Medical versus neurosurgical treatment in ICH patients: a single center experience.

BACKGROUND AND AIMS: The effect of surgical treatment for spontaneous intracerebral hemorrhage (ICH) remains uncertain. We conducted an observational retrospective cohort study on supra-centimeter spontaneous ICH treated with either neurosurgical or conservative management. The baseline demographics and risk factors were correlated with in-hospital mortality and 3 and 6-month survival rates stratified by management. METHODS: We included all patients with evidence of spontaneous ICH > 1 cm detected by CT and admitted between august 2020 and march 2021 to the "SMM" Hospital in Perugia. RESULTS: Onehundredandtwentytwo patients were included in the study, and 45% (n.55) were surgically treated. The mean age was 71.9 ± 15.3, and 61% (n.75) were males. Intra-hospital mortality ended up being 31% (n.38), 3 months-survival was 63% (n.77) and 6 months-survival was 60% (n.73). From the multivariate analysis of the surgical patients versus medical patient, we observed that the surgical patients were younger (67.5 ± 14.9 vs 75.5 ± 14.7 y; OR 0.87; Cl 95% 0.85-0.94; p 0.001), with greater ICH volume at the onset (61 ± 39.4 cc vs 51 ± 64 cc; OR 1.03; Cl 95% 1.005-1.07; p 0.05), more midline shift (7.61 ± 5.54 mm vs 4.09 ± 5.88 mm; OR 1.37; Cl 95% 1.045-1.79; p 0.023), and a higher ICH score (3 vs 2 mean ICH score; OR 21.12; Cl 95% 2.6-170.6; p 0.004). Intra-hospital mortality in the surgical group and in the conservative treatment group was respectively 33% vs 30%, 3 month-survival was 64% vs 63% and 6 month- survival were 60% in both groups. CONCLUSIONS: Our patient cohort shows no overall benefit from surgery over conservative treatment, but surgical patients were younger and had larger ICH volume.

Stroke in first-degree relatives of patients with cervical artery dissection.

BACKGROUND AND PURPOSE: Patients with ischaemic stroke (IS) caused by a spontaneous cervical artery dissection (CeAD) worry about an increased risk for stroke in their families. The occurrence of stroke in relatives of patients with CeAD and in those with ischaemic stroke attributable to other (non-CeAD) causes were compared. METHODS: The frequency of stroke in first-degree relatives (family history of stroke, FHS) was studied in IS patients (CeAD patients and age- and sex-matched non-CeAD patients) from the Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) database. FHS ≤ 50 and FHS > 50 were defined as having relatives who suffered stroke at the age of ≤50 or >50 years. FHS ≤ 50 and FHS > 50 were studied in CeAD and non-CeAD IS patients and related to age, sex, number of siblings, hypertension, hypercholesterolemia, smoking and body mass index (BMI). RESULTS: In all, 1225 patients were analyzed. FHS ≤ 50 was less frequent in CeAD patients (15/598 = 2.5%) than in non-CeAD IS patients (38/627 = 6.1%) (P = 0.003; odds ratio 0.40, 95% confidence interval 0.22-0.73), also after adjustment for age, sex and number of siblings (P = 0.005; odds ratio 0.42, 95% confidence interval 0.23-0.77). The frequency of FHS > 50 was similar in both study groups. Vascular risk factors did not differ between patients with positive or negative FHS ≤ 50. However, patients with FHS > 50 were more likely to have hypertension and higher BMI. CONCLUSION: Relatives of CeAD patients had fewer strokes at a young age than relatives of non-CeAD IS stroke patients.

No benefit from carotid intervention in fatal stroke prevention for >80-year-old patients.

BACKGROUND: Invasive management of patients ≥80 years of age with carotid stenosis may be questionable. The higher likelihood of stroke needs to be balanced with the increased perioperative risk and the reduced life expectancy of this ageing population. The purpose of this study was to evaluate the clinical relevance of carotid stenosis revascularisation in octogenarians. METHODS: All patients ≥80 years of age who received carotid revascularisation in 2001-2010 were reviewed for perioperative and 5-year outcomes. The experience was comprehensive of carotid endarterectomy (CEA) and carotid stenting (CAS) performed during the training frame when age was not a contraindication for this procedure. Mortality rates were compared to those of octogenarians of the same geographical territory according to all-cause and stroke-related mortality national statistics datasets. RESULTS: A total of 348 procedures performed in ≥80-year-old patients (272 males) were reviewed: 162 (46.6%) were by CAS and 169 (48.6%) were for symptomatic disease. Perioperative stroke/death rate was 5.5% and was non-significantly higher for symptomatic disease (7.1% vs. 3.9% asymptomatic; p = 0.24), after CAS (6.2% vs. 4.8% CEA; p = 0.64) and in females (6.6% vs. 5.1% males; p = 0.57). At median follow-up of 36.18 months, 95 deaths and 21 new ischaemic strokes (12 fatal) occurred with 5-year Kaplan-Meier freedom from stroke of 84.8% (78.7%, symptomatic vs. 90.3% asymptomatic; p = 0.003). According to national datasets, in 80-85-year-old resident population 5-year mortality was 29.9% (23.4% females, 40.6% males) and ischaemic stroke-related mortality was 14.9% (16.8% females, 13.0% males). Corresponding figures from treated population showed a 5-year mortality of 49.4%, higher in males (39.5% females, 52.5% males) and ischaemic stroke-related mortality of 20.2%, higher in females (40.0% females, 15.6% males). Comparing data from the study population with residents' figures, ischaemic stroke-related mortality hazard was significantly higher in the study females: odds ratio (OR) 3.2, 95% confidence interval (CI) 1.16-9.17; p = 0.029 (for males: OR 0.97, 95%CI 0.89-1.10; p = 0.99). CONCLUSIONS: Despite perioperative stroke/death risks being lower compared with CAS, the benefit of surgical carotid revascularisation in old patients remains controversial due to limited life expectancy and high fatality of stroke in this ageing population. Invasive treatment of carotid stenosis may not be warranted in most patients ≥80 years of age with carotid stenosis, especially when female and asymptomatic.

Is haemodynamic depression during carotid stenting a predictor of peri-procedural complications?

OBJECTIVE: The clinical significance of Haemodynamic Depression (HD) during carotid stenting (CAS) remains unclear. The aim of this study was to analyze the frequency and predictors of HD during CAS in a single centre experience. METHODS: A prospective protocol for CAS was applied in a 15-month interval. Patients with restenosis, on betablockers, or with arrhythmias were excluded. A standardized dose of atropine (0.4mg) was given prior to stent deployment. Changes in heart rate, blood pressure, and neurological status were monitored and recorded. HD was defined as systolic pressure <90mmHg and/or heart rate <50 beats/min. Fifteen potential predictors of HD (age, gender, hypertension, smoking, diabetes, coronary artery disease, previous myocardial infarction, symptoms, degree of carotid stenosis contralateral CEA or CAS, calcified/hyperechoic plaque, plaque length, stent oversizing and type of stent) were tested in multivariate analysis. RESULTS: Two hundred and twenty three consecutive patients were enrolled. HD occurred in 98 cases (44%): in 68 cases HD required additional pharmacological support. At 30 days, any stroke rate was 3.1% (3 major and 4 minor), TIA rate 1.8%, myocardial infarction rate 0.4%. No deaths were recorded. No difference in complication rates were found in patients with or without HD. From regression analysis only the presence of calcified plaque (HR 9.5; 95% CI 5.0 to 18.2; p<0.0001) and the plaque length (HR 1.77; 95% CI 1.03 to 3.06; p=0.038) were associated significantly with HD. CONCLUSIONS: HD during CAS is a common, relatively benign event, without increased risk of peri-operative complications. Careful pharmacological treatment is necessary to decrease HD and the potential complications, especially in patients with more severe calcified lesions. These results require confirmation in a separate, larger cohort.

Arterial hypertension as risk factor for spontaneous cervical artery dissection. A case-control study.

Because of the presumed non-atherosclerotic pathogenesis, the potential link between spontaneous cervical artery dissection (sCAD) and common risk factors for atherosclerosis has never been investigated systematically. Therefore, this prospective, multicentre, case-control study compared the frequency of tobacco use, hypertension, diabetes mellitus, and hypercholesterolaemia among a group of consecutive patients with sCAD (n = 153), a group of patients with ischaemic stroke, not related to CAD (non-CAD), and a group of controls. As opposed to the other variables, a trend towards a significant association was seen when the prevalence of hypertension was compared among patients with sCAD and controls (26.8% v 17.0%; odds ratio (OR) 1.79; 95% confidence interval (CI), 0.98 to 3.27; p = 0.058). Hypertension was also significantly associated with the subgroup of patients with sCAD and cerebral infarction (OR, 1.94; 95% CI, 1.01 to 3.70; p = 0.045), particularly when involving the vertebral arteries (OR, 2.69; 95% CI, 1.20 to 6.04; p = 0.017). These findings might help define the spectrum of pathogenic conditions predisposing to sCAD and provide information to help investigate the combined effect of such susceptibility factors in future studies.

Management of asymptomatic carotid stenosis in patients undergoing general and vascular surgical procedures.

Current available data do not seem to support the strategy for carotid endarterectomy prior to surgical intervention in patients with asymptomatic carotid stenosis. However, in patients with coronary artery disease, synchronous carotid endarterectomy and coronary artery bypass grafting should be considered where there is a proven surgical risk of <3% with unilateral asymptomatic stenosis >60% or bilateral carotid stenosis >75% on the same side as the most severe stenosis. Clarification of the optimal strategy requires an adequately powered, multicentre, randomised clinical trial.

Environmental factors and cervical artery dissection.

A history of a minor precipitating event is frequently elicited in patients with a spontaneous dissection of the carotid or vertebral artery. Other precipitating events associated with hyperextension or rotation of the neck include practicing yoga, painting a ceiling, coughing, vomiting, sneezing, the receipt of anesthesia, and the act of resuscitation. Chiropractic manipulation of the neck has been associated with carotid artery dissection and, particularly, vertebral artery dissection. Another risk factor for spontaneous dissections seems to be a recent history of a respiratory tract infection. The possibility of an infectious trigger is supported by the finding of a seasonal variation in the incidence of spontaneous dissections, with a peak incidence in fall. A potential link with common risk factors for vascular disease, such as tobacco use, hypertension, and the use of oral contraceptives, has not been systematically evaluated, but atherosclerosis appears to be distinctly uncommon in patients with a dissection of the carotid or vertebral arteries. In conclusion, although any hypotheses on the pathogenic mechanisms linking environmental factors and dissection remain speculative at present, we believe that these hypotheses may contribute to better define the spectrum of pathogenic conditions predisposing a cervical artery to dissection and provide arguments to better investigate the single or combined effect of such susceptibility factors in future studies.

Mild hyperhomocysteinemia is a risk-factor in all etiological subtypes of stroke.

The role of hyperhomocysteinemia as independent risk factor for stroke needs to be confirmed. The aims of our study were to assess (i) the association between risk of stroke and increasing values of plasma homocysteine and (ii) the interaction between mild hyperhomocysteinemia and conventional vascular risk factors. We studied 161 consecutive patients with first-ever ischemic stroke classified using TOAST criteria and 152 neurologically healthy controls. Homocysteine was measured using high performance liquid chromatography (HPLC). Homocysteinemia was elevated in all stroke subtypes: 13.0+/-2.5 micromol/l in patients with cardioembolic disease, 13.9+/-5.4 micromol/l in those with small vessel diseases, 15.5+/-6.8 micromol/l in cases of undetermined stroke, and 17.8+/-13.5 micromol/l in patients with large vessel disease. Mean homocysteinemia was 8.10 micromol/l (SD=2.5) in controls. The logistic regression analysis showed that important independent risk factors for ischemic stroke were hypertension (p<0.0001; OR= 3.205; 95% CI, 1.788-5.742), hyperhomocysteinemia (p<0.0001; OR=1.425; 95% CI, 1.300-1562) and hyperlipidemia (p=0.018; OR=2.243; 95% CI, 1.147-4.385). Hyperhomocyst(e)inemia is an independent risk factor for all stroke subtypes and should be routinely measured and treated in stroke patients.

Effects of propionyl-L-carnitine topical irrigation in distal ulcerative colitis: a preliminary report.

BACKGROUND/AIMS: To study the tolerability of propionyl-L-carnitine administered as rectal irrigation and its efficacy in improving the clinical picture of distal ulcerative colitis. METHODOLOGY: Ten male subjects (aged 18 to 55 years, with a body mass index ranging from 21 to 25 Kg/m2) with distal ulcerative colitis were treated with propionyl-L-carnitine enemas (6 g in 200 mL physiological solution) twice a day over 120 minutes each. All subjects had a disease activity index from 0 to 1. A clinical, laboratory, endoscopy and biopsy evaluation was performed at baseline and 14 days after treatment. Serum tumor necrosis factor-alpha and interleukin-2 concentration was measured. RESULTS: No side effects were reported by the entire patient population and the clinical conditions remained constant throughout the study period. The disease activity index improved significantly between the beginning and the end of the study in 80% of the patients. Histologic features (mucosal erosion, distortion of crypt architecture, inflammation and lamina propria gap) significantly improved in all treated patients. Serum interleukin-2 levels did not change significantly after propionyl-L-carnitine treatment (respectively: 14.7 +/- 15.8 before vs. 9.9 +/- 13.2 pg/mL), while tumor necrosis factor-alpha levels were undetectable both before and after propionyl-L-carnitine administration. CONCLUSIONS: The topical treatment with a new formulation containing propionyl-L-carnitine seems to be safe and effective in improving the histologic features in patients with inactive or mild ulcerative colitis, as an alternative to conventional therapy.

Carnitine protects mitochondria and removes toxic acyls from xenobiotics.

The carnitine system is altered by several xenobiotics (drugs and chemicals). These alterations are responsible for most toxic effects, which can be reverted or minimized by L-carnitine administration. Formation of nonmetabolizable acyl coenzyme A (CoA) is a typical step in the biotransformation of pivaloyl antibiotics, valproate and ifosfamide. The elevated levels of acylcarnitine occurring in human urine due to impaired metabolism of specific acyl CoA support the role of L-carnitine as an acceptor of specific, nonmetabolizable acyl CoA. The consequence of this process is a secondary carnitine deficiency. The formation of stable complexes with an essential component of mitochondrial membrane, cardiolipin, and the inhibition of myocardial specific isoform of carnitine-palmitoyl transferase are presumably the basis of adriamycin cardiotoxicity. L-carnitine interacts with cardiolipin, modifying membrane permeability and protecting the functions of the mitochondria. This mechanism can be proposed to explain the protective effects of L-carnitine against adriamycin cardiotoxicity, ammonium acetate and zidovudine-induced mitochondrial ultrastructural and functional alterations. Cisplatin, cephalosporin and carbapenem antibiotics inhibit carnitine reabsorption in renal tubules and cause proximal tubular damage. The study of peroxisomal producing agents belonging to largely different chemical classes showed that these agents caused carnitine system perturbations which may have the potential to be highly relevant biomarkers of exposure to the nongenotoxic peroxisomal proliferating agent class of hepatic tumorigens.