Paraneoplastic Neurologic Syndromes (PNS)
Paraneoplastic neurologic syndromes (PNS) are a group of conditions that affect the nervous system (brain, spinal cord, nerves and/or muscles) in patients with cancer. The term "paraneoplastic" means that the neurological syndrome is not caused by the tumor itself, but by the immunological reactions that the tumor produces. It is believed that the body’s normal immunological system interprets the tumor as an invasion. When this occurs, the immunological system mounts an immune response, utilizing antibodies and lymphocytes to fight the tumor. The end result is that the patient’s own immune system can cause collateral damage to the nervous system, which can sometimes be severe. In many patients, the immune response can cause nervous system damage that far exceeds the damage done to the tumor. The effects of PNS can remit entirely, although there can also be permanent effects.
Epidemiology
PNS are rare diseases occurring in less than about 0.01% of patients with cancer. Only the Lambert-Eaton myasthenic syndrome is relatively frequent, occurring in about 1% of patients with small-cell lung cancer
Classes : * Endocrine - can be related to :
> Cushing`s Syndrome
> Syndrome of Inappropriate Anti-Diuretic Hormone
> Hypercalcemia
> Hypoglycemia
> Carcinoid Hormone
> Polycythemia
> Hyperaldosteronism
* Neurological - can be related to :
> Lambert-Eaton myasthenic syndrome (LEMS)> Paraneoplastic cerebellar degeneration
> Encephalomyelitis
> Limbic encephalitis
> Brainstem encephalitis
>Paraneoplastic Opsoclonus (involving eye movement)-Myoclonus
> Anti-NMDA receptor encephalitis
> Polymyositis
Diagnosis and management
PNS may affect any part of the central and peripheral nervous system, the neuromuscular junction and muscle. They can be isolated or occur in association. An important point to keep in mind is that none of these disorders are specifically paraneoplastic, as each disorder can also occur in patients without cancer. The incidence of malignancy in patients with potential PNS varies depending on the disorder and ranging from 5 to 60%. In almost 80% of patients, the PNS antedates the diagnosis of cancer by several months to several years. Most tumors are diagnosed within 4–6 months. It is accepted that the risk of cancer development decreases significantly two years after diagnosing PNS and becomes very low after four years. All these data explain why it is often difficult to recognize a given neurological disorder as paraneoplastic.
Treatment
The different subtypes of PNS are defined by the presence or the absence of paraneoplastic antibodies and the type of antibodies. Management and treatment should be tailored to each subtype. For example, patients with SCLC and PCA have different course of the neurological disorder, response to treatment, tumor prognosis and cause of death, according to the presence or the absence of Hu-Ab. Patients with Ma2-Ab generally develop limbic and brainstem encephalitis with testis tumors, but patients with Ma2-Ab and additional antibodies directed against other Ma proteins develop additional cerebellar symptoms and have tumors other than testis neoplasms. The mean survival time for patients with SCLC and CV2-Ab is 2.5 times longer than for patients with the same cancer, similar neurological symptoms and Hu-Ab. All these data suggest that the type of the immunological stimulation against the tumor can determine a specific course of the neurological disorder and give information of whether the immunological response against the tumor is more or less effective.
However, PNS rarely improves with immunomodulatory treatment as in the majority of cases the neurological symptoms are due to neuronal damage. The early and non-reversible destruction of neural structures by the inflammatory process accounts for both the severity of most PNS and for the usual ineffectiveness of immunomodulatory treatments. The best chance of at least stabilizing the syndrome is to induce a complete response of the tumor. Although immunotherapy is rarely effective, the use of intravenous immunoglobulins, steroids or plasmapheresis is indicated because a few patients have been reported to improve with these treatments. Patients with Tr-Ab and Ma2-Ab and testicular cancer are more likely to improve than those with other antibodies.
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