The Research On Epidemiological Characteristics Of Cerebral Venous Sinus Thrombosis In China And The Safety And Efficacy Of Endovasular Therapy

Part One:The epidemiological characteristics of Cerebral Venous Sinus Thrombosis in ChinaObjective:Cerebral venous sinus thrombosis(CVST)is a rare disease.At present,most of its fundamental research was carried out in the European countries and the United States;but there is little research in Asia.The research on the causes and risk factors of CVST is even less in China,especially on the thrombophilic states of CVST,including protein C deficiency,protein S deficiency,antithrombin III deficiency,gene mutation on factor V mutation and prothrombin G20210A.The epidemiological characteristics of CVST are different due to different countries,regions and races.The aim of this study is to summarize the data of CVST in Qilu Hospital of Shandong University in the past 10 years,retrospectively analyze the epidemiological characteristics of CVST patients,and compare with the data of International CVST Research Center(ISCVT),in order to clarify the epidemiological characteristics of CVST in China and its similarities and differences with foreign related studies,and analyze the relationship between different factors and prognosis,so as to provide basic support for follow-up treatment.Methods:We retrospectively analyzed the clinical data of 172 CVST patients with complete follow-up records from January 2007 to January 2017 in Qilu Hospital of Shandong University.Basic date of CVST were recorded,including patients' age,gender,risk factors,presenting symptoms,hospitalization days,thrombus location,epilepsy,intracranial hemorrhage,treatment types and details.We also recorded whether there is a recurrence or not,improved mRS score and clinical outcomes,degree of neurological deficit at last follow-up,then compared the main data with ISCVT.The risk factors associated with the prognosis of CVST in China were analyzed statistically.Results:Of all the 172 CVST patients,the age range was 7 to 70 years old,the average age was 34.40 ± 12.71 years,7 patients were youth and children(<18 years old =,and the other 165 patients were adults,the average age of adult patients was 35.53 ±12.73 years.There were 78 male patients with an average age of 33.53 ± 12.84,and 94 female patients with an average age of 35.13 ± 12.55,male:female = 1:1.2.89.2%(148/166,6 missing)of the CVST patients had headache,31.4%(54/172)of them sufferred epilepsy during the period of illness,18.8%(31/165,7 missing)had focal motor deficits,7.2%(12/166,6 missing)had sensory disorder,13.4%(23/172)sufferred with mental status disorders,11.6%(19/164,8 missing)had diplopia or visual impairment,9.9%(17/172)presented with vomiting,5.23%(9/172)had motor or sensory or mixed aphasia.In terms of thrombus location,transverse sinus(TS)thrombosis involved 129 cases,followed by sigmoid sinus 99 cases,superior sagittal sinus 91 cases,straight sinus 48 cases,torcular Herophili 16 cases,internal jugular vein 12 cases,inferior sagittal sinus 12 cases and the vein of Galen 7 cases.Transverse sinus stenosis involved 7 patients.Thrombosis involved multiple venous sinuses in 154 cases and single sinus in 18 cases,including 15 cases of superior sagittal sinus and 3 cases of transverse sinus.In terms of risk factors of CVST,hyperhomocysteine accounted for 24.7%(40/162,10 missing),followed by pregnancy and puerperium 20.9%(36/172),which acounted for 38.3%(36/94)in femal,protein C deficiency and protein S deficiency 19.9%(33/161,11 missing),anemia 13.8%(26/167,7 missing),Otitis media,mastoiditis,and sinusitis was 12.2%(21/172),of which 2.9%of the patients were confirmed as suppurative infected(5/172),oral contraceptives was 8.7%(15/172),which acounted for 16.0%(15/94)in femal,antithrombin III deficiency accounted for 5.8%(10/172),diarrhea and dehydration ratio was 5.8%(10/172).history of cerebral venous sinus thrombosis or family history of deep vein thrombosis accounted for 3.5%(6/172),the rest few risks are described in detail later.38.4%(66/172)of the patients had intracranial hemorrhage during the onset of the disease.The main treatments included:130 patients received anticoagulant therapy alone,36 cases received EVT,6 cases received decompressive decompression(DC)(including 5 cases received combined interventional therapy),and the remaining 6 refused EVT treatment and received symptomatic treatment.Mean duration of illness at presentation was 25.45±36.44 days,and the average time of hospitalization was 15.38±7.54 days,at discharge 116 patients had a mRS score of 0,20 patients had a mRS score of 1,8 patients respectively had a mRS score of 2 and 3,9 patients had a mRS score of 4,4 patients had a mRS score of 5,7 patients had a mRS score of 6,and an average mRS score was 0.91 ± 1.66.Patients with good prognosis(mRS ? 2)at discharge were 83.7%(144/172)and patients with poor prognosis were 16.2%(28/172),including 6 cases of death.After 6 months of discharge,the average mRS dropped to 0.45 ± 1.03,and the patients with good prognosis(mRS ?2)were 86.6%(149/172).After 12 months of discharge,the average mRS was further reduced to 0.42±0.76,and the patients with good prognosis(mRS ?2)were 88.4%(152/172).The rate of complete recanalization was 84.9%,the rest 15.1%was partial recanalization.There were 5 cases of recurrence,3 of them were caused by the withdrawal of warfarin after discharge.No ICH or death occurred in the follow-up.Conclusions:1.This study showed that the average age of CVST patient in China was 34.40 years,among which the average age of adults was 35.53 years,male:female =1:1.2.The most common clinical symptoms and signs were headache 89.2.0%,followed by epilepsy 31.4%,dyskinesia 18.8%,disturbance of consciousness 13.4%,visual impairment 11.6%and sensory impairment 9.9%.Intracranial hemorrhage occurred in 38.4%of patients.In our study,hyperhomocysteinemia is accounted for the largest percentage 24.7%of all risk factors,followed by protein C deficiency and protein S deficiency account for 19.9%,antithrombin ? deficiency account for 5.8%,anemia account for 13.8%,diarrhea,dehydration account for 5.8%,pregnancy and puerperium in all female patients account for 38.3%,and oral contraceptive account for 16.0%;The most common sites of thrombosis were transverse,followed by sigmoid sinus,superior sagittal sinus,straight sinus,torcular Herophili,internal jugular vein,inferior sagittal sinus and the vein of Galen.The Mean duration of illness at presentation was 25.45 ±36.44 days.The average time of hospitalization was 15.38±7.54 days;the good prognosis rate was 83.7%at discharge and 88.4%at 12 months after discharge.2.The percentage of female patient in our study is less than the ISCVT group(54.7%<74.6%),and the adult average age at diagnosis was younger than that of ISCVT group(35.53<39.1 years),the percentage of pregnancy and puerperium in our study is higher than the ISCVT group,the percentage of oral contraceptive patient is less than the ISCVT group.In this study,mental status disorder,intracranial hemorrhage,and thrombosis of straight sinus were correlated with poor prognosis.The ISCVT group showed that age>37 years,male sex,coma,mental status disorder,hemorrhage on admission CT scan,thrombosis of the deep cerebral venous system,central nervous system infection,and cancer were correlated with poor prognosis.Part two:Study on the safety and efficacy of endovascular therapy for CVSTObjective:Anticoagulation therapy is the basic consensus of current guidelines for the treatment of the CVST patients,which include heparin,low molecular heparin and warfarin.But anticoagulation has the disadvantage of having too long process of thrombolysis and may aggravate ICH,especially for the patients with poor anticoagulant effect,severe disturbance of consciousness,extensive venous sinus thrombosis and ICH.So many clinicians have great concerns about the application of anticoagulant therapy,while intravascular interventional therapy can rapidly clear the clot in venous sinuses and relieve the symptoms of increased intracranial pressure,which,together with Decompressive Craniectomy(DC),has been recommended by the American stroke association(ASA)as one of the main treatment methods.For the randomized controlled study can not approved by Ethics Committee,there is lack of randomized controlled study worldwide at present.Because EVT's safety and effectiveness is based on case reports and small sample study data,so the EVT treatment is still controversial,and it is only the recommended treatment but not the guideline.Our aim was to assess the EVT's safety and effectiveness,and explore the best scheme for the future through our EVT treatment data on CVST patients,whom were retrospectively analyzed from QiLu Hospital of Shandong University in the past 10 years.Methods:36 cases of CVST patients who were treated by EVT were retrospectively analyzed in QiLu Hospital of Shandong University from January 2007 to January 2017 for 10 years,the complete follow-up record of CVST with EVT treatment were collected,which included treatment details such as type of EVT(stent retriever thrombectomy,mechanical thrombectomy,balloon-assisted thrombectomy,catheter thrombolysis,continuous thrombolysis,stenting et al),GCS score of pre-operation and post-operation,clinical outcomes,degree of sinus recanalization,thrombus recurrences,periprocedural complications.We also recorded the modified mRS score at discharge time and 6 month after discharge and 12month after discharge.Then analyze the clinical data(GCS score)by t analysis,summarize the preoperative and postoperative data and assess the EVT's safety and effectiveness.Result:In this study,33 patients received mechanical thrombectomy,33 patients received catheter thrombolysis,21 patients received stent retriever thrombectomy,18 patients received continuous thrombolysis,4 patients received balloon-assisted thrombectomy,and 4 patients received stenting.In addition to the EVT,five people also underwent DC.The preoperative GCS score of 36 CVST patients was 12.29 ±4.18,and the postoperative GCS score was 14.6 ± 3.03.At the time of discharge,the average modified mRS score was 1.54±1.78,and the ratio of good prognosis(mRS? 2)was 69.4%(25/36).After 6 months of discharge,the average modified mRS score was 1.03±1.15,and the ratio of good prognosis(mRS ? 2)were 77.8%(28/36).The mean value of modified mRS at 12 months after discharge was 0.89 ±1.02 and 83.3%(30/36)of patients with good prognosis(mRS ?2).None of the 36 patients with CVST who received EVT in this study died during hospitalization and follow-up.The rate of patients with complete recanalization after 12 months was 80.6%(29/36),and the rate of partial recanalization was 19.4%(7/36).It is a pitythat all of the 6 patients who refused the EVT therapy died in the same period.Conclusion:1.EVT is a safe and effective treatment for patients with CVST.2.Patients with severe CVST have a high risk on anticoagulation therapy,and have extremely high mortality rate by treating with symptomatic support only.Once accept timely and effective treatment,the overall prognosis is still good.