- Email: [email protected]
Can endogenous hallucinogens explain recurrence of hallucinations?
Correspondence / Medical Hypotheses 72 (2009) 753–761
extra-cellular fluid in the marrow and leads to increased intraosseous pressure [1]. This could affect signaling from nociceptors, giving rise to heightened pain. Mechanically reducing the intraosseous pressure appears to relieve pain in some patients [2,3]. Unfortunately the role of BME in OA remains obscure as contradictory results have been reported. Furthermore, the role of BME as a marker for progression of OA is open to discussion [4]. We hypothesize that the bone marrow edema seen in MRI images of osteoarthritic joints is a result of microfracture. Description, by many radiologists, of MRI views of the bone marrow edema in osteoarthritic knees may be insufficient. These hyper-intense MR imaging abnormalities are, rather, an expression of a number of non-characteristic histological abnormalities that include bone marrow necrosis, bone marrow fibrosis and trabeculae abnormalities [3,5,6]. The BME pattern seen on MR images is not specific for any single entity but encompasses the following differential diagnoses: 1transient osteoporosis or migratory osteoporosis, 2-transient BME syndrome 3-osteonecrosis 4-occult trauma or bone bruise, 4-infection, and 5-infiltrative neoplasm [1,5,6]. Injury and OA-related changes in bone marrow manifested by an increase in the signal intensity in bone marrow on fat-saturated T2-weighted images (bone marrow edema, BME) have been associated with severity and progression of OA [5,6]. Felson et al. reported that BME lesions occurred in 50% of persons with pain but in only 4% without pain, and that resolution of pain coincided with the disappearance of marrow edema. Felson et al. suggested that sub-chondral BME lesions markedly increase risk for local structural progression in the affected compartment [2]. The risk for medial progression was increased more than six fold in patients with medial lesions and BME was strongly related to frontal plane malalignment [6,7]. Pessis et al. indicated that OA progression was unlikely during the next year in the absence of BME, and emphasized the potential importance of sub-chondral BME in OA [8]. Sub-chondral BME is seen frequently on MRI scans of patients with articular cartilage degeneration of the knee. Higher grades of articular cartilage defects are associated with higher prevalence of BME lesions [9].
755
Kijowski et al. observed sub-chondral BME lesions in 60% of patients with degeneration of the articular cartilage of the knee [9]. Creamer and colleagues made intra-articular injections for patients with painful osteoarthritis and only 6 of 10 persons’ pain were relieved [10]. This suggests that in some patients, pain originates from extra-articular, non-capsular sources; the most likely of which is bone. If pain in some patients does emanate from bone, this finding would have important therapeutic implications and suggests that for these patients, anti-inflammatory treatments targeted at synovitis or intra-articular drainage to relieve capsular distention would be ineffective [2]. All this data supports the hypothesis that bone marrow edema as a MRI sign in tibial metaphysis of osteoarthritic knee is a microfracture, and it plays a major role in progression of deformity (varus or valgus) in OAK. References [1] Sowers MF, Hayes C, Jamadar D, et al. Magnetic resonance-detected subchondral bone marrow and cartilage defect characteristics associated with pain and X-ray-defined knee osteoarthritis. Osteoarthr Cartilage 2003;11(6): 387–393. [2] Felson DT, Chaisson CE, Hill CL, et al. The association of bone marrow lesions with pain in knee osteoarthritis. Ann Intern Med 2001;134(7):541–9. [3] Altman RD, Fries JF, Bloch DA, et al. Radiographic assessment of progression in osteoarthritis. Arthritis Rheum 1987;30(11):1214–25. [4] Kornaat PR, Kloppenburg M, Sharma R, et al. Bone marrow edema-like lesions change in volume in the majority of patients with osteoarthritis; associations with clinical features. Eur Radiol 2007;17:3073–8. [5] Lee JK, Yao L. Stress fractures: MR imaging. Radiology 1988;169(1):217–20. [6] Zanetti M, Bruder E, Romero J, Hodler J. Bone marrow edema pattern in osteoarthritic knees: correlation between MR imaging and histologic findings. Radiology 2000;215(3):835–40. [7] Schweitzer ME, White LM. Does altered biomechanics cause marrow edema? Radiology 1996;198(3):851–3. [8] Pessis E, Drape JL, Ravaund P, Chevrot A, Dougados M, Ayral X. Assessment of progression in knee osteoarthritis: results of a 1 year study comparing arthroscopy and MRI. Osteoarthr Cartilage 2003;11(5):361–9. [9] Kijowski R, Stanton P, Fine J, De Smet A. Subchondral bone marrow edema in patients with degeneration of the articular cartilage of the knee joint. Radiology 2006;238(3):943–9. [10] Creamer P, Hunt M, Dieppe P. Pain mechanisms in osteoarthritis of the knee: effect of intraarticlar anesthetic. J Rheumatol 1996;23(6):1031–6.
doi:10.1016/j.mehy.2009.01.013
Can endogenous hallucinogens explain recurrence of hallucinations? Wallach [5] has proposed an interesting hypothesis on endogenous hallucinogens and their possible role in sensory perceptions and hallucinatory experiences in psychosis [2,4]. Psychosis occurs when the release of endogenous hallucinogens is not correlated with external events or when their regulation is faulted; it has been postulated [5]. It would be interesting to see if psychotic relapses are related to endogenous hallucinogens in any particular way. Hoffman and McGlashan [3] had proposed that the same cognitive output and psychopathology in recurrent psychotic episodes were reproduced by hippocampal kindled cortical circuit parasitic foci with lowered thresholds. If Wallach’s [5] hypothesis needs clinical affirmation, recurrent episodes of psychosis in an individual should have consistency of type and content of hallucinations due to release of same endogenous hallucinogens, unrelated to external events. Since external events change with time and circumstances, one would expect lack of consistency of hallucinations over episodes, if the content was solely determined by external events.
Clinical validation of this hypothesis of endogenous hallucinogens and their possible role in disorders of sensory perceptions is provided by one of our previous study [1]. In this study on 48 patients with episodic psychosis, nature and content of hallucinations in consecutive episodes were examined and reported [1]. Of the 23 cases reporting hallucinations in consecutive episodes, 22 had the same type of hallucination (in the same sense organ modality). A recurrence of similar content was found in nearly half of the cases. Similar neurophysiological disturbances in similar neuroanatomical regions, rather than external events, were proposed to explain the persistence of the same hallucinations over episodes [1]. Endogenous hallucinogens could be the neurochemical substrate or transmitters [5], rekindled [3] during recurrent episodes. Interestingly, persistence of hallucinatory content had no relationship to persistence of delusional content, further supporting the role of endogenous hallucinogens in sensory perceptual abnormality and not in abnormality of thought content.
756
Correspondence / Medical Hypotheses 72 (2009) 753–761
Lastly, one wonders whether the endogenous hallucinogens are related to endorphins and enkephalins, which had also been implicated in occurrence of psychotic symptoms in the 1980s.
[5] Wallach JV. Endogenous hallucinogens as ligands of the trace amine receptors: a possible role in sensory perception. Med Hypothes 2009;72:91–4 .
Santosh K. Chaturvedi Department of Psychiatry, National Institute of Mental Health & Neurosciences, D.R. College P.O., Hosur Road, Bangalore 560029, India Tel.: +91 8026995264; fax: +91 8026564830 E-mail address: [email protected]
References [1] Chaturvedi SK, Sinha VK. Recurrence of hallucinations in consecutive episodes of schizophrenia and affective disorder. Schizophr Res 1990;3:103–6. [2] Ciprian-Ollivier J, Cetkovich-Bakmas MG. Altered consciousness states and endogenous psychosis: a common molecular pathway? Schizophr Res 1997;28:257–65. [3] Hoffman RE, McGlashan TH. Parallel distributed processing and emergence of schizophrenic patients. Schiz Bull 1993;19:119–40. [4] Murray RM, Oon MC, Rodnight R, Birley JL, Smith A. Increased excretion of dimethyltryptamine and certain features of psychosis: a possible explanation. Arch Gen Psychiat 1979;36:644–9.
doi:10.1016/j.mehy.2009.01.016
Definition of epilepsy: Significance of its revision on clinical neurophysiological basis to improve prognosis and quality of life of patients with epilepsy Dear Sir, Epilepsy is currently defined as a condition characterized by recurrent (two or more) unprovoked or spontaneous seizures. This definition instills a sense of fear and anxiety in patients with epilepsy owing to the spontaneity and un-predictability of the attacks and which contribute to unwarranted false perceptions about the disorder and its associated risks. An epileptic attack is generally the result of excitatory versus inhibitory influences in the epileptic zone and its surround. Many factors have been found to exercise significant influence on either of the two processes that can eventually determine the occurrence of the attack(s). Eggers [1] has also argued that all seizures are provoked in temporal lobe epilepsy, the commonest form of epilepsy. Further, a number of studies have reported high (62–90%) incidence of existence and self-perception of precipitants in patients with epilepsy [2–5]. In one study [4], 52% of the study-group attempted to avoid the precipitant(s) and 47% could even succeed in arresting their seizure sometimes. In the same study, 15% could even self-induce their attacks. The ability to abort and self-induce a seizure opens up a new interesting potential dimension of body–mind– body interactive circuitry operating in epilepsy, which however is a field for further exploration. The prevalence of seizure precipitants could be still higher than reported due to unidentifiable nature of the precipitant itself or due to the inability of identification by the patients owing to lack of awareness, very infrequent attacks and other factors pertaining to the patients’ perceiving ability. The above studies also reveal an inherent tendency in the patients to understand their disease along with an underlying desire to gain some degree of self-control over their seizures. This is a healthy positive attitude, which should be promoted and augmented further by educating the patients about the high possibility of existence of a precipitant, recognition of which can lead them to not only avoidance of the precipitant(s) with subsequent reduction in frequency and/or intensity of their seizures but also gain some degree of self-control over them. This realization of possible selfcontrol over seizures coupled with the observations that behavioral intervention can contribute favorably to anti-epileptic therapy [6,7] in the minds of both, the clinician and patients can have far reaching favorable implications in diagnosis and therapy with an improvement in prognosis and quality of life induced by an altered approach to epilepsy-management.
Although the precipitant(s) may be acting as modulators of seizures, their role in determining the timing of the attack(s) appears to be of paramount importance and which in itself can have significant impact on the patients’ psychology and behavior. Anxiety has been recognized to have profound influence on quality of life (QOL) of patients with epilepsy [8], which may render it imperative to address the psychosocial aspects also of the disorder in its management protocol. From the results of their study, de Souza and Salgado have also emphasized the importance of consideration of subjective aspects involved in epilepsy [9]. Therefore, based on interpretation of above cited studies, the author recommends promotion of epilepsy-definition revision to ‘‘a disorder associated with episode(s) of change(s) in awareness, sensation, behavior, cognition or muscle control due to altered electrical activity in a brain predisposed to its generation”. This revision encompasses the nature of clinical manifestation(s) and underlying neurophysiological basis of epilepsy and the deletion of the term ‘‘unprovoked or spontaneous” from the currently conventional definition is likely to allay the largely unwarranted fear and anxiety in the patients’ minds, at the same time boosting their morale along with a favorable impact on the social stigma associated with the disorder. Thus, this brief paper is intended to justify the revision of the current epilepsy-definition and emphasize the significance of its promotion in an attempt to improve the prognosis and QOL of patients with epilepsy.
References [1] Eggers AE. Temporal lobe epilepsy is a disease of faulty neuronal resonators rather than oscillators, and all seizures are provoked, usually be stress. Med Hypotheses 2007;69:1284–9. [2] Spatt J, Langbauer G, Mamoli B. Subjective perception of seizure precipitants: results of a questionnaire study. Seizure 1998;7:391–5. [3] Nakken KO, Solaas MH, Kjeldsen MJ, Friis ML, Pellock JM, Corey LA. Which seizure-precipitating factors do patients with epilepsy most frequently report? Epilepsy Behav 2005;6(1):85–9 [February]. [4] Spector S, Cull C, Goldstein LH. Seizure precipitants and perceived self-control of seizures in adults with poorly-controlled epilepsy. Epilepsy Res 2000 Feb;38(2– 3):207–16. [5] Frucht MM, Quigg M, Schwaner C, Fountain NB. Distribution of seizure precipitants among epilepsy syndromes. Epilepsia 2000;41(12):1534–9 [December].
extra-cellular fluid in the marrow and leads to increased intraosseous pressure [1]. This could affect signaling from nociceptors, giving rise to heightened pain. Mechanically reducing the intraosseous pressure appears to relieve pain in some patients [2,3]. Unfortunately the role of BME in OA remains obscure as contradictory results have been reported. Furthermore, the role of BME as a marker for progression of OA is open to discussion [4]. We hypothesize that the bone marrow edema seen in MRI images of osteoarthritic joints is a result of microfracture. Description, by many radiologists, of MRI views of the bone marrow edema in osteoarthritic knees may be insufficient. These hyper-intense MR imaging abnormalities are, rather, an expression of a number of non-characteristic histological abnormalities that include bone marrow necrosis, bone marrow fibrosis and trabeculae abnormalities [3,5,6]. The BME pattern seen on MR images is not specific for any single entity but encompasses the following differential diagnoses: 1transient osteoporosis or migratory osteoporosis, 2-transient BME syndrome 3-osteonecrosis 4-occult trauma or bone bruise, 4-infection, and 5-infiltrative neoplasm [1,5,6]. Injury and OA-related changes in bone marrow manifested by an increase in the signal intensity in bone marrow on fat-saturated T2-weighted images (bone marrow edema, BME) have been associated with severity and progression of OA [5,6]. Felson et al. reported that BME lesions occurred in 50% of persons with pain but in only 4% without pain, and that resolution of pain coincided with the disappearance of marrow edema. Felson et al. suggested that sub-chondral BME lesions markedly increase risk for local structural progression in the affected compartment [2]. The risk for medial progression was increased more than six fold in patients with medial lesions and BME was strongly related to frontal plane malalignment [6,7]. Pessis et al. indicated that OA progression was unlikely during the next year in the absence of BME, and emphasized the potential importance of sub-chondral BME in OA [8]. Sub-chondral BME is seen frequently on MRI scans of patients with articular cartilage degeneration of the knee. Higher grades of articular cartilage defects are associated with higher prevalence of BME lesions [9].
755
Kijowski et al. observed sub-chondral BME lesions in 60% of patients with degeneration of the articular cartilage of the knee [9]. Creamer and colleagues made intra-articular injections for patients with painful osteoarthritis and only 6 of 10 persons’ pain were relieved [10]. This suggests that in some patients, pain originates from extra-articular, non-capsular sources; the most likely of which is bone. If pain in some patients does emanate from bone, this finding would have important therapeutic implications and suggests that for these patients, anti-inflammatory treatments targeted at synovitis or intra-articular drainage to relieve capsular distention would be ineffective [2]. All this data supports the hypothesis that bone marrow edema as a MRI sign in tibial metaphysis of osteoarthritic knee is a microfracture, and it plays a major role in progression of deformity (varus or valgus) in OAK. References [1] Sowers MF, Hayes C, Jamadar D, et al. Magnetic resonance-detected subchondral bone marrow and cartilage defect characteristics associated with pain and X-ray-defined knee osteoarthritis. Osteoarthr Cartilage 2003;11(6): 387–393. [2] Felson DT, Chaisson CE, Hill CL, et al. The association of bone marrow lesions with pain in knee osteoarthritis. Ann Intern Med 2001;134(7):541–9. [3] Altman RD, Fries JF, Bloch DA, et al. Radiographic assessment of progression in osteoarthritis. Arthritis Rheum 1987;30(11):1214–25. [4] Kornaat PR, Kloppenburg M, Sharma R, et al. Bone marrow edema-like lesions change in volume in the majority of patients with osteoarthritis; associations with clinical features. Eur Radiol 2007;17:3073–8. [5] Lee JK, Yao L. Stress fractures: MR imaging. Radiology 1988;169(1):217–20. [6] Zanetti M, Bruder E, Romero J, Hodler J. Bone marrow edema pattern in osteoarthritic knees: correlation between MR imaging and histologic findings. Radiology 2000;215(3):835–40. [7] Schweitzer ME, White LM. Does altered biomechanics cause marrow edema? Radiology 1996;198(3):851–3. [8] Pessis E, Drape JL, Ravaund P, Chevrot A, Dougados M, Ayral X. Assessment of progression in knee osteoarthritis: results of a 1 year study comparing arthroscopy and MRI. Osteoarthr Cartilage 2003;11(5):361–9. [9] Kijowski R, Stanton P, Fine J, De Smet A. Subchondral bone marrow edema in patients with degeneration of the articular cartilage of the knee joint. Radiology 2006;238(3):943–9. [10] Creamer P, Hunt M, Dieppe P. Pain mechanisms in osteoarthritis of the knee: effect of intraarticlar anesthetic. J Rheumatol 1996;23(6):1031–6.
doi:10.1016/j.mehy.2009.01.013
Can endogenous hallucinogens explain recurrence of hallucinations? Wallach [5] has proposed an interesting hypothesis on endogenous hallucinogens and their possible role in sensory perceptions and hallucinatory experiences in psychosis [2,4]. Psychosis occurs when the release of endogenous hallucinogens is not correlated with external events or when their regulation is faulted; it has been postulated [5]. It would be interesting to see if psychotic relapses are related to endogenous hallucinogens in any particular way. Hoffman and McGlashan [3] had proposed that the same cognitive output and psychopathology in recurrent psychotic episodes were reproduced by hippocampal kindled cortical circuit parasitic foci with lowered thresholds. If Wallach’s [5] hypothesis needs clinical affirmation, recurrent episodes of psychosis in an individual should have consistency of type and content of hallucinations due to release of same endogenous hallucinogens, unrelated to external events. Since external events change with time and circumstances, one would expect lack of consistency of hallucinations over episodes, if the content was solely determined by external events.
Clinical validation of this hypothesis of endogenous hallucinogens and their possible role in disorders of sensory perceptions is provided by one of our previous study [1]. In this study on 48 patients with episodic psychosis, nature and content of hallucinations in consecutive episodes were examined and reported [1]. Of the 23 cases reporting hallucinations in consecutive episodes, 22 had the same type of hallucination (in the same sense organ modality). A recurrence of similar content was found in nearly half of the cases. Similar neurophysiological disturbances in similar neuroanatomical regions, rather than external events, were proposed to explain the persistence of the same hallucinations over episodes [1]. Endogenous hallucinogens could be the neurochemical substrate or transmitters [5], rekindled [3] during recurrent episodes. Interestingly, persistence of hallucinatory content had no relationship to persistence of delusional content, further supporting the role of endogenous hallucinogens in sensory perceptual abnormality and not in abnormality of thought content.
756
Correspondence / Medical Hypotheses 72 (2009) 753–761
Lastly, one wonders whether the endogenous hallucinogens are related to endorphins and enkephalins, which had also been implicated in occurrence of psychotic symptoms in the 1980s.
[5] Wallach JV. Endogenous hallucinogens as ligands of the trace amine receptors: a possible role in sensory perception. Med Hypothes 2009;72:91–4 .
Santosh K. Chaturvedi Department of Psychiatry, National Institute of Mental Health & Neurosciences, D.R. College P.O., Hosur Road, Bangalore 560029, India Tel.: +91 8026995264; fax: +91 8026564830 E-mail address: [email protected]
References [1] Chaturvedi SK, Sinha VK. Recurrence of hallucinations in consecutive episodes of schizophrenia and affective disorder. Schizophr Res 1990;3:103–6. [2] Ciprian-Ollivier J, Cetkovich-Bakmas MG. Altered consciousness states and endogenous psychosis: a common molecular pathway? Schizophr Res 1997;28:257–65. [3] Hoffman RE, McGlashan TH. Parallel distributed processing and emergence of schizophrenic patients. Schiz Bull 1993;19:119–40. [4] Murray RM, Oon MC, Rodnight R, Birley JL, Smith A. Increased excretion of dimethyltryptamine and certain features of psychosis: a possible explanation. Arch Gen Psychiat 1979;36:644–9.
doi:10.1016/j.mehy.2009.01.016
Definition of epilepsy: Significance of its revision on clinical neurophysiological basis to improve prognosis and quality of life of patients with epilepsy Dear Sir, Epilepsy is currently defined as a condition characterized by recurrent (two or more) unprovoked or spontaneous seizures. This definition instills a sense of fear and anxiety in patients with epilepsy owing to the spontaneity and un-predictability of the attacks and which contribute to unwarranted false perceptions about the disorder and its associated risks. An epileptic attack is generally the result of excitatory versus inhibitory influences in the epileptic zone and its surround. Many factors have been found to exercise significant influence on either of the two processes that can eventually determine the occurrence of the attack(s). Eggers [1] has also argued that all seizures are provoked in temporal lobe epilepsy, the commonest form of epilepsy. Further, a number of studies have reported high (62–90%) incidence of existence and self-perception of precipitants in patients with epilepsy [2–5]. In one study [4], 52% of the study-group attempted to avoid the precipitant(s) and 47% could even succeed in arresting their seizure sometimes. In the same study, 15% could even self-induce their attacks. The ability to abort and self-induce a seizure opens up a new interesting potential dimension of body–mind– body interactive circuitry operating in epilepsy, which however is a field for further exploration. The prevalence of seizure precipitants could be still higher than reported due to unidentifiable nature of the precipitant itself or due to the inability of identification by the patients owing to lack of awareness, very infrequent attacks and other factors pertaining to the patients’ perceiving ability. The above studies also reveal an inherent tendency in the patients to understand their disease along with an underlying desire to gain some degree of self-control over their seizures. This is a healthy positive attitude, which should be promoted and augmented further by educating the patients about the high possibility of existence of a precipitant, recognition of which can lead them to not only avoidance of the precipitant(s) with subsequent reduction in frequency and/or intensity of their seizures but also gain some degree of self-control over them. This realization of possible selfcontrol over seizures coupled with the observations that behavioral intervention can contribute favorably to anti-epileptic therapy [6,7] in the minds of both, the clinician and patients can have far reaching favorable implications in diagnosis and therapy with an improvement in prognosis and quality of life induced by an altered approach to epilepsy-management.
Although the precipitant(s) may be acting as modulators of seizures, their role in determining the timing of the attack(s) appears to be of paramount importance and which in itself can have significant impact on the patients’ psychology and behavior. Anxiety has been recognized to have profound influence on quality of life (QOL) of patients with epilepsy [8], which may render it imperative to address the psychosocial aspects also of the disorder in its management protocol. From the results of their study, de Souza and Salgado have also emphasized the importance of consideration of subjective aspects involved in epilepsy [9]. Therefore, based on interpretation of above cited studies, the author recommends promotion of epilepsy-definition revision to ‘‘a disorder associated with episode(s) of change(s) in awareness, sensation, behavior, cognition or muscle control due to altered electrical activity in a brain predisposed to its generation”. This revision encompasses the nature of clinical manifestation(s) and underlying neurophysiological basis of epilepsy and the deletion of the term ‘‘unprovoked or spontaneous” from the currently conventional definition is likely to allay the largely unwarranted fear and anxiety in the patients’ minds, at the same time boosting their morale along with a favorable impact on the social stigma associated with the disorder. Thus, this brief paper is intended to justify the revision of the current epilepsy-definition and emphasize the significance of its promotion in an attempt to improve the prognosis and QOL of patients with epilepsy.
References [1] Eggers AE. Temporal lobe epilepsy is a disease of faulty neuronal resonators rather than oscillators, and all seizures are provoked, usually be stress. Med Hypotheses 2007;69:1284–9. [2] Spatt J, Langbauer G, Mamoli B. Subjective perception of seizure precipitants: results of a questionnaire study. Seizure 1998;7:391–5. [3] Nakken KO, Solaas MH, Kjeldsen MJ, Friis ML, Pellock JM, Corey LA. Which seizure-precipitating factors do patients with epilepsy most frequently report? Epilepsy Behav 2005;6(1):85–9 [February]. [4] Spector S, Cull C, Goldstein LH. Seizure precipitants and perceived self-control of seizures in adults with poorly-controlled epilepsy. Epilepsy Res 2000 Feb;38(2– 3):207–16. [5] Frucht MM, Quigg M, Schwaner C, Fountain NB. Distribution of seizure precipitants among epilepsy syndromes. Epilepsia 2000;41(12):1534–9 [December].