Criteria of Graus et al for the Likelihood of a Paraneoplastic Neurological Syndrome (PNS)

 

Classical PNS:

(1) encephalomyelitis

(2) limbic encephalitis (targeting the hippocampus and amygdala)

(3) subacute cerebellar degeneration (targeting Purkinje cells)

(4) opsiclonus myoclonus

(5) subacute sensory neuropathy (targeting dorsal root ganglia)

(6) chronic gastrointestinal pseudo-obstruction (targeting the myenteric plexus)

(7) Lambert-Eaton myasthenic syndrome

(8) dermatomyositis

 

Nonclassical PNS:

(1) brainstem encephalitis (targeting the medulla oblongata)

(2) optic neuritis

(3) cancer-associated retinopathy

(4) melanoma-associated retinopathy

(5) stiff person syndrome

(6) necrotizing myelopathy

(7) motor neuron disease (targeting motor neurons in the anterior horn)

(8) Guillain-Barre syndrome

(9) brachial neuritis

(10) subacute or chronic sensorimotor neuropathies

(11) neuropathy with paraproteinemia

(12) neuropathy with vasculitis

(13) acute pandysautonomia

(14) myasthenia gravis

(15) acquired neuromyotonia

(16) acute necrotizing myopathy

 

Parameters for diagnosis:

(1) classical vs nonclassical

(2) cancer diagnosis present or absent or high risk

(3) onconeural antibodies

(4) clinical change after cancer therapy

Type	Cancer Diagnosis	Onconeural Antibodies	Change with Therapy	Diagnosis
classical	present	NA	NA	definite
classical	high risk	absent	NA	possible
classical	absent	present, well characterized	NA	definite
classical	absent	present, partially characterized	NA	possible
nonclassical	present	present	NA	definite
nonclassical	present	NA	improved	definite
nonclassical	present	absent	not improved	possible
nonclassical	absent	present, well characterized	NA	definite
nonclassical	absent	present, partially characterized	NA	possible

 

where:

• The appearance of a paraneoplastic syndrome may precede the clinical diagnosis of cancer. For a definite PNS with classical syndrome this period can be 5 years.

• Improvement after cancer therapy cannot be explained by spontaneous remission or concomitant immunotherapy.

• Well-characterized antibodies are anti-Hu, anti-Yo, anti-CV2, anti-Ri, anti-Ma2 and anti-amphiphysin.