Paraneoplastic syndrome

Neurologic paraneoplastic syndrome evolves in about 1% of oncologic diseases but it’s not locally connected with tumor or metastatises. This syndrome is caused by antibodies synthesized against tumor antigens and metabolites.

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Antibodies are attacking tumor cells but due to tumor’s similarity to neural cell’s antigens they causing autoimmune reactions with specific neural structures like presynaptic and postsynaptic membrane’s receptors, ion canals and cell’s components. Despite this, 40% of patients with paraneoplastic syndrome have no any detectable specific antibodies in their blood.

Depending on the part of nervous system affected evolves specific paraneoplastic syndrome.

Localization of pathology Classical paraneoplastic syndromes Non-classical paraneoplastic syndromes
Brain, cranial nerves and retina
  • Cerebellar degeneration
  • Limbic encephalitis
  • Opsoclonus-myoclonus
  • Neoplasia associated retinopathy
  • Partial seizures (focal encephalitis)
  • Hypothalamic encephalitis
  • Brainstem encephalitis
  • Chorea
  • Parkinosonims
  • Optical neuritis
  
Spinal cord -
  • Necrotic myelopathy
  • Subacute motor neuropathy
  • Stiff-person syndrome
Anterior horns of spinal cord - Motor neuron disease
Posterior horns of spinal cord
  • Subacute sensory polyneuropathy
  • Chronic sensory polyneuropathy
  • Subacute and chronic senorymotor polyneuropathy
  
Neuromuscular synapse
  • LEMS
  • Neuromyotonia
 Myasthenia gravis
Peripheral nerves and muscles
  • Dermatomyositis
  • Polymyositis
  • Nerve’s and muscle’s vasculitis
  
Multiple localization
  • Encephalomyelitis
  

 

There are three autoimmune neuromuscular diseases known to evolve as a paraneoplastic syndrome: 1) myasthenia gravis, 2) Eaton-Lambert syndrome, 3) neuromyotonia. In 30% tymoma or less often carcinoma of thymus is the causative agent of paraneoplastic syndrome in case of myasthenia gravis. Small cell lung cancer tend to cause paraneoplastic Eaton-Lambert syndrome, in turn neuromyotonia as paraneoplastic syndrome usually  is caused by tymoma (20%), prostate cancer, small cell lung cancer, breast cancer or Hodgkin’s disease.

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Diagnosis

If patient have a diagnosed tumor and some of syndromes mentioned above then specific antibodies should be determined. If antibodies are positive you have the diagnosis. But in case of paraneoplastic syndrome without a tumor and negative antibodies, extensive diagnostic workup should be started to find or exclude an oncologic process.

Diagnostic difficulties

Myasthenia gravis considered being a young people disease this is not right because parallel to young –onset form (before 50), late onset form exists (after 50 years).

Palpebral ptosis, diplopia, facial muscle pathologic fatigability, articulation difficulties are the main complaints which are easy seen in a young patient. Elderly patients tend to have non-horizontal eye opening, palpebra loses its elasticity and pouches under the eyes are seen all those changes are masking signs of ocular myasthenia.

Diplopia is difficult to evaluate because of frequent comorbidity with macular degeneration or cataract in elderly.

Slurred speech, hoarse voice, inability to swallow, accompanied by arterial hypertension, coronary artery disease and other risk factors are misdiagnosed as a stroke.

Therapy

Therapeutic effectiveness depends on early diagnosis and treatment of a tumor. If tumor is found and paraneoplastic syndrome proven then tumor centered therapy is necessary (resection, radiation therapy, chemotherapy), as also, paraneoplastic syndrome specific therapy with immunosuppressant, immunomodulation and symptomatic treatment is necessary.

If patient suffering from paraneoplastic syndrome but tumor is not diagnosed immunotherapy should be more aggressive administering steroids, cyclophosphamide, cyclosporine, plasmapheresis and/or IVIG.