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Background and purpose: Transient global amnesia (TGA) is characterized by a sudden onset of anterograde amnesia lasting up to 24 h. One major differential for TGA is transient epileptic amnesia, which typically lasts < 1 h. However, TGA can also be short in duration and little is known about the time trends, characteristics and prognosis of TGA cases lasting < 1 h. Methods: We compared the clinical features of TGA ascertained in two independent cohort studies in Oxfordshire, UK [Oxford cohort 1977–1987 versus Oxford Vascular Study (OXVASC) 2002–2018] to determine the time trends of clinical features of TGA. Results were validated in another independent contemporary TGA cohort in Italy [Northern Umbria TGA registry (NU) 2002–2018]. We compared the risk factors, clinical features and long‐term prognosis (major cardiovascular events, recurrent TGA and seizure/epilepsy) of patients presenting with episodes lasting < 1 h versus those lasting ≥ 1 h. Results: Overall, 639 patients with TGA were included (114 Oxford cohort, 100 OXVASC, 425 NU). Compared with the original Oxford cohort, there were more cases with TGA lasting < 1 h in OXVASC [32 (32.0%) vs. 9 (8.8%)] and NU (11.8% vs. 8.8% in Oxford cohort). In both OXVASC and NU, patient age, vascular risk factors and clinical features were largely similar between those with TGA lasting < 1 h versus those lasting ≥ 1 h. Moreover, there was no difference in the long‐term risk of seizure/epilepsy or major cardiovascular events between TGA lasting < 1 h versus TGA lasting ≥ 1 h. Conclusions: Short‐duration TGA episodes (<1 h) were not uncommon and were more frequent than in earlier studies. The clinical features and long‐term prognosis of short‐duration TGA did not differ from more typical episodes lasting ≥ 1 h. [ABSTRACT FROM AUTHOR]

Background and purpose: Biomarkers support the aetiological diagnosis of neurocognitive disorders in vivo. Incomplete evidence is available to drive clinical decisions; available diagnostic algorithms are generic and not very helpful in clinical practice. The aim was to develop a biomarker‐based diagnostic algorithm for mild cognitive impairment patients, leveraging on knowledge from recognized national experts. Methods: With a Delphi procedure, experienced clinicians making variable use of biomarkers in clinical practice and representing five Italian scientific societies (neurology – Società Italiana di Neurologia per le Demenze; neuroradiology – Associazione Italiana di Neuroradiologia; biochemistry – Società Italiana di Biochimica Clinica; psychogeriatrics – Associazione Italiana di Psicogeriatria; nuclear medicine – Associazione Italiana di Medicina Nucleare) defined the theoretical framework, relevant literature, the diagnostic issues to be addressed and the diagnostic algorithm. An N–1 majority defined consensus achievement. Results: The panellists chose the 2011 National Institute on Aging and Alzheimer's Association diagnostic criteria as the reference theoretical framework and defined the algorithm in seven Delphi rounds. The algorithm includes baseline clinical and cognitive assessment, blood examination, and magnetic resonance imaging with exclusionary and inclusionary roles; dopamine transporter single‐photon emission computed tomography (if no/unclear parkinsonism) or metaiodobenzylguanidine cardiac scintigraphy for suspected dementia with Lewy bodies with clear parkinsonism (round VII, votes (yes‐no‐abstained): 3‐1‐1); 18F‐fluorodeoxyglucose positron emission tomography for suspected frontotemporal lobar degeneration and low diagnostic confidence of Alzheimer's disease (round VII, 4‐0‐1); cerebrospinal fluid for suspected Alzheimer's disease (round IV, 4‐1‐0); and amyloid positron emission tomography if cerebrospinal fluid was not possible/accepted (round V, 4‐1‐0) or inconclusive (round VI, 5‐0‐0). Conclusions: These consensus recommendations can guide clinicians in the biomarker‐based aetiological diagnosis of mild cognitive impairment, whilst guidelines cannot be defined with evidence‐to‐decision procedures due to incomplete evidence. [ABSTRACT FROM AUTHOR]

Although alpha-synuclein is the main constituent of Lewy bodies, cerebrospinal fluid determination on its own does not seem fundamental for the diagnosis of synucleinopathies. We evaluated whether the combination of classical biomarkers, A[beta](1-42) , total tau, phosphorylated tau, and [alpha]-synuclein can improve discrimination of Parkinson's disease, dementia with Lewy bodies, Alzheimer's disease, and frontotemporal dementia. A[beta](1-42) , total tau, phosphorylated tau, and [alpha]-synuclein were measured in a series of patients with Parkinson's disease (n = 38), dementia with Lewy bodies (n = 32), Alzheimer's disease (n = 48), frontotemporal dementia (n = 31), and age-matched control patients with other neurological diseases (n = 32). Mean [alpha]-synuclein levels in cerebrospinal fluid were significantly lower in the pathological groups than in cognitively healthy subjects. An inverse correlation of [alpha]-synuclein with total tau (r = -0.196, P < .01) was observed. In the group of patients with Parkinson's disease, A[beta](1-42) , total tau, and phosphorylated tau values were similar to controls, whereas total tau/[alpha]-synuclein and phosphorylated tau/[alpha]-synuclein ratios showed the lowest values. Cerebrospinal fluid [alpha]-synuclein alone did not provide relevant information for Parkinson's disease diagnosis, showing low specificity (area under the curve, 0.662; sensitivity, 94%; specificity, 25%). Instead, a better performance was obtained with the total tau/[alpha]-syn ratio (area under the curve, 0.765; sensitivity, 89%; specificity, 61%). Combined determination of [alpha]-synuclein and classical biomarkers in cerebrospinal fluid shows differential patterns in neurodegenerative disorders. In particular, total tau/[alpha]-synuclein and phosphorylated tau/[alpha]-synuclein ratios can contribute to the discrimination of Parkinson's disease. © 2011 Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Magnetization transfer ratio (MTR) technique has identified brain changes in grey and white matter in Parkinson's disease (PD), even in the early phase. However, how these tissue changes differ along the course of the illness is still unclear. This study was aimed at investigating how MTR values change from mild PD (PD1) to patients with advanced PD (PD2). We measured MTR values by region of interest, in 11 PD1, 11 PD2 and 10 healthy age-matched subjects. Compared with controls, patients with PD1 exhibited a significant MTR reduction in substantia nigra pars compacta, substantia nigra pars reticulata, putamen, periventricular white matter and parietal white matter. In addition to the changes observed in PD1, the PD2 group exhibited a significant MTR reduction in caudate, pons, frontal white matter and lateral thalamus. These results suggest that MTR might reflect morphological changes induced by the disease in distinct brain areas at different stages. [ABSTRACT FROM AUTHOR]

BACKGROUND: Several studies were carried out to investigate the occurrence of headache attributed to acute stroke in patients with a lifetime history of migraine. METHODS: In a case-control series of 96 acute stroke patients with a lifetime history of migraine (M+) and 96 stroke patients without (M-), ischemic stroke patients only, without secondary infarction, were selected. The headache attributed to acute ischemic stroke was then analyzed. RESULTS: (M+) patients complained of headache more often than (M-) patients (P < .0001), mainly in the 24 hours before stroke onset (P < .0001). Migraine-like features of headache were recognized in a greater proportion of cases in the (M+) patient group with ischemic stroke (P < .018). A preferential brainstem location of ischemic stroke in (M+) patients emerged compared with (M-) patients (P = .014). DISCUSSION: The high prevalence of headache attributed to stroke in (M+) patients, in a relevant proportion of cases presenting as a sentinel headache, suggests that cerebral ischemia lowers the threshold for head pain more easily in these 'susceptible' patients. The most frequent involvement of the brainstem in (M+) patients with ischemic infarction concurs with recent reports that emphasized a greater headache frequency when cerebral infarctions are localized in this structure or deep brain gray matter. [ABSTRACT FROM AUTHOR]

Background and purpose: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) can be considered a useful model of pure subcortical vascular dementia (SVD) because it occurs in young adults, unlikely to have concomitant age- and Alzheimer’s disease (AD)-related pathology. In patients with CADASIL we evaluated the cerebrospinal fluid (CSF) levels of β-amyloid 1-42 (Aβ42), total tau protein (t-tau) and phosphorylated tau protein (p-tau), which are well-accepted biomarkers of AD. Methods: The CSF Aβ42, t-tau and p-tau levels were determined with Innotest β-amyloid 1-42, Innotest hTAU-Ag and Innotest Phospho-tau 181p sandwich enzyme-linked immunoassay, in 10 CADASIL patients and 17 healthy age-matched subjects. A case–control statistical analysis was carried out. Results: CSF Aβ42 levels were significantly lower in CADASIL patients than in controls, whereas CSF t-tau and p-tau levels did not differ between the two groups. Conclusions: The pattern found in CADASIL patients is similar to that reported in those with sporadic SVD, suggesting that decreased CSF Aβ42 might be related to the subcortical vascular lesions in the white matter. [ABSTRACT FROM AUTHOR]

An improvement in patient arrival time to stroke unit (SU) is recommended, since earlier stroke management seems to improve ‘per se’ functional outcome. The objective of this study was to determine if early admission influences the outcome, reduces disability and mortality at discharge and three months later independent of tlirombolytic treatment. Consecutive acute stroke patients admitted to SU between January 1st 2000 and December 31st 2003 were studied in order to analyze the actual role of acute management independent specific pharmacological treatment, we excluded subjects who underwent rt-PA. 35.8% of 2,041 consecutive stroke patients arrived within 3 hours; 62.4% within 6 hours; 37.6% arrived later. Approximately 80% of the <6 hour patients presented a National Institutes of Health Stroke Scale (NIHSS) >4 and modified Rankin Scale (mRS) score >2 in comparison with 60% of the >6 hour patients. In hospital (8.7%) and three-month (7.3%) mortality in <3 hour patients were not significantly different from what observed in >3 hour patients (6.8% and 6.1% respectively) while functional outcome after three months was better in <3 hour patients (NIHSS: 34.6 vs 15.2; mRS: 32.9% vs 16.8%). Old age, history of TIA, cardioembolic etiology, severity of neurological deficit and hemorrhagic stroke type all led to earlier arrival time. Admission within 3 hours ‘per se’ improves outcome and reduced disability at three months. [ABSTRACT FROM AUTHOR]

We studied the correlation between the potential causes of stroke (TOAST etiological groups) and the involvement of different vascular territories seen on computed tomography (CT) scans in patients with ischemic stroke. Information from consecutive patients with a first-ever stroke have been prospectively coded and entered into a computerized data bank (Perugia Stroke Registry). A population of 1719 patients were evaluated: 1284 patients (74.7%) had ischemic stroke. Large artery disease was the main cause of entire middle cerebral artery (MCA) territory infarcts (40.9%), superficial MCA territory infarcts (35.7%), and watershed infarcts (68.2%). The highest presence of emboligenic heart disease was found in the entire MCA territory infarcts (28.8%) or superficial (29.4%) supratentorial infarcts and in cerebellar infarcts (36.8%). Small artery disease was the most common presumed cause of deep MCA infarcts (75.0%) and posterior cerebral artery (PCA) territory infarcts (52.1%). In conclusion: stroke location could depend on its etiology. Lacunar infarcts are the most prevalent (36.7%), being mostly localized in the deep MCA territory; large artery disease includes more than two-thirds of watershed infarcts; the most prevalent territories involved in cardioembolic stroke are the entire MCA and posterior fossa. [ABSTRACT FROM AUTHOR]

Background and purpose: SCA15 is a recently identified spinocerebellar ataxia with pure cerebellar involvement. Here, we report a novel SCA15 Italian family with atypical clinical features. Methods: Three affected members from a three-generation family segregating an autosomal dominant cerebellar ataxia underwent clinical examination and genetic tests for hereditary ataxia. Results: All affected members present with cognitive impairment and two of them with mild intermittent involuntary movements in association with the clinical hallmarks of SCA15 (gait ataxia, balance impairment, and dysarthria). Genetic tests detected a large deletion spanning ITPR1 and SUMF1 genes in affected members. Conclusion: Our findings help enlarging the clinical spectrum of SCA15. [ABSTRACT FROM AUTHOR]

Levetiracetam (LEV) monotherapy was investigated in 25 patients with advanced Alzheimer's disease (AD) and new-onset epileptic seizures in a prospective open-label study. At a daily dose of 1000–1500 mg, 72% were seizure-free for at least one year; 16% discontinued for untolerability; 8% were unresponsive; 4% were lost to follow-up. These results suggest the need for controlled studies to confirm if LEV can be a first-choice drug in AD. [ABSTRACT FROM AUTHOR]

The article presents the author's views on the clinical consequences of white matter lesions (WMLs) on the brain. According to the author, several clinical studies have shown that WMLs have an impact on cognition and functional abilities, and other degenerative diseases of the brain. The author says that Alzheimer's disease and cerebrovascular diseases are two common age-related conditions, which are represented by the vascular effects of b-amyloid fragments.

Objectives:   To measure cerebrospinal fluid (CSF) activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in patients with Alzheimer's disease (AD) participating in randomized clinical trials from three European centers, before and after long-term treatment with different AChE inhibitors (AChEIs)., Materials and Methods:   Of the 144 patients included in the study, 104 were treated with donepezil, 15 with galantamine, 16 with rivastigmine, and nine with placebo. CSF AChE and BChE activities were measured at baseline and after 1- year treatment., Results: Donepezil and galantamine groups showed a significant increase in CSF AChE activity at follow-up, while no changes for BChE activity were observed; in donepezil group, a positive correlation between plasma concentration and AChE activity was documented. Conversely, in rivastigmine group, a decrease in CSF activity of both enzymes was observed. CSF AChE and BChE activities were not correlated with the clinical outcome in any group considered. CSF biomarkers did not show any change after treatment., Conclusions:   AChEIs differently influence the activity of target enzymes in CSF independent of their pharmacodynamic effects., (© 2010 John Wiley & Sons A/S.)

Aims: The aim of the Stroke and Atrial Fibrillation Ensemble (SAFE) II study was to identify the reasons underlying the under-utilization of oral anticoagulation (OAC) in patients with nonvalvular atrial fibrillation (NVAF)., Methods: We investigated from all available sources the reasons why patients hospitalized for a stroke, who had a previously known NVAF, were not receiving OAC beforehand. We interviewed general practitioners (GPs) and cardiologists with a structured questionnaire, to identify the reasons for their therapeutic choice., Results: Of 370 patients, 257 were theoretically eligible for OAC according to guidelines and the presence of contra-indications, but only 82 (22.2%) of them had actually received OAC before. We found that factors independently associated with the prescription of OAC were being followed-up by a cardiologist and having a younger GP. The leading reason evoked by GPs or cardiologists to explain why patients were not treated with OAC was the presence of a 'potential contra-indication', which was often inappropriate, followed by 'there was no indication', 'low compliance' and 'fear of bleeding'., Conclusions: An important reason for not prescribing OAC was the lack of knowledge about trials and guidelines. Medical education about OAC in NVAF should therefore be improved.

Introduction: A multicentre, randomized, double-blind, placebo-controlled, parallel group study was carried out in 123 patients suffering from never treated (de novo) idiopathic Parkinson's disease (PD). The aim of the study was to confirm the efficiency and safety of alpha-dihydroergocryptine (alpha-DHEC) given as monotherapy in the symptomatic treatment of PD. The total score of the Unified Parkinson's Disease Rating Scale (UPDRS) was identified as the efficacy target variable., Patients and Methods: Sixty-two patients (32 males, 30 females, mean age +/- SD 64 +/- 10) were randomized to alpha-dihydroergocryptine and 61 (30 males, 31 females, mean age 63.8 +/- 9.1) to placebo. According to the experimental design, a 18-month double-blind phase vs placebo was followed. Two interim analyses were planned both at the 3rd and 12th month of treatment, in order to avoid continuation on placebo, if clear differences between groups were found (stopping criterium: nominal significance level equal to 0.022 in the analysis of the target variable). Analysis of variance was performed both on the per protocol (PP) and intent-to-treat (ITT) sample., Results: The results on the first interim analysis showed significant differences between treatment groups of the UPDRS total score both in the ITT (115 patients, alpha-DHEC: No. 56; placebo: No. 59; P=0.019) and PP (96 patients, alpha-DHEC: No. 46; placebo: No. 50; P=0.001) sample, why the trial was stopped. At the time of stopping the trial, 73 patients (alpha-DHEC: No. 37; placebo: No. 36) had reached the 6-month observation visit; the analysis carried out on this subset of patients confirmed the efficacy of alpha-dihydroergocryptine in early PD and the correctness of the decision to stop. The incidence of adverse drug reactions (ADR) did not differ between alpha-dihydroergocryptine and placebo recipients, gastrointestinal complaints being the most frequent., Conclusion: The results indicate that alpha-dihydroergocryptine is safe and effective in improving symptoms of de novo parkinsonian patients.

Introduction: The usefulness of posatirelin (L-pyro-2-aminoadipyl-L-leucyl-L-prolinamide), a synthetic peptide having modulatory activity on the monoaminergic and cholinergic systems and neurotrophic effects, was evaluated in vascular dementia., Patients and Methods: A multicentre, parallel groups, double-blind clinical study vs placebo was carried out with patients suffering from probable vascular dementia according to the NINDS-AIREN criteria. The study consisted of a two-week run-in of a once daily, orally administered, placebo phase, followed by 12 weeks of intramuscular treatment with posatirelin 10 mg/ml or placebo given once a day and a follow-up after one month's withdrawal. Efficacy was assessed using the Gottfries-Bråne-Steen (GBS) Rating Scale for dementia, the Randt Memory Test and the Toulouse-Piéron Attention Test. Data were evaluated using analysis of variance and covariance., Results: As regards GBS scores, patients treated with posatirelin showed a significant improvement in intellectual performance, in orientation, motivation and memory as compared to controls. The improvement of memory performance was also confirmed by the acquisition score and memory index of the Randt Memory Test. At the end of the follow-up period the differences between treatments were still maintained. Tolerability was good., Conclusions: The significant improvement observed in cognitive functions, attention and motivation of demented patients treated with posatirelin suggests the potential usefulness of this drug in vascular dementia. Furthermore, the presence of a long-lasting effect after drug withdrawal suggests the possibility of administering the drug cyclically.

Introduction: Posatirelin (L-pyro-2-aminoadipyl-L-leucil-L-prolinamide) a new synthetic tripeptide with cholinergic, catecholaminergic and neurotrophic properties, was investigated in the treatment of Alzheimer's disease., Material and Methods: A multicentre, double-blind study vs citicoline (reference drug) and ascorbic acid (inactive drug) was carried out in elderly patients suffering from late-onset Alzheimer's disease. The once daily intramuscular treatment lasted for three months followed by one-month oral treatment with a placebo. Subscales and factors of GBS (Gottfries-Bråne-Steen) Rating Scale were identified as primary measures for efficacy assessment., Results: At the end of the treatment, GBS subscale and factor scores assessing intellectual and emotional impairments, orientation and memory, ability to perform activities of daily living, depression-anxiety, attention and motivation were improved in the postatirelin group, showing significant differences with respect to the citicoline and/or ascorbic acid groups. Tolerability was good in all groups., Conclusions: The improvement in the GBS Rating Scale score observed in the posatirelin group is clinically relevant. It is worth verifying the drug-induced functional improvements, in further studies with large samples.

Albumin and IgG were determined in serum and cerebrospinal fluid (CSF) of patients with early-onset Alzheimer's disease (AD, n. 13), senile dementia of Alzheimer type (SDAT, n. 33), vascular dementia divided into multi-infarct (MID, n. 9) and probable vascular (PVD, n. 11) dementia. Albumin and IgG ratio and IgG index were calculated. CSF albumin and albumin ratio were significantly higher in MID patients indicating an increased BBB permeability. IgG ratio and IgG index did not show any significant difference among groups. These results do not provide evidence for BBB damage in AD/SDAT, while in MID the increase of CSF albumin and albumin ratio is suggestive of BBB dysfunction.

Multi-infarct dementia (MID) indicates a dementia disorder primarily caused by multiple cerebral infarcts. Since other pathogenetic mechanisms cause vascular dementia we evaluated clinical, CT scan and CSF neurochemical parameters of 134 MID and 67 PVD (probable vascular dementia) patients. We found no differences with regard to the presence of major risk factors. Only TIA/stroke episodes and focal neurological signs were significantly more frequent in MID than in PVD cases, an anticipable result on the basis of MID definition. CT scan findings showed a prevalence of subcortical with respect to cortical lesions in both groups, with a higher frequency in MID patients. Subjects with deep infarcts more frequently showed TIA/stroke episodes and diabetes mellitus. No differences were detectable in CSF monoamine metabolite levels. We conclude that in the majority of vascular dementias subcortical damage seems to have a major pathogenetic role.