Paraneoplastic encephalitis

Rare: occurs in ą 1 % of cancer patients. Onconeuronal autoantibodies are directed against neural proteins and are responsible for paraneoplastic syndromes such as limbic encephalopathy, cerebellar ataxia or peripheric sensory neuropathies (Denny-Brown) classically associated with a small cell lung cancer but also with other cancers (breast, uterus, Hodgkin or non-Hodgkin lymphoma). The neurological signs often precede the discovery of cancer, and in some cases, the causal tumor may not be found. The current hypothesis is that these antibodies are a sign of an immune reaction against antigens common to the tumor and to the neural cells. Patients with these antibodies usually have a better prognosis to treatment and better survival. The vital risk associated with paraneoplastic syndrome may be greater than that associated with the initial tumor as if the autoimmune reaction persisted after tumor regression.

These antibodies are usually IgG that are found in blood or CSF.

Two types of antibodies can be distinguished:

- group I: onconeural antibodies with an intracellular target (nuclear or cytoplasmic)

- group II: onconeuronal antibodies with the cell membrane as target, as in the Lambert Eaton syndrome (see this term) (in italics in the table).

The main onconeuronal antibodies are:

autoimmune antibodies	possible paraneoplastic involvements	tumor
Anti-Hu (ANNA-1)	Encephalomyelitis, myelitis, cerebellar degeneration, sensory neuropathy	small cells bronchial cancer, neuroblastoma, prostatic cancer, rhabdomyosarcoma
Anti-Yo (PCA-1)	cerebellar degeneration	gynecologic or breast cancer
Anti-Ri (ANNA-2)	cerebellar degeneration, opsonias-myoclonias, brainstem encephalitis	gynecologic or breast cancer, small cells bronchial cancer
Anti-CV2/CRMP5	cerebellar degeneration, encephalomyelitis, chorea, uveitis, optic neuritis, peripheric neuropathy	small cells bronchial cancer, thymoma
Anti-Ma1 ou Ma2	limbic, hypothalamic or brainstem encephalitis, cerebellar degeneration	testicular germinal tumor, small cells bronchial cancer
Anti-amphiphysin	stiff man, encephalomyelitis, myelopathy	small cells bronchial cancer
Anti-Tr	cerebellar degeneration	Hodgkin
Anti-Zic4	cerebellar degeneration	small cells bronchial cancer
mGluR1	cerebellar degeneration	Hodgkin
ANNA-3	varia	small cells bronchial cancer
PCA2	varia	small cells bronchial cancer
Anti NR1/NR2 of the NMDA receptor	limbic encephalitis	teratoma (ovarian)
Anti-VGKC	limbic encephalitis, peripheric nerves hyperexcitability	thymoma, small cells bronchial cancer
Anti-VGCC	Lambert-Eaton Syndrome, cerebellous degeneration	small cells bronchial cancer
Anti-AChR	myasthenia	thymoma
Anti-nAChR	subacute dysautonomia	small cells bronchial cancer
Anti-AMPAR	limbic encephalitis	small cells bronchial cancer
Anti-GABA-A	limbic encephalitis	small cells bronchial cancer
Anti-Gly-R	encephalomyelitis with rigidity	thymoma
Anti-GAD	stiff man, cerebellous ataxia, partial epilepsy, limbic encephalitis	thymoma

The term 'paraneoplastic limbic encephalitis' is often referred to: limbic defines the preferential anatomical location of the lesions ie the cerebral structures located around the diencephalus (hippocampus, temporal amygdala, cingular gyrus, septum ganglia, mamillary bodies, etc ...).

Clinical presentation:

- convulsions

- progressive memory impairment (which can progress to dementia)

- psychiatric manifestations: depression, personality changes, loss of social inhibition, paranoid ideation, hallucinations.

- ataxia and dystonia,

- tremors, hypersomnia,

- keep that diagnosis in mind in the presence of an acute encephalitis with no identified infectious origin

- common characteristics: rapid progression of the neurological symptoms and presence of signs of inflammation in the CSF (pleiocytosis, hyperproteinachia, IgG)

Treatment: removal of the tumor associated with corticosteroids, immunoglobulins, plasmapheresis.

Anesthetic implications:

according to the primary tumor and the neurologic symptomatology.

References :

- de Broucker T.
Encéphalites paranéoplasiques et autoimmunes : quand y penser, comment en faire le diagnostic ?
Réanimation 2011 ; 242-50

Updated: January 2020