Ischemia In Young Adults Research Articles

Emerging trends in nationwide mortality, limb loss, and resource utilization for critical limb ischemia in young adults

Background/objectivesRecent trends indicate a rise in the incidence of critical limb ischemia (CLI) among younger adults. This study examines trends in CLI hospitalization and outcomes among young adults with peripheral arterial disease (PAD) in the United States. MethodsAdult hospitalizations (18–40 years) for PAD/CLI were analyzed from the 2016–2020 nationwide inpatient sample database using ICD-10 codes. Rates were reported per 1000 PAD or 100,000 cardiovascular disease admissions. Outcomes included trends in mortality, major amputations, revascularization, length of hospital stay (LOS), and hospital costs (THC). We used the Jonckheere–Terpstra tests for trend analysis and adjusted costs to the 2020 dollar using the consumer price index. ResultsApproximately 63,045 PAD and 20,455 CLI admissions were analyzed. The mean age of the CLI cohort was 32.7 ± 3 years. The majority (12,907; 63.1 %) were female and white (11,843; 57.9 %). Annual CLI rates showed an uptrend with 3265 hospitalizations (227 per 1000 PAD hospitalizations, 22.7 %) in 2016 to 4474 (252 per 1000 PAD hospitalizations, 25.2 %) in 2020 (Ptrend<0.001), along with an increase in PAD admissions from 14,405 (188 per 100,000, 0.19 %) in 2016 to 17,745 (232 per 100,000, 0.23 %%) in 2020 (Ptrend<0.0001). Annual in-hospital mortality increased from 570 (2.8 %) in 2016 to 803 (3.9 %) in 2020 (Ptrend = 0.001) while amputations increased from 1084 (33.2 %) in 2016 to 1995 (44.6 %) in 2020 (Ptrend<0.001). Mean LOS increased from 5.1 (SD 2.7) days in 2016 to 6.5 (SD 0.9) days in 2020 (Ptrend = 0.002). The mean THC for CLI increased from $50,873 to $69,262 in 2020 (Ptrend<0.001). The endovascular revascularization rates decreased from 11.5 % (525 cases) in 2016 to 10.7 % (635 cases) in 2020 (Ptrend = 0.025). Surgical revascularization rates also increased from 4.9 % (225 cases) in 2016 to 10.4 % (600 cases) in 2020 (Ptrend = 0.041). ConclusionHospitalization and outcomes for CLI worsened among young adults during the study period. There is an urgent need to enhance surveillance for risk factors of PAD in this age group.

Internal carotid and vertebral artery dissections - a comparison of clinical, radiological and prognostic characteristics.

To examine whether baseline characteristics, potential risk factors, clinical symptoms, radiological presentation, and long-term outcomes differ between internal carotid artery dissection (ICAD) and vertebral artery dissection (VAD). Cervical artery dissection (CeAD) is a major cause of cerebral ischaemia in young adults. Its clinical course is highly variable, resulting in challenges in making a proper diagnosis. We performed a retrospective analysis of 31 patients (mean age 42.2 years) with CeAD (18 with ICAD, 13 with VAD) treated in our neurology department from 2008 to 2018. Appropriate imaging confirmed the diagnosis of CeAD. Patients with ICAD presented Horner syndrome significantly more often (44.4% vs 7.6%; p = 0.04). Patients with VAD more often had ischaemic events (ischaemic stroke, TIA or transient blindness) (84.6% vs 44.6%; p = 0.0032). Ischaemic stroke was more severe in patients with ICAD [(median NIHSS 6, interquartile range 4-12) vs VAD (median NIHSS 4, interquartile range 1.5-5.5), p = 0,03]. Occlusion occurred more often in patients with VAD (69.2% vs 22.2%; p = 0.013). Most patients had a favourable outcome (mRS 0-2). In a series of patients with CeAD, we observed significant differences between VAD and ICAD in terms of clinical symptoms and radiological features.

Patent foramen ovale closure in non-lacunar cryptogenic ischemic stroke: where are we now?

Patent foram ovale (PFO) is the most common anatomical cause of an interarterial shunt. It is usually asymptomatic but may cause paradoxical embolism and is a risk factor for non-lacunar cryptogenic cerebral ischemia in young adults. Although the first clinical trials did not show a significant superiority of PFO closure in the secondary prevention of cerebral ischemia as compared with standard antithrombotic treatment, six subsequent randomized clinical trials (CLOSURE I, PC Trial, RESPECT, CLOSE, REDUCE, and DEFENSE-PFO) performed in a sample of cryptogenic stroke in patients aged 60 years or younger provided evidence of a significant reduction of recurrent cerebral ischemia after percutaneous PFO closure. However, the use of percutaneous PFO closure cannot be generalized to the entire population of patients with cerebral ischemia and PFO, but it is indicated in highly selected patients with non-lacunar cryptogenic cerebral infarction with a large right-to-left shunt, an atrial septal aneurysm and no evidence of atrial fibrillation, as well as in association with antithrombotic treatment for an optimal secondary prevention of cerebral ischemia.

Isquemia crítica de miembros inferiores en paciente joven: presentación atípica del síndrome de atrapamiento poplíteo

Introducción. El síndrome de atrapamiento poplíteo es una entidad infrecuente, cuya incidencia oscila entre 0,17 y 3,5 %, representando una de las principales causas de isquemia en miembros inferiores en adultos jóvenes. Suele manifestarse con claudicación intermitente (69 %) o isquemia aguda (26 %), siendo muy rara su presentación con isquemia crítica de miembros inferioresCaso clínico. Paciente de 30 años quien presentó úlcera subungueal en primer dedo de pie derecho con dolor intenso. En la exploración física no se palpaban pulsos distales y se observó palidez cutánea intensa y frialdad. Se realizó arteriografía donde se observó defecto de repleción de bordes regulares y desplazamiento medial de la arteria poplítea. La resonancia magnética mostró una inserción anómala del gastrocnemio medial, con lo que se hizo diagnóstico de síndrome de atrapamiento poplíteo tipo I. Mediante abordaje posterior se realizó reconstrucción vascular con injerto venoso y sección tendinosa del gastrocnemio medial. En el postoperatorio inmediato el paciente recupera pulso pedio y en el seguimiento a un año el paciente no presenta clínica de isquemia de miembros inferiores, encontrándose el baipás permeable. Discusión. A pesar de su baja incidencia, es importante incluir el síndrome de atrapamiento poplíteo en eldiagnóstico diferencial de isquemia en miembros inferiores en adultos jóvenes. Su presentación con isquemia crítica es excepcional, encontrando muy pocos casos publicados en la literatura. La reconstrucción arterial precoz mediante injerto o plastia con material autólogo constituye el tratamiento de elección.

Spontaneous Coronary Artery Dissection in a Young Man with a Factor V Leiden Gene Mutation: A Case Report and Review of the Literature

Spontaneous coronary artery dissection is a rare but increasingly recognized cause of acute myocardial ischemia in young adults, especially in women. We report a case of spontaneous coronary dissection in a young healthy man who was also a carrier of the factor V Leiden gene mutation.

Bilateral Cervical-Artery Dissection Associated with Leri-Weill Dyschondrosteosis. A Case Report and Literature Review (P01.022)

Objective: To report the first case of spontaneous cervical-artery dissection (sCAD) associated with Leri-Weill dyschondrosteosis (LWD) and a comprehensive review of the literature. Background CAD is a major cause of cerebral ischemia in young adults. Skin biopsies from many patients with sCAD show mild connective tissue alterations. An underlying arteriopathy, which could be in part genetically determined, is believed to have a role in the development of sCAD. There are few case reports of sCAD in patients with inherited connective tissue disorders like Ehlers-Danlos syndrome, Marfan syndrome or Osteogenesis Imperfecta. LWD is an osteochondrodysplasia whith mesomelic short stature and Madelung deformity of the wrist. Expression of LWD is variable but the clinical features are generally more severe in females. In around 70% of cases, LWD is caused by haploinsufficiency of the short stature homeobox (SHOX) gene and remains unknown in the remaining 30%. Design/Methods: Case report followed by a literature review. Results: A 36-years-old woman was admitted in July 2009 for sudden-onset right hemiplegia and Wernicke aphasia. Her NIHSS was 9. Her past medical history consisted in LWD and hypothyroidism treated with levothyroxine sodium. She had had no injuries during the previous days or weeks. The diffusion-weighted MRI showed a left carotid infarct. Laboratory test results and cardiac explorations were normal. Magnetic resonance angiography combined with T1-weighted with the fat-saturation technique confirmed bilateral carotid artery dissection. Anticoagulation was conducted for 6 months then was relayed by antiplatelet. When last seen in April, 2011, the patient had only minor aphasia and the MRI was back to normal. Conclusions: Even though this association is rare, screening patients with sCAD for clinical signs that are suggestive of connective tissue seems important. In such cases, a longer and closer follow-up is recommended because of the heightened risk of recurrence. Disclosure: Dr. Bonnet has nothing to disclose. Dr. Cogez has nothing to disclose. Dr. Bataille has nothing to disclose. Dr. Defer has received personal compensation for activities with BiogenIdec, Novartis, Teva Pharmaceutical Industries Ltd, Merck Serono, and Guerbet. Dr. Viader has nothing to disclose.

Congenital vertebral duplication: A predisposing risk factor for dissection

Spontaneous cervical-artery dissection (CAD) is a major cause of cerebral ischaemia in young adults. While their pathophysiology remains still poorly understood, CAD is considered today as a multifactorial disease determined by general and local predisposing factors; these predisposing factors being predominantly constitutional abnormalities of the arterial wall.Here, we report an MRI-confirmed dissection of a duplicated vertebral artery, in a patient with attacks of vertigo due to cerebellar infarction following a minor neck trauma.Knowing that another case of vertebrobasilar CAD on a duplicated vertebral artery has been reported, these rare anatomical variants probably predispose to vertebral CAD, via local histological defects or significant hemodynamics alterations, as reported for the classical local predisposing conditions for vertebral dissection, i.e.: fibromuscular dysplasias or carotid redundancies (including loops, kinks and coils).

Etiología y factores de riesgo para un primer episodio de isquemia cerebral en adultos jóvenes

Introduction To determinate the etiology and risk factors for a first episode of cerebral ischemia in young adults at three hospitals of Lima and Callao-Peru. Methods Multicentric study carried out at three national hospitals in Lima. The sample included 30 patients with a first episode of stroke and 60 controls matched by age and sex 2:1 with the patients. Serum biochemistry studies, EKGs and echocardiograms were done. Etiologies were classified based on the classification of Baltimore-Washington Cooperative Young Stroke Study. Results The most frequent etiologies were cardiac embolism and atherosclerotic valvular heart disease, which were 30% of the cases (9 patients) each one. Hypertriglyceridemia (p = 0.014), valvular heart disease (p = 0.001) and hormonal contraception/replacement therapy (p = 0.002) were independent risk factors for a first episode of cerebral ischemia in peruvian young adults. Motor deficiency was the most frequent presentation (50.0%). Intracraneal hypertension and urinary tract infection were the most frequent complications during acute ischemia and mortality was raised up to 10%. Conclusions The hypertriglyceridemia, valvular heart disease and the use of oral contraceptives are independent risk factors for a first episode of ischemia in young adults from three hospitals of Lima and Callao. The most frequent etiologies were cardiac embolism and atheroesclerotic valvular heart disease.

Estudio mediante técnicas de imagen no invasivas del síndrome de atrapamiento de la arteria poplítea. A propósito de dos casos

Popliteal artery entrapment syndrome is a cause of lower limb claudication and ischemia in young adults. This syndrome is due to extrinsic arterial compression secondary to a congenital anomaly in the anatomic relations between the popliteal artery and its neighboring musculotendinous structures. Popliteal artery entrapment leads to chronic, progressive vascular microtrauma with atheromatosis and thrombus formation. Accurate early diagnosis is crucial to enable appropriate surgical planning and avoid complications.

Etiology and risk factors for a first episode of cerebral isquemia in young adults

Introduction To determinate the etiology and risk factors for a first episode of cerebral ischemia in young adults at three hospitals of Lima and Callao-Peru. Methods Multicentric study carried out at three national hospitals in Lima. The sample included 30 patients with a first episode of stroke and 60 controls matched by age and sex 2:1 with the patients. Serum biochemistry studies, EKGs and echocardiograms were done. Etiologies were classified based on the classification of Baltimore-Washington Cooperative Young Stroke Study. Results The most frequent etiologies were cardiac embolism and atherosclerotic valvular heart disease, which were 30% of the cases (9 patients) each one. Hypertriglyceridemia (p = 0.014), valvular heart disease (p = 0.001) and hormonal contraception/replacement therapy (p = 0.002) were independent risk factors for a first episode of cerebral ischemia in peruvian young adults. Motor deficiency was the most frequent presentation (50.0%). Intracraneal hypertension and urinary tract infection were the most frequent complications during acute ischemia and mortality was raised up to 10%. Conclusions The hypertriglyceridemia, valvular heart disease and the use of oral contraceptives are independent risk factors for a first episode of ischemia in young adults from three hospitals of Lima and Callao. The most frequent etiologies were cardiac embolism and atheroesclerotic valvular heart disease.

Functional polymorphisms in matrix metalloproteinases -1, -3, -9 and -12 in relation to cervical artery dissection

BackgroundCervical artery dissection is a leading cause of cerebral ischemia in young adults. Morphological investigations have shown alterations in the extracellular matrix (ECM) of affected vessel walls. As matrix metalloproteinases (MMP) play a central role in the regulation of the ECM, an increased expression of these enzymes might lead to the endothelial damage in spontaneous cervical artery dissection (sCAD). Five different DNA polymorphisms in MMP-1, -3, -9 and -12 were tested for their frequency in patients with sCAD and compared with those of a control population.MethodsBlood was sampled from 70 unrelated patients presenting consecutively in the department of neurology of the Aachen University Medical School with sCAD and from 87 control subjects living in the same area as the patients. The MMP polymorphisms were analyzed with hybridization probes using the LightCycler™ (Roche Diagnostics), by sequencing using the ABI 310 Genetic Analyzer (Applied Biosystems) and with the GeneScan program on a ABI 310 Genetic Analyzer.ResultsNo statistically significant differences in the allelic distribution were found between sCAD patients and the controls.ConclusionAlleles of these 5 functional polymorphisms of MMPs seem not to be associated with structural alterations in the blood vessel wall of sCAD patients. However, this does not exclude a pathogenetic role for MMPs in sCAD via secondary factors such as cytokines that are able to induce these enzymes in cervical blood vessel walls.

Cervical-artery dissections: predisposing factors, diagnosis, and outcome

Cervical-artery dissection (CAD) is a major cause of cerebral ischaemia in young adults and can lead to various clinical symptoms, some of which are benign (eg, headache, neck pain, Horner's syndrome, and cranial-nerve palsy), but most patients have a stroke or transient ischaemic attack. In addition to trauma to the neck, other risk factors have been suggested, such as infection, migraine, hyperhomocysteinaemia, and the 677TT genotype of the 5,10-methylenetetrahydrofolate reductase gene (MTHFR 677TT), although evidence is sparse. An underlying arteriopathy, which could in part be genetically determined, is believed to have a role in the development of CAD. Importantly, both research on and optimum management of CAD strongly rely on diagnostic accuracy. Although the functional outcome of CAD is good in most patients, socioprofessional effects can be important. Incidence of the disorder in the general population is underestimated. Mortality and short-term recurrence rates are low but possibly also underestimated. Further research is warranted to improve our understanding of the underlying pathophysiology, to assess the long-term outcome, and ultimately to provide treatment and prevention strategies.

A case series of young stroke in Rome

In this hospital case series study we enrolled 394 consecutive ischemic stroke patients aged 14-47 years, all of whom were submitted to a diagnostic protocol. We evaluated the incidence of cerebral ischemia in young adults, as well as the risk factors and the etiopathogenesis of this pathology. Modified diagnostic criteria adopted from the TOAST and Baltimore-Washington Cooperative Young Stroke Study were used for the etiologic classification. The crude annual incidence rate was 8.8/100,000 (95% CI 7.7-9.9), which is in keeping with the rates reported in comparable registries. Risk factors were distributed as follows: smoking in 56% of patients, hypertension in 23%, dyslipidemia in 15%, migraine in 26%, and diabetes mellitus in 2%. Oral contraceptives were being taken by 38% of the women enrolled. The etiology of stroke in the patients was as follows: cardioembolism in 34%, atherothrombosis in 12%, non-atherosclerotic vasculopathies in 14% (including arterial dissection in 12%), other determined causes in 13%, lacunar stroke in 2.5%, migraine in 1%, and undetermined causes in 24%. Despite its biased sampling frame, this large hospital case series, in which risk factor distribution and etiopathogenesis were investigated, stresses the need for an adequate diagnostic approach in young ischemic patients.

Transient ischaemic attacks in two cases of internal carotid artery hypoplasia

Congenital anomalies of the internal carotid arteries (ICA) and cerebral arteries have not been frequently reported. Moreover, in the literature there is no clear association between hypoplastic carotid and cerebral vessel systems and the occurrence of cerebral ischaemia. We report two cases of unilateral hypoplasia of the ICA affecting two young patients suffering from an episode of minor stroke and from recurrent transient ischaemic attacks, respectively. Congenital variations in the configuration and size of the carotid and cerebral arteries should not always be considered benign conditions and may predispose to cerebral ischaemia in young adults.

Cumulative Effect of Predisposing Genotypes and Their Interaction With Modifiable Factors on the Risk of Ischemic Stroke in Young Adults

Combinations of multiple predisposing polymorphisms and their interactions with modifiable factors may result in synergistic effects on the risk of ischemic stroke. These mechanisms are more likely to play a relevant role in younger individuals. The cumulative effect of the 20210A variant of prothrombin gene, the 1691A variant of factor V gene, the TT677 genotype of the methylenetetrahydrofolate reductase (MTHFR) gene, and the epsilon4-carriership of the apolipoprotein (APOE) gene, as well as their interactions with modifiable predisposing factors, were determined in a series of 163 stroke patients aged younger than 45 years and 158 controls. Odds ratios (ORs) for stroke were 1.73 (95% confidence interval [CI], 1.20 to 2.51) in subjects with 1 polymorphism and 3.00 (95% CI, 1.43 to 6.30) in those with > or =2. Compared with nonsmokers with none of the studied polymorphisms, ORs for stroke were 1.88 (95% CI, 1.18 to 3.00) and 3.55 (95% CI, 1.40 to 8.98) for nonsmokers with 1 and 2 polymorphisms, respectively, and 3.99 (95% CI, 2.00 to 7.96) and 15.99 (95% CI, 4.01 to 63.3) for smokers. Compared with nonhypertensive subjects bearing no polymorphisms, ORs were 1.91 (95% CI, 1.28 to 2.87) and 3.68 (95% CI, 1.64 to 8.26) for nonhypertensive subjects with 1 and 2 polymorphisms, 3.28 (95% CI, 1.01 to 10.7) and 10.79 (95% CI, 1.01 to 115.4) for hypertensive. These data suggest a gene-dose effect of the examined prothrombotic and proatherogenic gene variants and a synergistic effect of these polymorphisms and modifiable risk factors in the pathogenesis of cerebral ischemia in young adults.

Accidents ischémiques cérébraux du sujet jeune

The main differences between ischemic strokes occurring in young adults and those occurring in the elderly are the breakdown of causes with a prominence of “unknown causes” and “other determined causes”, and an overall favorable outcome. Cervical-artery dissection is the leading cause of cerebral ischemia in young adults and is usually associated with a good outcome in patients who survive the acute stage. The association of a patent foramen ovale and an interatrioseptal aneurysm is a marker of an increased risk of recurrence. Depending on how exhaustive the diagnostic work-up was, up to 45 % of patients had no clear cause. Mortality and recurrence rates are low, especially in patients with a negative diagnostic work-up, but epilepsy is frequent.

Cerebral ischemia in young adults and genetic polymorphisms of coagulation factors II, V and VII

Cerebral ischemia in young adults and genetic polymorphisms of coagulation factors II,V and VII -

A common polymorphism of the protein Z gene is associated with protein Z plasma levels and with risk of cerebral ischemia in the young.

The vitamin K-dependent protein Z (PZ) has been shown to possess anticoagulant as well as procoagulant properties. Plasma levels of PZ show a broad interindividual variation, but it is unknown to which extent this variation is under genetic control. Recent clinical studies revealed contradictory results on the association of PZ plasma levels and the risk of ischemic stroke. We performed a case-control study including 200 patients with cerebral ischemia aged < or =50 years and 199 control subjects from the same South German region. We investigated a possible association of 2 common single nucleotide mutations in the PZ gene with the risk of cerebral ischemia. Furthermore, enzyme-linked immunosorbent assay measurements were done in control subjects without vascular disease to detect a potential association of different genotypes with PZ plasma (antigen) levels. In patients, the frequency of the A allele of the intron F polymorphism G79A was significantly lower than in controls (15.7% versus 24.4%; odds ratio, 0.58; 95% CI, 0.39 to 0.86; P=0.007; adjusted for age, sex, and conventional risk factors). The G allele of the promoter polymorphism A-13G tended to be less common in patients (4.2% versus 7.0%; adjusted odds ratio, 0.56; 95% CI, 0.28 to 1.13; P=0.105). In 42 control subjects, the A allele of the intron F polymorphism was associated with lower PZ antigen levels (P=0.0032; Spearman correlation coefficient rs=-0.48). The A allele of an intron F polymorphism of the PZ gene appears to be a novel protective genetic marker for the risk of cerebral ischemia in young adults. In the context of juvenile stroke, high PZ plasma levels may represent a prothrombotic condition.

Les accidents ischémiques cérébraux du sujet jeune

Purpose. – The incidence of cerebral ischemia occurring between 15 and 45 years of age is of 60 to 200 new cases per year per million inhabitants. The causes of cerebral ischemia consist of complications of atherosclerosis, cardio embolism, small-vessel occlusion, other determined causes and unknown causes. The breakdown of the causes differ from that of elderly subjects with a prominence of “unknown causes” and “other determined causes”. Key message. – The association of a patent foramen ovale and an interatrioseptal aneurysm is a marker of an increased risk of recurrence. Cervical-arterydissections are the leading cause of cerebral ischemia in young adults and are usually associated with a good outcome in patients who survive the acute stage. Depending on the exhaustivity of the diagnostic work-up, 30 to 50% of cases have no clear cause. Mortality rate and recurrence rates in cerebral ischemia occurring in young adults are low. A negative diagnostic work-up is associated with a low risk of recurrence. Epilepsy is frequent. The incidence of cerebral ischemia occurring during pregnancies is 4,3 for 100,000 deliveries. Specific causes are led by eclampsia, and reversible angiopathies of the post partum period. Future. – If the outcome is good, the causes are multiple and research should focus on the identification of new causes and the natural history in many of them.

Antiphospholipid Antibodies in the Acute Phase of Cerebral Ischaemia in Young Adults: A Descriptive Study of 139 Patients

A total of 139 young stroke patients were consecutively examined and tested for antiphospholipid antibodies (APLA) to evaluate the role of these antibodies in cerebral ischaemia before the age of 45. APLA were found in 28.8% of patients. Two factors, hypertriglyceridaemia and alcohol abuse, were significantly more frequent in patients with a positive APLA test. The demographic characteristics, other risk factors, history of prior thrombotic events and distribution of aetiopathogenic types of cerebral ischaemia were not different in patients with or without APLA. Laboratory assays for APLA were highly positive for only two patients, who both had autoimmune diseases. These results suggest that with the exception of a clinical context of antiphospholipid syndrome or other autoimmune diseases, the usefulness of this diagnostic tool in the management of cerebral ischaemia remains limited.