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Paraneoplastic Neurological Syndromes

Neurological syndromes of unknown cause that often

associate with cancer

Immune-mediated?

Onconeural antibodies

•Hu (ANNA1)

•CV2 (CRMP5)

•Amphiphysin

•Yo (PCA1)

•Ri (ANNA2)

•Ma2

• Tr

Lung

Breast, ovary

testis

Hodgkin

Classical syndromes• Encephalomyelitis• Limbic encephalitis• Subacute cerebellar degeneration• Opsoclonus-myoclonus• Subacute sensory neuronopathy• Gastrointestinal pseudoobstruction• Lambert-Eaton myasthenic syndrome• Dermatomyositis

A 61 year-old, non smoker, woman presented with a 2 week history of vertigo, diplopia, and gait instability.

Unable to walk or to stand alone in the last 48 hours

Detection of onconeural (Hu, Yo, Ri, Ta, Tr, CV2, amphiphysin) antibodies: negative

CSF: Normal;

Brain MR: Normal

Breast Cancer

A 75 year-old man presented with a 6-month history of weight loss (10 Kg) and abnormal movements

No previous medical problems

- May ’05: Admitted to Hospital Clinic

Normal general examination

Cognitive evaluation: Normal

Neuroexam: Normal except video

Blood analysis: Normal

Cranial MR: Normal

Thorax CT scan:

enlarged mediastinal lymph node

Node biopsy: SCLC

Diagnosis: CV2-associated chorea

A 50 year-old man presented with a 13-month history of pruritus in left leg and trunk and progressive muscle rigidity and spasms in the same distribution

Previous medical problems: Type 2 DM

- April ’05:Normal general examination

Neuroexam: Rigidity in both legs L>R (video) and lower trunk.

Blood and CSF analysis, cranial and spinal MR : Normal

Anti-GAD antibodies: negative

EMG:Continuous motor unit discharges simultaneously from opposite muscles

Mediastinoscopy and biopsy showed normal lymph node

Patient made an important improvement of rigidity with oral steroids and IVIG

September ’05: severe pruritus involving left leg and trunk. More rigidity in left leg. Development of myoclonus (video) and rigidity in right arm.

A new thorax CT: enlarged lymph nodes in mediastinum

Biopsy: SCLC

Diagnosis:

Paraneoplastic SMS and spinal myoclonus

Amphiphysin antibody: positive

A 76 year-old man presented with a 1 weekhistory of progressive confusion and severe memory deficit

-August’04: Admitted to Hospital Clinic

Normal general examination

Neuroexam: Disoriented,severe short-term memory deficit with confabulations.

Detection of onconeural (Hu, Yo, Ri, Ta, CV2, amphiphysin) and VGKC antibodies: negative

CSF: Normal; Brain MR: Normal

General autopsy: SCLC CNS: neuronal loss in hippocampus with inflammatory infiltrates. Study of herpes virus: negative

Diagnosis:

Seronegative limbic encephalitis

Anti-GABAR-B1 LCR Co-localización

Antibodies against neuronal surface antigens

• Probably pathogenic

•Markers of the neurological syndrome

•Frequency of cancer variable

• Good response to immunotherapy

Antibodies against neuronal surface antigens

Ab Syndrome % paraneo DetectionVGCC LEMS/PCD 50 RIAmGluR1 PCD 0? CBAVGKC LE 5 RIANMDAR Encephalitis 30 CBAAMPAR LE 70 CBAGABAR LE 47 CBA

LEMS: Lambert-Eaton; LE: limbic encephalitis; PCD: Paraneoplastic cerebellar degeneration. RIA: radioimmunoassay; CBA: “cell based assay”

A 68 year-old man presented with a 2-month history of progressive gait instability and mild memory deficit

No previous medical problems

- May ’05: Admitted to Hospital Clinic

Normal general examination

Cognitive evaluation: mild short-term memory deficit

Neuroexam: Normal except gait (video)

Blood analysis: Normal

Cranial MR: Questionable LE

Highest-level gait disorders

• Cautious gait• Subcortical disequilibrium• Frontal disequilibrium• Isolated gait ignition failure• Frontal gait disorder

Nutt et al. Neurology 1993;43:268-79

PET PET-CT