Stroke and the need for immediate assistance at the place of onset: the future of mandatory training for lay people in Italy.

Introduction: Lay training is essential to manage emergencies properly, although patients or bystanders need increased recognition of medical urgencies such as strokes. In Italy, as defined by Legislative Decree 81/08, all companies must train employees responsible for correctly recognizing and managing medical emergencies. Our study aims to evaluate the characteristics of medical emergencies concerning patients with a possible stroke in the Lombardy Region. Methods: A retrospective observational study was conducted. All missions performed by Regional Agency for Emergencies and Urgencies (Agenzia Regionale Emergenza Urgenza - AREU) in which the patient presented a possible stroke, recorded in the SAS-Areu database, were analyzed. The study period was from January 1, 2019, to December 31, 2019. Results: 10,201 patients with possible stroke were rescued, of whom only 540 (5.3%) occurred in workplaces. In workplaces, the percentage of males with a possible stroke was higher (62.2% vs 45.2%; p<0.01) and the mean age of rescued patients was lower (64.7 vs 77.5; p<0.01). Conclusions: A stroke occurs less frequently in the workplace, while most events occur at home. Man-datory training on early stroke recognition should be extended to schools and conveyed through a media information campaign. Lay training is the first point in the chain of survival; redefining training is critical for the future.

Public health impact of the COVID-19 pandemic on the emergency healthcare system.

BACKGROUND: The Lombardy region has been the Italian region most affected by the coronavirus disease 2019 (COVID-19) pandemic in 2020. The emergency healthcare system was under deep stress throughout the past year due to the admission of COVID-19 patients to the emergency department (ED) and had to be thoroughly reorganized. METHODS: We performed a retrospective descriptive analysis of patients admitted into the ED recorded in the Lombardy online regional portal called EUOL (Emergenza e Urgenza OnLine). We compared the data registered in the EUOL with the patients admitted to the EDs from 1 January 2019 to 31 December 2019 and from 1 January 2020 to 31 December 2020. RESULTS: The number of admissions to the ED decreased by 32.5% in 2020 compared with 2019, reaching the lowest number in March and April. However, the percentage of patients hospitalized after ED significantly increased in 2020 compared with 2019 (P < 0.0001), reflecting the management of patients with a more severe clinical condition. More patients arrived at the ED by ambulance in 2020 (21.7% in 2020 versus 15.1% in 2019; P < 0.0001), particularly during March and April. CONCLUSIONS: This analysis showed the importance of monitoring the pandemic's evolution in order to treat more critically ill patients, despite a lower number of patients.

Humoral immunity response to human endogenous retroviruses K/W differentiates between amyotrophic lateral sclerosis and other neurological diseases.

BACKGROUND AND PURPOSE: Human endogenous retroviruses (HERV) K/W seem to play a role in fostering and exacerbation of some neurological diseases, including amyotrophic lateral sclerosis (ALS). Given these findings, the immunity response against HERV-K and HERV-W envelope surface (env-su) glycoprotein antigens in serum and cerebrospinal fluid (CSF) was investigated for ALS, multiple sclerosis (MS) and Alzheimer's disease patients and in healthy controls. METHODS: Four antigenic peptides derived respectively from HERV-K and HERV-W env-su proteins were studied in 21 definite or probable ALS patients, 26 possible or definite relapsing-remitting MS patients, 18 patients with Alzheimer's disease and 39 healthy controls. An indirect enzyme-linked immunosorbent assay was set up to detect specific antibodies (Abs) against env-su peptides. RESULTS: Amongst the measured levels of Abs against the four different HERV-K peptide fragments, only HERV-K env-su19-37 was significantly elevated in ALS compared to other groups, both in serum and CSF. Instead, amongst the Abs levels directed against the four different HERV-W peptide fragments, only HERV-W env-su93-108 and HERV-W env-su248-262 were significantly elevated, in the serum and CSF of the MS group compared to other groups. In ALS patients, the HERV-K env-su19-37 Abs levels were significantly correlated with clinical measures of disease severity, both in serum and CSF. CONCLUSIONS: Increased circulating levels of Abs directed against the HERV-W env-su93-108 and HERV-W env-su248-262 peptide fragments could serve as possible biomarkers in patients with MS. Similarly, increased circulating levels of Abs directed against the HERV-K env-su19-37 peptide fragment could serve as a possible early novel biomarker in patients with ALS.

Homologous HSV1 and alpha-synuclein peptides stimulate a T cell response in Parkinson's disease.

Environmental factors are implicated in the development of Parkinson's disease (PD). The aim of this study is to investigate the role of cell-mediated immunity upon a specific immune-stimulation with HSV-1 and human alpha-synuclein homologues peptides by using the intracellular cytokine method on Parkinson's patients and healthy controls. The study showed, for the first time, a specific response to TNF-α CD8, CD4 and NK cells after stimulation in PD patients. Our data show a possible role of the immune system in the pathogenesis of Parkinson's disease, and that HSV-1 infections may lead to a progression of the disease.

Mitochondrial DNA haplogroups may influence Fabry disease phenotype.

While the genetic origin of Fabry disease (FD) is well known, it is still unclear why the disease presents a wide heterogeneity of clinical presentation and progression, even within the same family. Emerging observations reveal that mitochondrial impairment and oxidative stress may be implicated in the pathogenesis of FD. To investigate if specific genetic polymorphisms within the mitochondrial genome (mtDNA) could act as susceptibility factors and contribute to the clinical expression of FD, we have genotyped European mtDNA haplogroups in 77 Italian FD patients and 151 healthy controls. Haplogroups H and I, and haplogroup cluster HV were significantly more frequent in patients than controls. However, no correlation with gender, age of onset, organ involvement was observed. Our study seems to provide some evidence of a contribution of mitochondrial variation in FD pathogenesis, at least in Italy.

Male longevity in Sardinia, a review of historical sources supporting a causal link with dietary factors.

The identification of a hot spot of exceptional longevity, the Longevity Blue Zone (LBZ), in the mountain population of Sardinia has aroused considerable interest toward its traditional food as one of the potential causal factors. This preliminary study on the traditional Sardinian diet has been supported by the literature available, which has been carefully reviewed and compared. Up to a short time ago, the LBZ population depended mostly upon livestock rearing, and consumption of animal-derived foods was relatively higher than in the rest of the island. The nutrition transition (NT) in urbanized and lowland areas began in the mid-1950s, fueled by economic development, whereas in the LBZ it started later owing to prolonged resistance to change by a society organized around a rather efficient pastoral economy. Even nowadays a large proportion of the population in this area still follows the traditional diet based on cereal-derived foods and dairy products. The LBZ cohorts comprising individuals who were of a mature age when NT began may have benefited both from the high-quality, albeit rather monotonous, traditional diet to which they had been exposed most of their life and from the transitional diet, which introduced positive changes such as more variety, increased consumption of fruits and vegetables and moderate meat intake. It could be speculated that these changes may have brought substantial health benefits to this particular aging group, which was in need of nutrient-rich food at this specific time in life, thereby resulting in a decreased mortality risk and, in turn, life-span extension.

Cardiac side effects of phenytoin and carbamazepine. A dose-related phenomenon?

Three patients with dystrophia myotonica and echocardiographic signs of subclinical cardiopathy had cardiac side effects during oral treatment with phenytoin sodium or carbamazepine. These side effects were dose related: ventricular tachycardia appeared at a toxic serum phenytoin level in one patient and disappeared as the concentration fell within the therapeutic range, and atrioventricular block grade 1 developed in two patients at low serum carbamazepine levels, its severity increasing with the drug level. Given the risk of dangerous side effects, cardiac status needs to be carefully assessed before administration of phenytoin or carbamazepine in the treatment of dystrophia myotonica.

Relationship between Meige syndrome and alpha-methyldopa-induced parkinsonism.

We studied two patients with Meige syndrome who developed alpha-methyldopa-induced parkinsonism. Opposite responses of parkinsonian and dystonic symptoms to antiparkinson drugs in some cases suggest a functionally reciprocal relationship between these disorders.

Fatal hyperpyrexia after withdrawal of levodopa.

We studied a patient affected with idiopathic Parkinson's disease and levodopa-induced dyskinesias. Fatal hyperpyrexia followed simultaneous levodopa withdrawal and a decrease in the dosage of diphenhydramine. The clinical features were those of the neuroleptic malignant syndrome. The rapid decrease in dopaminergic activity may have been important in causing the syndrome.

Treatment of cerebellar tremors with carbamazepine: a controlled trial with long-term follow-up.

We studied the effects of carbamazepine (CBZ) (400 and 600 mg per day) in 10 patients with cerebellar tremors in a single-blind manner. All patients improved on a clinical rating scale and by accelerometric recording; there was no improvement with placebo. Our data suggest that CBZ may be a valuable drug in cerebellar tremors.

Multiple sclerosis-associated retrovirus (MSRV) in Sardinian MS patients.

Blood and CSF of Sardinian patients with MS and neurologic control subjects were tested for MS-associated retrovirus (MSRV). CSF detection in MS was 50% at clinical onset, increasing with temporal disease progression, and 40% in control subjects. In blood, MSRV was detected in all MS patients, in most patients with inflammatory neurologic diseases, and rarely in healthy blood donors. MSRV may represent a marker of neurologic diseases of inflammatory origin.

Hyperinsulinemia and hypertension. Do intestinal hormones play a role?

Gastric inhibitory polypeptide (GIP) is one of the strongest insulinotropic gut factors. Its secretion is induced by oral (but not intravenous) glucose and it has been implicated in the pathogenesis of hyperinsulinemic states (NIDDM, obesity). To determine its relevance to hypertension, 54 subjects were studied: 26 normotensives (12 with and 14 without family history of essential hypertension), and 28 essential hypertensive subjects. Plasma glucose, serum insulin (IRI), and GIP were evaluated after a mixed meal containing a total of 82 g of carbohydrates, and 2 g sodium chloride. Venous blood was collected at baseline and every 15 min during a 3-h period. Baseline levels of glucose, IRI, and GIP were comparable in the three groups. At 30 min, however, IRI and GIP were higher in normotensives with a family history of hypertension and in established hypertensive versus control subjects. Both in normotensive and in hypertensive groups, glucose, IRI, and GIP responses to the meal were significantly correlated. Our data suggest the contribution of altered GIP secretion in the pathogenesis of hyperinsulinemia in essential hypertension.

Brain interstitial fluid collected through implanted tissue cages.

The physicochemical properties of the whole-brain interstitial fluid (IF) are unknown. A volume of whole-brain IF sufficient for analysis was obtained through a small, hollow, multiperforated polypropylene sphere implanted for 4-5 weeks into the dog brain parenchyma. The main physicochemical properties of the whole-brain IF were characterized, in comparison with the physicochemical properties of cerebrospinal fluid and blood/serum.

Co-variation of free amino acids in brain interstitial fluid during pentylenetetrazole-induced convulsive status epilepticus.

Effects of pentylenetetrazole (PTZ)-induced convulsive status epilepticus on free amino acids changes in venous blood, CSF and interstitial fluid (IF) of the brain were examined in dogs. A volume of brain IF sufficient for analysis was obtained by chronically implanted tissue cages. The onset of PTZ-induced convulsive seizures seemed mainly related to a marked increase of glutamate, aspartate, taurine, glycine and phosphoserine while, the maintenance and frequency of seizures seemed related to a marked increase of serine and glycine, in combination with a moderate rise of glutamate. L-alpha-Aminoadipate was recovered in moderate amount in epileptic brain IF, while, in controls, this compound was present in minimal amount. The observed complex temporal variation of the amino acidic pattern may play a role in PTZ-induced seizures and, possibly, in pharmacological kindling and brain structural alterations induced by PTZ.

Efficacy of carbamazepine on cerebellar tremors in patients with superior cerebellar artery syndrome.

Three patients with postural and intention cerebellar tremor caused by a cerebellar infarction in the superior cerebellar artery distribution were studied; treatment with carbamazepine resulted in marked improvement.

Acute hyponatremia and neuroleptic malignant syndrome in Parkinson's disease.

1. The neuroleptic malignant syndrome (NMS) may occur, occasionally, in Parkinson's disease (PD) after withdrawal of antiparkinsonian drugs. However, the circumstances in which the NMS occurs and the pathophysiologic mechanisms remain uncertain. 2. The authors studied a woman with PD, who developed hyperthermia, increased muscular tone, tremor, signs of autonomic dysfunction and stupor as symptoms of acute hyponatremia due to gastrointestinal loss of sodium in excess of water. 3. The correction of hyponatremia led to a complete recovery after about 6 hours. During this period the antiparkinsonian therapy was not modified. 4. An acute imbalance of sodium in the central nervous system may play a role in the pathophysiology of NMS.

Risperidone, neuroleptic malignant syndrome and probable dementia with Lewy bodies.

1. Conflicting reports are available regarding the sensitivity of patients with Dementia with Lewy bodies (DLB) to risperidone. 2. The authors studied a rare familial case of probable DLB, who developed a documented episode of neuroleptic malignant syndrome (NMS) following the exposure to risperidone. Previously, the patient had had an episode of NMS on trifluoperazine. 3. The discontinuance of risperidone, in combination with a mild increase of dopaminergic therapy, led to a complete recovery in few days. 4. In patients with DLB, a continued vigilance for extrapyramidal side effects, including NMS, would be advisable during the use of risperidone.

Cerebral and cerebellar diaschisis following carbamazepine therapy.

1. The regional cerebral blood flow was studied by SPECT in patients with partial epilepsy before and after 30 days of monotherapy with carbamazepine (CBZ). 2. Both a qualitative visual interpretation and a semiquantitative analysis of SPECT was performed. All patients underwent EEG, CT scan, and MRI studies. The CBZ serum concentrations were assayed. 3. After therapy, in three patients with focal epilepsy, both a crossed cerebral and cerebellar diaschisis were observed, with respect to the side of the epileptic focus in the opposite hemisphere. No morphologic changes were detected at MRI in the cerebral or cerebellar remote hypometabolic areas found at SPECT. 4. CBZ may have a depressant action on the corticopontocerebellar pathways and on the corticocallosal connections.

Reduced intravenous glutathione in the treatment of early Parkinson's disease.

1. Several studies have demonstrated a deficiency in reduced glutathione (GSH) in the nigra of patients with Parkinson's Disease (PD). In particular, the magnitude of reduction in GSH seems to parallel the severity of the disease. This finding may indicate a means by which the nigra cells could be therapeutically supported. 2. The authors studied the effects of GSH in nine patients with early, untreated PD. GSH was administered intravenous, 600 mg twice daily, for 30 days, in an open label fashion. Then, the drug was discontinued and a follow-up examination carried-out at 1-month interval for 2-4 months. Thereafter, the patients were treated with carbidopa-levodopa. 3. The clinical disability was assessed by using two different rating scale and the Webster Step-Second Test at baseline and at 1-month interval for 4-6 months. All patients improved significantly after GSH therapy, with a 42% decline in disability. Once GSH was stopped the therapeutic effect lasted for 2-4 months. 4. Our data indicate that in untreated PD patients GSH has symptomatic efficacy and possibly retards the progression of the disease.

Which syringomyelia is truly associated with multiple sclerosis?

Necrosis of the spinal cord within multiple sclerosis (MS) lesions was suggested as a putative cause of syringomyelic cavity development in MS. A number of evidences suggest however that mechanisms other than necrosis are pathogenetically relevant for cavity formation, possibly depending on the atypical topographical distribution of the demyelinative lesion and on the increased cerebrospinal fluid pressure into the central canal below the compression. Not coincidentally, the hypothesis of post-necrotic and ex-vacuo mechanisms leading to cavitation derives from Japanese studies where MS is characterised by high tissue destructive capability and, besides its rarity, has many differences from the more common Western MS type and similarities with the acute disseminated encephalomyelitis (ADEM). Our opinion is that different MS types (Asian and Western) are accompanied by nonuniform mechanisms of syrinx formation and that the Asian MS type shares common, post-necrotic mechanisms with ADEM.