CHA2DS2-VASc score predicts short- and long-term outcomes in patients with acute ischemic stroke treated with intravenous thrombolysis.

The CHA2DS2-VASc score is a validated tool to assess the thromboembolic risk in patients with atrial fibrillation. Pre-stroke CHA2DS2-VASc score may predict outcome in patients with acute ischemic stroke (AIS) without atrial fibrillation. The aim of this study was to investigate if the pre-stroke CHA2DS2-VASc score is able to predict short- and long-term outcomes in AIS patients treated with intravenous thrombolysis (IVT). The study group consisted of 256 consecutive patients admitted to the Udine University Hospital with AIS and underwent IVT between January 2015 to March 2017. The pre-stroke CHA2DS2-VASc score for each patient was calculated from the collected baseline data. Patients were classified into three groups according to their pre-stroke CHA2DS2-VASc score: a score of 0 of 1, a score of 2 or 3 and a score above 3. Primary outcome measures were: rate of favorable outcome at 90-days and at 1-year, and mortality at 90-days and at 1-year. Data on functional outcome and mortality 1 year after stroke were collected in 165 patients (65% of the entire sample). Favorable outcome was defined as a modified Rankin Scale score ≤ 2. Compared with the CHA2DS2-VASc score 0-1 group, patients with higher CHA2DS2-VASc scores had a worse outcome and a higher mortality 3 months and 1 year after stroke. The diagnostic performance of the CHA2DS2-VASc score as judged with AUC-ROC was 0.70 (95% CI, 0.64-0.76; p < 0.001) for favorable outcome at 90-days, 0.78 (95% CI, 0.71-0.85; p < 0.001) for favorable outcome at 1-year, 0.71 (95% CI 0.61-0.79) for mortality at 90-days, 0.73 (95% CI 0.64-0.80; p < 0.001) for mortality at 1-year. Pre-stroke CHA2DS2-VASc score represents a good predictor for short- and long-term outcomes in AIS patients treated with IVT.

Short and long-term outcomes after combined intravenous thrombolysis and mechanical thrombectomy versus direct mechanical thrombectomy: a prospective single-center study.

Recent clinical trials demonstrated that mechanical thrombectomy (MT) using second-generation endovascular devices has beneficial effects in acute ischemic stroke (AIS) due to large vessel occlusion (LVO). However, it remains controversial if intravenous thrombolysis (IVT) prior to MT is superior compared to direct mechanical thrombectomy (DMT). The aims of this study were to compare short and long-term outcomes between IVT + MT and DMT patients. We prospectively recruited AIS patients with LVO in the anterior or posterior circulation eligible for MT with and without prior IVT. Modified Rankin Scale (mRS) and mortality were assessed at baseline, at discharge, 90-days and 1-year after stroke. Favorable outcome was defined as a mRS score ≤2. Of the 66 patients included, 33 (50%) were in IVT + MT group and 33 (50%) were in DMT group. Except for a higher prevalence of patients using anticoagulants at admission in DMT group, baseline characteristics did not differ in the two groups. Procedural characteristics were similar in IVT + MT and DMT group. Rate of favorable outcome was significantly higher in IVT + MT patients than DMT ones both 90-days (51.5 vs. 18.2%; p = 0.004) and 1-year (51.5 vs. 15.2%; p = 0.002) after stroke. DMT patients were six times more likely to die during the 1-year follow-up compared to IVT + MT patients. This study suggests that bridging therapy may improve short and long-term outcomes in patients eligible for endovascular treatment. Further studies with larger patient numbers and randomized design are needed to confirm our findings.

Are Early Seizures Predictive of Epilepsy after a Stroke? Results of a Population-Based Study.

BACKGROUND: In addition to determining the cumulative incidence and risk factors for early seizures (ES), late seizures (LS) and post stroke epilepsy (PSE), we aimed at checking if ES represented a risk factor for epilepsy and if early treatment after ES prevented the occurrence of subsequent seizures. METHODS: This study was part of a 2-year prospective community-based registry of all cerebrovascular events in the district of Udine (153,312 inhabitants), North-Eastern Italy, between April 1, 2007 and March 31, 2009. People with transient ischemic attacks (TIAs) were excluded from this study. RESULTS: In all, 782 cases of stroke (79.28% ischemic, 14.83% hemorrhagic, 3.20% subarachnoid hemorrhage and 2.69% undetermined) were identified. The incidence of ES, LS and PSE was 5.10, 3.14 and 2.22%, respectively. Intracerebral hemorrhage, subarachnoid hemorrhage, stroke of undetermined origin and hyponatremia, represented risk factors for ES (p < 0.05). Among ischemic strokes, ES risk factors were hyponatremia (p = 0.024) and hemorrhagic transformation (p = 0.046). LS risk factors were younger age (p = 0.004) and cortical location of stroke (p = 0.004). Within ischemic strokes, LS risk factors were younger age (p = 0.020) and cortical location (p < 0.0001). Within intracerebral hemorrhages, the only risk factor for LS was the presence of a previous ES (p = 0.017). PSE risk factors were the same as for LS. CONCLUSIONS: All acute conditions related to the occurrence of stroke are implicated in the pathogenesis of ES, which becomes a risk factor for LS only in the setting of intracerebral hemorrhages. Therefore, early antiepileptic treatment is needed only in this situation.

Drug-coated balloon dilation before carotid artery stenting of post-carotid endarterectomy restenosis.

PURPOSE: To investigate if drug-coated balloon (DCB) predilation may improve the efficacy of carotid artery stenting (CAS) for restenosis after carotid endarterectomy (CEA). METHODS: Eighteen consecutive patients (11 men; median age 75 years) with significant restenosis within 24 months of CEA were treated with a paclitaxel-coated DCB prior to CAS. Clinical outcomes and stent patency were systematically appraised. RESULTS: All patients were successfully treated according to this clinical protocol. The only complication occurred in a patient who had a transient ischemic attack during prolonged DCB inflation. At a median follow-up of 18 months, no >50% restenosis was observed on duplex ultrasound scans; however, moderate hyperplasia at the proximal stent edge was found in 4 patients. One patient died at 9 months from a myocardial infarction. CONCLUSION: Despite the small sample size and in keeping with the historically high risk of recurrent restenosis after CAS for CEA restenosis, this case series suggests that DCB dilation followed by CAS for postsurgical restenosis is feasible, safe, and may be associated with favorable clinical outcomes at midterm follow-up.

Stroke incidence and 30-day and six-month case fatality rates in Udine, Italy: a population-based prospective study.

BACKGROUND: Stroke incidence in high-income countries is reported to decrease, and new data on stroke incidence and outcome are needed to design stroke services and to ameliorate stroke management. METHODS: This study is part of a two-year prospective community-based registry of all cerebrovascular events in the district of Udine (153,312 inhabitants), Friuli-Venezia Giulia region, northeast of Italy, between 1 April 2007 and 31 March 2009. Overlapping sources for case finding were used, combining hot and cold pursuit. RESULTS: We identified 784 stroke cases, 640 (81.6%) incident. The crude overall annual incidence rate per 100,000 residents was 256 (95% confidence interval 241-271) for all strokes and 209 (95% confidence interval 195-223) for first-ever strokes. Incidence rate for first-ever strokes was 181 (95% confidence interval 155-211) after adjustment to the 2007 Italian population and 104 (95% confidence interval 88-122) compared with the European standard population. Incidence rates for first-ever strokes was 215 (196-235) for women, 202 (183-223) for men. Crude annual incidence rates per 100,000 population were 167 (153-178) for ischemic stroke, 31 (26-37) for intracerebral hemorrhage, 8.1 (5.7-11.4) for sub-arachnoid hemorrhage, and 4.6 (2.8-7.1) for undetermined stroke. Overall case fatality rates for first-ever stroke were 20.6% at 28 days and 30.2% at 180 days. CONCLUSIONS: Our study shows incidence rates higher than previously reported in our region but not supporting the view of higher incidence rates in Northern than in Southern Italy. Results contribute to time-trends analysis on epidemiology, useful for dimensioning services in Italy and show the persistence of a gap between the outcome of stroke in Italy and that of the best performing European countries, urging to adopt better stroke management plans.

Incidence of transient ischemic attack and early stroke risk: validation of the ABCD2 score in an Italian population-based study.

BACKGROUND AND PURPOSE: The importance of transient ischemic attack (TIA) lies on the short-term risk of stroke, and the ABCD2 score may improve early stroke risk prediction. However, population-based studies are still needed. We aimed to provide data on TIA incidence and to evaluate the ABCD2 predictive ability for early recurrent stroke in a population-based study. METHODS: This study is part of a 2-year prospective community-based registry of all cerebrovascular events in the district of Udine (153 312 inhabitants), Friuli Venezia Giulia region, northeast of Italy, between April 1, 2007 and March 31, 2009. Multiple overlapping sources for finding cases were used, combining hot and cold pursuit. RESULTS: We identified 178 TIA, 161 (90.4%) of which were incident. The crude overall annual TIA incidence rate per 1000 residents was 0.52 (95% confidence interval [CI], 0.45-0.61). Incidence rate was 0.45 (95% CI, 0.31-0.65) when standardized to the 2007 Italian population and 0.25 (95% CI, 0.16-0.39) when standardized to the European standard population. Estimates of stroke risk after the index TIA within 2, 7, 30, and 90 days were, respectively, 2.5% (95% CI, 0.7-6.2), 5.6% (95% CI, 2.6-10.3), 6.2% (95% CI, 3.0-11.1), and 11.2% (95% CI, 6.8-17.1). ABCD2 score was strongly associated with stroke occurrence after index TIA: the areas under the receiver operating characteristic curve at 2, 7, 30, and 90 days were, respectively, 0.85 (95% CI, 0.72-0.97), 0.69 (95% CI, 0.56-0.82), 0.69 (95% CI, 0.56-0.85), and 0.76 (95% CI, 0.67-0.86). No patients with an ABCD2 score <4 had a stroke within the 90-day follow-up period. CONCLUSIONS: This study adds new data on TIA incidence and prognosis and it further validates the ability of the ABCD2 score to identify patients at early risk for stroke.

Drugs with anticholinergic properties: a potential risk factor for psychosis onset in Alzheimer's disease?

Psychosis in Alzheimer's disease is common and troublesome. The impact on the quality of life of both patients and caregivers is high and drug treatments raise concern in terms of both efficacy and safety. Therefore, identifying the risk factors that play an important role in the onset of psychosis is mandatory for the prevention of this clinical condition. From a biological point of view, drugs with anticholinergic properties are a reasonable cause of psychosis. Demented patients have been found to use a disproportionate amount of drugs with anticholinergic properties. On the other hand, new evidence suggests that the cholinergic system may be implicated not only with the onset of cognitive impairment, but even in the genesis of psychosis symptoms. This review focuses on biological and clinical data which suggest that anti-cholinergic drugs should be regarded as a potential risk factor for psychosis in Alzheimer's disease.

Drugs with anticholinergic properties: cognitive and neuropsychiatric side-effects in elderly patients.

Drug consumption in older people is usually high and many prescribed medications have unsuspected anticholinergic (ACH) (Table 1) properties. Drug induced ACH side-effects are particularly severe in aging brain and even more in demented patients. This review will focus on the association between ACH drug intake and the risk of developing central nervous system side-effects in elderly people. The threat of developing cognitive impairment, psychosis and delirium will be particularly analyzed.

Drugs with anticholinergic properties as a risk factor for cognitive impairment in elderly people: a population-based study.

Prevention of drug-related problems is a key issue in the aged. Anticholinergic (ACH) drugs are a biologically plausible and potentially modifiable risk factor for cognitive impairment. Therefore, we intended to evaluate the association between ACH drugs and cognitive impairment. Our study comprised 750 subjects aged 65 years or older. Cognitive impairment was evaluated using Mini-Mental State Examination and Global Deterioration Scale. Patients were classified into ACH-drug users and non-ACH-drug users. Those using ACH drugs (20.1%) were more likely to have cognitive impairment than those using non-ACH drugs (odds ratio, 3.18; 95% confidence interval, 1.93-5.23; P < 0.001); this association remained significant even after adjusting for potential confounding variables (odds ratio, 2.30; 95% confidence interval, 1.19-4.45). Our data suggest that ACH drug intake should be regarded a potentially modifiable risk factor for cognitive impairment in the elderly.

Sarcoidosis as risk factor for cryptococcal meningitis in an apparently immunocompetent patient.

Cryptoccus neoformans meningitis (CNM) is an opportunistic infection that typically occurs in immunosuppressed patients. Subjects affected by sarcoidosis, a systemic granulomatous disease of unknown cause, are predisposed to CNM because of the impairment of cell-mediated immunity and because of the chronic corticosteroid therapy they frequently receive. Here we report the case of a 38-year-old man who developed CNM as the first clinical manifestation of sarcoidosis. The patient developed CNM even though he was apparently immunocompetent and was not on therapy with either corticosteroid or cytotoxic drugs.

Association of restless legs syndrome in type 2 diabetes: a case-control study.

STUDY OBJECTIVE: To look for an association between restless legs syndrome (RLS) and type 2 diabetes in a case-control study; to analyze the characteristics of RLS in diabetic patients; and to identify possible risk factors for the development of RLS in diabetic patients. DESIGN: A case-control study. SETTING: Diabetic outpatient clinic of a major university hospital. PARTICIPANTS: One hundred twenty-four consecutive outpatients with diabetes and 87 consecutive controls with a previous diagnosis of other endocrine disease. INTERVENTIONS: RLS was diagnosed using the criteria of the International RLS Study Group, and severity of RLS was assessed using the International RLS Study Group Rating Scale. Characteristics of RLS and several laboratory parameters were investigated in diabetic patients and controls affected by the sleep disorder. A clinical diagnosis of polyneuropathy was assessed to evaluate its role as a risk factor for RLS in diabetic patients. MEASUREMENT AND RESULTS: RLS was diagnosed in 22 diabetic patients (17.7%) and in only 5 controls (5.5%), 3 of whom had pituitary and 2 had adrenal gland disorders, and RLS was independently associated with type 2 diabetes (P < 0.04). Even if a clinical diagnosis of polyneuropathy was made in only 27% of diabetic patients affected by RLS, after multivariate logistic regression, the presence of polyneuropathy was the only variable associated with RLS in diabetics (odds ratio, 7.88; 95% confidence interval, 1.34-46.28; P < 0.02). RLS in diabetics showed a frequency of positive family history lower than that known for primary RLS, showed a late age of onset, and manifested itself after the diagnosis of diabetes was made. CONCLUSIONS: This is the first controlled study confirming a significant association between RLS and type 2 diabetes. In diabetic patients, polyneuropathy represents the main risk factor for RLS. However, polyneuropathy only partially explains the increased prevalence of RLS in type 2 diabetics. Clinical characteristics of RLS in diabetic patients are those of a secondary form.

Sensory gating deficit assessed by P50/Pb middle latency event related potential in Alzheimer's disease.

Sensory gating is defined as the brain's ability to inhibit repetitive and irrelevant incoming sensory stimuli and is supposed to be related to cholinergic transmission. Indeed, Alzheimer's disease (AD) is characterized by a cholinergic deficit that is believed to be involved in cerebral cortex hyperexcitability and short latency afferent inhibition deficit. Therefore, a sensory gating deficit may be supposed present in AD within the frame of cortex hyperexcitability and loss of cortex modulation of sensory inputs. The authors investigated whether a sensory gating deficit may be present in AD and whether this deficit may be related to the presence of neuropsychiatric symptoms (NPS) and reversed by donepezil treatment. Sensory gating was evaluated using a paired-stimulus auditory P50 event-related potential paradigm. Eighteen drug-naïve probable AD patients (mean age 76.1 years; SD 5.6 years; 13 females and 5 males) and 15 healthy elderly controls (mean age 74.2 years; SD 5.4 years; 10 females and 5 males) were recruited. Sensory gating was evaluated in AD patients before starting therapy and after 1 and 3 months of donepezil treatment. Auditory P50 sensory gating was impaired in AD patients but no correlation was found between gating deficit and NPS. Moreover, AD patients displayed increased P50 amplitude when compared with healthy elderly subjects. Donepezil treatment did not improve P50 sensory gating in AD patients but decreased P50 amplitude. Patients with AD displayed an augmented P50 amplitude, in accordance with previous studies, suggesting increased cortex excitability. Donepezil does not affect P50 sensory gating but reduces P50 amplitude. Donepezil may induce P50 amplitude reduction by means of enhanced dopamine release. Indeed, it has been demonstrated that donepezil induces dopamine release "in vitro." The findings suggest that AD patients have a sensory gating impairment but the link with both NPS and the cholinergic deficit is doubtful.

Detection of anti-brain serum antibodies using a semi-quantitative immunohistological method.

The number of autoimmune disorders that may involve the nervous system is increasing. The diagnosis of neurological involvement in the context of systemic diseases may be helped by the detection of autoantibodies reacting against neural autoantigens. If the autoantigen is not known but the target tissue is suspected, immunohistochemistry is one of the main techniques used to certify the presence of autoantibodies. Autoreactive antibodies are also present in the healthy population but in low quantity compared to patients with such diseases. Quantification of such autoantibodies could help to discriminate between disease and healthy states. We have developed a densitometric immunohistological method for the evaluation of human serum anti-neural reactivity. Using a densitometric analysis of rat brain sections incubated with the serum from 107 healthy subjects, we have defined the baseline of natural anti-neural autoreactivity, and the cut-off for subsequent quantification of anti-neural reactivity in patients with neurological involvement in the context of autoimmune diseases, including systemic lupus erythematosus, paraneoplastic cerebellar degeneration, and stiff person syndrome. The test sensitivity was 81% with a positive predictive value of 52%, a specificity of 89% with a negative predictive value as high as 97%. In conclusion, this standardised semi-quantitative procedure makes immunohistochemistry a reliable diagnostic test for autoimmune neuropathologies and represents an excellent exclusion test for anti-neural autoimmunity.

Sleep disorders in patients with end-stage renal disease undergoing dialysis therapy.

BACKGROUND: Many patients with end stage renal disease (ESRD) undergoing dialysis therapy suffer from sleep disturbances. The aim of this study was to investigate the prevalence of sleep disorders in a large population of uraemic patients recruited from 20 different dialytic centres in Triveneto. METHODS: 883 patients on maintenance dialysis were enrolled in the study. Demographic, lifestyle, renal and dialysis data were recorded. Renal parameters were compared with the database of the Veneto Dialysis Register. Using a self-administered questionnaire we assessed the presence of the following sleep disorders: insomnia, restless leg syndrome (RLS), obstructive sleep apnoea syndrome (OSAS), excessive daytime sleepiness (EDS), possible narcolepsy, sleepwalking, nightmares and possible rapid eye movement behaviour disorders (RBD). Moreover, in order to determine the prevalence of sleep disturbances and the possible effect of demographic or clinical data on sleep, we divided our population into two groups: with (SLEEP+) and without (SLEEP-) sleep disorders. RESULTS: The questionnaire revealed the presence of insomnia (69.1%), RLS (18.4%), OSAS (23.6%), EDS (11.8%), possible narcolepsy (1.4%), sleepwalking (2.1%), nightmares (13.3%) and possible RBD (2.3%). Eighty percent demonstrated SLEEP+, having at least one sleep disorder. Independent risk factors for sleep disorders were advanced age (P<0.001), excessive alcohol intake (P<0.04), cigarette smoking (P<0.006), polyneuropathy (P<0.05) and dialysis shift in the morning (P<0.001). CONCLUSIONS: The questionnaire showed a high presence of sleep disruption in dialytic populations. Awareness by Italian nephrologists regarding sleep disruption seems to be insufficient. Our data might help nephrologists to deal with uraemic patients with possible sleep disorders. Concerning the high prevalence of possible narcolepsy, further studies using polysomnographic records are necessary to confirm our results.

The acute effect of a low dosage of pramipexole on severe idiopathic restless legs syndrome: an open-label trial.

BACKGROUND: Pramipexole is a D3 dopaminergic agonist that has shown a major effect on both sensory and motor manifestations of restless legs syndrome (RLS) in long-term trials. No data regarding the acute effect of low doses of pramipexole have been reported. OBJECTIVE: To evaluate the acute effect of a low dosage of pramipexole (0.125 mg) on sensory symptoms and motor signs of RLS and on the macro- and microstructure of sleep. METHODS: We initially recruited 13 patients affected by severe idiopathic RLS and included 10 of them in our study. For 2 consecutive nights the selected patients were evaluated. Pramipexole 0.125 mg was administered before the second night at 9:00 p.m. A visual analog scale was used to assess the sensory symptoms of RLS. The motor manifestations of RLS and the architecture of sleep were analyzed by polysomnography. RESULTS: After the acute administration of pramipexole, we observed a significant improvement of the sensory symptoms and motor signs of RLS. Several sleep macrostructure and microstructure parameters improved as well. CONCLUSIONS: Our results suggest that low doses of pramipexole are effective in reducing sensory symptoms and motor signs of RLS, even after the first administration.

Factors associated with complex visual hallucinations during antidepressant treatment.

Published case reports on complex visual hallucinations (CVH) occurring during antidepressant (AD) treatment were reviewed. Thirteen cases of CVH associated with SSRI treatment, 16 cases during tricyclic drug treatment and seven cases with other AD drug treatments were found. Nine patients were taking concomitant drugs while on therapy with SSRIs and four had a neurological disease in addition to depression. The cholinergic impoverishment occurring in dementia states or during concomitant therapy with anticholinergic drugs could increase the sensitivity to serotonergic agonists, triggering the manifestation of CVH. During tricyclic drug treatment, half of the reports were of hypnopompic or hypnagogic hallucinations and this can be associated with the effects of tricyclics (TCA) on sleep architecture. It is likely that the potent anticholinergic effect of amitriptyline was potentiated in a situation of a rapidly changing state of consciousness. In general, the review supports the view that an imbalance between serotonin and acetylcholine systems is at the root of AD-induced CVH, with a profile defined by a cholinergic hypoactivity and a serotonergic hyperactivity. Caution is needed when administering a combination of serotonergic and anticholinergic AD in the treatment of the demented population and in other already compromised patients because there is a risk of precipitating CVH.