Stroke and stroke-like episodes in inborn errors of metabolism: Pathophysiological and clinical implications.

Inborn errors of metabolism causing stroke (ischemic or haemorrhagic) or stroke-like episodes (e.g., that are also called "metabolic strokes" and include acute brain lesions not related with alterations of blood flow) cover a wide range of diseases in which acute metabolic decompensations after trigger events (e.g., fever, dehydration, sepsis etc.) may have a variable frequency. The early diagnosis of these conditions is essential because, despite their rarity, effective symptomatic treatments may be available for acute settings (e.g., arginine for Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes- MELAS) while in other cases disease modifying therapies may be useful to prevent stroke occurrence, recurrence, or relapse (e.g., Fabry disease). The detection of a non-vascular distribution of lesions and the diffuse use of 1HMRS are often diriment in the differential of ischemic and metabolic strokes. This review summarized the main clinical features and the pathophysiological mechanisms of stroke and stroke-like episodes in inborn errors of metabolism presenting with stroke as part of natural history of the disease. These conditions belong to different etiological groups, such as organic acidurias, mitochondrial encephalopathies, homocystinuria and remethylation disorders, urea cycle disorders, lysosomal diseases (e.g. Fabry disease, glycogen storage disease), congenital disorders of glycosylation, neurotransmitter disorders, adenosine deaminase 2 deficiency and few other neurometabolic disorders.

Acute ischemic stroke in childhood: a comprehensive review.

This review provides an updated analysis of the main aspects involving the diagnosis and the management of children with acute ischemic stroke. Acute ischemic stroke is an emergency of rare occurrence in children (rate of incidence of 1/3500 live birth in newborns and 1-2/100,000 per year during childhood with peaks of incidence during the perinatal period, under the age of 5 and in adolescence). The management of ischemic stroke in the paediatric age is often challenging because of pleomorphic age-dependent risk factors and aetiologies, high frequency of subtle or atypical clinical presentation, and lacking evidence-based data about acute recanalization therapies. Each pediatric tertiary centre should activate adequate institutional protocols for the optimization of diagnostic work-up and treatments.Conclusion: The implementation of institutional standard operating procedures, summarizing the steps for the selection of candidate for neuroimaging among the ones presenting with acute neurological symptoms, may contribute to shorten the times for thrombolysis and/or endovascular treatments and to improve the long-term outcome. What is Known: •Acute ischemic stroke has a higher incidence in newborns than in older children (1/3500 live birth versus 1-2/100,000 per year). •Randomized clinical trial assessing safety and efficacy of thrombolysis and/or endovascular treatment were never performed in children What is New: •Recent studies evidenced a low risk (2.1% of the cases) of intracranial haemorrhages in children treated with thrombolysis. •A faster access to neuroimaging and hyper-acute therapies was associated with the implementation of institutional protocols for the emergency management of pediatric stroke.

Neurophysiological correlates of bradykinesia in Parkinson's disease.

Many neurophysiological abnormalities have been described in the primary motor cortex of patients with Parkinson's disease. However, it is unclear whether there is any relationship between them and bradykinesia, one of the cardinal motor features of the condition. In the present study we aimed to investigate whether objective measures of bradykinesia in Parkinson's disease have any relationship with neurophysiological measures in primary motor cortex as assessed by means of transcranial magnetic stimulation techniques. Twenty-two patients with Parkinson's disease and 18 healthy subjects were enrolled. Objective measurements of repetitive finger tapping (amplitude, speed and decrement) were obtained using a motion analysis system. The excitability of primary motor cortex was assessed by recording the input/output curve of the motor-evoked potentials and using a conditioning-test paradigm for the assessment of short-interval intracortical inhibition and facilitation. Plasticity-like mechanisms in primary motor cortex were indexed according to the amplitude changes in motor-evoked potentials after the paired associative stimulation protocol. Patients were assessed in two sessions, i.e. OFF and ON medication. A canonical correlation analysis was used to test for relationships between the kinematic and neurophysiological variables. Patients with Parkinson's disease tapped more slowly and with smaller amplitude than normal, and displayed decrement as tapping progressed. They also had steeper input/output curves, reduced short-interval intracortical inhibition and a reduced response to the paired associative stimulation protocol. Within the patient group, bradykinesia features correlated with the slope of the input/output curve and the after-effects of the paired associative stimulation protocol. Although dopaminergic therapy improved movement kinematics as well as neurophysiological measures, there was no relationship between them. In conclusion, neurophysiological changes in primary motor cortex relate to bradykinesia in patients with Parkinson's disease, although other mechanisms sensitive to dopamine levels must also play a role.

Clinical profiles of acute arterial ischemic neonatal stroke.

INTRODUCTION: Perinatal stroke includes a heterogeneous group of early focal neurological injuries affecting subsequent brain development, often resulting in motor sequelae, symptomatic epilepsies, and cognitive, language and behavioral impairment. The incidence of perinatal stroke is about 1/3500 live birth. EVIDENCE ACQUISITION: A PubMed and SCOPUS search strategy included the entries "neonatal ischemic stroke" OR "perinatal ischemic stroke" and the age of the filter under 18 years and January 2000-August 2022. EVIDENCE SYNTHESIS: The cumulative literature analysis highlighted 3880 published patients (from 98 articles) with stroke, mainly presenting with clinical or electro-graphical seizures (2083 patients). The mean age at presentation was 2,5±2,4 days (data available for 1182 patients). Stroke occurred in the first week of life in 1164 newborns. The mainly involved ischemic areas were within the territories of the middle cerebral artery (1403 patients). Predisposing risk factors included fetal/newborn factors (1908 patients), dystocial birth (759 patients), maternal (678 patients), and placental factors (63 patients). No thrombolysis and/or endovascular treatments were performed, while data about other pharmacological treatments were restricted to a single article. The death occurred in 29 newborns. Motor, neurocognitive and language impairment were cumulatively reported in 875 patients. Epileptic seizures during the follow-up were reported in 238 cases. CONCLUSIONS: The literature analysis highlighted that every term newborn presenting with acute neurological signs and symptoms during the first week of life should always be considered for the identification of an ischemic stroke.

Hospitalization for Pneumonia is Associated With Decreased 1-Year Survival in Patients With Type 2 Diabetes: Results From a Prospective Cohort Study.

Diabetes mellitus is a frequent comorbid conditions among patients with pneumonia living in the community.The aim of our study is to evaluate the impact of hospitalization for pneumonia on early (30 day) and late mortality (1 year) in patients with type 2 diabetes mellitus.Prospective comparative cohort study of 203 patients with type 2 diabetes hospitalized for pneumonia versus 206 patients with diabetes hospitalized for other noninfectious causes from January 2012 to December 2013 at Policlinico Umberto I (Rome). Enrolled patients were followed up to discharge and up to 1 year after initial hospital admission or death.Overall, 203 patients with type 2 diabetes admitted to hospital for pneumonia were compared to 206 patients with type 2 diabetes admitted for other causes (39.3% decompensated diabetes, 21.4% cerebrovascular diseases, 9.2% renal failure, 8.3% acute myocardial infarction, and 21.8% other causes). Compared to control patients, those admitted for pneumonia showed a higher 30-day (10.8% vs 1%, P < 0.001) and 1-year mortality rate (30.3% vs 16.8%, P < 0.001). Compared to survivors, nonsurvivor patients with pneumonia had a higher incidence of moderate to severe chronic kidney disease, hemodialysis, and malnutrition were more likely to present with a mental status deterioration, and had a higher number of cardiovascular events during the follow-up period. Cox regression analysis found age, Charlson comorbidity index, pH < 7.35 at admission, hemodialysis, and hospitalization for pneumonia as variables independently associated with mortality.Hospitalization for pneumonia is associated with decreased 1-year survival in patients with type 2 diabetes, and appears to be a major determinant of long-term outcome in these patients.

Impaired flow-mediated dilation in hospitalized patients with community-acquired pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) is complicated by cardiovascular events as myocardial infarction and stroke but the underlying mechanism is still unclear. We hypothesized that endothelial dysfunction may be implicated and that endotoxemia may have a role. METHODS: Fifty patients with CAP and 50 controls were enrolled. At admission and at discharge, flow-mediated dilation (FMD), serum levels of endotoxins and oxidative stress, as assessed by serum levels of nitrite/nitrate (NOx) and isoprostanes, were studied. RESULTS: At admission, a significant difference between patients with CAP and controls was observed for FMD (2.1±0.3 vs 4.0±0.3%, p<0.001), serum endotoxins (157.8±7.6 vs 33.1±4.8pg/ml), serum isoprostanes (341±14 vs 286±10 pM, p=0.009) and NOx (24.3±1.1 vs 29.7±2.2µM). Simple linear correlation analysis showed that serum endotoxins significantly correlated with Pneumonia Severity Index score (Rs=0.386, p=0.006). Compared to baseline, at discharge CAP patients showed a significant increase of FMD and NOx (from 2.1±0.3 to 4.6±0.4%, p<0.001 and from 24.3±1.1 to 31.1±1.5µM, p<0.001, respectively) and a significant decrease of serum endotoxins and isoprostanes (from 157.8±7.6 to 55.5±2.3pg/ml, p<0.001, and from 341±14 to 312±14 pM, p<0.001, respectively). Conversely, no changes for FMD, NOx, serum endotoxins and isoprostanes were observed in controls between baseline and discharge. Changes of FMD significantly correlated with changes of serum endotoxins (Rs=-0.315; p=0.001). CONCLUSIONS: The study provides the first evidence that CAP is characterized by impaired FMD with a mechanism potentially involving endotoxin production and oxidative stress.