- Email: [email protected]
Auto-Descemet membrane endothelial keratopalsty (auto-DMEK)
Medical Hypotheses 80 (2013) 102–104
Contents lists available at SciVerse ScienceDirect
Medical Hypotheses journal homepage: www.elsevier.com/locate/mehy
Correspondence
Auto-Descemet membrane endothelial keratopalsty (auto-DMEK) Tushar Agarwal a, Vishal Jhanji b,⇑ a b
Dr. R.P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi 110029, India Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong
a r t i c l e
i n f o
Article history: Received 30 July 2012 Accepted 23 September 2012
a b s t r a c t Corneal autotransplantation has been described for cases with partial corneal pathology as well as for high-risk corneal grafts. With lamellar surgeries taking the lead in the field of corneal transplantation, reattachment of detached DM is like an auto DMEK whereby the patient’s own partially damaged cornea is salvaged to provide viable vision. In case this procedure fails, an allograft DMEK graft should be the next treatment option in line. Ó 2012 Elsevier Ltd. All rights reserved.
Descemet’s membrane detachment (DMD) after ocular surgery is a very important yet under-reported complication [1]. In clinical practice, we come across many cases with partial or complete, and peripheral or central Descemet’s membrane deatchment. Whereas a focal or peripheral DMD usually resolves on its own, more central or extensive DMDs warrant timely management in order to obviate permanent corneal damage. Injection of air and other gases such as octafluoropropane or sulfur hexafluoride is a well-accepted treatment in cases with Descemet’s detachment. Although successful reattachment of a detached DM can be achieved in majority of the cases, nonethelsss, visual loss due to failure of the corneal endothelial pump may ensue. In cases with failed ‘descemetopexy’, whereas a penetrating keratoplasty would have been the most appropriate surgical option a few years back, with the current trend towards lamellar corneal transplantation surgery, these patients can be treated with selective endothelial transplantation surgeries like, Descemet stripping endothelial keratoplasty (DSEK), which involves transplantation of donor lenticule consisting of corneal endothelium, Descemet’s membrane and partial-thickness corneal stroma, or, Descemet membrane endothelial keratoplasty (DMEK) in which an allograft donor lenticule consists of only donor endothelium–Descemet’s complex [2,3]. Therefore, in our opinion, reattachment of a patient’s detached Descemet’s membrane with the aid of surgical intervention such as intracameral gas injection is akin to performing an auto corneal transplantation. Corneal autotransplantation has been described for cases with partial corneal pathology as well as for high-risk corneal grafts [4]. A corneal autograft can be obtained from the contralateral eye that may be blind due to a posterior segment pathology such as chronic end-stage glaucoma or a vascular occlusion. In such cases, cornea is relatively unaffected and may have a good endothelial cell count. This healthy cornea can be transplanted to the contralateral eye of the patient. In contrast to this, a full-thickness
⇑ Corresponding author. Tel.: +852 2762 3180; fax: +852 2715 9490. E-mail address: [email protected] (V. Jhanji).
corneal autotransplant can also be successfully performed in selective cases with careful autorotation of the opaque segment of host cornea away from the visual axis. This surgery is usually possible in cases with partial corneal opacification sparing some part of the cornea that can be rotated into the visual axis. With lamellar surgeries taking the lead in the field of corneal transplantation, reattachment of detached DM is like an auto DMEK whereby the patient’s own partially damaged cornea is salvaged to provide viable vision. In case this procedure fails, an allograft DMEK graft should be the next treatment option in line. We hope that the continuing advances in the field of corneal transplantation surgery would further our knowledge and broaden the concepts of selective corneal transplantation. Conflict of interest Statement None. Proprietary/Financial interest None. Funding/support None. Acknowledgements None. References [1] Samuels B. Detachment of Descemet’s membrane. Trans Am Ophthalmol Soc 1928;26:427–37. [2] Jhanji V, Mehta JS, Sharma N, Sharma B, Vajpayee RB. Targeted corneal transplantation. Curr Opin Ophthalmol 2012;23(4):324–9.
T. Agarwal, V. Jhanji / Medical Hypotheses 80 (2013) 102–104 [3] Tong CM, Melles GR. Where is endothelial keratoplasty going: from Descemet stripping (automated) endothelial keratoplasty to Descemet membrane endothelial keratoplasty to Descemet membrane endothelial transfer? Can J Ophthalmol 2012;47(3):197–200. [4] Agarwal T, Sharma N, Jhanji V, Vajpayee RB. Computer simulation-assisted rotational autokeratoplasty with pupillary enlargement for management of cases with partial corneal opacification. Br J Ophthalmol 2010;94(1):24–5.
doi:http://dx.doi.org/10.1016/j.mehy.2012.09.015
Blue-green algae or cyanobacteria in the intestinal micro-flora may produce neurotoxins such as Beta-N-Methylamino-L-Alanine (BMAA) which may be related to development of amyotrophic lateral sclerosis, Alzheimer’s disease and Parkinson-DementiaComplex in humans and Equine Motor Neuron Disease in Horses
Blue-green algae, or cyanobacteria (CB) are the source of BetaN-Methylamino-L-alanine (BMAA), a neurotoxin found in the brains of patients with Amyotrophic Lateral Sclerosis (ALS), Alzheimer Disease (AD), and Parkinson-Dementia-Complex (PDC) [1]. BMAA acts through multiple mechanisms including the N-Methyl-D-Asparate (NMDA) receptor, Glutamate 5 receptor and oxidative stress, in the nervous system [1]. A similar disease to ALS occurs in horses, Equine Motor Neuron Disease (EMND), when they are deficient in Vitamin E and restricted from fresh pasturage [2]. The source of CB associated BMAA has been considered environmental, however CB are in the intestinal micro-flora of both men [3] and horses [4]. Usually CB are a minor component of the intestinal micro-flora, however disease or malnutrition may alter the proper balance between pathogens and the normal bacterial micro-flora, enabling overgrowth of CB with production of neurotoxins such as BMAA, with subsequent development of neurodegenerative diseases, in both horses and men. Assessing intestinal contents for the presence of CB, BMAA and other CB neurotoxins such as saxitoxin and anatoxin-a, could be helpful in determining the cause of ALS, AD and PDC in humans and EMND in horses. If CB in the intestinal micro-flora produce neurotoxins, it may be possible to control them through diet or medications, in the treatment of such diseases of the nervous system. References [1] Banack SA, Caller TA, Stommel EW. The cyanobacteria derived toxin beta-Nmethylamino-L-alanine and amyotrophic lateral sclerosis. Toxins (Basel) 2010;2(12):2837–50. http://dx.doi.org/110.3390/toxins2122837. [2] Mohammed HO, Divers TJ, Summers BA. De Lahunta A vitamin e deficiency and risk of equine motor neuron disease. Acta Vet Scand 2007;49:17. [3] Ley RE, Peterson DA, Gordon JI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 2006;124:837–48. [4] Shepherd ML, Swecker Jr WS, Jensen RV, Ponder MA. Characterization of the fecal bacterial communities of forage-fed horses by pyrosequencing of 16S rRNA V4 gene amplicons. FEMS Microbiol Lett 2012;326:62–8.
Steven R. Brenner Dept. of Neurology and Psychiatry, Saint Louis University School of Medicine, Montelone Hall, 1438 South Grand Blvd., St. Louis, MO 63104, USA E-mail address: [email protected] doi:http://dx.doi.org/10.1016/j.mehy.2012.10.010
103
How Doppler effect occurs in absence of intracranial blood flow in brain death?
Lack of intracranial arterial and venous circulation (cerebral circulatory arrest) is major confirmatory criterion of brain death diagnosis. Circulatory arrest can be demonstrated by angiography, single photon emission computed tomography or transcranial Doppler ultrasound (TCD). TCD is more practical mainly due to its bed-side applicability [1]. TCD sonogram patterns compatible with brain death are to-and-fro pattern (TaFP, complete diastolic flow reversal), systolic spikes (SS) and flow absence within internal carotid arteries (ICA) and vertebral arteries, bilaterally [2,3]. Flow absence cannot be used for confirmation unless there is a loss of definite flow signals previously recorded through the same bone window and hemodynamic condition. The pathophysiology underlying these sonogram patterns (sometimes erroneously referred as flow patterns) are not fully evaluated. In brain death, intracranial pressure is higher than systolic blood pressure preventing blood entry into the intracranial cavity. Accordingly, these sonographic patterns are significantly correlated with the level of flow arrest in angiography. The TaFP signal corresponds to contrast blockage at the supraclinoid segment level, the SS at the petrous segment level and flow absence at the cervical segment level [4]. This observation in turn raises the question of how these TCD signals are generated in absence of any blood flow within intracranial cerebral arteries. The usual explanation has been the detection of flow reversal or just systolic entry (in case of SS) into the rostral extracranial ICA by TCD sample volume side lobes. We, however, propose another mechanism. Given absence of any angiographic flow in cerebral vasculature in brain dead cases, the cause of the Doppler effect observed cannot be a real flow at all. On the other hand, the stagnant blood column in cerebral arteries is moved back-and-forth due to the percussive effect of every heart beat at its proximal tip. In the early stages of brain death, the forward push and then backward movement of this blood column leads to a TaFP pattern on TCD. With further deterioration, the clot retracts and becomes stickier to push, thereby eliminating any movement in the blood column; at this stage the sonogram turns into SS pattern probably only reflecting the percussions of the heart beat. Change in SS amplitude by the phase of respiration, observance of increase in SS amplitude or sometimes reappearance of TaFP pattern after blood pressure augmentation in a case with SS supports this idea further. Another explanation could be that the signals might reflect heart beat related alternative compression and relaxation within the blood column, rather than en-bloc back and forth movements, But, the amplitude of the signal should be very small if this mechanism plays a role. Therefore, we propose to refrain from using the word ‘flow’ while describing TCD patterns observed in brain dead cases, until the nature of these sonographic signals are better understood. Conflict of interest statement None declared. References [1] Orban JC, El-Mahjoub A, Rami L, Jambou P, Ichai C. Transcranial Doppler shortens the time between clinical brain death and angiographic confirmation: a randomized trial. Transplantation 2012;94:585–8. [2] Ducrocq X, Hassler W, Moritake K, et al. Consensus opinion on diagnosis of cerebral circulatory arrest using Doppler-sonography: Task Force Group on cerebral death of the Neurosonology Research Group of the World Federation of Neurology. J Neurol Sci 1998;159:145–50.
Contents lists available at SciVerse ScienceDirect
Medical Hypotheses journal homepage: www.elsevier.com/locate/mehy
Correspondence
Auto-Descemet membrane endothelial keratopalsty (auto-DMEK) Tushar Agarwal a, Vishal Jhanji b,⇑ a b
Dr. R.P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi 110029, India Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong
a r t i c l e
i n f o
Article history: Received 30 July 2012 Accepted 23 September 2012
a b s t r a c t Corneal autotransplantation has been described for cases with partial corneal pathology as well as for high-risk corneal grafts. With lamellar surgeries taking the lead in the field of corneal transplantation, reattachment of detached DM is like an auto DMEK whereby the patient’s own partially damaged cornea is salvaged to provide viable vision. In case this procedure fails, an allograft DMEK graft should be the next treatment option in line. Ó 2012 Elsevier Ltd. All rights reserved.
Descemet’s membrane detachment (DMD) after ocular surgery is a very important yet under-reported complication [1]. In clinical practice, we come across many cases with partial or complete, and peripheral or central Descemet’s membrane deatchment. Whereas a focal or peripheral DMD usually resolves on its own, more central or extensive DMDs warrant timely management in order to obviate permanent corneal damage. Injection of air and other gases such as octafluoropropane or sulfur hexafluoride is a well-accepted treatment in cases with Descemet’s detachment. Although successful reattachment of a detached DM can be achieved in majority of the cases, nonethelsss, visual loss due to failure of the corneal endothelial pump may ensue. In cases with failed ‘descemetopexy’, whereas a penetrating keratoplasty would have been the most appropriate surgical option a few years back, with the current trend towards lamellar corneal transplantation surgery, these patients can be treated with selective endothelial transplantation surgeries like, Descemet stripping endothelial keratoplasty (DSEK), which involves transplantation of donor lenticule consisting of corneal endothelium, Descemet’s membrane and partial-thickness corneal stroma, or, Descemet membrane endothelial keratoplasty (DMEK) in which an allograft donor lenticule consists of only donor endothelium–Descemet’s complex [2,3]. Therefore, in our opinion, reattachment of a patient’s detached Descemet’s membrane with the aid of surgical intervention such as intracameral gas injection is akin to performing an auto corneal transplantation. Corneal autotransplantation has been described for cases with partial corneal pathology as well as for high-risk corneal grafts [4]. A corneal autograft can be obtained from the contralateral eye that may be blind due to a posterior segment pathology such as chronic end-stage glaucoma or a vascular occlusion. In such cases, cornea is relatively unaffected and may have a good endothelial cell count. This healthy cornea can be transplanted to the contralateral eye of the patient. In contrast to this, a full-thickness
⇑ Corresponding author. Tel.: +852 2762 3180; fax: +852 2715 9490. E-mail address: [email protected] (V. Jhanji).
corneal autotransplant can also be successfully performed in selective cases with careful autorotation of the opaque segment of host cornea away from the visual axis. This surgery is usually possible in cases with partial corneal opacification sparing some part of the cornea that can be rotated into the visual axis. With lamellar surgeries taking the lead in the field of corneal transplantation, reattachment of detached DM is like an auto DMEK whereby the patient’s own partially damaged cornea is salvaged to provide viable vision. In case this procedure fails, an allograft DMEK graft should be the next treatment option in line. We hope that the continuing advances in the field of corneal transplantation surgery would further our knowledge and broaden the concepts of selective corneal transplantation. Conflict of interest Statement None. Proprietary/Financial interest None. Funding/support None. Acknowledgements None. References [1] Samuels B. Detachment of Descemet’s membrane. Trans Am Ophthalmol Soc 1928;26:427–37. [2] Jhanji V, Mehta JS, Sharma N, Sharma B, Vajpayee RB. Targeted corneal transplantation. Curr Opin Ophthalmol 2012;23(4):324–9.
T. Agarwal, V. Jhanji / Medical Hypotheses 80 (2013) 102–104 [3] Tong CM, Melles GR. Where is endothelial keratoplasty going: from Descemet stripping (automated) endothelial keratoplasty to Descemet membrane endothelial keratoplasty to Descemet membrane endothelial transfer? Can J Ophthalmol 2012;47(3):197–200. [4] Agarwal T, Sharma N, Jhanji V, Vajpayee RB. Computer simulation-assisted rotational autokeratoplasty with pupillary enlargement for management of cases with partial corneal opacification. Br J Ophthalmol 2010;94(1):24–5.
doi:http://dx.doi.org/10.1016/j.mehy.2012.09.015
Blue-green algae or cyanobacteria in the intestinal micro-flora may produce neurotoxins such as Beta-N-Methylamino-L-Alanine (BMAA) which may be related to development of amyotrophic lateral sclerosis, Alzheimer’s disease and Parkinson-DementiaComplex in humans and Equine Motor Neuron Disease in Horses
Blue-green algae, or cyanobacteria (CB) are the source of BetaN-Methylamino-L-alanine (BMAA), a neurotoxin found in the brains of patients with Amyotrophic Lateral Sclerosis (ALS), Alzheimer Disease (AD), and Parkinson-Dementia-Complex (PDC) [1]. BMAA acts through multiple mechanisms including the N-Methyl-D-Asparate (NMDA) receptor, Glutamate 5 receptor and oxidative stress, in the nervous system [1]. A similar disease to ALS occurs in horses, Equine Motor Neuron Disease (EMND), when they are deficient in Vitamin E and restricted from fresh pasturage [2]. The source of CB associated BMAA has been considered environmental, however CB are in the intestinal micro-flora of both men [3] and horses [4]. Usually CB are a minor component of the intestinal micro-flora, however disease or malnutrition may alter the proper balance between pathogens and the normal bacterial micro-flora, enabling overgrowth of CB with production of neurotoxins such as BMAA, with subsequent development of neurodegenerative diseases, in both horses and men. Assessing intestinal contents for the presence of CB, BMAA and other CB neurotoxins such as saxitoxin and anatoxin-a, could be helpful in determining the cause of ALS, AD and PDC in humans and EMND in horses. If CB in the intestinal micro-flora produce neurotoxins, it may be possible to control them through diet or medications, in the treatment of such diseases of the nervous system. References [1] Banack SA, Caller TA, Stommel EW. The cyanobacteria derived toxin beta-Nmethylamino-L-alanine and amyotrophic lateral sclerosis. Toxins (Basel) 2010;2(12):2837–50. http://dx.doi.org/110.3390/toxins2122837. [2] Mohammed HO, Divers TJ, Summers BA. De Lahunta A vitamin e deficiency and risk of equine motor neuron disease. Acta Vet Scand 2007;49:17. [3] Ley RE, Peterson DA, Gordon JI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 2006;124:837–48. [4] Shepherd ML, Swecker Jr WS, Jensen RV, Ponder MA. Characterization of the fecal bacterial communities of forage-fed horses by pyrosequencing of 16S rRNA V4 gene amplicons. FEMS Microbiol Lett 2012;326:62–8.
Steven R. Brenner Dept. of Neurology and Psychiatry, Saint Louis University School of Medicine, Montelone Hall, 1438 South Grand Blvd., St. Louis, MO 63104, USA E-mail address: [email protected] doi:http://dx.doi.org/10.1016/j.mehy.2012.10.010
103
How Doppler effect occurs in absence of intracranial blood flow in brain death?
Lack of intracranial arterial and venous circulation (cerebral circulatory arrest) is major confirmatory criterion of brain death diagnosis. Circulatory arrest can be demonstrated by angiography, single photon emission computed tomography or transcranial Doppler ultrasound (TCD). TCD is more practical mainly due to its bed-side applicability [1]. TCD sonogram patterns compatible with brain death are to-and-fro pattern (TaFP, complete diastolic flow reversal), systolic spikes (SS) and flow absence within internal carotid arteries (ICA) and vertebral arteries, bilaterally [2,3]. Flow absence cannot be used for confirmation unless there is a loss of definite flow signals previously recorded through the same bone window and hemodynamic condition. The pathophysiology underlying these sonogram patterns (sometimes erroneously referred as flow patterns) are not fully evaluated. In brain death, intracranial pressure is higher than systolic blood pressure preventing blood entry into the intracranial cavity. Accordingly, these sonographic patterns are significantly correlated with the level of flow arrest in angiography. The TaFP signal corresponds to contrast blockage at the supraclinoid segment level, the SS at the petrous segment level and flow absence at the cervical segment level [4]. This observation in turn raises the question of how these TCD signals are generated in absence of any blood flow within intracranial cerebral arteries. The usual explanation has been the detection of flow reversal or just systolic entry (in case of SS) into the rostral extracranial ICA by TCD sample volume side lobes. We, however, propose another mechanism. Given absence of any angiographic flow in cerebral vasculature in brain dead cases, the cause of the Doppler effect observed cannot be a real flow at all. On the other hand, the stagnant blood column in cerebral arteries is moved back-and-forth due to the percussive effect of every heart beat at its proximal tip. In the early stages of brain death, the forward push and then backward movement of this blood column leads to a TaFP pattern on TCD. With further deterioration, the clot retracts and becomes stickier to push, thereby eliminating any movement in the blood column; at this stage the sonogram turns into SS pattern probably only reflecting the percussions of the heart beat. Change in SS amplitude by the phase of respiration, observance of increase in SS amplitude or sometimes reappearance of TaFP pattern after blood pressure augmentation in a case with SS supports this idea further. Another explanation could be that the signals might reflect heart beat related alternative compression and relaxation within the blood column, rather than en-bloc back and forth movements, But, the amplitude of the signal should be very small if this mechanism plays a role. Therefore, we propose to refrain from using the word ‘flow’ while describing TCD patterns observed in brain dead cases, until the nature of these sonographic signals are better understood. Conflict of interest statement None declared. References [1] Orban JC, El-Mahjoub A, Rami L, Jambou P, Ichai C. Transcranial Doppler shortens the time between clinical brain death and angiographic confirmation: a randomized trial. Transplantation 2012;94:585–8. [2] Ducrocq X, Hassler W, Moritake K, et al. Consensus opinion on diagnosis of cerebral circulatory arrest using Doppler-sonography: Task Force Group on cerebral death of the Neurosonology Research Group of the World Federation of Neurology. J Neurol Sci 1998;159:145–50.