Download Paraneoplastic Antibodies in Clinical Practice

Paraneoplastic Antibodies
in Clinical Practice
Mohammed El lahawi
New Cross Hospital
Wolverhampton
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Effects of Neoplasm
• Direct mass ( pressure ) effect
• Metastasis effect
• Remote effect
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The Nervous System
1- Central NS :
- Brain
- Cranial Nerves
- Cerebellum
- Spinal Cord
2- Peripheral NS :
- Peripheral nerves
- Neuromuscular junctions
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The Nervous System
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The Brain
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The Brain
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Tumours presentations
• Directly from the tumour
• Remote effect from the tumour
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Tumours of the Nervous System
• Primary tumours
• Secondary tumours ( metastatic )
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Spinal cord tumour
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Paraneoplastic Syndromes Definition
(…….. 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 - Definition
(..….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 - PNSs
( These occur when cancer fighting
antibodies or white blood cells – T cells –
mistakenly attack normal cells in the
nervous system …… )
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PNS
• 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 ?
• 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 - pathophysiology
( 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 – Which Tumours ??
• All tumours
• Commonest tumours are :
~ lung
~ Ovarian
~ Lymphatic
~ Breast
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PNS – Which parts of NS
# The brain
# The Cerebellum
# The peripheral nerves
# The Neuromuscular junction
# The eyes
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Neurological paraneoplastic
diseases
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Cerebellar ataxia and C degeneration
Lambert-Eaton myasthenic syndrome
Stiff person syndrome
Encephalomyelitis
Myasthenia gravis
Opsoclonus
Sensory neuropathy
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The Cerebellum
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The Cerebellum
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The Cerebellum
• Forms about 10% of the brain weight
• Responsible for co-ordination of almost all
fine and sophisticated movements
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The 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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Cerebellar ataxia
• 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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Cerebellar Ataxia
• 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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Cerebellar ataxia
• May be from structural causes like :
# tumours : primary or secondary
# haemorrhage
# infarction
# multiple sclerosis
# inflammation
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Cerebellar ataxia
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Cerebellar ataxia
( 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 disorders
• Myasthenia Gravis :
- Neoplasm : Thymoma
- Patients : > 25 years
- Antibodies : * Antiacetylcholine
receptors antibodies
* Anti – skeletal muscles
antibodies
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LEMS (Lambert-Eaton)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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Stiffman Syndrome
• Tumour : usually breast
• Other tumours : lung and thymoma
• Antibodies : Amphiphysin
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Encephalopathies
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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/Myoclonus syndrome
• 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
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