Protein S Deficiency and Ischemic Stroke

Table of contents

1. Introduction

troke constituted the principal causes of hospitalisation in African neurological unit. The ischemic strokes are more frequent than haemorrhage, 63% to 80.9%, [1][2][3] , with high frequency of multiples infarcts, 13.50% and leucoaraiosis, 58.75%. [2] The main risk factors were high blood pressure, heart diseases, diabetes, infectious and other indeterminate causes. Since the discovered of the protein S, many last studies established it's implication in thrombotic states. The hereditary protein S deficit was found in 12.4% and acquired in 21.5%. Recently, the deficit on fibrinolysis factor or coagulation inhibitor (proteins S and C) were found as the important aetiology of ischemic stroke in young people, with frequency range from 13.8% to 16%. [4][5][6] The authors reported three ischemic strokes with protein S deficiency as the only risk factor in African young people. All patients and their relatives have given informed consent. The study was approved by the local ethic committee. Table I show the patients clinical characteristic II.

2. Observation a) Case 1

A 37 years old trader woman with a long personal history of left leg stepped and lameness a year ago due to intramuscular injection came to our visit because of weakness of half right body. Her waist was 1,64m with 60 Kg of weight. The neurological exam revealed half right paresis with 3/5 muscular force in leg and 4/5 in arm, with hyper reflexivity, and Babinski sign. None body sensibility disturbance was noted. All routine blood analysis was normal except low protein S with 15% (normal: 80-130%). Hearts recording and ultrasonic exam were normal. Ct-scan showed left fronto parietal hypo density directed to ischemic stroke. No other risk factor was found. The patient received enoxaparin 0.6mlx2/day, relieved by salicylic acetyl acid 250 mg/day and daily kinesitherapy. After three months of treatment a slight regression of neurologic symptoms was noted with Rankin scale at 2/6. At eight months later the patient died by stroke relapse.

3. c) Case 3

A 56 years old carpenter man, with no personal and family history of cardiovascular diseases came to our observation with four hours of brutal left half body deficit. His height was 1,70m for 58 kg weighted and 130/80 mmHg for blood pressure. Neurological examination revealed, speech disturbance, left hemi paresis predominant on arm and face (2/5 arm, 4/5 leg). The left reflexes were low with Babinski sign, and left half body sensibility disturbed was noted. Routine blood analysis were normal except low protein S at 32% (normal: 80-130%). Hearts recording and ultrasonic performed were normal. Doppler of suproaortic vessels was normal. Ct-scan and MRI revealed right thalamus, corona radiate and parietal cortex ischemia with cortical and sub cortical atrophy that directed to ischemic stroke with multiples infarcts. Enoxaparin 0.6ml/day was started and relieved by clopidogrel 75 mg/day associated to daily kinesitherapy. The patient had completely health recovery after six months of follow up.

4. III.

5. Discussion

The main known risk factors of ischemic stroke in young African people are high blood pressure, heart diseases, diabetes, alcohol, tobacco, and lipids. Our b) Case 2 A 45 years old man, with no cardiovascular diseases diagnosed beforehand and other stroke risk factor came to our visit because of rapid left half body deficit and dysphasia. He weighed 70 kg for 1,72m of size and 140/90 mmHg of blood pressure after several controlled. Neurological examination revealed left hemi body palsy. The left reflexes were low with Babinski sign, right half body sensibility was normal. All routine blood analysis were normal except low protein S at 22% (normal: 80-130%). Doppler of supraaortic trunk, electrocardiogram and heart ultrasonic recording were normal. Ct-scan and MRI revealed right internal capsule and lenticular nucleus infarcts. Enoxaparin 0.7ml two times daily was started and relieved by clopidogrel 75 mg/day. A daily kinesitherapy was made. The patient remains with partial deficit recovery after eight months.

IV.

6. Conclusion

The protein S deficiency constitutes an ischemic stroke risk factor in black young people, and must be researched forwards all cerebral infarct to reduce the indeterminate stroke aetiology. A wide prospective study is necessary to measure the real prevalence and frequency of coagulation disturbance factors in our countries, in the setting of stroke prevention. Legend: M: male; F: female; SAA: salicylic acetyl acid.

three patients had not presented any of this main risk factor. It was necessary to make the research of coagulation inhibiting factor as protein C and S. We only make the research of protein S because patients had no much money and this test was not available done in our country. The patients had not forwards used anticoagulant and oestroprogestatif treatment or other treatment that could lead to diminish the protein S level. The deficit in protein S was not acquired in our patients. We did not make the protein S and CT scan control because the needy patients had to pay themselves. We did not also make the patient and their family biological and genetic survey but we retain a constitutional deficit in protein S as the ischemic stroke risk factor in these three patients. The protein S deficiency can be asymptomatic and explained the absence of familial thromboembolic disease that could be related. The deficiency in protein S as the cerebral infarct aetiology is rarely reported in young African people. [4] The estimation of the frequency of the protein S deficient in general population, and in black African in particular is difficult because of the lack of epidemiologic data and the studies were extremely rare. The frequency of protein S deficiency range around 11% to 34% in black African and Caribbean population. [5,7] This large diversity of the prevalence and the frequency must due to population heterogeneity and rare studies. The age of first onset reported range around 15 to 45 years old in patients with ischemic stroke, and the abnormities seemed to be autosomal dominant transmission. [4,6,8] This high prevalence of protein S deficiency must exist in African countries but still unknown.

Figure 1. Table 1 :
1
N° Age/Sex Clinical features CT-scan/ MRI Protein Treatment Follow up
S level
01 37 F Right hemi paresis with 3/5 Left fronto parietal 15% -Enoxaparin Rankin scale at
in leg and 4/5 in arm, high hypo density (N: 80- 0.6mlx2/day, -SAA 3/6, stroke relapse,
reflex, Babinski sign 130%) 100 mg/day - died.
Kinesitherapy.
02 45 M -Left half body deficit and Right internal 22% -Enoxaparine Partial deficit
speech disturbance, capsule and (N: 60- 0.7ml/day relieved recovery after eight
-The right reflexes were lenticular nucleus 130%) by months
abolish with Babinski infarct, Clopidogrel 75
mg/day. -
Kinesitherapy
03 56 M -Left hemi paresis (2/5 arm, -Right thalamus, 32% -Enoxaparin Completely health

Appendix A

  1. Les accidents ischémiques cérébraux du sujet jeune. D Leys . Rev. Med. Interne 2003. 24 p. .
  2. Natural anticoagulant (antithrombin III, protein S and protein C) in patients with mild to moderate ischemic stroke. E Haapaniemi , T Tatlisumak , L Soinne , M Syrjala , M Kaste . Acta Neurol Scand 2002. 105 p. .
  3. Natural coagulation inhibitor proteins in young patients with cerebral ischemia. L Olah , M Misz , J Kappelmayer , E Ajzner , T Csepany , I Fekete . Cerebrovasc Dis 2001. 12 p. .
  4. Incidence and pattern of cerebrovascular diseases in Benghazi, Libya. P P Ashok , K Radhakrishman , R Sridharan , M A El-Mangoush . J Neurol Neurosurg Neuropsychiatry 1986. 49 p. .
  5. Protein S and ischemic brain disease. R Raicevic , A Jovicic , S Mandic-Radic , D Dordevic , L Markovic , E Dincic . Vojnosanit Pregl 2003. 60 p. .
  6. Hereditary deficiencies of antithrombin III, protein C, protein S pathway in Jordanian thrombosis patients. S S Eid . Clin Lab Sci 2002. 15 p. .
  7. Les infarctus cérébraux de petite taille en Cote d'Ivoire: étude rétrospective clinique et scannographique de 113 cas. T Sonan-Douayoua , P Yapo , B Assi , F Akani , P Cowpli-Boni , E Aka-Diarra . African Journal of Neurological Sciences 2004. 23 p. .
  8. The prevalence of protein C, protein S and antithrombin III deficiencies in non APS/SLE Chinese adults with non cardiac and cerebral ischemia. W H Chen , M Y Lan , Y Y Chang , S S Chen , J S Liu . Clin Appl Thromb Hemost 2003. 9 p. .
Date: 2014-01-15