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=== Introduction ===

=== Introduction ===

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In this chapter prodromal symptoms and dreams related to poor prognosis of diseases- fatality are described. In the first verse, Charaka has emphasized that he will describe both common and special prodromal symptoms. This indicates that while there may be some prodromata which result out of normal pathogenesis, some are unusual and unexpected. In the next verse it has been said that if all prodromal symptoms are manifesting and are severe in nature then such a condition will be fatal. This principle is applicable to all other diseases also. Prodromal symptoms of ''kushta'' and ''prameha'' suggest that complications manifest before cardinal symptoms of the disease appear. If body metabolism in any disease is altered severely during latent phase of disease and complications are appearing before manifestation of full-fledged disease then such condition will be difficult to cure. Example of ''gulma'' suggests that there are certain diseases which are incurable in nature and prodromal symptoms related to such clinical conditions will always be precursors of imminent death. It is commonly seen that any person who is emaciated and have low immunity and strength, when affected by disease, has fatal consequences due to less resistance. This fact is explained with the example of ''shosha''. Another important aspect regarding disease prognosis is that, if a person is continuously partaking causative factors or is in constant exposure to the causative factors, body will be unable to fight disease properly and thus there will be less chances of recovery from the disease. This point is also mentioned while describing prognosis of ''shosha''.

In this chapter prodromal symptoms and dreams related to poor prognosis of diseases- fatality are described. In the first verse, Charak has emphasized that he will describe both common and special prodromal symptoms. This indicates that while there may be some prodromata which result out of normal pathogenesis, some are unusual and unexpected. In the next verse it has been said that if all prodromal symptoms are manifesting and are severe in nature then such a condition will be fatal. This principle is applicable to all other diseases also. Prodromal symptoms of ''kushta'' and ''prameha'' suggest that complications manifest before cardinal symptoms of the disease appear. If body metabolism in any disease is altered severely during latent phase of disease and complications are appearing before manifestation of full-fledged disease then such condition will be difficult to cure. Example of ''gulma'' suggests that there are certain diseases which are incurable in nature and prodromal symptoms related to such clinical conditions will always be precursors of imminent death. It is commonly seen that any person who is emaciated and have low immunity and strength, when affected by disease, has fatal consequences due to less resistance. This fact is explained with the example of ''shosha''. Another important aspect regarding disease prognosis is that, if a person is continuously partaking causative factors or is in constant exposure to the causative factors, body will be unable to fight disease properly and thus there will be less chances of recovery from the disease. This point is also mentioned while describing prognosis of ''shosha''.

From the above discussion it is clear that prodromal symptoms can be useful in predicting diagnosis of any disease. But now question arises whether it is practically possible to predict prognosis with prodromal symptoms? We should admit that it is very difficult and one will need years of experience to attain such competence. Another important fact is that the prediction of prognosis can be done from ''purvarupa'' only after disease manifestation. Charaka states that ''purvarupa'' converting into a particular disease in future can be termed a prognostic sign. This indicates that we cannot predict by only prodromal symptoms. We have to look into whether disease was produced after ''purvarupa'' or not. For example, delirium in ''raktapitta'' is indicator of poor prognosis. If delirium is seen in any patient but he is not developing ''raktapitta'' we cannot predict poor prognosis. In this condition, after manifestation of ''raktapitta'' we need to ask the patient whether he suffered from delirium before disease manifestation or not. It is a retrospective inquiry about ''purvarupa'' based on which a prospective prediction may be made. We will have to follow detailed retro-prospective approach and will need proper patient history comprising of each and every detail from prodromal symptoms to disease manifestation. Thus practically, prodromal symptoms are helpful only after disease manifestation as they are not independent. Since accompanying symptoms may also lead to predictions, they can also be regarded as tools of predictive prognosis. This might be the reason that Sushruta and Vagbhata have not described dreams in reference of ''purvarupa'' but have described in ''rupavastha'' (stage of disease manifestation).

From the above discussion it is clear that prodromal symptoms can be useful in predicting diagnosis of any disease. But now question arises whether it is practically possible to predict prognosis with prodromal symptoms? We should admit that it is very difficult and one will need years of experience to attain such competence. Another important fact is that the prediction of prognosis can be done from ''purvarupa'' only after disease manifestation. Charak states that ''purvarupa'' converting into a particular disease in future can be termed a prognostic sign. This indicates that we cannot predict by only prodromal symptoms. We have to look into whether disease was produced after ''purvarupa'' or not. For example, delirium in ''raktapitta'' is indicator of poor prognosis. If delirium is seen in any patient but he is not developing ''raktapitta'' we cannot predict poor prognosis. In this condition, after manifestation of ''raktapitta'' we need to ask the patient whether he suffered from delirium before disease manifestation or not. It is a retrospective inquiry about ''purvarupa'' based on which a prospective prediction may be made. We will have to follow detailed retro-prospective approach and will need proper patient history comprising of each and every detail from prodromal symptoms to disease manifestation. Thus practically, prodromal symptoms are helpful only after disease manifestation as they are not independent. Since accompanying symptoms may also lead to predictions, they can also be regarded as tools of predictive prognosis. This might be the reason that Sushruta and Vagbhata have not described dreams in reference of ''purvarupa'' but have described in ''rupavastha'' (stage of disease manifestation).

   

   

Biomarkers are recent advancements can be the answer to above problem as we do not need to wait for disease manifestation and can predict prognosis by seeing values of biomarkers related to that disease. In 2001, a consensus panel at the National Institutes of Health defined the term biomarker as ‘a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention or other health care intervention’.<ref>Torres-Bugarín O, Zavala-Cerna MG, Nava A, Flores-García A, Ramos-Ibarra ML. Potential Uses, Limitations, and Basic Procedures of Micronuclei and Nuclear Abnormalities in Buccal Cells. Disease Markers. 2014;2014:956835. </ref> Biomarker defined as alteration in the constituents of tissues or body fluids provide a powerful approach to understanding the spectrum of chronic disease with application in at least 5 areas like screening, diagnosis, prognostics, prediction of disease recurrence and therapeutic monitoring.<ref>Pradeep Sahu et al, Biomarkers: An Emerging Tool for Diagnosis of a Disease and Drug Development, Asian J. Res. Pharm. Sci. 2011; Vol. 1: Issue 1, Pg 09-16 </ref> The biomarker is either produced by the diseased organ (e.g., tumor) or by the body in response to disease. Before diagnosis, markers could be used for screening and risk assessment. Tumor classification, stage and sometimes grade are generally used to assess prognosis. Researches in the field of biomarkers may give us chance to know prognosis of disease in early stage.

Biomarkers are recent advancements can be the answer to above problem as we do not need to wait for disease manifestation and can predict prognosis by seeing values of biomarkers related to that disease. In 2001, a consensus panel at the National Institutes of Health defined the term biomarker as ‘a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention or other health care intervention’.<ref>Torres-Bugarín O, Zavala-Cerna MG, Nava A, Flores-García A, Ramos-Ibarra ML. Potential Uses, Limitations, and Basic Procedures of Micronuclei and Nuclear Abnormalities in Buccal Cells. Disease Markers. 2014;2014:956835. </ref> Biomarker defined as alteration in the constituents of tissues or body fluids provide a powerful approach to understanding the spectrum of chronic disease with application in at least 5 areas like screening, diagnosis, prognostics, prediction of disease recurrence and therapeutic monitoring.<ref>Pradeep Sahu et al, Biomarkers: An Emerging Tool for Diagnosis of a Disease and Drug Development, Asian J. Res. Pharm. Sci. 2011; Vol. 1: Issue 1, Pg 09-16 </ref> The biomarker is either produced by the diseased organ (e.g., tumor) or by the body in response to disease. Before diagnosis, markers could be used for screening and risk assessment. Tumor classification, stage and sometimes grade are generally used to assess prognosis. Researches in the field of biomarkers may give us chance to know prognosis of disease in early stage.

Another important aspect mentioned in this chapter is concept of dreams. The descriptions related to dreams are found abundantly in the ancient oriental classics, specifically the Atharvaveda, Upanishadas, Puranas, Darshanas and [https://en.wikipedia.org/wiki/Ayurveda Ayurveda]. The description of the ''doshika'' dreams of the Atharvaveda is similar to that in [https://en.wikipedia.org/wiki/Ayurveda Ayurveda]. Dreams are mentioned while describing ''purvarupa'', ''rupa'' and ''arishta lakshanas''.<ref>Sonali S. Tendulkar and R. R. Dwivedi, ‘Swapna’ in the Indian classics: Mythology or science?,Ayu. 2010 Apr-Jun; 31(2): 170–174. </ref> Sushruta states that sex of the unborn child can be predicted and Vagbhata says that ''doshika prakriti'' can be known by the help of dreams.

Another important aspect mentioned in this chapter is concept of dreams. The descriptions related to dreams are found abundantly in the ancient oriental classics, specifically the Atharvaveda, Upanishadas, Puranas, Darshanas and [https://en.wikipedia.org/wiki/Ayurveda Ayurveda]. The description of the ''doshika'' dreams of the Atharvaveda is similar to that in [https://en.wikipedia.org/wiki/Ayurveda Ayurveda]. Dreams are mentioned while describing ''purvarupa'', ''rupa'' and ''arishta lakshanas''.<ref>Sonali S. Tendulkar and R. R. Dwivedi, ‘Swapna’ in the Indian classics: Mythology or science?,Ayu. 2010 Apr-Jun; 31(2): 170–174. </ref> Sushruta states that sex of the unborn child can be predicted and Vagbhata says that ''doshika prakriti'' can be known by the help of dreams.

Subject of dreams is dealt in very scientific manner. According to Charaka, dreams occur when person is in relatively wakeful state. This has been proved now by the researches that dreams mainly occur in the rapid-eye movement (REM) stage of sleep—when brain activity is high and resembles that of being awake. In the late 19th century, psychotherapist Sigmund Freud developed a theory that the content of dreams is driven by unconscious wish fulfillment. Freud called dreams the "royal road to the unconscious”.<ref>Jeannette Y. Wick; Guido R. Zann, Drugs and Dreams, J Am Pharm Assoc (2003) 2002;42:385-390. </ref> To Freud, no dream was of entertainment value, they all held important meanings. Dreams reflect the dreamer’s mental, emotional, and physical state. This fact is well established in this chapter while describing classification of dreams. Dreams are based on our day to day interactions and so are classified as dreams seen, heard, felt etc. Two of the seven types, one which predict prognosis and one which is due to vitiation of ''doshas'' are said to have fatal consequences.

Subject of dreams is dealt in very scientific manner. According to Charak, dreams occur when person is in relatively wakeful state. This has been proved now by the researches that dreams mainly occur in the rapid-eye movement (REM) stage of sleep—when brain activity is high and resembles that of being awake. In the late 19th century, psychotherapist Sigmund Freud developed a theory that the content of dreams is driven by unconscious wish fulfillment. Freud called dreams the "royal road to the unconscious”.<ref>Jeannette Y. Wick; Guido R. Zann, Drugs and Dreams, J Am Pharm Assoc (2003) 2002;42:385-390. </ref> To Freud, no dream was of entertainment value, they all held important meanings. Dreams reflect the dreamer’s mental, emotional, and physical state. This fact is well established in this chapter while describing classification of dreams. Dreams are based on our day to day interactions and so are classified as dreams seen, heard, felt etc. Two of the seven types, one which predict prognosis and one which is due to vitiation of ''doshas'' are said to have fatal consequences.

Research studies are needed to prove that dreams can be used as markers of prognosis. Some studies have been conducted in this regard but we cannot make strong conclusion on basis of their results. In a few studies it has been shown that hormone levels affect dreams. One of the studies states that cortisol plays an important role in controlling the state of memory systems during sleep. High levels of cortisol, as are observed late at night and, typically in the context of REM sleep, disrupt normal hippocampal → neocortical communication, thereby interfering with forms of memory consolidation dependent upon this communication. At the same time, the content of dreams is also affected.<ref>Jessica D. Payne, Lynn Nadel, Sleep, dreams, and memory consolidation: The role of the stress hormone cortisol, Learning Memory 2004 November; 11(6): 671–678. </ref> In neurological and psychological diseases dream disturbances are often seen but few other diseases have also been found to affect dreams. Patients with sleep apnea are reported to have intense nightmares.<ref>J. F. Pagel, Carol Kwiatkowski, The Nightmares of Sleep Apnea: Nightmare Frequency Declines with Increasing Apnea Hypopnea Index, J Clin Sleep Med. 2010 February 15; 6(1): 69–73. </ref> Abnormal dreams have also been reported in diseases like Relapsing fever,<ref>Harrison’s-Principles of Internal Medicine-17th edition, The McGraw-Hill Companies, Inc, , Chapter 165. </ref> Cardiac ischemia<ref>Harrison’s-Principles of Internal Medicine-17th edition, The McGraw-Hill Companies, Inc, , Chapter 28. </ref> etc. Certain drugs also affect dreams e.g. Anti malarial drug has shown to alter dream types.<ref>Harrison’s-Principles of Internal Medicine-17th edition, The McGraw-Hill Companies, Inc, , Chapter 203. </ref> This proves that at times diseases certainly affect dreams but intense research studies are needed to actually establish this fact on scientific grounds.

Research studies are needed to prove that dreams can be used as markers of prognosis. Some studies have been conducted in this regard but we cannot make strong conclusion on basis of their results. In a few studies it has been shown that hormone levels affect dreams. One of the studies states that cortisol plays an important role in controlling the state of memory systems during sleep. High levels of cortisol, as are observed late at night and, typically in the context of REM sleep, disrupt normal hippocampal → neocortical communication, thereby interfering with forms of memory consolidation dependent upon this communication. At the same time, the content of dreams is also affected.<ref>Jessica D. Payne, Lynn Nadel, Sleep, dreams, and memory consolidation: The role of the stress hormone cortisol, Learning Memory 2004 November; 11(6): 671–678. </ref> In neurological and psychological diseases dream disturbances are often seen but few other diseases have also been found to affect dreams. Patients with sleep apnea are reported to have intense nightmares.<ref>J. F. Pagel, Carol Kwiatkowski, The Nightmares of Sleep Apnea: Nightmare Frequency Declines with Increasing Apnea Hypopnea Index, J Clin Sleep Med. 2010 February 15; 6(1): 69–73. </ref> Abnormal dreams have also been reported in diseases like Relapsing fever,<ref>Harrison’s-Principles of Internal Medicine-17th edition, The McGraw-Hill Companies, Inc, , Chapter 165. </ref> Cardiac ischemia<ref>Harrison’s-Principles of Internal Medicine-17th edition, The McGraw-Hill Companies, Inc, , Chapter 28. </ref> etc. Certain drugs also affect dreams e.g. Anti malarial drug has shown to alter dream types.<ref>Harrison’s-Principles of Internal Medicine-17th edition, The McGraw-Hill Companies, Inc, , Chapter 203. </ref> This proves that at times diseases certainly affect dreams but intense research studies are needed to actually establish this fact on scientific grounds.

*In present era we do not predict prognosis by prodromal symptoms except in few cases as prodromal symptoms are not exactly known in most of the diseases. Due to ambiguity, prodromal symptoms are not considered reliable and this might be the reason they are not given importance in disease diagnosis and prognosis. [Verse No.3-5]

*In present era we do not predict prognosis by prodromal symptoms except in few cases as prodromal symptoms are not exactly known in most of the diseases. Due to ambiguity, prodromal symptoms are not considered reliable and this might be the reason they are not given importance in disease diagnosis and prognosis. [Verse No.3-5]

*In the example of tuberculosis, if person is severely debilitated and then consumption is occurring then there are more chances that he will succumb to disease. Persistence of cause like sexual indulgence in such condition will further precipitate the possibility of fatality. Here one point is noticeable that rhinorrhea is not a symptom of tuberculosis. It can occur as complication of extra-pulmonary tuberculosis which may lead to bony erosion, out-pouching of the dura, CSF leak, and subsequent bacterial meningitis which is a fatal condition. This condition suggests that if severe complications are occurring earlier than manifestation of cardinal feature of the disease, it indicates poor prognosis of disease.<ref>Waqas Wahid Baig et al., Spontaneous Cerebrospinal Fluid Rhinorrhea with Pneumocephalus: An Unusual Manifestation of Nasal Tuberculosis, Korean J Intern Med. 2012 September; 27(3): 350–352 </ref> This rule applies to all other diseases: if prior health status of person is poor, he continues to partake etiological agents and complications are appearing in very early stage then disease produced in future will be fatal in nature.

*In the example of tuberculosis, if person is severely debilitated and then consumption is occurring then there are more chances that he will succumb to disease. Persistence of cause like sexual indulgence in such condition will further precipitate the possibility of fatality. Here one point is noticeable that rhinorrhea is not a symptom of tuberculosis. It can occur as complication of extra-pulmonary tuberculosis which may lead to bony erosion, out-pouching of the dura, CSF leak, and subsequent bacterial meningitis which is a fatal condition. This condition suggests that if severe complications are occurring earlier than manifestation of cardinal feature of the disease, it indicates poor prognosis of disease.<ref>Waqas Wahid Baig et al., Spontaneous Cerebrospinal Fluid Rhinorrhea with Pneumocephalus: An Unusual Manifestation of Nasal Tuberculosis, Korean J Intern Med. 2012 September; 27(3): 350–352 </ref> This rule applies to all other diseases: if prior health status of person is poor, he continues to partake etiological agents and complications are appearing in very early stage then disease produced in future will be fatal in nature.

*Horrible dreams in a person indicate the decreased mental strength of the person. ‘Mind’ is component of health and patient can combat diseases easily with strong mind and will power. Disease is always difficult to cure in a depressed person with low will power. This might be a reason why Charaka has mentioned importance of dreams while predicting prognosis of any disease. Lifestyle has changed since this text was composed, the type of dreams and their interpretation should also be changed, requiring research. We often give importance to ''sharira doshas'' and neglect the importance of ''manasa doshas'' in causation and continuation of disease process. Perhaps this chapter gives us a scope to view things from different dimension. For all dreams the role of ''manasa doshas'' are pivotal. This needs further research [Verse No.6-9]

*Horrible dreams in a person indicate the decreased mental strength of the person. ‘Mind’ is component of health and patient can combat diseases easily with strong mind and will power. Disease is always difficult to cure in a depressed person with low will power. This might be a reason why Charak has mentioned importance of dreams while predicting prognosis of any disease. Lifestyle has changed since this text was composed, the type of dreams and their interpretation should also be changed, requiring research. We often give importance to ''sharira doshas'' and neglect the importance of ''manasa doshas'' in causation and continuation of disease process. Perhaps this chapter gives us a scope to view things from different dimension. For all dreams the role of ''manasa doshas'' are pivotal. This needs further research [Verse No.6-9]

*From above verse it can be inferred that delirium before bleeding disorders will be fatal for the patient. Important cause of delirium is old age and other risk factors are poor overall health, anemia, malnutrition, underlying medical or neurologic illness etc.<ref>Harrison’s-Principles of Internal Medicine-17th edition, The McGraw-Hill Companies, Inc,chapter 26 </ref> If we critically analyze these factors we can infer that each of these will deteriorate general condition  of the patient and so even slight bleeding can produce fatal results in such persons. [Verse No.10-11]

*From above verse it can be inferred that delirium before bleeding disorders will be fatal for the patient. Important cause of delirium is old age and other risk factors are poor overall health, anemia, malnutrition, underlying medical or neurologic illness etc.<ref>Harrison’s-Principles of Internal Medicine-17th edition, The McGraw-Hill Companies, Inc,chapter 26 </ref> If we critically analyze these factors we can infer that each of these will deteriorate general condition  of the patient and so even slight bleeding can produce fatal results in such persons. [Verse No.10-11]

*''Kushta'' literally means discoloration, disgrace, disfiguration of the normal skin texture. From above verse it can be inferred that here ''kushta'' wound refers to non healing ulcers of leprosy. Leprosy is a chronic infectious disease caused by Mycobacterium Leprae, the only pathogenic bacteria able to infect peripheral nerves. About 30% of people with leprosy develop nerve damage. Neural impairment results in a set of sensitive, motor and autonomic disturbances, with ulcers originating primarily on the hands and feet. Neuropathic ulcers are one of the most common squeal of leprosy, but little is known about their clinical and epidemiological aspects.<ref>Josafá G Barreto, Claudio G Salgado, Clinic-epidemiological evaluation of ulcers in patients with leprosy sequelae and the effect of low level laser therapy on wound healing: a randomized clinical trial, BMC Infect Dis. 2010; 10: 237 </ref> If wounds are occurring before change in normal texture of skin it shows that wounds are occurring in prodromal stage and sensory loss has occurred till this stage and so slight injuries are resulting into wound formation. Such condition will lead to late diagnosis and hence chances of recovery will be minimal. [Verse No.14-15]

*''Kushta'' literally means discoloration, disgrace, disfiguration of the normal skin texture. From above verse it can be inferred that here ''kushta'' wound refers to non healing ulcers of leprosy. Leprosy is a chronic infectious disease caused by Mycobacterium Leprae, the only pathogenic bacteria able to infect peripheral nerves. About 30% of people with leprosy develop nerve damage. Neural impairment results in a set of sensitive, motor and autonomic disturbances, with ulcers originating primarily on the hands and feet. Neuropathic ulcers are one of the most common squeal of leprosy, but little is known about their clinical and epidemiological aspects.<ref>Josafá G Barreto, Claudio G Salgado, Clinic-epidemiological evaluation of ulcers in patients with leprosy sequelae and the effect of low level laser therapy on wound healing: a randomized clinical trial, BMC Infect Dis. 2010; 10: 237 </ref> If wounds are occurring before change in normal texture of skin it shows that wounds are occurring in prodromal stage and sensory loss has occurred till this stage and so slight injuries are resulting into wound formation. Such condition will lead to late diagnosis and hence chances of recovery will be minimal. [Verse No.14-15]