|Year : 2021 | Volume
| Issue : 1 | Page : 5-6
Editorial commentary: Paraneoplastic syndromes
Sarosh M Katrak
Professor Emeritus, Department of Neurology, Grant Medical College & Sir J.J. Group of Hospitals, Mumbai, India
|Date of Submission||30-Oct-2020|
|Date of Acceptance||18-Nov-2020|
|Date of Web Publication||16-Feb-2021|
Prof. Sarosh M Katrak
419 D. K. Sandu Marg, Chembur, Mumbai-400 071
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Katrak SM. Editorial commentary: Paraneoplastic syndromes. Ann Indian Acad Neurol 2021;24:5-6
Paraneoplastic syndromes (PNS) are a group of clinically heterogenous neurological syndromes which share a common pathogenesis of immune-mediated neuronal degeneration triggered by distal neoplasm. In the majority of cases, antibodies (Ab) against intracellular antigen (Ag) are expressed by the tumour and central nervous system (CNS)—onco-neural Ab—and are detected in the serum and cerebrospinal fluid (CSF).
PNS are rare and are present in less than 1% of cancer patients. They usually present to the neurologist as the neurological syndrome precedes the detection of the tumour in the majority of cases. Phenotypes involving the central, peripheral, and rarely the autonomic nervous systems have been described. In 2004 Graus et al. formulated diagnostic criteria and basically divided them into classical and non-classical syndromes. The classical syndromes were the ones described initially, occur more commonly, are clinically well established and have well characterized Ab, e.g., Progressive cerebellar degeneration with Anti-Hu or Anti-Yo antibodies. On the other hand, non-classical syndromes: brain-stem encephalitis—are usually caused by other diseases, amongst which a tumour-triggered immune response is only one of the possibilities. Myasthenia gravis and tumour-associated acquired neuro-myotonia are considered PNS involving the peripheral nervous system.
Another problem with PNS, is that more than one-third of the patients have more than one Ab expressed by the neoplasm and that some of the antibodies may be expressed in low titres in individuals with a tumour but without a PNS. To compound the problem further, the same Ab can produce more than one syndrome e.g., Anti-Hu Ab can produce a progressive cerebellar degeneration as well as a sub-acute sensory neuropathy. These points stress the importance of doing a panel of Abs even in classical syndromes.
As mentioned earlier, the classical syndromes have a high likelihood of paraneoplastic etiology with an underlying cancer, whereas non-classical syndromes are rarely associated with cancer. Hence, quoting Rosenfeld and Dalmau “….in the right clinical context, the detection of paraneoplastic Abs in the serum and CSF helps to diagnose the PNS and focuses the search for the neoplasm.” The “right clinical context” is a sub-acute (6-12 weeks) relentlessly progressive syndrome with simultaneous or tandem involvement of the central and peripheral nervous system and a high risk of neoplasm (elderly individual, heavy smoker, significant weight loss and an afebrile problem). Imaging studies are important to exclude differential diagnosis like meningeal infection, metastatic spread or complications related to chemo- or radiation therapy. The CSF in PNS of the central nervous system suggests an inflammatory process—increased protein concentration with pleocytosis. Importantly the glucose content is normal.
The diagnosis of PNS is classified as definite or possible based on the syndrome (classical or non-classical), Anti-bodies (present/absent, well/partially characterized) and tumor (present/absent). The diagnosis is definite in (1) a classical syndrome with a tumor and presence/absence of Abs (2) a classical syndrome without a tumor but with well characterized Abs and (3) a non-classical syndrome with a tumor and presence of Abs or improvement in clinical status after resection of the tumor. The diagnosis is possible when there is (1) a classical syndrome in the absence of a tumor or Abs but with a high risk of cancer (2) a classical/non-classical syndrome in the presence of partially characterized Abs but no tumor (3) a non-classical syndrome in the presence of a tumor but no Abs.
Although any tumour can produce a PNS, the most common tumors are small-cell lung cancer (SCLC), cancers of the breast and ovaries, thymomas, neuroblastomas, and plasma-cell tumors.
Most of the literature on PNS has come from Europe and the USA. There are very few documented case series from India.,, Hence it is very heartening to note that Vijayaraghavan A, et al. have reported a series of 97 patients with classical and non-classical PNS studied over an 11 year period. Importantly a definite diagnosis was achieved in 76.3% of their cases. An interesting feature was a practically even distribution between central (51.4%) and peripheral (47.6%) nervous system PNS. The onset to diagnosis, as expected, was shorter in the classical syndromes and in those with a tumor. Progressive cerebellar degeneration was the most common syndrome and occurred in combination with other PNS in 12.3% of their cases. Lung and ovarian cancers were the most common in this cohort. Contrary to the western literature, the most frequent well-characterized Abs were anti-Yo and anti-Ma2 antibodies. A surprising finding was an initial improvement in 53 patients at 6 months follow-up. Unfortunately, 19 of these patients subsequently deteriorated with progression of the tumor. The limitation of this study is that it is retrospective, the Ab screening could not be done in 29 patients (perhaps in the initial years of their study) and the recently characterized Abs like DPPX were not studied. In spite of all these limitations, this study should be considered as a seminal study of PNS in India.
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