The comments of Sanjeev Chawla et al are interesting. Their previous report on the study of fertility assessment of hydatid cysts included only two patients with cerebral cysts and it is also not clear whether the cysts were fertile or sterile (1). This may be important, since local tissue response to cyst infestation, which is different between tissues, may determine variations in cyst viability. Hence the results of the study of liver hydatid cysts may have to be extrapolated to that of the brain with caution. Their observation that succinate and not pyruvate should be considered the marker of cestodal infestation is based on the support of the works of Kreis et al (2) and Wilker et al (3). It is obvious that the only supportive evidence of the presence of succinate in parasitic fluid we have is that of Kreis et al (2) who presented the evidence of the 13C chemical shift of 34 ppm for succinate. But it by no means disproves the possibility of the presence of pyruvate in a parasitic cyst given the varied course of the evolution and degeneration of different kinds of parasitic cysts in the brain. In addition, the 13C chemical shift of 34 ppm may be due to other additional metabolites and not necessarily of only succinate (4). These include glucose (34.7 ppm and 2.34 ppm) and β-alanine (34.8 ppm and 2.5 ppm) (4). Given the reports of the presence of large quantities of glucose (1) and the possibility of an active amino acid metabolism (1), it is likely that the resonance attributed to succinate could as well be due to glucose and alanine. The metabolic reasons adduced by Garg et al (1) to account for the presence of succinate are in many ways simplistic. They explain the presence of succinate based on an active Krebs cycle, which may not be efficient in the first place, given the hypoxic state in the “walled-off” parasitic cyst that may only further worsen with degeneration. Specifically, 1) they themselves quote that more carbon being directed towards oxaloacetate (OAA) than pyruvate under in vivo conditions is speculative and therefore all further discussion regarding subsequent metabolic pathways remains unsubstantiated (1). 2) Conversion of phosphoenolpyruvate (PEP) to OAA requires high-energy phosphates (adenosine triphosphate [ATP]) and is therefore unlikely to be the preferred mechanism under hypoxic conditions (5). 3) PEP to OAA conversion is catalyzed by phosphoenolpyruvate carboxykinase, which is inhibited by antihydatid drugs (1). However, PEP accumulation has not been demonstrated in studies so far. 4) The worm is in a hypoxic state and hypoxia would definitely affect the Krebs cycle as much as the glycolytic pathway. Therefore, it is possible that PEP more likely goes to form pyruvate, which in turn goes on to form lactate or OAA, which is again converted to PEP (6). 6) Phosphoenolpyruvate creatinine kinase (PEPCK) is the key enzyme of gluconeogenesis and there is no evidence to suggest that gluconeogenesis plays an important role in parasitic metabolism (5). 7) In the Krebs cycle, conversion of α-ketoglutaric acid to succinyl coenzyme A (Co-A) requires the presence of cofactors like thiamine diphosphate, lipoate, NAD, FAD, and Co-A with the formation of a high-energy bond (6). In the state of mitochondrial hypofunction due to hypoxia and the likelihood of nutritional deprivation of the degenerating worm in the brain parenchyma, it is highly unlikely that succinate would be formed from α-ketoglutarate (6). 8) The absence of malate and fumarate in some infertile parasitic cyst fluids in earlier studies are based almost exclusively on hydatid cysts of the liver (1) and would require confirmation on human cerebral parasitic cysts. Hence, we believe that while there is currently not enough evidence to support the concept of the exclusive presence of succinate, the possibility of pyruvate, glucose, and alanine remain. PN Jayakumar MD, MNAMS Professor and Head*, * Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences, Bangalore, India.
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Sep 1, 2005
K J Emmertsen + 3
Open Access
