Long-term predictors of remission in patients treated for medication-overuse headache at a specialized headache center: A prospective cohort study.

Objective To evaluate long-term predictors of remission in patients with medication-overuse headache (MOH) by prospective cohort study. Background Knowledge regarding long-term predictors of MOH outcome is limited. Methods Two hundred and forty MOH patients recruited from 2000 to 2005 were included in a one-year follow-up study and then subsequently followed until 31 December 2013. The median follow-up was three years (interquartile range, three years). Predictive values of selected variables were assessed by the Cox proportional hazard regression model. Results At the end of follow-up, 102 (42.5%) patients were in remission. The most important predictors of remission were lower number of headache days per month before the one-year follow-up (HR-hazard ratio = 0.936, 95% confidence interval (CI) 0.884-0.990, p = 0.021) and efficient initial drug withdrawal (HR = 0.136, 95% CI 0.042-0.444, p = 0.001). Refractory MOH was observed in seven (2.9%) and MOH relapse in 131 patients (54.6%). Conclusions Outcome at the one-year follow-up is a reliable predictor of MOH long-term remission.

Comprehensive Ultrasound Assessment of the Craniocervical Circulation in Transient Global Amnesia.

OBJECTIVES: Structural changes and metabolic stress have been reported on diffusion-weighted magnetic resonance imaging in the cornu ammonis 1 area of the hippocampus in patients with transient global amnesia (TGA), but a consensus on pathogenesis is still lacking. The aim of our study was to perform a comprehensive ultrasound analysis of the cerebrovascular circulation in our population of patients with TGA. METHODS: One hundred patients with TGA and 50 age- and sex-matched control participants underwent ultrasound examinations of the cervicocranial circulation. RESULTS: The most significant risk factor for TGA was arterial hypertension (P < .01). There were no significant atherosclerotic lesions on the large arteries of the neck (mean internal carotid artery stenosis ± SD, 28.7% ± 11.7%) or on the large intracerebral arteries (good structural and hemodynamic status; P > .05). Rarely detected microembolic signals or a right-left cardiopulmonary shunt excluded an emboligenic mechanism of TGA (P > .05). The internal jugular vein valves were incompetent in 54% of patients with TGA, and this condition was associated with an increased risk of TGA (odds ratio, 4.16; 95% confidence interval, 1.91-9.04). The mean values of the breath holding index and pulsatility index, as parameters of small-vessel function, were within normal ranges and without differences between the TGA and control groups (P > .05). CONCLUSIONS: Our ultrasound examination did not detect significant structural atherosclerotic changes of cervicocranial arteries, and an emboligenic mechanism was excluded. Only a significant rise of blood pressure in TGA and significant valvular insufficiency of the internal jugular vein were established. New research should clarify whether these simultaneous functional circulatory changes have relevance for metabolic stress in the cornu ammonis of the hippocampus.

Brain sonography insight into the midbrain in myotonic dystrophy type 2.

INTRODUCTION: The aim of this study was to analyze transcranial sonography (TCS) findings in genetically confirmed myotonic dystrophy type 2 (DM2) patients. METHODS: Forty DM2 patients and 38 gender- and age-matched healthy controls (HCs) underwent TCS through the pre-auricular acoustic bone window. RESULTS: Substantia nigra hyperechogenicity was found in 20% of DM2 patients compared with 3% of HCs. Brainstem raphe (BR) hypoechogenicity was more common in DM2 patients compared with HCs (56% vs. 10%, P < 0.01), and it was more common in patients with fatigue and excessive daytime sleepiness (P < 0.05). Diameter of the third ventricle was increased in DM2 patients compared with HCs (5.8 ± 1.7 vs. 5.1 ± 1.0 mm, P < 0.05). CONCLUSIONS: Finding BR hypoechogenicity might have clinical implication because of the potential response to serotonin-reuptake inhibitors. TCS revealed alterations in brain structures previously not seen in MRI studies.

Baseline characteristic of patients presenting with lacunar stroke and cerebral small vessel disease may predict future development of depression.

OBJECTIVE: Cerebral small vessel disease (SVD) is associated with late-onset depression and increases the risk for depression after stroke. We aimed to investigate baseline predictors of depression after long-term follow-up in patients with SVD, initially presenting with first-ever lacunar stroke, free of depression and cognitive impairment. METHODS: A total of 294 patients with SVD were evaluated 3-5 years after the qualifying event. We analyzed baseline demographic data, vascular risk factors, functional status expressed as a score on modified Rankin Scale (mRS), cognitive status, presence of depression, total number of lacunar infarcts and severity of white matter hyperintensities (WMH) on MRI with Age-Related White Matter Changes scale total score (tARWMC) and Fazekas scale periventricular and deep subcortical scores. RESULTS: On follow-up, depression was registered in 117 (39.8%) SVD patients. At the baseline, patients with depression compared with non-depressed were older (64.4 vs 60.9 years; p = 0.007), had higher mRS score (2.8 ± 0.7 vs 1.5 ± 0.7; p < 0.0001) and had more severe lesions on MRI scales (p < 0.0001 for all parameters). On follow-up, depressed patients more frequently exhibited cognitive decline (75.2% depressed vs 56.5% non-depressed; p = 0.003). No difference was detected in risk factor frequency between groups. Multivariate Cox regression analysis adjusted by age and gender revealed independent predictors of depression: baseline mRS >2 (HR 2.17, 95%CI 1.74-2.72; p < 0.0001) and tARWMC (HR 1.05, 95%CI 1.02-1.09; p = 0.005), and cognitive decline on follow-up (HR 1.80, 95%CI 1.12-2.89; p = 0.015). CONCLUSIONS: Baseline functional status and severity of WMH and development of cognitive decline predict the occurence of late-onset depression in patients with SVD.

Transcranial Parenchymal Sonographic Findings in Patients With Cerebral Small Vessel Disease: A Preliminary Study.

OBJECTIVES: Patients with cerebral small vessel disease often present with various motor, cognitive, and emotional changes, including gait disturbances, parkinsonism, and depression. Substantia nigra hyperechogenicity, brain stem raphe hypoechogenicity, ventricle diameters, and sonographic characteristics of other brain structures on transcranial sonography have been increasingly used as biomarkers in a range of neurologic diseases. We aimed to explore the frequency and clinical correlates of transcranial sonographic findings in symptomatic patients with small vessel disease. METHODS: In a cross-sectional study, neurologic, cognitive, and emotional statuses and transcranial sonographic and magnetic resonance imaging findings were compared between 102 patients with small vessel disease and 45 healthy age- and sex-matched control participants. RESULTS: Compared to healthy controls, small vessel disease cases had more frequent brain stem raphe hypoechogenicity (55.9% versus 11.1%; P < .0001), substantia nigra hyperechogenicity (30.4% versus 11.1%; P = .022), and enlarged third ventricles (P < .0001). Substantia nigra hyperechogenicity correlated with gait disturbances, extrapyramidal features, and cognitive impairment. Brain stem raphe hypoechogenicity was associated with the diagnosis of depression. Enlargement of the third and lateral ventricles was more frequent in patients with cognitive impairment. Pathologic substantia nigra hyperechogenicity and enlarged ventricles were associated with the severity of cerebral ischemic lesions. CONCLUSIONS: Transcranial sonography shows pathologic findings in a substantial number of patients with small vessel disease, probably reflecting disruption of frontostriatal pathways.

Transcranial Doppler assessment of cerebral vasomotor reactivity in evaluating the effects of vinpocetine in cerebral small vessel disease: a pilot study.

BACKGROUND: There are still dilemmas about the vasodilating effect of vinpocetine, a synthetic ethyl alkaloid vincamine. The method of measuring cerebral vasomotor reactivity (VMR) by transcranial Doppler (TCD) technique before and after administration of the medication was used to estimate the degree of arterioles vasodilatation. The aim of this study was to test of the vasodilating effect of vinpocetine in patients with cerebral small vessel disease (SVD) by measuring cerebral VMR. MATERIAL AND METHODS: Thirty patients with SVD were on 3-month-long oral treatment with 15 mg vinpocetine daily. Cerebral VMR was determined by breath holding test. The breath holding index (BHI) was calculated in standard manner and values > 0.69 were considered normal. At the baseline, before treatment (I), BHI, modified Rankin scale (mRS) score, Mini Mental State Examination (MMSE) score were determined. One month later (II) BHI was assessed again, while after 3 months of treatment (III) we analyzed BHI, mRS score and MMSE score. RESULTS: The average age of patients was 61.4 +/- 11.5 years (range 40 to 77 years), 18 (60%) female and 12 (40%) males. Values of BHIs were increased during treatment at the right MCA (I) 1.18 +/- 0.53, (II) 1.26 +/- 0.54, (III) 1.37 +/- 0.41, with statistical significance between I and III measurement (p < 0.05). An increase was noted on the left MCA (I) 1.25 +/- 0.53, (II) 1.31 +/- 0.55 and (III) 1.32 +/- 0.42, but it did not reach statistical significance (p > 0.05). Mean MMSE score significantly increased from baseline 27.4 +/- 2.3 to 28.5 +/- 2.0 after three months of treatment (p < 0.001). Functional status showed a statistically significant improvement with mRS score increasing from 2.1 +/- 1.0 to 1.1 +/- 0.6 (p < 0.001). CONCLUSION: This pilot study showed that 3-month-long oral treatment with vinpocetine 15 mg daily had tendency to increase BHI, indicating improvement of cerebral VMR. It is possible that higher doses of vinpocetine are needed to achieve substantial increase of VMR.

Carotid artery wall stiffness is increased in patients with small vessel disease: A case-control study.

INTRODUCTION: Cerebral ischemic small-vessel disease (SVD), causing lacunar infarcts and white matter hyperintensities on brain magnetic resonance imaging (MRI), is a progressive disease associated with an increased risk of stroke, dementia and death. Increased arterial stiffness has been associated with ischemic stroke and cerebral SVD independently of common vascular risk factors. OBJECTIVE: The aim of the study was to analyze arterial stiffness in our patients with symptomatic SVD. METHODS: In a cross-sectional study design we included 30 patients with clinical and MRI evidence of cerebral SVD and 30 age-, gender- and risk factor-matched control subjects with no neurological diseases. Patients were evaluated at the Ultrasound Laboratory at the Neurology Clinic, Clinical Center of Serbia in Belgrade, during a three-month period (from September 1st to December 1st 2012). Baseline demographic and vascular risk factors were recorded. All patients underwent standard carotid ultrasound scans with measuring of intima-media thickness (IMT) and analysis of atheromatous plaques. Internal carotid artery stiffness was evaluated with the use of e-tracking option as beta stiffness index (BSI) value. RESULTS: There were no differences between study groups in regard to degree of carotid stenosis and type of carotid plaques (p > 0.05). Patients in SVD group had significantly higher mean IMT (p = 0.0093) and mean BSI (p < 0.0001) than subjects in the control group. No significant correlation was detected between IMT and BSI in SVD group (r = 0.168; p = 0.376). Brain lesions severity correlated with BSI (r = 0.733; p < 0.0001). CONCLUSION: Arterial stiffness is increased in symptomatic patients with SVD, independently of vascular risk factors and IMT.

Cerebral small vessel disease in pseudoxanthoma elasticum: three cases.

BACKGROUND: Cerebral small vessel disease is rarely described in association with pseudoxanthoma elasticum (PXE), a hereditary connective tissue disorder with skin, eye and vascular manifestations. This autosomally inherited elastic tissue disease has been attributed to mutations in the ABCC6 gene located on chromosome 16p13.1. Different stroke mechanisms are suggested in PXE patients, arterial hypertension and accelerated atherosclerosis being the leading ones. CASE DESCRIPTIONS: Case 1: A 49-year-old man with history of mild hypertension presented with recurrent transient ischemic attacks. At the age of 42, evaluation for progressive visual loss and skin changes led to diagnosis of PXE. Brain magnetic resonance imaging (MRI) disclosed multiple lacunar infarctions and confluent periventricular white matter lesions (WML). Case 2: A 71-year-old woman with history of mild hypertension suffered right-sided stroke. Diagnosis of PXE was made at the age of 48 due to severe visual loss and skin changes. Brain MRI revealed multiple lacunar infarctions and subcortical ischemic leukoencephalopathy. Case 3: A 47-year-old woman with prominent skin changes and bilateral amblyopia developed right-sided weakness. Skin biopsy confirmed PXE. Several lacunar infarcts in deep white matter and pons were revealed on MRI. DISCUSSION: We present three patients with clinical and histopathological features of PXE who presented with multiple lacunar strokes, two with extensive confluent WML. These cases illustrate that PXE is a rare but significant risk factor for small vessel disease and stroke in patients of all age groups. Occlusive small vessel disease and subsequent lacunar infarcts and WML represent important PXE manifestations.

Increased frequency of pathologic findings on transcranial B-mode parenchymal sonography in patients with sporadic amyotrophic lateral sclerosis.

Although amyotrophic lateral sclerosis (ALS) is characterized by involvement of motor neurons in the motor cortex, brainstem and spinal cord, there is accumulating evidence that it is a multisystem degenerative disease, with dysfunction of the striatonigral dopaminergic system as well. Transcranial B-mode sonography of the parenchyma enables depiction of the differing tissue echogenicity of midbrain and basal ganglia structures in various movement disorders. Transcranial B-mode sonography was performed in the standard manner in 101 patients with sporadic newly diagnosed ALS and 60 age- and gender-matched controls. Increased frequencies of pathologic substantia nigra hyper-echogenicity (p = 0.027), interrupted brainstem raphe (p = 0.003) and increased third ventricle diameter (p < 0.0001) were detected in ALS patients as compared with healthy controls. Only four ALS patients exhibited some features of parkinsonism. Pathologic findings on transcranial B-mode sonography of parenchyma did not correlate with clinical presentation, functional status or disease subtype. Our study provides additional evidence of multisystem involvement in ALS patients, particularly in subcortical areas.

Migraine with aura and TCD bubble-test: The significance of positive result.

BACKGROUND/AIM: The association between the right-to-left shunt (RLS) and migraine with aura (MA) has been proven so far. The aim of this study was to determine if the presence of RLS detected as a result of transcranial doppler (TCD) bubble-test, makes any difference in clinical presentation, aura and headache in patients with MA. METHODS: A single-group descriptive study was conducted on 153 patients diagnosed with MA. TCD bubble-test was performed on 135 of them. The recorded demographic and clinical features of patients were analyzed and compared with the results of the TCD bubble test. RESULTS: In the group of 135 patients, 88 (65.2%) had positive TCD bubble-test. The difference in the investigated clinical features of patients of the patients and aura between the patients with and without RLS, was not found. CONCLUSION: The results of our study confirm a high prevalence of right-to-left shunt in patients with MA, but the clinical relevance of this association was not shown.

What are the differences between younger and older patients with symptomatic small vessel disease?

OBJECTIVE: Although typically linked to aging, small vessel disease (SVD) is also observed in younger adult patients, with common vascular risk factors (RF). We aimed to investigate features of SVD occurrence at an early adult age. PATIENTS AND METHODS: Vascular RF, functional and cognitive status and severity of lesions on MRI expressed as total score on Age-Related White Matter Changes (ARWMC) scale were analyzed in 200 consecutive patients with cerebral SVD admitted to a tertiary neurological hospital. Variables were compared between younger (35-55 years) and older (>56 years) patients. RESULTS: In this study, 63 (31.5%) of patients were 55 years or younger. Both age groups had comparable RF profiles, but smoking emerged as an independent predictor for SVD at a younger age (OR 2.9; 95% CI 1.5-5.5; p=0.002). Younger patients had better functional (OR 1.8; 95% CI 1.3-2.5; p=0.0001) and cognitive (χ(2) 13.94; p=0.0009) status compared to older patients. However, two thirds of younger patients had some degree of cognitive deficit. Total score on ARWMC scale was lower in younger patients (mean 12.3 in younger versus 15.2 in older, OR 1.11; 95% CI 1.0-1.18; p=0.001). There was a strong correlation in both groups between functional score, cognitive status and ARWMC score (p<0.0001). CONCLUSION: In our dataset, younger patients with SVD shared common vascular RF with older patients. In the group aged ≤55, better functional and cognitive status and less severe MRI changes were noted. However, a substantial number of younger SVD patients presenting with TIA or ischemic stroke had various deficits.

[Incompetence of internal jugular vein valve in patients with transient global amnesia].

BACKGROUND/AIM: Transient global amnesia (TGA) could be related to acute ischemic disturbances in mesial parts of temporal lobes, which are important for memory. Incompetence of internal jugular vein (IJV) valve with venous congestion causes venous microthrombosis of hippocampus. The aim of this study was to investigate the frequency of IJV valve incompetence, as well as other hemodynamic and structural properties of cerebral circulation in TGA patients. METHODS: IJV valve competence was investigated in 40 TGA patients and 30 persons of the control group (matched by age and sex), as well as detection of microembolic signals and detection of right to left cardiopulmonal shunt, cerebral vasomotor reactivity and echocardiography by color triplex ultrasonography and transcranial doppler. RESULTS: A significant difference in frequency of IJV valve incompetence was found between the TGA patients and the control persons (55% TGA vs. 30% controls; p < 0.001). We did not find a significant structural (plaques frequency) or hemodynamic (flow velocity, pulsatility index) differences on arteries of the neck and cerebral arteries between the TGA patients and the controls, except for the increased pulsatility index on the basilar artery (40% TGA vs. 16.6% controls; p < 0.01) and decreased vasomotor reactivity in TGA patients (50% TGA vs 26.6% controls;p < 0.001). Microembolic signals were detected very rarely (17.5% TGA patients vs. 13.3% controls; p > 0.05), as well as right to left cardiopulmonal shunt (15% TGA vs. 16.6% controls; p > 0.05), indicating that embolism was not important for pathogenesis of TGA. Transesophageal echocardiography confirmed it, because only one TGA patient had a potent foramen ovale. CONCLUSION: We found a significantly increased frequency of IJV incompetence in the TGA patients, which confirmed the role of vein drainage disturbances in pathogenesis of TGA.

Speech and language disorders secondary to diffuse subcortical vascular lesions: Neurolinguistic and acoustic analysis. A case report.

BACKGROUND AND PURPOSE: Subcortical white matter (WM) plays an important role in speech production and language processing. Most frequently, cerebral WM lesions are secondary to small vessel disease in patients with vascular risk factors. We report the case of a 53-year-old man with history of hypertension and ischemic subcortical lesions, who presented with speech difficulties and mild cognitive impairment. METHODS: Language and cognitive assessment included Boston Diagnostic Aphasia Examination, Boston Naming Test, Rey Auditory-Verbal Learning Test, Rey-Osterrieth Complex Figure Test, Trail Making Test A and B, Wisconsin Card Sorting Test, Scale for Evaluation of Perceptive Characteristics of Voice and Speech, and Multidimensional Evaluation of Speech and Voice. RESULTS: Brain MRI showed ischemic WM lesions and lacunar infarcts in the brainstem and right cerebellum. Cognitive testing revealed mild cognitive impairment, predominantly affecting attention and executive functions. Speech and language analysis demonstrated dysarthria, dysphonia with hypophonia, and imprecise articulation, as well as short rushes of speech, palilalia and mild subcortical dysphasia. CONCLUSIONS: Neurolinguistic and acoustic analysis in patients with ischemic WM lesions can provide additional information in the understanding of language and speech disturbances, and can assist in patient management.

[Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)--three case reports from Serbia].

INTRODUCTION: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary microangiopathy leading to recurrent strokes and vascular dementia in young and middle-aged patients. The diagnosis of CADASIL is based on typical clinical presentation and characteristic magnetic resonance imaging (MRI) changes, and has to be confirmed by biopsy of the sural nerve, muscle and skin, as well as by genetic analysis. Mutations within the Notch3 gene were identified as the underlying genetic defect in CADASIL. CASE OUTLINE: The clinical manifestations of the first presented patient with migraine from the age of thirteen, stroke without vascular risk factors and stepwise progression of vascular dementia comprising the typical clinical picture of CADASIL, were confirmed after seven years with pathological verification. The second presented case did not satisfy the clinical criteria for CADASIL. His stroke was considered to be related with vascular risk factors--diabetes mellitus and hypertension. The aetiological diagnosis was established only when his brother without vascular risk factors presented with similar clinical manifestations. CONCLUSION: Until the development of the new neuroimaging techniques like MRI, pathologic and genetic analysis, CADASIL was considered as a rare disorder. However, the increasing number of CADASIL families has been identified throughout the world showing that this entity is usually underdiagnosed. This article presents three patients from two Serbian families with clinical suspicion of CADASIL verified by pathologic examination.

[Transcranial Doppler test for evaluation of cerebral artery embolism--microemboli detection].

About one third of ischaemic cerebrovascular diseases have embolic properties. Because of that, transcranial Doppler (TCD) test for detection of microembolic signals (MES), as the only one method for detection of microemboli, is a very important test for the evaluation of cerebral artery embolism. Cerebral emboli are particles of thrombus or atheromatous plaque, platelet aggregates, lipid or air particles in cerebral circulation, which can occlude arterioles and cause ischaemic transient attack (TIA) or stroke. Most frequently, they derive from exulcerated plaques of the carotid bifurcation or the aortic arch, from the atrial thrombus, prosthetic heart valves, as well as during carotid endarterectomy, arterial stent, aortocoronary by-pass. For MES detection, bilateral monitoring of a. cerebri mediae (ACM) is performed with each probe held in place over a temporal bone. MES are represented as brightly coloured embolic tracks as they pass through the insonated arteries. A computer hard disk provides continuous recording that is replayed for counting embolic signals. Colour intensity or acoustic range indicate the size and structure of MES. MES in the range of one ACM indicate the source of embolism on the ipsilateral carotid artery, while the bilateral detection of MES suggests a cardiogenic source. Indications for TCD detection of MES are the evaluation of pathogenesis and risk for embolic stroke or TIA and assessing the source of embolism. We started applying this method at the Institute of Neurology in Belgrade 2 years ago. We have investigated 78 patients till today and detected MES in 23 patients (28.7%). The Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology, 2004, considers that TCD is probably useful for detection of cerebral MES in various cardiovascular and cerebrovascular disorders and procedures.

[Paroxysmal hemicrania]. / Paroksizmalna hemikranija.

Paroxysmal hemicrania (PH) is one of the trigeminal autonomic cephalgias (TACs), a group of primary headache disorders characterized by unilateral trigeminal distribution pain that occurs in association with prominent ipsilateral cranial autonomic features. The TACs are relatively rare, which is likely to be why they are poorly recognized in primary care. TACs will thus be referred to neurologists eventually, offering an excellent opportunity to diagnose and treat these patients. PH responds in a dramatic and absolute fashion to indomethacin. The importance of recognizing these syndromes is underscored by their excellent but highly selective response to treatment. This is the case report of our patient with PH and the review of current knowledge about pathophysiology of TACs, as well as differential diagnosis of other entities from this headache group.

[Plasminogen activator inhibitor-1 in the evolution of stroke]. / Inhibitor 1 aktivatora plazminogena u evoluciji mozdanog udara.

Fibrinolytic activity in the acute stroke was examined by monitoring the level of plasminogen activator inhibitor-1 (PAI-1), as one of the indicators of fibrinolytic activity. Given the role of PAI-1 in the processes of atherogenesis and thrombogenesis, plasma PAI-1 level was measured in 59 patients (up to 50 years of age) with atherothrombotic stroke (verified by computed tomography scanning or magnetic resonance imaging of brain) in the period from 12 to 24 hours (I analysis) and 30 days after the onset of stroke (II analysis); then, it was correlated with plasma PAI-1 level in the control group (57 healthy subjects), which was 2.86 +/- 0.70 U/ml. It was found that PAI-1 level was significantly higher in the acute stroke (I analysis: PAI-1 = 4.10 +/- 1.40 U/ml, p < 0.001; II analysis: PAI-1 = 3.64 +/- 0.90 U/ml, p < 0.001), while fibrinolytic activity was lower, especially on the first day from the stroke that was not completely increased even after 30 days. There was no difference in PAI-1 levels between the subgroups of patients with infarction and lacunar cerebral ischemia (p > 0.05), as well as between females and males (p > 0.05). Along with significantly increased fibrinogen level (4.65 +/- 1 g/l, in the controls--2.83 +/- 0.64 g/l, p < 0.001), significantly higher triglycerides (2.04 +/- 0.76 mmol/l, in the controls--1.38 +/- 0.54 mmol/l, p < 0.001) and lipoproteins(a) (0.405 +/- 0.29 g/l, in the controls--0.172 +/- 0.14 g/l, p < 0.001) were found, correlating with higher plasma PAI-1 level in these patients. The increased plasma level of PAI-1 pointed to possibility of decreased fibrinolytic activity in pathogenesis of ischemic stroke, as well as, risk of reinsult, which had been the greatest after the onset of stroke and declined gradually within several weeks.