Professional Documents
Culture Documents
• Carcinomas
– GU
– Lung • Prostate
• Small Cell
• Renal Cell
• Non-small Cell
• Testicular
– Gynecologic
• Ovarian
• Lymphomas
– Hodgkin’s Disease
• Fallopian tube
– Non-Hodgkin’s Disease
• Endometrial
• Breast • Miscellaneous
– GI – Sarcoma
• Colon – Carcinoid
• Gastric – Melanoma
• Esophageal – Thymoma/Malignant
• Pancreas Thymoma
Recognition of the associated cancer
Uterus, ovary
Recognition of the paraneoplastic antibodies
Clinical Syndrome Associated Tumour(s) Autoantibodies
Multifocal SCLC Anti-Hu (ANNA-1)
encephalomyelitis/sensory SCLC, others Anti-CV2 (CRMP-5)
neuronopathy SCLC, breast Anti-amphiphysin
Various carcinomas Anti-Ma
Cerebellar Degeneration Breast, ovarian, others Anti-Yo (PCA-1)
SCLC Anti-Hu (ANNA-1), PCA-2
SCLC, others Anti-CV2
Hodgkin’s lymphoma Anti-Tr, Anti-mGluR1
Breast carcinoma Anti-Ri (ANNA-2)
Various carcinomas Anti-Ma
Limbic encephalopathy SCLC Anti-Hu (ANNA-1), Anti-CV2, PCA-2, Anti-
amphiphysin
Testicular, breast Anti-Ta
Definite PND:
1. A classical syndrome and cancer that develops within five
years of the diagnosis of the neurological disorder.
2. A non-classical syndrome that resolves or significantly
improves after cancer treatment without concomitant
immunotherapy, provided that the syndrome is not susceptible
to spontaneous remission.
3. A non-classical syndrome with onconeural antibodies (well
characterized or not) and cancer that develops within five years
of the diagnosis of the neurological disorder.
4. A neurological syndrome (classical or not) with well
characterized onconeural antibodies (anti-Hu, Yo, CV2, Ri,
Ma2, or amphiphysin), and no cancer.
Diagnostic criteria for PND
Possible PND
1. A classical syndrome, no onconeural antibodies, no cancer
but at high risk to have an underlying tumour.
2. A neurological syndrome (classical or not) with partially
characterized onconeural antibodies and no cancer.
3. A non-classical syndrome, no onconeural antibodies, and
cancer present within two years of diagnosis.
Diagnostic criteria for PND
Neurological syndrome
Classical Non-Classical
breast/SCLC
Osteosclerotic myeloma
– Only 3% of myeloma, but ½ have ssociated
motor neuropathy
– POEMS syndrome (Polyneuropathy, rganomegaly,
Endocrinopathy, M protein, Skin changes)
Peak onset 40-60, more common in
Japanese
Other changes – thrombocytosis,
anasarca
– Rx – resect sclerotic lesion, radiation, prednisone, chemo
(melphalan, cyclophosphamide)
Lymphoproliferative disorders
– Paraprotein-associated, amyloid
deposition
– Dx through immunoelectrophoresis
detection of paraprotein, skeletal survey
(sclerotic lesion)
– CSF protein ↑
– Pathology: mixed axonal/demyelinating
Ocular Paraneoplastic Syndromes
Electroencephalogram
exclude herpes simplex encephalitis, non-
convulsive status and CJD. It may show
slowing over the temporal lobes or frontally in
limbic encephalitis and PEM
Electro-retinogram
is flat in most cases of paraneoplastic
retinopathy even though vision may be
retained. In melanoma-associated retinopathy
the dark adapted B wave has reduced
amplitude.
IMPORTANT TESTS TO NARROW THE DIFFERENTIAL DIAGNOSIS OF PND
Neurophysiology.
In paraneoplastic sensory neuropathy, nerve
conduction usually confirms the sensory neuropathy
with reduced amplitude of SNAP in the presence of
normal motor amplitudes and conduction.
Tensilon test
is not usually necessary although it is sometimes
positive in LEMS, but seldom dramatically. It may give
some idea of how the patient might respond to
pyridostigmine.
Biopsies.
Brain biopsy is seldom indicated except perhaps in
some antibody negative cases to exclude cerebral
vasculitis or intravascular lymphoma. Sural nerve
biopsy is very rarely needed to exclude vasculitis,
demyelination or lymphomatous infi ltration of the
nerves. Muscle biopsy may exclude myositis or
myopathy in the occasional diffi cult case.
TREATMENT
Approach to treatment :
PND of the CNS
*For all paraneoplastic neurologic syndromes, initial treatment should focus on detecting and
treating the tumor.
**Immunosuppression includes steroids and azathioprine.
ACTH—adrenocorticotropic hormone; IVIG—intravenous immunoglobulin.
Pharmacologic treatment
• Immunosuppressive treatments are used for those
PND in which the antibodies are directly pathogenic,
such as LEMS.
Prednisone
Azathioprine
Standard dosage 2 to 3 mg/kg. Dose is adjusted to leukocyte
and platelet counts.