Caterina Motta

Long-term potentiation-like cortical plasticity is disrupted in Alzheimer's disease patients independently from age of onset

Alzheimers disease (AD) is considered an age‐related disorder. However, it is unclear whether AD induces the same pathological and neurophysiological modifications in synaptic functions independently from age of disease onset. We used transcranial magnetic stimulation tools to investigate the mechanisms of cortical plasticity and sensory‐motor integration in AD patients with a wide range of disease onset.

LTP‐like cortical plasticity is disrupted in Alzheimer's disease patients independently from age of onset

Alzheimers disease (AD) is considered an age‐related disorder. However, it is unclear whether AD induces the same pathological and neurophysiological modifications in synaptic functions independently from age of disease onset. We used transcranial magnetic stimulation tools to investigate the mechanisms of cortical plasticity and sensory‐motor integration in AD patients with a wide range of disease onset.

CT angiography-based collateral flow and time to reperfusion are strong predictors of outcome in endovascular treatment of patients with stroke

Background Collateral flow (CF) is an effective predictor of outcome in acute ischemic stroke (AIS) with potential to sustain the ischemic penumbra. However, the clinical prognostic value of CF in patients with AIS undergoing mechanical thrombectomy has not been clearly established. We evaluated the relationship of CF with clinical outcomes in patients with large artery anterior circulation AIS treated with mechanical thrombectomy. Methods Baseline collaterals of patients with AIS (n=135) undergoing mechanical thrombectomy were independently evaluated by CT angiography (CTA) and conventional angiography and dichotomized into poor and good CF. Multivariable analyses were performed to evaluate the predictive effect of CF on outcome and the effect of time to reperfusion on outcome based on adequacy of the collaterals. Results Evaluation of CF was consistent by both CTA and conventional angiography (p<0.0001). A higher rate of patients with good collaterals had good functional outcome at 3-month follow-up compared with those with poor collaterals (modified Rankin Scale (mRS) 0–2: 60% vs 10%, p=0.0001). Patients with poor collaterals had a significantly higher mortality rate (mRS 6: 45% vs 8%, p=0.0001). Multivariable analyses showed that CF was the strongest predictor of outcome. Time to reperfusion had a clear effect on favorable outcome (mRS ≤2) in patients with good collaterals; in patients with poor collaterals this effect was only seen when mRS ≤3 was considered an acceptable outcome. Conclusions CTA is a valid tool for assessing the ability of CF to predict clinical outcome in patients with AIS treated with mechanical thrombectomy. Limiting time to reperfusion is of definite value in patients with good collaterals and also to some extent in those with poor collaterals.

Endovascular Stroke Treatment of Acute Tandem Occlusion: A Single-Center Experience

PURPOSEnTo evaluate outcomes and prognostic factors in patients with acute ischemic stroke caused by tandem internal carotid artery/middle cerebral artery occlusion undergoing endovascular treatment.nnnMATERIALS AND METHODSnCharacteristics of consecutive patients with tandem occlusion (TO) were extracted from a prospective registry. Collateral vessel quality on pretreatment computed tomographic (CT) angiography was evaluated on a 4-point grading scale, and patients were dichotomized as having poor or good collateral flow. Outcome measures included successful reperfusion according to Thrombolysis In Cerebral Infarction score, good outcome at 3 months defined as a modified Rankin scale score ≤ 2, symptomatic intracranial hemorrhage (ICH; sICH), and mortality.nnnRESULTSnA total of 72 patients with TO (mean age, 65.6 y ± 12.8) were treated. Intravenous thrombolysis was performed in 54.1% of patients, and a carotid stent was inserted in 48.6%. Successful reperfusion was achieved in 64% of patients, and a good outcome was achieved in 32%. sICH occurred in 12.5% of patients, and the overall mortality rate was 32%. Univariate analysis demonstrated that good outcome was associated with good collateral flow (P = .0001), successful reperfusion (P = .001), and lower rate of any ICH (P = .02) and sICH (P = .04). On multivariate analysis, good collateral flow (odds ratio [OR], 0.18; 95% confidence interval [CI], 0.04-0.75; P = .01) and age (OR, 1.08; 95% CI, 1.01-1.15; P = .01) were the only predictors of good outcome. The use of more than one device for thrombectomy was the only predictor of sICH (OR, 10.74; 95% CI, 1.37-84.13; P = .02).nnnCONCLUSIONSnEndovascular treatment for TO resulted in good outcomes. Collateral flow and age were independent predictors of good clinical outcomes at 3 months.

Efficacy and Safety of Mechanical Thrombectomy in Older Adults with Acute Ischemic Stoke

To evaluate the safety and efficacy of endovascular therapy in elderly adults treated for acute ischemic stroke.

CT Angiography ASPECTS Predicts Outcome Much Better Than Noncontrast CT in Patients with Stroke Treated Endovascularly

BACKGROUND AND PURPOSE: Noncontrast CT ASPECTS has been investigated as a predictor of outcome in patients with acute ischemic stroke. Our purpose was to investigate whether CTA source images are a better predictor of clinical and radiologic outcomes than NCCT ASPECTS in candidates for endovascular stroke therapy. MATERIALS AND METHODS: CT scans of patients (n = 124) were independently evaluated by 2 readers for baseline NCCT and CTA source image ASPECTS and for follow-up ASPECTS. An mRS of ≤2 at 3 months was considered a favorable outcome. Receiver operating characteristic curve analysis was used to assess the ability of NCCT and CTA source image ASPECTS to identify patients with favorable outcomes. A stepwise multiple regression analysis was performed to find independent predictors of outcome. RESULTS: Baseline CTA source image ASPECTS correlated better than NCCT ASPECTS with follow-up ASPECTS (r = 0.76 versus r = 0.51; P for comparison of the 2 coefficients < .001). Receiver operating characteristic curve analysis showed that baseline CTA source image ASPECTS compared with NCCT ASPECTS can better identify patients with favorable outcome (CTA source image area under the curve = 0.83; 95% CI, 0.76–0.91; NCCT area under the curve = 0.67; 95% CI, 0.58–0.77; P < .001). Finally, the stepwise regression analysis showed that lower age, good recanalization, lower time to recanalization, and good baseline CTA source image ASPECTS, not NCCT ASPECTS, were independent predictors of favorable outcome. CONCLUSIONS: CTA source image ASPECTS predicts outcome better than NCCT ASPECTS; this finding suggests CTA rather than NCCT as a main step in the decision-making process for patients with acute ischemic stroke.

Management of flu-like syndrome with cetirizine in patients with relapsing-remitting multiple sclerosis during therapy with interferon beta: Results of a randomized, cross-over, placebo-controlled pilot study

Background Flu-like syndrome (FLS) is a common adverse event experienced by patients with relapsing-remitting multiple sclerosis (RRMS) treated with interferon beta (IFNβ). FLS can lead to poor treatment adherence and early IFNβ discontinuation. The involvement of interleukin-6 (IL-6) in the occurrence of FLS has been suggested. We hypothesized that cetirizine, a second-generation histamine H1 receptor antagonist able to reduce the levels of IL-6, might improve IFNβ-induced FLS. Methods We conducted a pilot, cross-over, randomized, placebo-controlled, double-blind study to evaluate the efficacy of cetirizine 10 mg added after each IFNβ injection to the standard of care for FLS (acetaminophen or nonsteroidal anti-inflammatory drugs) on FLS in patients with RRMS treated with IFNβ. Patients were randomized to two treatment sequences: 1) 4-week treatment with placebo added to the standard treatment for FLS, followed by 4-week treatment with cetirizine added to the standard of care, and 2) first addition of cetirizine, then of placebo. The primary efficacy endpoint was the mean change of FLS severity [11-point visual analog scale (VAS)] after 4 weeks of treatment within each sequence. Results Forty-five patients (71.1% female, mean age 39.1 years, mean time from RRMS diagnosis 5.8 years) were randomized to treatment sequences 1 and 2. The differences between cetirizine and placebo in the intensity of FLS were not statistically significant: total mean VAS scores at 4 hours from IFNβ injection were 3.57 and 3.42 for cetirizine and placebo, respectively (difference –0.15; 95% confidence interval: from –0.74 to 0.44; p = 0.6029). The two treatments were similar also with regard to other efficacy measures considered and to the safety/tolerability profile. Conclusions The addition of cetirizine to the standard of care for IFNβ-induced FLS in patients with RRMS does not seem to provide significant benefits compared with placebo. Further effort is required to understand the mechanisms underlying IFNβ-induced FLS. Trial registration EudraCT 2013-001055-12.

Reply to: Efficacy and Safety of Mechanical Thrombectomy in Older Adults with Acute Ischemic Stroke: Methodological Concerns

To the Editor: We were interested to read the paper by Sallustio and colleagues. The authors aimed to evaluate the efficacy and safety of endovascular treatment of acute ischemic stroke in elderly adults. Although the results were interesting, we believe the effect of the variables in the multivariable analysis was overestimated and that there is clear evidence of sparse data bias. The authors investigated 23 potential predictors for inclusion in their multivariable model, with only those reaching a preset univariate criterion (P < .01) being selected for further analysis. In other words, the authors used a conservative P-value from their univariate analyses as the criterion for inclusion in the multivariate analysis. This approach to model building leads to overestimating the effect of the selected predictors in the multivariate analysis. This type of bias, because of the selection of predictors and model building, is known as testimation bias. Testimation bias is considered to be large when only predictors with P < .05 (in univariate analysis) are included in multivariate models. Of the 23 potential predictors included in their study, a number of these, such as onset National Institute of Health Stroke Scale (NIHSS) score and 24-hour improvement, had a large effect (P < .001), whereas others such as thromboaspiration device (P = .02) and intracranial hemorrhage (ICH) (P = .04) had a small effect. When a conservative P-value (e.g., <.01) is used to determine which variables are included in the multivariate model, the effect of variables with P < .01 (those with relatively large effects) will be overestimated in the subsequent multivariable analysis. Finally, the effect of the predictor 24-hour clinical improvement on the outcome 3-month functional independence in individuals aged 80 and older is biased because of data sparsity. The estimated odds ratio for the predictor 24-hour clinical improvement was large (141.13), and its confidence interval was extremely wide (2.96–6,720.7). As reported in Table S1, 24-hour clinical improvement and 3-month functional independence were measured in only a few individuals aged 80 and older. In this situation, the estimated effect size can be very large and the estimated confidence interval extremely wide. This type of bias is known as sparse data bias, and there are several recommended statistical approaches that can be used to limit or minimize the level of this bias.

CSF tau is associated with impaired cortical plasticity, cognitive decline and astrocyte survival only in APOE4-positive Alzheimer’s disease

In Alzheimer’s disease (AD) patients, apopoliprotein (APOE) polymorphism is the main genetic factor associated with more aggressive clinical course. However, the interaction between cerebrospinal fluid (CSF) tau protein levels and APOE genotype has been scarcely investigated. A possible key mechanism invokes the dysfunction of synaptic plasticity. We investigated how CSF tau interacts with APOE genotype in AD patients. We firstly explored whether CSF tau levels and APOE genotype influence disease progression and long-term potentiation (LTP)-like cortical plasticity as measured by transcranial magnetic stimulation (TMS) in AD patients. Then, we incubated normal human astrocytes (NHAs) with CSF collected from sub-groups of AD patients to determine whether APOE genotype and CSF biomarkers influence astrocytes survival. LTP-like cortical plasticity differed between AD patients with apolipoprotein E4 (APOE4) and apolipoprotein E3 (APOE3) genotype. Higher CSF tau levels were associated with more impaired LTP-like cortical plasticity and faster disease progression in AD patients with APOE4 but not APOE3 genotype. Apoptotic activity was higher when cells were incubated with CSF from AD patients with APOE4 and high tau levels. CSF tau is detrimental on cortical plasticity, disease progression and astrocyte survival only when associated with APOE4 genotype. This is relevant for new therapeutic approaches targeting tau.

P295 APOE polymorphism and cortical plasticity are independently associated with cognitive decline in Alzheimer’s disease

Hereditary motor and sensory neuropathies (HMSN) often present a set of challenges on the electrophysiological diagnosis. Genetic tests are available for most of the subtypes, but electromyography (EMG) still plays a fundamental role in diagnosis. Despite classic division into demyelinating and axonal, many forms of Charcot-Marie-Tooth (CMT) are not easy to diagnose, and ultrasound (US) can make this distinction a bit easier. The presence of an underlying neuropathy can complicate diagnosis of overlapping entrapment syndromes. Were investigated 5 patients with HMSN type I (CMT Tipe I) (3 M and 2 F, mean age 53 ± 7.4 aa). As control we adopted data of healthy volunteers from our laboratory matched for age and sex. We used Telemed Echo-wave II, with patients lying on a bed or sitting in a wheelchair; cross section area (CSA) of the nerve trunks was measured. Average sizes of nerves were increased in upper limbs and nerve US provided information on type of neuropathy. Literature datas concerning US are still limited, but is desirable, in future, to implement US as a complementary diagnostic tool in the assessment of different kind of neuropathies.