The frontal assessment battery is not useful to discriminate progressive supranuclear palsy from frontotemporal dementias.

BACKGROUND: The frontal assessment battery (FAB) has been suggested as a useful tool in the differential diagnosis of progressive supranuclear palsy (PSP) from Parkinson's disease (PD) and multiple system atrophy with parkinsonism (MSA-P). However, the utility of the FAB in the differential diagnosis of PSP from frontotemporal dementia (FTD) phenotypes is still under research. METHODS: We performed the FAB, in a multi-centre cohort of 70 PSP, 103 FTD (N = 84 behavioral variant FTD, N = 10 semantic dementia, N = 9 progressive non-fluent aphasia), 26 PD and 11 MSA-P patients, diagnosed according to established criteria. Patients were also rated with the mini mental state examination and motor scales. RESULTS: The FAB total score showed a poor discriminatory power between PSP and FTD as a group [area under the curve (AUC) = 0.523]. Moreover, the FAB score showed no correlation with disease duration in PSP (r = 0.05) or FTD group (r = 0.04). In contrast, we confirmed that the FAB is clinically useful to differentiate PSP from PD and MSA-P (AUC = 0.927). In fact, the sum of two FAB subscores together (verbal fluency and Luria motor series) were as good as the total score in differentiating PSP from PD and MSA-P (AUC = 0.957). CONCLUSIONS: The FAB may not be a useful tool to differentiate PSP from FTDs, and shows no correlation with disease duration in these disorders. On the other hand, the essential information to differentiate PSP from PD and MSA-P is contained in the sum of only two FAB subscores. This should be taken into consideration in both clinical practice and the planning of clinical trials.

Safety of early endarterectomy in patients with symptomatic carotid artery stenosis: an international multicenter study.

BACKGROUND AND PURPOSE: Although the latest recommendations suggest that carotid endarterectomy (CEA) should be performed in symptomatic carotid artery stenosis (sCAS) patients within 2 weeks of the index event, only a minority of patients undergo surgery within the recommended time-frame. The aim of this international multicenter study was to prospectively evaluate the safety of early CEA in patients with sCAS in everyday clinical practice settings. METHODS: Consecutive patients with non-disabling acute ischaemic stroke (AIS) or transient ischaemic attack (TIA) due to sCAS (≥ 70%) underwent early (≤ 14 days) CEA at five tertiary-care stroke centers during a 2-year period. Primary outcome events included stroke, myocardial infarction (MI) or death occurring during the 30-day follow-up period and were defined according to the International Carotid Stenting Study criteria. RESULTS: A total of 165 patients with sCAS [mean age 69 ± 10 years; 69% men; 70% AIS; 6% crescendo TIA; 8% with contralateral internal carotid artery (ICA) occlusion] underwent early CEA (median elapsed time from symptom onset 8 days). Urgent CEA (≤ 2 days) was performed in 20 cases (12%). The primary outcomes of stroke and MI were 4.8% [95% confidence interval (CI) 1.5%-8.1%] and 0.6% (95% CI 0%-1.8%). The combined outcome event of non-fatal stroke, non-fatal MI or death was 5.5% (95% CI 2.0%-9.0%). Crescendo TIA, contralateral ICA occlusion and urgent CEA were not associated (P > 0.2) with a higher 30-day stroke rate. CONCLUSIONS: Our findings indicate that the risk of early CEA in consecutive unselected patients with non-disabling AIS or TIA due to sCAS is acceptable when the procedure is performed within 2 weeks (or even within 2 days) from symptom onset.

A review of physical and cognitive interventions in aging.

Maintaining a healthy brain is a critical factor for the quality of life of elderly individuals and the preservation of their independence. Challenging aging brains through cognitive training and physical exercises has shown to be effective against age-related cognitive decline and disease. But how effective are such training interventions? What is the optimal combination/strategy? Is there enough evidence from neuropsychological observations, animal studies, as well as, structural and functional neuroimaging investigations to interpret the underlying neurobiological mechanisms responsible for the observed neuroplasticity of the aging brain? This piece of work summarizes recent findings toward these questions, but also highlights the role of functional brain connectivity work, an emerging discipline for future research in healthy aging and the study of the underlying mechanisms across the life span. The ultimate aim is to conclude on recommended multimodal training, in light of contemporary trends in the design of exergaming interventions. The latter issue is discussed in conjunction with building up neuroscientific knowledge and envisaged future research challenges in mapping, understanding and training the aging brain.

Genetic assessment of familial and early-onset Parkinson's disease in a Greek population.

BACKGROUND AND PURPOSE: Although the first mutation associated with Parkinson's disease (PD) was identified several years ago in the alpha-synuclein (SNCA) gene in families of Greek and Italian ancestry, a more systematic study of this and other known PD mutations has not been performed in the Greek population. METHODS: A genetic analysis in 111 familial or sporadic with early-onset (≤50 years, EO) PD patients was performed for the presence of the A53T SNCA mutation. In separate subgroups of these patients, further mutations in the SNCA, LRRK2, Parkin, PINK1 and DJ-1 genes were searched for. Additionally, a subgroup of familial cases was analysed for mutations in the glucocerebrosidase (GBA) gene. RESULTS: In total, five patients (4.5% of our whole population) were identified with the A53T SNCA mutation, two with a heterozygote dosage mutation and one with a heterozygote point mutation in the Parkin gene, and seven patients (10.3% of our familial cohort) with GBA gene mutations. CONCLUSIONS: The A53T mutation in the SNCA gene, although uncommon, does represent a cause of PD in the Greek population, especially of familial EOPD with autosomal dominant inheritance. GBA mutations in the familial cohort tested here were as common as in a cohort of sporadic cases previously examined from the same centres. For the remainder of the genes, genetic defects that could definitively account for the disease were not identified. These results suggest that further Mendelian traits that lead to PD in the Greek population remain to be identified.

The role of allogeneic haematopoietic progenitor cell transplantation in patients with diffuse large B-cell non-Hodgkin lymphomas (DLBCL).

Despite the undoubted improvement in the prognosis of patients with diffuse large B-cell lymphomas (DLBCLs) with the addition of rituximab in the front-line treatment, a significant proportion of patients still relapse. Salvage immune-chemotherapy followed by high-dose therapy with autologous haematopoietic cell transplantation (auto-HCT) remains the treatment of choice for such patients, especially in those who demonstrate chemosensitive disease. In recent years, allogeneic haematopoietic cell transplantation (allo-HCT) has increasingly been used for patients who are resistant to salvage treatment or relapse after an auto-HCT. Strategies using reduced intensity conditioning regimens have allowed application of this approach to a broader range of patients. PFS is up to 55% with a risk of relapse up to 80% depending on different studies. In multivariate analysis, several factors have been associated with favourable outcome including chemosensitivity of the disease, younger age and Karnofsky performance status at the time of the transplant being the strongest ones. DLIs have shown to induce durable responses in relapsed or progressed disease; however, its role remains controversial as the results are inferior to the responses seen in other haematological malignancies. More recently, the addition of MoAbs in the non-myeloablative conditioning regimens has shown encouraging results. In conclusion, allo-HCT is a feasible option in selective patients with chemosensitive DBCL, as it reduces the risk of relapse; however, this is achieved at the cost of significant non-relapse mortality.

Time-frequency analysis methods to quantify the time-varying microstructure of sleep EEG spindles: possibility for dementia biomarkers?

The time-varying microstructure of sleep EEG spindles may have clinical significance in dementia studies and can be quantified with a number of techniques. In this paper, real and simulated sleep spindles were regarded as AM/FM signals modeled by six parameters that define the instantaneous envelope (IE) and instantaneous frequency (IF) waveforms for a sleep spindle. These parameters were estimated using four different methods, namely the Hilbert transform (HT), complex demodulation (CD), matching pursuit (MP) and wavelet transform (WT). The average error in estimating these parameters was lowest for HT, higher but still less than 10% for CD and MP, and highest (greater than 10%) for WT. The signal distortion induced by the use of a given method was greatest in the case of HT and MP. These two techniques would necessitate the removal of about 0.4s from the spindle data, which is an important limitation for the case of spindles with duration less than 1s. Although the CD method may lead to a higher error than HT and MP, it requires a removal of only about 0.23s of data. An application of this sleep spindle parameterization via the CD method is proposed, in search of efficient EEG-based biomarkers in dementia. Preliminary results indicate that the proposed parameterization may be promising, since it can quantify specific differences in IE and IF characteristics between sleep spindles from dementia subjects and those from aged controls.

CSF biomarker profile and diagnostic value in vascular dementia.

BACKGROUND AND PURPOSE: The differential diagnosis between vascular dementia (VD) and Alzheimer's disease (AD) or mixed dementia (MD) is not always easy in clinical practice. The purpose of the present study was to evaluate the cerebrospinal fluid (CSF) biomarkers tau protein in its total (tau(T)) or hyperphosphorylated at threonin-181(tau(P-181)) form and beta amyloid peptide 1-42 (A beta 42) alone and their combinations to investigate their diagnostic value in the discrimination between VD and AD or MD. METHODS: The above CSF biomarkers were determined in duplicate and blind to the clinical diagnosis by double sandwich, enzyme-linked immunosorbent assay (ELISA) commercial kits (Innogenetics, Gent, Belgium) in 92 AD patients, 23 VD patients, 17 patients with MD and 68 controls. RESULTS: Alzheimer's disease and MD showed increased levels of tau(T), tau(P) and reduced levels of A beta 42 as compared with the controls. The best discrimination between VD and AD or MD was achieved by the combination of all three biomarkers, correctly classifying >or=85% of patients, either in the form of a discriminant function or in the form of the tau(T) x tau(P-181)/A beta 42 formula. CONCLUSIONS: Cerebrospinal fluid biomarkers may be a useful adjunct for the discrimination between AD/ MD and VD in every day clinical practice.

A case of refractory secondary paroxysmal kinesigenic dyskinesia with high sensitivity to phenytoin monotherapy.

We report on a 42-year-old man with paroxysmal kinesigenic dyskinesia who was referred as a refractory case to any drug used in the past as monotherapy or in combination. Our decision to discontinue his current combined medication and to administer only high-dose phenytoin led to significant improvement. It is of interest to note that the previous use of phenytoin in combination with other antiepileptic and neuroleptic drugs had no effect. In addition, the co-administration of gabapentin led to a dramatic recurrence of the episodes.

Allogeneic stem cell transplantation as treatment for myelofibrosis.

Idiopathic myelofibrosis (IMF) is a clonal disorder resulting from the proliferation of aberrant hematopoietic stem cells. Conventional treatment is unsatisfactory, and with the exception of supportive blood transfusions, none of the standard therapies have been shown to confer a survival advantage. Allogeneic stem cell transplantation represents the only treatment modality with proven curative potential. Myeloablative conditioning regimens are associated with high transplant-related mortality, particularly in the elderly, making most patients with IMF ineligible for this treatment. Strategies using reduced intensity conditioning regimes have allowed application of allogeneic transplantation to a broader range of patients and a number of recent reports have demonstrated potential efficacy.