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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