Therapy insight: stroke risk and its management in patients with sickle cell disease

Children with sickle cell disease, a chronic hemolytic anemia, present with a wide variety of neurological syndromes, including ischemic and hemorrhagic stroke, transient ischemic attacks, 'soft neurological signs', seizures, headache, coma, visual loss, altered mental status, cognitive difficulties, and covert or 'silent' infarction. Those with ischemic stroke usually have stenosis or occlusion of the distal internal carotid and proximal middle cerebral arteries. Indefinite transfusion prevents recurrence in most patients who have had a stroke, and can prevent first stroke in those with high transcranial Doppler velocities. High white cell count, low hemoglobin and oxyhemoglobin desaturation predict neurological complications. Other risk factors for overt ischemic stroke include hypertension, previous transient ischemic attack, covert infarction and chest crisis. For hemorrhagic stroke, aneurysms are common in adults but not children, who often present with hypertension after transfusion or corticosteroids. Seizures are particularly common in patients with cerebrovascular disease and covert infarction; the latter is also associated with hyposplenism and infrequent pain. Factors associated with cognitive difficulties include thrombocytosis, infarction, large-vessel disease, and perfusion abnormality on neuroimaging. As well as investigating the role of genes and the possibility that hydroxyurea or blood pressure control reduce neurological complications, we should explore the modifiable effects of poor nutrition, chronic infection, hemolysis and oxyhemoglobin desaturation on stroke risk.     

Ischaemic cerebrovascular events in HIV infection: a cohort study

Several case reports and series described ischaemic cerebrovascular events in HIV infection. However, the exact prevalence and the clinical features of these events are unknown. We performed a cohort study on 772 consecutive HIV infected patients and evaluated the rate of transient ischaemic attacks (TIA) and of completed stroke. A total prevalence of 1.9% for TIA (0.8%) and stroke (1.2%) was calculated resulting in an annual incidence rate of 216 per 100000. The prevalence was highest in the later stages of the infection. Stroke patients had a poorer immunological state than the TIA and the cohort patients. Probable (n = 3) and possible (n = 2) vasculitis and cardiogenic embolism (n = 2) could be detected as aetiology, the remaining patients had a cryptogenic event. Our data suggest that ischaemic cerebrovascular events are more common in HIV infected patients than in the general population and that a part of these events might be caused by HIV associated vasculitis or vasculopathy.     

Ischaemic stroke in two children with HIV-1

Cerebral ischaemia caused by inflammatory vasculopathies has been described as a complication of human immunodeficiency virus (HIV) infection. The goal of our study is to report two cases of pediatric human immunodeficiency virus infection and cerebrovascular manifestations. We describe two pre-school boys, from a group of 204 outpatients, who presented fever, seizures, hemiparesis and impairment of conscience level as a first symptom of HIV-1 infection. The serial imaging studies revealed infarction of middle cerebral artery in both cases. The first one child had a severe spastic tetraparesis and partial epilepsy and died four years later without any improvement despite of the antiretroviral therapy. The second patient had a right hemiparesis and global aphasia totally recovered two years later with antiretroviral and rehabilitation therapies. HIV infection should be included in differential diagnosis of children who present with seizures, mental status change or focal neurological deficits and seizures.     

Long-term prognosis of ischemic stroke in young adults

Prognostic information is provided for 74 young adults (age 16-40 yrs, mean age at stroke 29.5 yrs), who suffered from ischemic stroke and survived the first month after the stroke. The patients were followed for 13-26 yrs; in total for 1190 yrs after their stroke. At follow-up 12 of the patients were dead, mostly from severe underlying disease that was complicated by ischemic stroke. In 3 cases death was unrelated to cerebrovascular disease. Among the surviving 62 patients, 7 had experienced recurrent ischemic events (3 reinfarctions, 4 TIA:s). These 7 patients all had risk factors for cerebrovascular complications already at the time of their primary stroke. It is concluded that the long-term prognosis for ischemic stroke in the young adult is favourable. The recovery from neurological deficits is usually good (exceptions are occlusions within the internal carotid and middle cerebral arteries), the risk for recurrence is low (1.1-1.2% annually), and the social prognosis with respect to working capacity and family relation is fair.     

COVID-19 presenting as stroke

ObjectiveAcute stroke remains a medical emergency even during the COVID-19 pandemic. Most patients with COVID-19 infection present with constitutional and respiratory symptoms; while others present with atypical gastrointestinal, cardiovascular, or neurological manifestations. Here we present a series of four patients with COVID-19 that presented with acute stroke.MethodsWe searched the hospital databases for patients that presented with acute stroke and concomitant features of suspected COVID-19 infection. All patients who had radiographic evidence of stroke and PCR-confirmed COVID-19 infection were included in the study. Patients admitted to the hospital with PCR- confirmed COVID-19 disease whose hospital course was complicated with acute stroke while inpatient were excluded from the study. Retrospective patient data were obtained from electronic medical records. Informed consent was obtained.ResultsWe identified four patients who presented with radiographic confirmation of acute stroke and PCR-confirmed SARS-CoV-2 infection. We elucidate the clinical characteristics, imaging findings, and the clinical course.ConclusionsTimely assessment and hyperacute treatment is the key to minimize mortality and morbidity of patients with acute stroke. Stroke teams should be wary of the fact that COVID-19 patients can present with cerebrovascular accidents and should don appropriate personal protective equipment in every suspected patient. Further studies are urgently needed to improve current understandings of neurological pathology in the setting of COVID-19 infection.     

Stroke and seizures as the presenting signs of pediatric HIV infection

The authors report two pediatric patients with definite human immunodeficiency virus infection whose initial presentation was stroke and seizure. The first patient was a 3-year-old female who developed acute hemiparesis as the first manifestation. The other, a 2-month-old infant, had focal seizures secondary to cerebral infarction. Investigations revealed ischemic infarction of the thalamus, hypothalamus, and internal capsule in the first patient and cerebral cortex in the second. Further investigations failed to demonstrate any other causes of these cerebral infarctions. Opportunistic infection of the central nervous system was not documented. The authors emphasize that cerebrovascular accident may be the initial presentation in human immunodeficiency virus infection in children. Human immunodeficiency virus infection must be included in the differential diagnosis, and testing for the disease is mandatory in the investigation of stroke in any child who is at risk of having this infection.     

Clinical significance of carotid and ocular bruits in cerebrovascular disease]

We investigated the clinical significance of carotid and ocular bruits in 250 consecutive patients with cerebrovascular disease (CVD). The incidence of bruits was compared with that in 100 age- and sex-matched neurological controls without CVD. In the cerebrovascular disease group, carotid bruits alone were found in 12 patients, both carotid and ocular bruits in 7, and ocular bruits alone in 2. Carotid bruits were found only in 3 controls. We then evaluated cerebrovascular disease in the 25 patients (16 men and 9 women) who had bruits. The patients ranged from 55 to 81 years in age (mean: 70.6 years). The patients with carotid bruits alone constituted the largest group, and those with ocular bruits alone were the smallest group. Carotid bruits were heard and abnormal blood flow was observed in 19/28 arteries of the 21 patients who underwent echo-flow studies. Carotid artery stenosis/occlusion was detected in 24/31 arteries (77%) in 23 patients who underwent digital subtraction angiography (DSA). Thus, the sensitivity was 0.77 and specificity of a carotid bruit 0.91, respectively. In 9/10 patients with unilateral ocular bruits, ipsilateral or contralateral carotid artery stenosis/occlusion was detected. Diminished cerebral blood flow was observed in 10/15 patients with bruits who underwent SPECT. Of these 8 had reduced cerebral blood flow ipsilaterally to the bruit. Blood flow was reduced in the carotid artery territory in all of the patients, and watershed reductions were commonest. Among the 25 patients, some showed neurological semiology of the vertebrobasilar territory in addition to that of the carotid territory.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebrovascular disease in young, HIV-infected, black Africans in the KwaZulu Natal province of South Africa

The objective of this study was to elucidate the mechanisms of an ischemic stroke in a human immunodeficiency virus, type 1 (HIV)-infected population. Several clinical and autopsy studies have suggested an increased incidence of strokes in HIV-infected persons. These studies have been performed on diverse populations with numerous confounds for strokes, including, drug abuse and coexistent opportunistic infection. Because of these confounding factors, it has been difficult to assess whether a unique stroke propensity exists among HIV-infected persons. A retrospective case-controlled study was carried out of patients registered in the Durban Stroke Data Bank (DSDB) (n=1298) located in KwaZulu Natal province of South Africa. Sixteen per cent of all strokes in young (<50 year old) black Africans living in KwaZulu Natal province on the east coast of South Africa reported to the DSDB occurred in association with HIV infection. This HIV-infected population was free of drug abuse and relatively devoid of opportunistic infections. The incidence rate of HIV in this stroke population paralleled that of the young black population at large, suggesting no significant overall increased rate of stroke in association with HIV. However, when compared to strokes occurring in an age- and sex-matched, HIV-seronegative control population, the cryptogenic stroke was more common in the HIV-infected population. Although the incidence of rate of stroke appeared to be no higher among HIV-infected young black Africans in the KwaZulu province than among HIV-seronegative controls, the increased incidence of a large vessel cryptogenic stroke in the former suggests the presence of a co-existent prothromobotic state.     

Recent developments in childhood arterial ischaemic stroke

Stroke is increasingly recognised as a cause of childhood disability and lifelong morbidity: population-based estimates of the annual incidence of childhood stroke (ischaemic and haemorrhagic) range from 2.3 to 13.0 per 100,000 children, and incidence rates in neonates are closer to 1 per 5000 livebirths. Stroke in childhood can have many causes. Diagnosis is often delayed owing to low clinical suspicion and the need to exclude the frequent mimics of stroke in childhood. Outcomes are related to presentation, associated illnesses, the underlying cause, size, and location of the infarct, and stroke subtype, but more than a half of the children who have had a stroke will have long-term neurological sequelae. Furthermore, estimates of recurrence rates range from 6-19% in the first few years. Arteriopathy-including arterial dissection and other progressive and non-progressive arteriopathies-might account for up to 80% of childhood stroke in otherwise healthy children. Because children with cerebrovascular abnormalities are at the highest risk of recurrence (66% at 5 years), understanding of the nature and course of these arteriopathies is crucial to the development of secondary stroke prevention strategies.     

Cerebrovascular disease in children with HIV‐1 infection

An estimated 3.2 million children worldwide have human immunodeficiency virus (HIV) infection. Antiretroviral therapy (ART) has resulted in prolonged survival, leading to an increase in complications previously recognized in adults. Children with HIV infection have increased risk of cerebrovascular disease from multiple aetiologies including HIV‐associated vasculopathy, opportunistic vasculitis, cardioembolism or coagulopathy, all of which may be secondary to the infection. Prevalence of cerebrovascular disease in HIV‐infected children is underestimated because of limited neuroimaging in low and middle income countries, silent events without overt motor manifestations, and mislabeling as HIV encephalopathy for non‐motor manifestations such as behavioural and cognitive difficulties. No management guidelines for cerebrovascular disease in HIV‐infected children exist but common practices target risk factors for stroke in low and middle income countries. Where capacity permits, screening for opportunistic infections, vasculitis, coagulopathy and cardioembolism is important. Optimising virological suppression, correction of anaemia, control of seizures and aspirin prophylaxis are management priorities. Neurosurgical interventions may have a role.     

Human immunodeficiency virus encephalitis is the pathological correlate of dementia in acquired immunodeficiency syndrome

While dementia has been observed in approximately one-fourth of terminally ill patients with acquired immunodeficiency syndrome, it has been difficult to attribute this clinical disorder to a single neuropathological substrate. We used a simple and readily reproducible scale for estimating the burden of human immunodeficiency virus (HIV) in the central nervous system (i.e., severity of HIV encephalitis) and compared this to autopsy neurological summaries of dementia. Like others, we found that multinucleated giant cells were present in only half of the dementia patients. However, all of the dementia patients had severe HIV encephalitis as assessed by measurements of intra–central nervous system viral burden. Additional patients had severe HIV encephalitis without clinical histories of dementia. We interpret these latter findings as evidence that HIV encephalitis exists for a period of time before the clinical symptomatology develops. Comparison of presence or absence of concurrent cytomegalovirus encephalitis showed no association with dementia.     

EEG and evoked potentials in HIV-infected children.

Forty-seven HIV-seropositive children were investigated by EEG and evoked potentials (BAEP, SEP). Twenty-three children were symptomatic (P2), 8 seropositive without symptoms (P1), and 16 children were less than 15 months of age (P0). Some of them were investigated at different stages of HIV infection. During the neonatal period, 7 newborns of drug-addicted mothers had seizures and frequent spikes and sharp waves in their EEGs. Among (P2) children 6/23 showed background slowing and 1 had rhythmic theta activity (6 with and 1 without neurological symptoms). In BAEP, bilateral prolonged interpeak latencies (IPL) were found in 1 child with severe AIDS encephalopathy. Side differences greater than or equal to 0.4 ms in IPL were seen in 2 (P2), 1 without and 1 with neurological symptoms. A late onset was seen in 2 (P1) and 4 (P2) children. Median SEPs were normal in 24/26 patients; N20/N13 amplitude ratio was reduced in 2 (P1) patients. EEG and BAEP revealed nonspecific abnormal features in HIV encephalopathy. The the progression of the disease. However, also in the symptomatic group, normal results of EEG and BAEP dominated. SEP in the symptomatic group revealed only normal values. For monitoring the effectiveness of AZT treatment in HIV encephalopathy, EEG seems to be a relevant investigation; for evoked potentials more data and experience are needed.     

Inflammatory bowel disease and cerebrovascular arterial and venous thromboembolic events in 4 pediatric patients: a case series and review of the literature

Inflammatory bowel disease has been linked to cerebrovascular lesions, but the mechanisms of these vascular complications and their frequency among children with inflammatory bowel disease are unclear. We present 4 children with inflammatory bowel disease who developed ischemic or hemorrhagic stroke or cerebral sinovenous thrombosis. All 4 patients were female; 3 had Crohn's disease and 1 had indeterminate colitis. All of the patients had additional risk factors for thrombosis including thrombocytosis, severe dehydration attributable to an inflammatory bowel disease exacerbation, and, in 2 instances, genetically mediated coagulation defects. It is believed that the occurrence of thrombotic complications in individuals with inflammatory bowel disease is attributable to multifactorial causes. The current literature on cerebrovascular complications and treatment in the setting of pediatric inflammatory bowel disease is reviewed.     

Early superficial temporal artery to middle cerebral artery bypass in acute ischemic stroke

Objective

To evaluate the effects and safety of superficial temporal artery–middle cerebral artery (STA–MCA) anastomosis in the early stage after an acute ischemic event and the improvement of present symptoms in patients with intracranial atherosclerotic occlusive disease with stroke/stroke in progress.

Methods

From 2006 to 2010, 20 patients (15 males and five females) with atherosclerotic cerebrovascular disease were treated with an STA–MCA bypass. All of the patients presented with an acute ischemic stroke or stroke in progress despite maximal medical treatment. The patients underwent an STA–MCA bypass within 7 days from symptom onset. The clinical outcome and hemodynamic study of the 20 patients were preoperatively and postoperatively investigated. A pooled analysis was performed, and the results were compared with those obtained from other delayed STA–MCA bypass studies.

Results

Among the 20 patients who underwent an early STA–MCA bypass, fourteen (70%) patients achieved a good functional outcome (mRS 0, n = 3; mRS 1, n = 9; mRS 2, n = 2). Prior to surgery, the mean basal regional cerebral blood flow (rCBF) and cerebrovascular reserve capacity (CVR) in the symptomatic hemisphere were 37.3 ± 4.3 ml/100 g/min and −1.68 ± 2.9%. The mean basal rCBF and CVR had significantly increased postoperatively, and no reperfusion-induced hemorrhage had occurred. In the pooled analysis, no significant differences were observed in the clinical outcome (P = 0.328) or in the incidence of postoperative complications (P = 0.516) between patients who underwent an early STA–MCA bypass and in patients who underwent a delayed STA–MCA bypass in previous studies.

Conclusions

In this study, which consisted of 20 carefully selected patients with acute ischemic stroke, an early STA–MCA bypass was safely and effectively performed, and in some cases, an early STA–MCA bypass resulted in rapid neurological improvement. An early STA–MCA bypass was beneficial in select patients who had acute ischemic stroke with imaging evidence of a small infarction.     

Dementia associated with lacunar infarction.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the number of patients with lacunar lesions who develop dementia and to evaluate in patients with and without dementia the relevance of risk factors for cerebrovascular disease, the occurrence of leukoaraiosis, the volume and location of vascular lesions, the size of ventricular and subarachnoid spaces, and stroke recurrence. METHODS: One hundred eight patients in whom computed tomograms revealed lacunar lesions that could account for their clinical neurological pictures were followed up for an average of 4 years after their first lacunar stroke. RESULTS: Twenty-five patients (23.1%) developed dementia. The prognosis regarding occurrence of dementia during the follow-up period, evaluated by the Kaplan-Meier method, was significantly worse in subjects with the greatest evidence of cerebral atrophy (p less than 0.009) and in subjects who underwent new focal cerebrovascular episodes (p less than 0.000001). No differences were seen in the frequency of vascular risk factors or the site or volume of lesions between the demented and nondemented groups. CONCLUSIONS: Patients with lacunar infarcts suffer from dementia 4-12 times more frequently than the normal population. Cerebral atrophy and recurrent stroke, as well as other as-yet unclarified factors, are involved in producing dementia.     

缺血性脑血管病患者脑主要供血动脉狭窄分布的DSA分析

目的探讨缺血性脑血管病(ICVD)患者脑主要供血动脉狭窄分布特征。方法对2007-2009年诊治的脑主要供血动脉狭窄92例ICVD患者的临床和DSA资料进行回顾性分析。结果脑主要供血动脉颅外段病变发生率(82.6%)高于颅内段动脉(66.3%);多支动脉及前后循环同时病变的发生率较高(79.3%、57.6%);颈动脉系统常见狭窄部位是颈内动脉颅外段(57.6%)、大脑中动脉(34.8%),椎基底动脉系统常见狭窄部位是椎动脉颅外段(57.6%)、椎动脉颅内段(20.7%)。可干预危险因素越多,颅外合并颅内动脉狭窄的发生率越高,但无显著性差别(χ2=7.1;P=0.069)。结论 ICVD患者以颅外段动脉狭窄多见;颈动脉系统狭窄好发于颈内动脉颅外段、大脑中动脉,椎基底动脉系统好发于椎动脉颅外段。伴不同可干预危险因素组颅内合并颅内动脉狭窄的发生率无显著差异。     

Stroke in patients with sickle cell disease: clinical and neurological aspects

The aim of this study was to characterize a group of patients (n=8) with sickle cell disease (SCD) and ischemic stroke concerning the clinical, neurological, imaging and progressive aspects. Data were collected from records and completed with an interview of patients and their parents. In this study there were 8 patients with ages ranging from 10 to 23 years old; SCD diagnosis was given between one and two years of age with clinical features of fatigue and anemia. The stroke was ischemic in all individuals and the first cerebrovascular event occurred before 6 years of age; 3 patients had recurrence of stroke despite prophylactic blood transfusion therapy and both cerebral hemispheres were affected in 4 patients. Clinical and neurological current features observed were: acute pain crises, sialorrhea, mouth breathing, motor, and neuropsychological impairments resulting from cortical-subcortical structure lesions.     

Hemorrhage and epilepsy in cryptic cerebrovascular malformations

A series of 15 angiographically cryptic, histologically proved, cerebrovascular malformations occurred. Nine patients were admitted to the hospital with evidence of recent neurological deterioration or onset of headache. Six patients had convulsions. Computed tomographic scan and surgical exploration disclosed a substantial cerebral hematoma in eight instances. The pathological diagnosis was arteriovenous malformation in 11 cases, cavernous angioma in three, and venous angioma in one. Histological evidence of previous microhemorrhage was present in the majority of the specimens, including the patients who had seizures. A change in neurological status or onset of seizures probably indicates recent hemorrhage in cryptic cerebrovascular malformations.     

Risk factors and outcomes of childhood ischemic stroke in Taiwan

In this retrospective study, we reviewed the charts and collected clinical and radiographic data on children (age range, 1 month to 18 years) with symptoms and radiographic confirmation of ischemic stroke for the period of January 1996 to July 2006. Ninety-four children were enrolled. Eighty-eight had arterial ischemic stroke and six had sinovenous thrombosis. Twenty-nine percent of the children had seizures. Twenty-six percent had diffuse neurological signs and 76% had focal neurological signs. Risk factors included vascular disease (33%), infection (27%), metabolic disorders (18%), trauma (11%), prothrombotic states (13%), cardiac disease (10%), and mitochondrial disease (6%). Ten percent (n=9) had no identifiable cause. Twenty-two percent of the children had more than one risk factor. Anterior territory (70%) was more involved than posterior territory (18%) in arterial ischemic stroke. Unilateral infarctions were more common on the left side (51%) than on the right (24.5%). Neurological deficits were present in 45% (n=34/75) of the children; the most frequent deficit was motor impairment (24%). Seven children (9%) died in the acute stage. There were 12 children (16%) who had recurrent stroke and 8 children (8/12) who had underlying vascular disease. The vascular disease included moyamoya disease (5), CNS lupus (1) and ill-defined vasculopathy (2). The etiology pattern in Taiwan was different from that in Western countries. Vascular disease was a significant risk factor for recurrence in childhood ischemic stroke.     

A prospective study of HIV-infected haemophilic boys and the prognostic significance of immune and haematological abnormalities

Fifty-seven haemophilic boys have been studied prospectively determining T lymphocyte subsets and haematological parameters over a period of 26 months. Clinical follow up of these patients has continued for a further 41 months. At the beginning of the study 21 boys were HIV antibody seropositive and seroconversion was documented in a further 9 during the study period, giving a 52.6% incidence of HIV seropositivity. It has been possible to define a group of patients with persistently falling T4 values and these have shown clinical evidence of HIV infection. Although persistent generalized lymphadenopathy has been observed in 30% of HIV antibody positive boys and some boys have had unexplained fevers, only one boy has progressed to have the acquired immune deficiency syndrome (AIDS) some 5 years and 3 months from HIV seroconversion. This boy had a persistently falling T4 value. The importance of these findings is discussed. To date the abnormalities found in these haemophilic boys irrespective of their age are similar to those already reported in adult haemophiliacs.