Citicoline Treatment in Acute Ischemic Stroke: A Randomized, Single-Blind TMS Study.

Background: Recent research on animal models of ischemic stroke supports the idea that pharmacological treatment potentially enhancing intrinsic brain plasticity could modulate acute brain damage, with improved functional recovery. One of these new drugs is citicoline, which could provide neurovascular protection and repair effects. Objectives: The objective of this randomized, single-blind experimental study was to evaluate whether the treatment with Rischiaril® Forte was able to restore intracortical excitability measures, evaluated through transcranial magnetic stimulation (TMS) protocols, in patients with acute ischemic stroke. Methods: Patients with acute ischemic stroke were recruited and assigned to an eight-week therapy of standard treatment (control group - CG) or CDP-choline (Rischiaril® Forte, containing 1,000 mg of citicoline sodium salt) added to conventional treatment (treatment group - TG). Each subject underwent a clinical evaluation and neurophysiological assessment using TMS, pretretament and posttreatment. Results: A total of thirty participants (mean [SD] age, 68.1 [9.6] years; 11 women [37%]) completed the study. We did not observe significant changes in clinical scores after CDP-choline treatment (all p > 0.05), but we observed a significant improvement in short-interval intracortical inhibition (SAI) (p = 0.003) in the TG group compared to the CG group. Conclusions: The eight-week treatment with citicoline after acute ischemic stroke may restore intracortical excitability measures, which partially depends on cholinergic transmission. This study extends current knowledge of the application of citicoline in acute ischemic stroke.

Arterial tortuosity syndrome causing recurrent transient ischemic attacks in young adult: a case report.

BACKGROUND: Arterial Tortuosity Syndrome (ATS) is a rare autosomal recessive disorder characterized by elongated and tortuous arteries. Although ATS showed a significant clinical and pathophysiological overlap with other syndromes involving connective tissues, only few cases of cerebrovascular events related to this syndrome have been described so far. CASE PRESENTATION: We report the case of a 33-years-old male diagnosed with ATS since childhood, that experienced three sudden episodes of expressive aphasia and right hemiparesis with spontaneous resolution. He was treated with recombinant tissue plasminogen activator (r-TPA) at a dosage of 0.9 mg/kg with a complete recovery. Brain Magnetic Resonance Imaging (MRI) showed the absence of acute ischemic lesions and the patient was diagnosed with recurrent transient ischemic attacks (TIA). Intracranial and supra-aortic trunks Magnetic Resonance Angiography (MRA) and Angio-CT scan of the thoracic and abdominal aorta showed marked vessel tortuosity without stenosis. To our knowledge, this is the first reported case of an ATS patient with TIA in young age that was treated with intravenous thrombolysis with recombinant plasminogen activator. CONCLUSION: Our report strengthens the relationship between ATS and juvenile cerebrovascular events, suggesting that an extensive study of body vessels in order to detect potential stenoses or occlusions in these cases is needed. The greater predisposition to cerebrovascular events in ATS could benefit from a more aggressive primary and secondary prevention therapy.

Clinical characteristics and outcomes of inpatients with neurologic disease and COVID-19 in Brescia, Lombardy, Italy.

OBJECTIVE: To report clinical and laboratory characteristics, treatment, and clinical outcomes of patients admitted for neurologic diseases with and without coronavirus disease 2019 (COVID-19). METHODS: In this retrospective, single-center cohort study, we included all adult inpatients with confirmed COVID-19 admitted to a neuro-COVID unit beginning February 21, 2020, who had been discharged or died by April 5, 2020. Demographic, clinical, treatment, and laboratory data were extracted from medical records and compared (false discovery rate corrected) to those of neurologic patients without COVID-19 admitted in the same period. RESULTS: One hundred seventy-three patients were included in this study, of whom 56 were positive and 117 were negative for COVID-19. Patients with COVID-19 were older (77.0 years, interquartile range [IQR] 67.0-83.8 years vs 70.1 years, IQR 52.9-78.6 years, p = 0.006), had a different distribution regarding admission diagnoses, including cerebrovascular disorders (n = 43, 76.8% vs n = 68, 58.1%), and had a higher quick Sequential Organ Failure Assessment (qSOFA) score on admission (0.9, IQR 0.7-1.1 vs 0.5, IQR 0.4-0.6, p = 0.006). In-hospital mortality rates (n = 21, 37.5% vs n = 5, 4.3%, p < 0.001) and incident delirium (n = 15, 26.8% vs n = 9, 7.7%, p = 0.003) were significantly higher in the COVID-19 group. Patients with COVID-19 and without COVID with stroke had similar baseline characteristics, but patients with COVID-19 had higher modified Rankin Scale scores at discharge (5.0, IQR 2.0-6.0 vs 2.0, IQR 1.0-3.0, p < 0.001), with a significantly lower number of patients with a good outcome (n = 11, 25.6% vs n = 48, 70.6%, p < 0.001). In patients with COVID-19, multivariable regressions showed increasing odds of in-hospital death associated with higher qSOFA scores (odds ratio [OR] 4.47, 95% confidence interval [CI] 1.21-16.5, p = 0.025), lower platelet count (OR 0.98, 95% CI 0.97-0.99, p = 0.005), and higher lactate dehydrogenase (OR 1.01, 95% CI 1.00-1.03, p = 0.009) on admission. CONCLUSIONS: Patients with COVID-19 admitted with neurologic disease, including stroke, have a significantly higher in-hospital mortality and incident delirium and higher disability than patients without COVID-19.

Cortical Inhibitory Imbalance in Functional Paralysis.

BACKGROUND: Functional neurological disorders are characterized by neurological symptoms that have no identifiable pathology and little is known about their underlying pathophysiology. OBJECTIVES: To analyze motor cortex excitability and intracortical inhibitory and excitatory circuits' imbalance in patients with flaccid functional weakness. METHODS: Twenty-one consecutive patients with acute onset of flaccid functional weakness were recruited. Single and paired-pulse transcranial magnetic stimulation (TMS) protocols were used to analyze resting motor thresholds (RMT) and intracortical inhibitory (short interval intracortical inhibition - SICI) and excitatory (intracortical facilitation - ICF) circuits' imbalance between the affected and non-affected motor cortices. RESULTS: We observed a significant increase in RMT and SICI in the affected motor cortex (p < 0.001), but not for ICF, compared to the contralateral unaffected side. CONCLUSION: This study extends current knowledge of functional weakness, arguing for a specific central nervous system abnormality which may be involved in the symptoms' pathophysiology.

Intravenous fibrinolysis plus endovascular thrombectomy versus direct endovascular thrombectomy for anterior circulation acute ischemic stroke: clinical and infarct volume results.

BACKGROUND: endovascular therapy (ET) is the standard of care for anterior circulation acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). The role of adjunctive intravenous thrombolysis (IVT) in these patients remains unclear. The present study aims to investigate whether IVT followed by ET (CoT, combined therapy) provides additional benefits over direct ET for anterior circulation AIS with LVO. METHODS: we achieved a single center retrospective study of patients with AIS caused by anterior circulation LVO, referred to our center between January 2014 and January 2017 and treated with ET. Functional recovery (modified Rankin at 3-months follow-up), recanalization rate (thrombolysis in cerebral infarction [TICI] score) and time, early follow-up brain CT scan infarct volume (EFIV) (for recanalized patients only), symptomatic intracerebral hemorrhage (sICH) and 3-month mortality were the outcomes of interests. Independent predictors of the outcomes were explored with multivariable logistic regression. RESULTS: 145 subjects were included in the study, of whom 70 underwent direct ET and 75 were treated with CoT. Functional independence at 3-months was more frequent in CoT subjects compared to patients who received direct ET (mRS score 0-1: 48.5% vs 18.6%; P < 0.001. mRS score 0-2: 67.1% vs 37.3%; P < 0.001); CoT patients had also higher first-pass success rate (62.7% vs 38.6%, P < 0.05), higher recanalization rate (84.3% vs 65.3%; P = 0.009) and, in recanalized subjects, smaller EFIV (16.4 ml vs 62.3 ml; P = 0.003). Mortality and intracranial bleeding did not differ between the two groups. In multivariable regression analysis, low baseline NIHSS score (P < 0.05), vessel recanalization (P = 0.05) and CoT (P = 0.03) were independent predictors of favorable outcome at three months. CONCLUSIONS: CoT appears more effective than ET alone for anterior circulation AIS with LVO, with similar safety profile.

Leukoaraiosis is a predictor of futile recanalization in acute ischemic stroke.

Futile recanalization occurs when successful recanalization fails to improve clinical outcome in acute ischemic stroke patients. Predictors of futile recanalization are still debated and may help in selecting patients for reperfusion strategies. We aim to determine whether leukoaraiosis may be useful in predicting futile recanalization in acute ischemic stroke patients treated by endovascular mechanical thrombectomy. We included in the analysis patients with acute ischemic stroke due to anterior circulation large vessel occlusion undergoing endovascular mechanical thrombectomy obtaining complete vessel recanalization. Demographics, vascular risk factors, baseline National Institutes of Health Stroke Scale score, time from symptoms onset to recanalization, Alberta Stroke Program Early CT Score, and leukoaraiosis graded on a 4-point van Swieten scale were collected. We dichotomized patients into those with moderate-severe leukoaraiosis (2-4) versus those with absent-slight leukoaraiosis (0, 1). Outcome measures were symptomatic intracranial hemorrhage, and modified Rankin scale score at 90 days. The relationships among radiological parameters and clinical data with outcome measures were studied with univariate and multivariable analyses. Sixty-eight patients were identified. Recanalization was futile in 32.4% of cases. On multivariable logistic regression analysis, the presence of moderate-severe LA was independent predictors of FR (P = 0.01). Furthermore, higher NIHSS score at baseline (P < 0.01) end endovascular mechanical thrombectomy alone treatment (P < 0.01) resulted associated with futile recanalization. Our results showed that the presence of moderate-severe leukoaraiosis is associated with poor outcome in recanalized patients.

Infective Endocarditis Presenting with Intracranial Bleeding.

BACKGROUND: Infective endocarditis (IE) can be complicated by intracranial bleeding (ICB) caused by different pathologic mechanisms. The occurrence of ICB in patients with IE significantly influences therapeutic decisions and has a negative impact on outcome. CASE REPORT: We describe the clinical courses of 3 patients with aortic prosthetic valve IE presenting with ICB. Patients 1 and 2 experienced subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH), respectively, caused by rupture of an intracranial infectious aneurysm (IIA). Both underwent endovascular treatment of IIA with good outcome. In patient 3, ICB was the hemorrhagic conversion of an acute ischemic lesion from septic brain embolization. In the subacute phase of the disease, aortic valve replacement was performed, with excellent outcome. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: ICB is a relevant complication and sometimes the first clinical feature of IE. Imaging of brain vessels should be performed to investigate the pathologic mechanism underlying ICB. The prevalence of IIA is probably underestimated and may influence the therapeutic strategy. Cerebrovascular imaging may therefore also be considered in asymptomatic subjects with left-sided IE. Withdrawal of anticoagulant treatment and delay of cardiac surgery are recommended in all cases of IE complicated by ICB. Because of the impact of ICB on IE management and outcome, a high level of clinical suspicion and prompt recognition and treatment of this complication are necessary.

Endovascular mechanical thrombectomy in basilar artery occlusion: variables affecting recanalization and outcome.

Ischemic stroke due to basilar artery occlusion (BAO) is frequently associated with a poor prognosis. To date the most effective therapeutic approach has not been established and little is known about the predictors of clinical outcome. The aim of this study was to describe safety and efficacy of intra-arterial mechanical thrombectomy (IAMT) through latest generation devices in patients with BAO, focusing on those variables that may affect recanalization and clinical outcome. We analyzed retrospectively a series of 32 patients with BAO who underwent IAMT. We assessed the association of some clinical and neuroradiological features with recanalization rate and clinical outcome. Successful recanalization was achieved in 28 out of 32 patients (87.5 %). Symptomatic intracerebral hemorrhage (SICH) was observed in 2/32 patients (6.3 %) and mortality in the first 3 months was 25.0 %. At 3-month follow up evaluation, 13/32 patients (40.6 %) showed a good functional outcome (mRS score ≤2). There were no statistical differences in term of age, gender, risk factors, cause of stroke, recanalization rate, pre-treatment pc-ASPECTS score and SICH frequencies between patients with favorable and unfavorable outcome. Increased length of thrombi was associated with unfavorable clinical outcome at 3 months. Recanalization rate was not affected by any of the variables considered. In BAO, IAMT through newest generation devices has high recanalization rates and low complication frequencies. Length of BAO is an important predictor of clinical outcome.

The importance of Alzheimer disease assessment scale-cognitive part in predicting progress for amnestic mild cognitive impairment to Alzheimer disease.

The aim of this study was to verify the usefulness of Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-Cog), in screening participants at risk of developing Alzheimer disease (AD) among populations with amnestic mild cognitive impairment(aMCI). 98 outpatients with aMCI were recruited. Participants were revaluated after 1 year: 44 (44.9%) were progressed to AD (progressors), while 54 (55.1%) did not convert (nonprogressors MCI). At baseline, cognitive performances were more impaired in progressors assessed by MMSE and by a neuropsychological battery. When tested with the ADAS-Cog subscale, the 2 groups of participants at baseline, progressors, and nonprogressors MCI, were significantly different regarding total score, memory, and nonmemory subitems. Considering a cutoff of 9.5 total score, adjusted for education, ADAS-Cog subscale showed a good performance (area under the curve = 0.67; sensitivity = 0.62%; specificity = 0.73%) in predicting conversion from aMCI to AD. Progressors aMCI were characterized at baseline by a greater cognitive impairment. ADAS-Cog subscale is a useful and brief cognitive assessment tool to screen aMCI participants converting to AD within 1 year.

Mild parkinsonian signs and psycho-behavioral symptoms in subjects with mild cognitive impairment.

BACKGROUND: Mild cognitive impairment (MCI) may be accompanied by extra pyramidal signs (EPS), which are related to the severity and type of cognitive impairment. We aimed to elucidate further the relationship between MCI and EPS, analyzing the correlation between the severity of EPS and cognitive functions, and the presence of EPS and neuro-psychiatric features. METHODS: Data were obtained from a longitudinal study of 150 MCI outpatients. Participants underwent a clinical assessment including the Unified Parkinson Disease Rating Scale, the Neuropsychiatric Inventory, the Tinetti Scale, and a standardized neuropsychological battery. Mild EPS could be defined as being present (MCI with mild EPS) using a subscale of UPDRS, based on three specific symptoms: bradykinesia, rigidity and tremor. RESULTS: The two groups, one with mild EPS (24%) and one without EPS (76%), differed in gait abnormalities and presence of extrapyramidal symptoms. Groups did not differ in terms of general cognitive functions evaluated using the Mini-mental State Examination, while subjects with MCI with mild EPS performed significantly worse than those with MCI without EPS in total global score and in non-memory items of the Alzheimer's Disease Assessment Scale. Moreover, severity of EPS was significantly correlated with low performance on executive functions and with high performance on episodic memory. The group with MCI with mild EPS were observed to have a greater prevalence of patients with anxiety, depression, apathy and sleep disturbances than in MCI without EPS. CONCLUSION: MCI may be associated with mild parkinsonian signs, the severity of which are related to the severity of cognitive impairment, in particular of non-memory functions, and to a differential pattern of psycho-behavioral symptoms.

Conversion of amnestic Mild Cognitive Impairment to dementia of Alzheimer type is independent to memory deterioration.

BACKGROUND: Mild Cognitive Impairment defines a transitional stage between normal ageing and dementia, and reflects the clinical situation where a person has memory complaints and objective evidence of cognitive impairment but no evidence of dementia. To plan the care of patients with MCI, it is important to predict as accurately as possible potential risk factors modulating the conversion to AD. AIM: To investigate the risk factors associated of conversion to dementia of Alzheimer type (AD) for subjects with amnestic Mild Cognitive Impairment (aMCI). METHODS AND MATERIALS: One hundred nineteen subjects consecutively recruited who met the operational criteria for aMCI (with or without deficits in other cognitive domains). They underwent multidimensional assessment and a neuropsychological battery at baseline and at follow-up, after 1 year. Diagnosis for dementia was based on a deficit in two or more cognitive domains severe enough to affect the participant functional abilities. Subjects converted to AD over time were classified as Demented; subjects that remained unchanged, or became cognitively normal during follow-up, were defined as Stable. RESULTS: Demented MCI (N = 40; 33.6%) were older (mean age 73.5 +/- 8.5 vs. 69.2 +/- 7.0; p = 0.006) when compared to Stable (N = 79; 66.4) and their global cognitive performances, at baseline, were more compromised when assessed by ADAS-Cog (mean score 10.7 +/- 3.9 vs 6.7 +/- 3.4; p = .000) and by MMSE (mean score 26.1 +/- 1.9 vs. 27.3 +/- 1.8; p = 0.002). Demented were similarly compromised in basic activities of daily living (BADL mean 0.2 +/- 0.4 vs 0.1 +/- 0.3 functions lost; p = NS) but more compromised on instrumental daily functions (IADL mean 0.7 +/- 0.8 vs. 0.1 +/- 0.5 functions lost; p = 0.001). The presence of white matter lesions (WML) on CT or MRI was more pronounced in Demented group (p = 0.02). After 1 year; Demented worsened on phonemic verbal fluency (PFL) (p = 0.009), Raven's coloured matrices (p = 0.003), Trail Making test A and B (p = 0.008 and p = 0.007 respectively) and in Instrumental Activities of Daily Living (IADL) (p =0 .000) respect to Stable. Logistic regression analysis revealed that ADAS-Cog basal score, Trail Making B, IADL but not memory deterioration were significantly associated to the conversion to AD. CONCLUSIONS: In subjects with aMCI poor global cognitive performance at baseline, the worsening on executive functions and on functional status but not the worsening on memory functions are independently associated with the conversion to dementia of Alzheimer type at 1 year, follow-up.

Cognitive and psychopathologic response to rivastigmine in dementia with Lewy bodies compared to Alzheimer's disease: a case control study.

Cholinesterase inhibitors (ChEIs) are effective in improving cognition and behavior in patients affected by Alzheimer's disease (AD) as well as by Lewy bodies dementia (DLB). The authors compared the effect of rivastigmine in the treatment of cognitive impairment and behavioral and psychological symptoms of dementia (BPSD) in 30 AD and in 30 DLB patients. At baseline, DLB compared to AD patients showed a greater number of extrapyramidal symptoms (P < .005) and were similar regarding cognitive symptoms and BPSD. After treatment, both groups showed a comparable cognitive and psycho-behavioral improvement. A significant difference between AD and DLB patients was found for hallucinations (P < .002). Rivastigmine produces comparable cognitive benefits in patients with DLB and AD and also a significant improvement of behavioral disorders. These findings support the view that ChEIs should be considered a first-line treatment of the cognitive and psycho-behavioral symptoms of both AD and DLB.