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The relationship of intrathecal immunoglobulin levels with clinic symptoms and prognosis for acute phase ischemic stroke patients

Yıl 2014, Cilt: 36 Sayı: 4, 512 - 522, 21.10.2014
https://doi.org/10.7197/cmj.v36i4.5000071471

Öz

Abstract

Aim. Ischemic strokes are about 80-85% of the strokes, third common cause of mortality in the world. Due to ischemia, neurons are damaged, blood brain barrier (BBB) is disrupted and inflammation is triggered. Although the cell mediated immun response in ischemic stroke has been showed by previous studies,there is no excessive database is available for humoral immun response. In this study, we aim to determine presence and amount of intrathecal immunglobulins after ischemic strokes as a result of humoral immun response in patients with the first and recurrent ischemic stroke. Thus,we could elucidate the presence of humoral immune response effect in long-term prognosis of ischemic stroke. Methods. In this study, 51 patient were included. 32 patients had first and 19 patients had recurrent ischemic stroke. Cerebrospinal fluid (CSF) samples were taken within 72 hours from the symptoms onset by lomber punction. Cell count, CSF Ig G, M, A and microalbumin levels were assessed in CSF samples, also serum Ig G, M, A and albumin levels were measured simultaneously. Albumin and Ig G index and CSF Ig G/CSF albumin ratios were calculated. Infarct volumes of the patients were calculated from computed cranial tomography (CCT) and/or magnetic resonance diffusion weighted imaging ( DW MRI). Glasgow Coma Scale (GCS) and National İnstitutes of Health Stroke Scale (NIHSS) were used at the admission, modified Rankin Scale (MRS),Barthel index (BI) and NIHSS were used at the time of discharge from the hospital. Results. Albumin index was normal in the patients with their first ischemic stroke but slightly elevated in the recurrent ischemic stroke group. The CSF Ig G levels(p<0.001), CSF Ig G/CSF albumin ratio (0.32 ± 0.04) and CSF Ig G index, (1.13 ± 0.16) were higher in the recurrent ischemic stroke group. Also unlike the first group, in the recurrent ischemic stroke, there was a a significant positive correlation between the infarct volumes and levels of IgG (p<0.001). Considering to MRS and BI, MRS was higher in recurrent ischemic stroke group(p=0.001) and Barthel index was lower (p=0.009). Conclusion. Our results showed the intrathecal synthesis of IgG in recurrent ischemic stroke and the role of humoral immune system in the pathophysiology of recurrent ischemic stroke. However the effect of humoral immune system on the patients’clinic, the prognosis of stroke and disability due to stroke is contraversial.

Keywords: Ischemic stroke, cerebrospinal fluid, blood brain barrier, intrathecal immunoglobulin synthesis, humoral immune system, inflamation

 

Özet

Amaç. İskemik inme, dünya genelinde mortalitenin 3. en sık nedeni olan inmenin, yaklaşık %80-85’ini oluşturur. İskemiye bağlı olarak nöronlarda yıkım meydana gelir, kan beyin bariyeri(KBB) bozulur ve inflamasyon tetiklenir. İskemik inmede hücresel immün yanıtın rolü önceki çalışmalarda gösterilmiş olup humoral immun yanıtla ilgili oldukça sınırlı sayıda veri mevcuttur. Bu çalışmayla iskemik inmeli hastalarda humoral immun cevabın sonucu olarak intratekal sentezlenen immunglobulinlerin varlığını ve miktarını saptamayı amaçlıyoruz. Böylece, iskemik inmenin uzun dönem prognozu üzerinde humoral immun cevabın etkisinin varlığına ışık tutabiliriz. Yöntem. Bu çalışmaya, 32 ilk ve 19 tekrarlayan iskemik inme atağı geçiren ve şikayetlerinin başladığı andan itibaren ilk 72 saat içinde lomber ponksiyonla beyin omurilik sıvısı (BOS) örneği alınan toplam 51 hasta dahil edildi. Alınan BOS örneklerinden hücre sayısı, Ig G, M, A ve mikroalbumin düzeyleri, eş zamanlı alınan serumdan ise Ig G,M,A ve albumin düzeyleri ölçüldü. Albumin ve Ig G indeksi ile BOS Ig G/BOS albumin oranları hesaplandı. Hastaların çekilen bilgisayarlı beyin tomografisi (BBT) ve/veya difüzyon ağırlıklı manyetik rezonans görüntülemelerinden (DA MRG) infarkt hacmi hesaplandı. Hastalara servise yatışında Glaskow koma skalası (GKS ), National İnstitutes of Health Stroke Scale (NIHSS); taburcu olurken ise NIHSS, modifiye Rankin skalası (MRS) ve Barthel indeksi (BI) skalası uygulandı. Bulgular. Albumin indeksi; ilk iskemik inmesini geçiren hastalarda normalken tekrarlayan iskemik inmesini geçiren grupta hafif yükselmiş olarak saptandı. BOS Ig G/BOS albumin oranı (0,32 ± 0,04) ile BOS Ig G indeksi(1,13 ± 0,16 ) ve BOS Ig G düzeyleri; tekrarlayan iskemik inme geçiren hastalarda ilk iskemik inmesini geçiren gruptakine kıyasla yüksek bulundu. Ayrıca ilk iskemik inme grubunun aksine tekrarlayan iskemik inme geçiren grupta lezyon volümü ile BOS Ig G düzeyleri arasında pozitif yönde anlamlı bir ilişki izlendi (p<0,001). MRS’na ve BI’ne bakıldığında ise, MRS tekrarlayan iskemik inmesini geçiren grupta daha yüksekken (p=0,001). Barthel indeksi daha düşük tespit edildi (p=0,009). Sonuç. Bu sonuçlarlarla tekrarlayan iskemik inme grubunda artmış BOS Ig G sentezi ve dolayısıyla tekrarlayan iskemik inme fizyopatolojisinde humoral immun sistemin rolü ortaya konulmuştur. Ancak bunun hastaların kliniğindeki, inmenin prognozu ve inmeye bağlı özürlülükteki yeri tartışmalıdır.

Anahtar sözcükler: İskemik inme, beyin omurilik sıvısı, kan beyin bariyeri, intratekal immun globulin sentezi, humoral immun sistem, inflamasyon

 

Kaynakça

  • Sacco PL. Vascular diseases. Ed: Merrit, Rowland LP, Merrit‘s Neurology. Hagerstown. Williams&Wilkins 2000; 10: 177-85.
  • Raymond D. Adams, Maurice Victor, Allan H. Ropper. Principles of Neurology, 6th edition 777-810.
  • Utku U, Çelik Y. Strokta etyoloji, sınıflandırma ve risk faktörleri. Balkan S: Serebrovaskuler Hastalıklar. Güneş Kitabevi Yayınları, Ankara 2002; 17: 236-55
  • Johnson RT, Griffin JW, McArthur JC, Saver JL. Current Therapy in Neurologic Disease. Sixth edition 2002; 200-6.
  • Badenier MM, Braunersreuther V, Viviani G.L, Dallegri F, Quercioli A, Veneselli E, Mach F, Montecucco F. CC and CXC chemokines are pivotal mediators of cerebral injury in ischaemic stroke. Thrombosis and Haemostasis 2011; 105.
  • Del Zoppo GJ, Schmid-Schonbein GW, Mori E, Copeland BR, Chang CM. Polymorphonuclear leukocytes occlude capillaries following middle cerebral artery occlusion and reperfusion in baboons. Stroke 1991; 22: 1276-83.
  • Ginhoux F. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 2010; 330: 841-5.
  • Davalos D. ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 2005; 8: 752-8.
  • Nimmerjahn A, Kirchhoff F, Helmchen F. Resting microglial cells are highly dynamicsurveillants of brain parenchyma in vivo. Science 2005; 308: 1314-8.
  • Mantovani A, Sica A, Locati M. Macrophage polarization comes of age. Immunity 2005; 23: 344-6.
  • Konsman JP, Drukarch B, Van Dam AM. (Peri) vascular production and action of proinflammatory cytokines in brain pathology. Clin Sci 2007; 112: 1-25.
  • Rao KN, Brown MA. Mast cells: Multifaceted immune cells with diverse roles in health and disease. Ann N Y Acad Sci 2008; 1143: 83-104.
  • Iadecola C, Anrather J. The immunology of stroke: From mechanisms to translation. Nat Med 2011; 17: 796-808.
  • Felger JC. Brain dendritic cells in ischemic stroke: time course, activation state, and origin. Brain Behav Immun 2010; 24:724-37.
  • Tanaka R. Migration of enhanced green fluorescent protein expressing bone marrow-derived microglia/macrophage into the mouse brain following permanent focal ischemia. Neuroscience 2003; 117:531-9.
  • Abbas AK, Lichtmman AH, Pillai S. Effector Mechanisms of Humoral İmmunity (7.Baskı) Celluler and Molecular İmmunology.Elsevier Saunders, Philadelphia, ABD 2012; 269-93.
  • Karabudak R. Temel ve Klinik Nöroimmunoloji (1.Baskı).Edinsel İmmunite. 2013; 27 67.
  • Abbas AK, Lichtman AH. (2007)Temel İmmunoloji: İmmun sistemin işlev ve bozuklukları.Camcıoğlu,Y Kitapevi,İstanbul,s.21-39 ve Deniz G(Çeviri ed).İstanbul Tıp
  • Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 7th edition. Elsevier Sauders, Philadelphia, 2012; 55-88.
  • Badenier MM, Braunersreuther V, Viviani GL, Dallegri F, Quercioli A, Veneselli E, Mach F, Montecucco F. CC and CXC chemokines are pivotal mediators of cerebral injury in ischaemic stroke. Thrombosis and Haemostasis 2011; 105.
  • Abbas, AK, Lichtmman AH, Pillai S. Activation of T lmphocytes Celluler and Molecular İmmunology.Elsevier Saunders,Philadelphia, ABD 2012; 203-25.
  • Kono H, Rock KL. How dying cells alert the immune system to danger. Nat Rev Immunol 2008.
  • Abbas, AK. Basic Immunology Updated Edition: Functions and Disorders of the Immune System. Saunders 2010.
  • Yilmaz A. Transient decrease in circulating dendritic cell precursors after acute stroke: potential recruitment into the brain. Clin Sci 2010; 118:147-57.
  • Becker KJ, Kindrick DL, Lester MP, Shea C, Ye ZC. Sensitization to brain antigens after stroke is augmented by lipopolysaccharide. J Cereb Blood Flow Metab 2005; 25: 1634-44.
  • Balkan S. Serebral vasküler anatomi. İç: Klinik Nöroloji. Oğul E 2002: 3-15.
  • Şener RN. Diffusion MRI: Apperent diffusion coefficient (ADC) values in the normal brain, and a classification of brain disorders based on ADC values.Comput Met Imaging Graph 2001; 25: 299-326.
  • Harald P, Deetje I, Baldinger T. Evidence of intrathecal immunoglobulin synthesis in stroke. Arch Neurol 2012; 69: 714-7.
  • Strand T, Alling C, Karlsson B, Karlsson I, Winblad B. Brain and plasma proteins in spinal fluid as markers for brain damage and severity of stroke. Stroke 1984; 15: 138-44.
  • Sörnas R, Ostlund H, Muller R. Cerebrospinal fluid cytology after stroke. Arch Neurol 1972; 26: 489-501.
  • Akopov SE, Simonian NA, Grigorian GS. Dynamics of polymorphonuclear leukocyte accumulation in acute cerebral infarction and their correlation with brain tissue damage. Stroke 1996; 27: 1739-43.
  • Chuaqui R, Tapia J. Histologic assessment of the age of recent brain infarcts in man. J Neuropathol Exp Neurol 1993; 52: 481-9.
  • Reiber H, Lange P. Quantification of virus-specific antibodies in cerebrospinal fluid and serum: Sensitive and specific detection of antibody synthesis in brain. Clin Chem 1991; 37: 1153-60.
  • Hurn PD. T-and B-cell-deficient mice with experimental stroke have reduced lesion size and inflammation. J Cereb Blood Flow Metab 2007; 27: 1798-805.
  • Kleinschnitz C. Early detrimental T-cell effects in experimental cerebral ischemia are neither related to adaptive immunity nor thrombus formation. Blood 2010; 115: 3835-42.
  • Thompson EJ. Proteins of the cerebrospinal fluid. Elsevier, London 2005.
  • Leys D, He´non H, Mackowiak-Cordoliani MA, Pasquier F. Poststroke dementia. Lancet Neurol 2005; 4: 752-9.
  • Tatemichi TK, Foulkes MA, Mohr JP, Hewitt JR, Hier DB, Price TR, Wolf PA. Dementia instroke survivors in the stroke data bank cohort: Prevalence, incidence, risk factors and computed tomographic findings. Stroke 1990; 21: 858- 66.
  • Lin JH, Lin RT, Tai CT, Hsieh CL, Hsiao SF, Liu CK. Prediction of poststroke dementia. Neurology 2003; 61: 343-8.
  • Mok VC, Wong A, Lam WW, Fan YH, Tang WK, Kwok T, Hui AC, Wong KS. Cognitive impairment and functional outcome after stroke associated with small vessel disease. J Neurol Neurosurg Psychiatry 2004; 75: 560-6.
  • Zhou DH, Wang JY, Li J, Deng J, Gao C, Chen M. Study on frequency and predictors of dementia after ischemic stroke: the Chongqing stroke study. J Neurol 2004; 251: 421-7.

Original research-Orijinal araştırma

Yıl 2014, Cilt: 36 Sayı: 4, 512 - 522, 21.10.2014
https://doi.org/10.7197/cmj.v36i4.5000071471

Öz

Amaç. İskemik inme, dünya genelinde mortalitenin 3. en sık nedeni olan inmenin, yaklaşık %8085’ini oluşturur. İskemiye bağlı olarak nöronlarda yıkım meydana gelir, kan beyin bariyeri(KBB) bozulur ve inflamasyon tetiklenir. İskemik inmede hücresel immün yanıtın rolü önceki çalışmalarda gösterilmiş olup humoral immun yanıtla ilgili oldukça sınırlı sayıda veri mevcuttur. Bu çalışmayla iskemik inmeli hastalarda humoral immun cevabın sonucu olarak intratekal sentezlenen immunglobulinlerin varlığını ve miktarını saptamayı amaçlıyoruz. Böylece, iskemik inmenin uzun dönem prognozu üzerinde humoral immun cevabın etkisinin varlığına ışık tutabiliriz. Yöntem. Bu çalışmaya, 32 ilk ve 19 tekrarlayan iskemik inme atağı geçiren ve şikayetlerinin başladığı andan itibaren ilk 72 saat içinde lomber ponksiyonla beyin omurilik sıvısı (BOS) örneği alınan toplam 51 hasta dahil edildi. Alınan BOS örneklerinden hücre sayısı, Ig G, M, A ve mikroalbumin düzeyleri, eş zamanlı alınan serumdan ise Ig G,M,A ve albumin düzeyleri ölçüldü. Albumin ve Ig G indeksi ile BOS Ig G/BOS albumin oranları hesaplandı. Hastaların çekilen bilgisayarlı beyin tomografisi (BBT) ve/veya difüzyon ağırlıklı manyetik rezonans görüntülemelerinden (DA MRG) infarkt hacmi hesaplandı. Hastalara servise yatışında Glaskow koma skalası (GKS), National İnstitutes of Health Stroke Scale (NIHSS); taburcu olurken ise NIHSS, modifiye Rankin skalası (MRS) ve Barthel indeksi (BI) skalası uygulandı. Bulgular. Albumin indeksi; ilk iskemik inmesini geçiren hastalarda normalken tekrarlayan iskemik inmesini geçiren grupta hafif yükselmiş olarak saptandı. BOS Ig G/BOS albumin oranı (0,32 ± 0,04) ile BOS Ig G indeksi(1,13 ± 0,16) ve BOS Ig G düzeyleri; tekrarlayan iskemik inme geçiren hastalarda ilk iskemik inmesini geçiren gruptakine kıyasla yüksek bulundu. Ayrıca ilk iskemik inme grubunun aksine tekrarlayan iskemik inme geçiren grupta lezyon volümü ile BOS Ig G düzeyleri arasında pozitif yönde anlamlı bir ilişki izlendi (p<0,001). MRS’na ve BI’ne bakıldığında ise, MRS tekrarlayan iskemik inmesini geçiren grupta daha yüksekken (p=0,001). Barthel indeksi daha düşük tespit edildi (p=0,009). Sonuç. Bu sonuçlarlarla tekrarlayan iskemik inme grubunda artmış BOS Ig G sentezi ve dolayısıyla tekrarlayan iskemik inme fizyopatolojisinde humoral immun sistemin rolü ortaya konulmuştur. Ancak bunun hastaların kliniğindeki, inmenin prognozu ve inmeye bağlı özürlülükteki yeri tartışmalıdır

Kaynakça

  • Sacco PL. Vascular diseases. Ed: Merrit, Rowland LP, Merrit‘s Neurology. Hagerstown. Williams&Wilkins 2000; 10: 177-85.
  • Raymond D. Adams, Maurice Victor, Allan H. Ropper. Principles of Neurology, 6th edition 777-810.
  • Utku U, Çelik Y. Strokta etyoloji, sınıflandırma ve risk faktörleri. Balkan S: Serebrovaskuler Hastalıklar. Güneş Kitabevi Yayınları, Ankara 2002; 17: 236-55
  • Johnson RT, Griffin JW, McArthur JC, Saver JL. Current Therapy in Neurologic Disease. Sixth edition 2002; 200-6.
  • Badenier MM, Braunersreuther V, Viviani G.L, Dallegri F, Quercioli A, Veneselli E, Mach F, Montecucco F. CC and CXC chemokines are pivotal mediators of cerebral injury in ischaemic stroke. Thrombosis and Haemostasis 2011; 105.
  • Del Zoppo GJ, Schmid-Schonbein GW, Mori E, Copeland BR, Chang CM. Polymorphonuclear leukocytes occlude capillaries following middle cerebral artery occlusion and reperfusion in baboons. Stroke 1991; 22: 1276-83.
  • Ginhoux F. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 2010; 330: 841-5.
  • Davalos D. ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 2005; 8: 752-8.
  • Nimmerjahn A, Kirchhoff F, Helmchen F. Resting microglial cells are highly dynamicsurveillants of brain parenchyma in vivo. Science 2005; 308: 1314-8.
  • Mantovani A, Sica A, Locati M. Macrophage polarization comes of age. Immunity 2005; 23: 344-6.
  • Konsman JP, Drukarch B, Van Dam AM. (Peri) vascular production and action of proinflammatory cytokines in brain pathology. Clin Sci 2007; 112: 1-25.
  • Rao KN, Brown MA. Mast cells: Multifaceted immune cells with diverse roles in health and disease. Ann N Y Acad Sci 2008; 1143: 83-104.
  • Iadecola C, Anrather J. The immunology of stroke: From mechanisms to translation. Nat Med 2011; 17: 796-808.
  • Felger JC. Brain dendritic cells in ischemic stroke: time course, activation state, and origin. Brain Behav Immun 2010; 24:724-37.
  • Tanaka R. Migration of enhanced green fluorescent protein expressing bone marrow-derived microglia/macrophage into the mouse brain following permanent focal ischemia. Neuroscience 2003; 117:531-9.
  • Abbas AK, Lichtmman AH, Pillai S. Effector Mechanisms of Humoral İmmunity (7.Baskı) Celluler and Molecular İmmunology.Elsevier Saunders, Philadelphia, ABD 2012; 269-93.
  • Karabudak R. Temel ve Klinik Nöroimmunoloji (1.Baskı).Edinsel İmmunite. 2013; 27 67.
  • Abbas AK, Lichtman AH. (2007)Temel İmmunoloji: İmmun sistemin işlev ve bozuklukları.Camcıoğlu,Y Kitapevi,İstanbul,s.21-39 ve Deniz G(Çeviri ed).İstanbul Tıp
  • Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 7th edition. Elsevier Sauders, Philadelphia, 2012; 55-88.
  • Badenier MM, Braunersreuther V, Viviani GL, Dallegri F, Quercioli A, Veneselli E, Mach F, Montecucco F. CC and CXC chemokines are pivotal mediators of cerebral injury in ischaemic stroke. Thrombosis and Haemostasis 2011; 105.
  • Abbas, AK, Lichtmman AH, Pillai S. Activation of T lmphocytes Celluler and Molecular İmmunology.Elsevier Saunders,Philadelphia, ABD 2012; 203-25.
  • Kono H, Rock KL. How dying cells alert the immune system to danger. Nat Rev Immunol 2008.
  • Abbas, AK. Basic Immunology Updated Edition: Functions and Disorders of the Immune System. Saunders 2010.
  • Yilmaz A. Transient decrease in circulating dendritic cell precursors after acute stroke: potential recruitment into the brain. Clin Sci 2010; 118:147-57.
  • Becker KJ, Kindrick DL, Lester MP, Shea C, Ye ZC. Sensitization to brain antigens after stroke is augmented by lipopolysaccharide. J Cereb Blood Flow Metab 2005; 25: 1634-44.
  • Balkan S. Serebral vasküler anatomi. İç: Klinik Nöroloji. Oğul E 2002: 3-15.
  • Şener RN. Diffusion MRI: Apperent diffusion coefficient (ADC) values in the normal brain, and a classification of brain disorders based on ADC values.Comput Met Imaging Graph 2001; 25: 299-326.
  • Harald P, Deetje I, Baldinger T. Evidence of intrathecal immunoglobulin synthesis in stroke. Arch Neurol 2012; 69: 714-7.
  • Strand T, Alling C, Karlsson B, Karlsson I, Winblad B. Brain and plasma proteins in spinal fluid as markers for brain damage and severity of stroke. Stroke 1984; 15: 138-44.
  • Sörnas R, Ostlund H, Muller R. Cerebrospinal fluid cytology after stroke. Arch Neurol 1972; 26: 489-501.
  • Akopov SE, Simonian NA, Grigorian GS. Dynamics of polymorphonuclear leukocyte accumulation in acute cerebral infarction and their correlation with brain tissue damage. Stroke 1996; 27: 1739-43.
  • Chuaqui R, Tapia J. Histologic assessment of the age of recent brain infarcts in man. J Neuropathol Exp Neurol 1993; 52: 481-9.
  • Reiber H, Lange P. Quantification of virus-specific antibodies in cerebrospinal fluid and serum: Sensitive and specific detection of antibody synthesis in brain. Clin Chem 1991; 37: 1153-60.
  • Hurn PD. T-and B-cell-deficient mice with experimental stroke have reduced lesion size and inflammation. J Cereb Blood Flow Metab 2007; 27: 1798-805.
  • Kleinschnitz C. Early detrimental T-cell effects in experimental cerebral ischemia are neither related to adaptive immunity nor thrombus formation. Blood 2010; 115: 3835-42.
  • Thompson EJ. Proteins of the cerebrospinal fluid. Elsevier, London 2005.
  • Leys D, He´non H, Mackowiak-Cordoliani MA, Pasquier F. Poststroke dementia. Lancet Neurol 2005; 4: 752-9.
  • Tatemichi TK, Foulkes MA, Mohr JP, Hewitt JR, Hier DB, Price TR, Wolf PA. Dementia instroke survivors in the stroke data bank cohort: Prevalence, incidence, risk factors and computed tomographic findings. Stroke 1990; 21: 858- 66.
  • Lin JH, Lin RT, Tai CT, Hsieh CL, Hsiao SF, Liu CK. Prediction of poststroke dementia. Neurology 2003; 61: 343-8.
  • Mok VC, Wong A, Lam WW, Fan YH, Tang WK, Kwok T, Hui AC, Wong KS. Cognitive impairment and functional outcome after stroke associated with small vessel disease. J Neurol Neurosurg Psychiatry 2004; 75: 560-6.
  • Zhou DH, Wang JY, Li J, Deng J, Gao C, Chen M. Study on frequency and predictors of dementia after ischemic stroke: the Chongqing stroke study. J Neurol 2004; 251: 421-7.
Toplam 41 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Bölüm Dahili Tıp Bilimleri Araştırma Yazıları
Yazarlar

Aslı Bolayır

Hesna Bektaş

Zeynep Issı

Fatma Eren

Selvi Okundu

Yayımlanma Tarihi 21 Ekim 2014
Yayımlandığı Sayı Yıl 2014Cilt: 36 Sayı: 4

Kaynak Göster

AMA Bolayır A, Bektaş H, Issı Z, Eren F, Okundu S. The relationship of intrathecal immunoglobulin levels with clinic symptoms and prognosis for acute phase ischemic stroke patients. CMJ. Aralık 2014;36(4):512-522. doi:10.7197/cmj.v36i4.5000071471