff person syndrome• Encephalomyelitis• Myasthenia gravis• Opsoclonus• Sensory neuropathy
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The CerebellumThe Cerebellum
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The CerebellumThe Cerebellum
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The CerebellumThe Cerebellum
• Forms about 10% of the brain weight• Responsible for co-ordination of almost all
fine and sophisticated movements
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The CerebellumThe Cerebellum
• The cerebellum form about 10% of the brain volume and occupied the posterior fossa
• The main function is co-ordination of all fine movements
• Main symptoms : ataxia , lack of coordination and difficulty in speech
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CerebellarCerebellar ataxiaataxia
• The cerebellum is commonly involved in the paraneoplastic process
• The commonest tumours are : lung , breast , genital and lympho- proliferative
• The symptoms and / or signs may precede the cancer by months or even years
• The cerebellum may appear normal in the scan• May be isolated or with involvement of other
parts of the nervous system
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CerebellarCerebellar AtaxiaAtaxia
• Before neoplasm• Gait disorder• Rapid progression over weeks to months,then
stabilization• Small ca of the lung : Hu or Calcium channel
antibodies• Ovarian :Yo antibody• Breast : Yo or Ri antibody• Hodgkins lymphoma
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CerebellarCerebellar ataxiaataxia
• May be from structural causes like :# tumours : primary or secondary# haemorrhage# infarction# multiple sclerosis# inflammation
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CerebellarCerebellar ataxiaataxia
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CerebellarCerebellar ataxiaataxia
( In any patient with cerebellar ataxia , specially elderly patients , when no obvious cause like : tumour, haematoma , infarction, genetic …… etc had been found paraneoplastic syndrome should be considered as the cause until proved otherwise ………….. )
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Neuromuscular junction disordersNeuromuscular junction disorders
• Myasthenia Gravis :- Neoplasm : Thymoma- Patients : > 25 years - Antibodies : * Antiacetylcholine
receptors antibodies * Anti – skeletal muscles
antibodies
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LEMS (LEMS (LambertLambert--EatonEaton)syndrome)syndrome
• Very similar to MG• Usually associated with small cell
carcinoma of the lung• Symptoms may precede the cancer by
weeks or months• Prognosis is not good
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StiffmanStiffman SyndromeSyndrome
• Tumour : usually breast• Other tumours : lung and thymoma• Antibodies : Amphiphysin
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EncephalopathiesEncephalopathies
• Limbic and Brain stem encephaloparhy• Male = Female• Tumour : small cell lung• Antibodies : Hu• Progressive over days to weeks• Memory loss, seizures, hallucinations lethargy ,
dysarthria and ataxia• Onset : 3 years before to 1 year after• Prognosis : poor
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Opsoclonus/MyoclonusOpsoclonus/Myoclonus syndromesyndrome
• Tumour : breast and lung• Onset age : 35 – 82• May be associated with ataxia ,myopathy
and peripheral neuropathy• In 15% of cases the tumour was
discovered before the syndrome• Good response to steroids