Thrombolysis and bridging therapy in patients with acute ischaemic stroke and Covid-19.

BACKGROUND AND PURPOSE: Comorbidity of acute ischaemic stroke with Covid-19 is a challenging condition, potentially influencing the decision of whether to administer intravenous thrombolysis (IVT). We aimed to assess the 1-month outcome in ischaemic stroke patients with Covid-19 infection who received IVT alone or before thrombectomy (bridging therapy). METHODS: As a collaboration initiative promoted by the Italian Stroke Organization, all Italian stroke units (n = 190) were contacted and invited to participate in data collection on stroke patients with Covid-19 who received IVT. RESULTS: Seventy-five invited centers agreed to participate. Thirty patients received IVT alone and 17 received bridging therapy between 21 February 2020 and 30 April 2020 in 20 centers (n = 18, Northern Italy; n = 2, Central Italy). At 1 month, 14 (30.4%) patients died and 20 (62.5%) survivors had a modified Rankin Scale (mRS) score of 3 to 5. At 24 to 36 hours, asymptomatic intracerebral hemorrhage (ICH) was reported in eight (17.4%) patients and symptomatic ICH (sICH) in two (4.3%) patients. Causes of death were severe ischaemic stroke (n = 8), a new ischaemic stroke (n = 2), acute respiratory failure (n = 1), acute renal failure (n = 1), acute myocardial infarction (n = 1), and endocarditis (n = 1). In survivors with a 1-month mRS score of 3 to 5, baseline glucose level was higher, whereas endovascular procedure time in cases of bridging therapy was longer. Baseline National Institutes of Health Stroke Scale glucose and creatinine levels were higher in patients who died. CONCLUSIONS: Intravenous thrombolysis for patients with stroke and Covid-19 was not a rare event in the most affected areas by pandemic, and rates of 1-month unfavorable outcomes were high compared to previous data from the pre-Covid-19 literature. However, risk of sICH was not increased.

Outcome in lacunar stroke: A cohort study.

OBJECTIVES: We evaluated a prospective cohort of 150 patients under observation in our centre for lacunar strokes. The purpose of this study was to evaluate the outcome at time of discharge and 6 months after lacunar stroke, as well as the correlation with cardiovascular risk factors and selected biochemical parameters already evaluated on admission. Focus was to identify possible prognostic factors, which might be targeted through appropriate intervention concentrating on reduction in the incidence and impact of early clinical deterioration. METHODS: 150 patients with a lacunar stroke were included in the present study. A clinical 6-month follow-up was available for 98.7% of the patients. Infarcts were classified by size, shape and location. RESULTS: The most important predictors of high NIHSS score at time of discharge resulted NIHSS on admission (P < .001), leukocytosis (P = .013), in-hospital infections (P = .016) and size of lacunae (P = .005). Similarly, the most important predictors of poor outcome 6 months later were NIHSS on admission (P = .01), leukocytosis (P = .014), elevated CRP (P = .019), in addition to pre-admission Rankin (P < .001). CONCLUSION: Although infections are not causatively related to lacunar strokes, their prompt recognition and early treatment, control of inflammatory markers and fever are most important in influencing functional outcome in lacunar stroke.

Long-term prognosis of epilepsy, prognostic patterns and drug resistance: a population-based study.

BACKGROUND AND PURPOSE: Seizures in most people with epilepsy remit but prognostic markers are poorly understood. There is also little information on the long-term outcome of people who fail to achieve seizure control despite the use of two antiepileptic drugs (drug resistance). METHODS: People with a validated diagnosis of epilepsy in whom two antiepileptic drugs had failed were identified from primary care records. All were registered with one of 123 family physicians in an area of northern Italy. Remission (uninterrupted seizure freedom lasting 2 years or longer) and prognostic patterns (early remission, late remission, remission followed by relapse, no remission) were determined. RESULTS: In all, 747 individuals (381 men), aged 11 months to 94 years, were followed for 11 045.5 person-years. 428 (59%) were seizure-free. The probability of achieving 2-year remission was 18% at treatment start, 34% at 2 years, 45% at 5, 52% at 10 and 67% at 20 years (terminal remission, 60%). Epilepsy syndrome and drug resistance were the only independent predictors of 2- and 5-year remission. Early remission was seen in 101 people (19%), late remission in 175 (33%), remission followed by relapse in 85 (16%) and no remission in 166 (32%). Treatment response was the only variable associated with differing prognostic patterns. CONCLUSION: The long-term prognosis of epilepsy is favourable in most cases. Early seizure remission is not invariably followed by terminal remission and seizure outcome varies according to well-defined patterns. Prolonged seizure remission and prognostic patterns can be predicted by broad syndromic categories and the failure of two antiepileptic drugs.

A cross-sectional survey among physicians on internet use for epilepsy-related information.

OBJECTIVE: We investigated views towards the Internet in a sample of Italian healthcare specialists involved in epilepsy field, to identify factors associated with the attitude of being influenced by information found on the Internet. METHODS: This study was a self-administered survey conducted in a group of members of the Italian Chapter of the International League Against Epilepsy (ILAE) in January 2018. RESULTS: 184 questionnaires were analyzed. 97.8 % of responders reported to seek online information on epilepsy. The Internet was most frequently searched to obtain new information (69.9 %) or to confirm a diagnostic or therapeutic decision (37.3 %). The influence of consulting the Internet on clinical practice was associated with registration to social network(s) (OR: 2.94; 95 %CI: 1.28-6.76; p = 0.011), higher frequency of Internet use (OR: 3.66; 95 %CI: 1.56-9.21; p = 0.006) and higher confidence in reliability of online information (OR: 2.61; 95 %CI: 1.09-6.26; p = 0.031). No association was found with age, sex, years in epilepsy practice or easiness to find online information. CONCLUSION: Internet is frequently used among healthcare professionals involved in the epilepsy to obtain information about this disease. The attitude of being influenced by the Internet for diagnostic and/or therapeutic decisions in epilepsy is independent on age and years of experience in epilepsy, and probably reflects an individual approach towards the Web.

A validation study of the clinical diagnosis of Dup15q syndrome: Which symptoms matter most?

PURPOSE: Dup15q syndrome is a rare genetic disease with a fairly nonspecific phenotype, clinical heterogeneity, and a wide spectrum of severity. However, no formal characterization has been attempted to select clusters of symptoms, signs and instrumental tests, to be used in the differential diagnosis with other neurodevelopmental disorders. Thus, our purpose was to identify symptoms, signs and instrumental findings, singly or in various combinations, favoring the early diagnosis of the Dup15q syndrome and the indication for genetic testing. METHODS: 25 patients with Dup15q syndrome and 25 age and sex matched controls with other neurodevelopmental disorders were the study population. Patients' history, clinical and instrumental assessment were examined by five expert child neurologists blind to the genetic diagnosis. Each rater was asked to make the diagnosis in three subsequent steps: 1. Revision of the medical records; 2. Examination of the videorecorded clinical findings; 3. Assessment of the instrumental tests. Inter-rater agreement was measured with the Kendall's coefficient of concordance) and the Kappa statistic. Sensitivity, specificity and predictive values for symptoms, signs and instrumental findings, singly or in various combinations, were measured. RESULTS: The Kendall's coefficient for the diagnosis of Dup15q syndrome was 0.43 at step 1 was 0.43, at step 2 was 0.42, at step 3. Patients with past feeding difficulties, hypotonia during the neonatal period, and epilepsy had >80 % probability of having the Dup15q syndrome. CONCLUSION: Feeding difficulties, hypotonia and epilepsy, though unspecific, can be used as signals of Dup15q syndrome and focused search of genetic abnormalities.

Immunological and clinical surveillance in Recklinghausen's neurofibromatosis (NF1).

Neurofibromatosis evolution is described in relation to the factors that may favour its expansion and immune modifications. NF1 monitorization should employ periodic clinical and immune surveillance. Such an approach would allow the application of immunomodulating treatment (e.g. adapted therapy) only when indicated, thereby reducing its duration and potentiating its efficacy.

Tumour suppressor genes, immunology and local manifestations of neurofibromatosis phenotypes.

Research on Neurofibromatosis (NF) has been directed at understanding what determines disease quiescence, exacerbation, and the possible malignant evolution. Studies on NF have examined the role of genetic oncosuppression in the evolution of the defence against the non-self. Paraffin fixed specimens of benign and malignant neoplasia, occurring in patients with NF1 and NF2, were tested for the presence of p53: a reliable marker of genetic oncosupression. The wild type variant of p53 is expressed in malignant neoplasia, and is usually not expressed in benign tumors. Contrariwise, an immune reaction it is seen in benign tumors and is practically absent in malignant tumors. Evidence of protein p53 in the various malignant neoplasias studied by our group seems to reflect the up-regulation on the oncosuppresive genetic potential that occurs while there is a lack of immunological defence. In the presence of an immunological defence, the expression p53 is normally not seen e.g. plexiform neurofibromas. The evolution of the various neoplastic types here reported was the same as that reported by current clinical and experimental models: the cell's defective genes are no longer suppressed and after activation the genes undergo initiation, promotion, and the cell sustains inflammatory-immune reactions that lead to fibrosis; what follows is a variable period of apparent quiescence. Severe pathogenic stimuli may act on predisposed cells and deteriorate pre-existing genetic damage, casting the cell into a phase of dysplastic or neoplastic proliferation that overcomes the body's defences. Hope for future therapy lies in the development of drugs that can either mimic the immune system or the proteins encoded by the oncosuppressor genes.

[Local immune response in neurofibromatosis type 1 and type 2]. / L'immunoreazione locale nelle neurofibromatosi di von Recklinghausen e del neurinoma bilaterale del nervo acustico.

Neurofibromatosis, in all its variant forms, is a hereditary disease characterized by dysplasia, neoplasia, and the tendency to expand and undergo malignant transformation. We underline the presence of chronic inflammation and of immunologic interdependency. The immune reactions against the non-self have been investigated histologically in light of the concepts of immunosurveillance and immunotolerance. Such investigations would ameliorate subsequent studies and favour the employment of immunomodulatory treatments.

[The clinico-immunological surveillance of neurofibromatosis]. / La sorveglianza clinico-immunologica delle neurofibromatosi.

Considering the more recent physiopathogenetic advancements in neurofibromatosis (NF), we propose to employ novel instrumental and laboratory procedures for the immunological and clinical surveillance of NF. In NF the evolution of the non-self can lead to disease expansion, at times transforming into malignancy. Contemporarily, the resulting immunological reactivity can either lead to the type of fibrosis that one sees in paraneoplastic connective tissue disease or be deficient. Through interdisciplinary biohumoral analyses were carried out contemporarily so as to gain comparative insight into the eventual unfolding of immunological and fibrotic phenomena. The range of the clinical follow-up varied from one to four years with periodic day hospital admissions. We studied ten NF patients that originated from southern Italy and belonged to middle and lower middle class status; we also studied one healthy subject who had the same HLA haplotype as his NF affected twin. We performed biohumoral analyses in clinical stable patients and saw moderate variations in induces useful for monitoring the evolution of this dysplastic-neoplastic condition, e.g. procollagens, interleukin-2, NSE (assayed with radioimmunological methods) and complement these parameters proved to be of use in monitoring the fibrotic evolution of NF. The intent of our work was to complete the earlier studies on NF surveillance, especially during periods of disease evolution and immuno-fibrotic alteration.

[Immune reaction in von Recklinghausen's neurofibromatosis]. / La reazione immunitaria nelle neurofibromatosi di von Recklinghausen.

A multidisciplinary study was performed on cases of neurofibromatosis to highlight the immunological reaction using broad-spectrum hematic tests and multiphase evaluation together with clinical and instrumental monitoring. The aim of the study was to focus attention on this rare disease and prompt further sequential immunological studies. A greater knowledge of the disease would allow the promising potential of new drugs to be exploited, in particular selective immunomodulatory drugs, in the hope of controlling the symptoms of disease (and overcoming further obstacles to the surgical removal of any neurofibromas that the patient wishes.

[Neurofibromatosis (NF1) and neuroleprosy: immunoreaction against pathologic Schwann-cells. Physiopathogenetic observations]. / Neurofibromatosi (NF1) e neurolebbra: immunoreazione verso cellule di Schwann patologiche. Considerazioni fisiopatogenetiche.

BACKGROUND: We reviewed the literature evaluating the immune reaction in neurofibromatosis (NF1) and neuroleprosy, so as to underline the immunopathegenetic parallelism and the possible therapeutic implications regarding the treatment of these two disorders. In particular we evaluated the systemic modifications and the local fibrotic events that lead to nerve damage in NF1 and complete neuronal destruction as in leprosy. METHODS: With the above aim in mind we studied the histology, histochemistry and immunohistochemistry (Schwann cells and immunoglobulins) of four plexiform neurofibroma, one common neurofibroma and one case of borderline neuroleprosy (BT). RESULTS: Two plexiform neurofibromas showed an evident immune reaction that was antibody mediated with numerous IgG; the remaining neurofibromas represented other stages of disease evolution and disease quiescence and thus showed a scarce immune reaction with a reduced presence of immunoglobulins. All the neurofibromas showed the presence of fibrous bundles. In the case of neuroleprosy (BT), the immune reaction was modest, immunoglobulins were present and fibrotic transformation on neuronal fibers was observed. CONCLUSIONS: Being that pathologic Schwann cell are the site of immune reactions that can become abnormal (at times with autoimmune reactions), clinical as well as biochemical surveillance of leprous neuropathy and NF1 could allow for a timely modification of the abnormal reaction with selective immunomodulators. The inactivation of the mycobacterial RNA polymerase or of the NF1 gene could offer hope for controlling disease activity and disease evolution of the two disorders.

[Primary retroperitoneal tumors]. / I tumori retroperitoneali primitivi.

The Authors report 7 cases of primary retroperitoneal tumors observed in a five-year period. On the basis of the literature data, they examine the diagnostic, therapeutic and prognostic features, emphasizing the need for a surgical treatment supported, only when useful, by radio- and chemotherapy. The importance of an early diagnosis, thanks to modern technologic progress, is also stressed, echography in particular.

[Primary volvulus of the omentum: a report of 4 cases]. / I volvoli primitivi dell'omento: presentazione di 4 casi.

The authors report their experience in the diagnosis and treatment of primary torsion of the omentum. They emphasize the clinical findings of the cases observed for a better understanding of this uncommon abdominal pathology.

[Cancer of the gallbladder]. / II cancro della colecisti.

The Authors report their experience about 20 patients operated on since 1975 for primary carcinoma of the gallbladder. They remark their disappointment because of the poor percentage of preoperative and early diagnosis, that only allows a radical surgical therapy. More attention, therefore, should be payed to this not so rare pathology in the hope the survival of the patients radically operated will increase.

Validation of healthcare administrative data for the diagnosis of epilepsy.

BACKGROUND: Administrative databases have become an important tool to monitor diseases. Patients with epilepsy could be traced using disease-specific codes and prescriptions, but formal validation is required to obtain an accurate case definition. The aim of the study was to correlate administrative data on epilepsy with an independent source of patients with epilepsy in a district of Lombardy, Northern Italy, from 2000 to 2008. METHODS: Data of nearly 320 600 inhabitants in the district of Lecco collected from the Drug Administrative Database of the Lombardy Region were analysed. Among them were included patients who fulfilled the International Classification of Diseases 9 (ICD-9) codes and/or the disease-specific exemption code for epilepsy and those who had at least one EEG record and took antiepileptic drugs (AEDs) as monotherapy or in variable combinations. To ascertain epilepsy cases, 11 general practitioners (GPs) with 15 728 affiliates were contacted. Multiple versions of the diagnostic algorithm were developed using different logistic regression models and all combinations of the four independent variables. RESULTS: Among the GP affiliates, 71 (4.5/1000) had a gold standard diagnosis of epilepsy. The best and most conservative algorithm included EEG and selected treatment schedules and identified 61/71 patients with epilepsy (sensitivity 85.9%, CI 76.0% to 92.2%) and 15 623/15 657 patients without epilepsy (specificity 99.8%,CI 99.7% to 99.8%). The positive and negative predictive values were 64.2% and 99.9%. Sensitivity (86.7%) and the positive predictive value (68.4%) increased only slightly when patients with single seizures were included. CONCLUSIONS: A diagnostic algorithm including EEG and selected treatment schedules is only moderately sensitive for the detection of epilepsy and seizures. These findings apply only to the Northern Italian scenario.