Tracking inflammation in the epileptic rat brain by bi-functional fluorescent and magnetic nanoparticles.

Correct localization of epileptic foci can improve surgical outcome in patients with drug-resistant seizures. Our aim was to demonstrate that systemically injected nanoparticles identify activated immune cells, which have been reported to accumulate in epileptogenic brain tissue. Fluorescent and magnetite-labeled nanoparticles were injected intravenously to rats with lithium-pilocarpine-induced chronic epilepsy. Cerebral uptake was studied ex vivo by confocal microscopy and MRI. Cellular uptake and biological effects were characterized in vitro in murine monocytes and microglia cell lines. Microscopy confirmed that the nanoparticles selectively accumulate within myeloid cells in the hippocampus, in association with inflammation. The nanoparticle signal was also detectable by MRI. The in vitro studies demonstrate rapid nanoparticle uptake and good cellular tolerability. We show that nanoparticles can target myeloid cells in epileptogenic brain tissue. This system can contribute to pre-surgical and intra-surgical localization of epileptic foci, and assist in detecting immune system involvement in epilepsy.

Cerebral Aneurysms and Recurrent TIAs in a 42-Year-Old Patient With DADA2 Mutation: A Case Report.

Objectives: Deficiency of adenosine deaminase 2 (DADA2) is a rare, recessively inherited autoinflammatory disease with a wide clinical spectrum of manifestations, including strokes and vasculitis. Methods: We report a case of a patient with DADA2 who presented with neurologic manifestations. Results: A 42-year-old woman with a known diagnosis of polyarteritis nodosa experienced several episodes of TIAs. Neuroimaging revealed 2 aneurysms in unusual locations. Her young age, ethnic origin, absent of cardiovascular risk factors, and skin involvement raised the suspicion of DADA2. Genetic testing confirmed the diagnosis, and a directed treatment with anti-TNF was initiated. Discussion: DADA2, although thought to be rare, needs to be borne in mind when evaluating patients with a combination of neurologic and systemic symptoms, as early diagnosis and treatment are imperative in preventing permanent disability.

Sex-dependent outcomes of recanalization-treated acute ischemic stroke patients at Shamir (Assaf Harofeh) medical center, Israel, 2011-2020.

BACKGROUND/OBJECTIVES: Sex-based differences in incidence, etiologies, severity and recanalization treatment outcomes of patients with acute ischemic stroke (AIS) have been studied extensively. We set out to determine if there were sex-based differences in outcomes among AIS patients who received recanalization treatments at Shamir (Assaf Harofeh) Medical Center (SMC), Israel, between 2011 and 2020. METHODS: This was a single-center, retrospective chart review. The primary analysis compared outcomes for men and women, overall and stratifying by disease severity. We compared also demographics, risk factors and workflow data. RESULTS: Eight hundred and eleven patients received recanalization treatment between 2011 and 2020: 472 (58.1%) men and 339 (41.8%) women. Mean age, NIHSS score and proportion with an NIHSS score ≥ 6 were higher for women. Cerebrovascular risk factors were more prevalent in women, particularly atrial fibrillation, except that current smoking was more prevalent in men. Six hundred and twenty patients (78.1%) were treated with TPA alone, 89 (11.2%) with TPA and endovascular treatment (EVT), and 85 (10.7%) with EVT alone. Fifty percent of patients were discharged home, 41% to a rehabilitation hospital or nursing home, and 9% did not survive. Twenty-four patients (3%) sustained symptomatic bleeds. Outcomes were worse in patients with NIHSS score ≥ 6. Outcomes did not differ by sex. CONCLUSIONS: While treated women presented with more severe AIS and more risk factors, we did not find significant sex-related differences in outcomes. Meticulous adherence to risk factor modification remains the best strategy to reduce stroke incidence, morbidity, and mortality in women and in men.

Reasons for delayed treatment initiation in Guillain-Barre syndrome.

OBJECTIVE: The goal of this study was to analyze the reasons for delayed diagnosis of Guillain-Barre syndrome (GBS). METHODS: We retrospectively reviewed the records of all adult patients with GBS treated at Shamir Medical Center (SMC) from 2006 to 2018. We divided the patients into two groups: those with early initiation of treatment (within 24 h of arrival to ED), and those with later initiation of treatment (>24 h after arrival). We extracted epidemiological and clinical data regarding those groups, and compared them. RESULTS: 100 patients with GBS were treated between 2006 and 2018 at SMC. 50 patients were treated within 24 h of arrival, and in 50 - treatment was initiated later. Of those with delayed treatment, 9 had mild disease, but did receive a working diagnosis of GBS. 41 patients were not diagnosed initially as a clear-cut GBS, and alternative diagnoses were considered, the most common were orthopedic (11/41), vascular (7/41) or nutritional deficiency (6\41). Findings that increased the likelihood for alternative diagnoses to be considered first were severe limb or back pain (26/41); intact or brisk reflexes (17/41); and an atypical pattern of weakness (7\41). CONCLUSIONS: GBS is a challenging diagnosis. Acknowledging the heterogeneity of its presentation and knowing its pitfalls is crucial for the prompt and accurate diagnosis of the disease.

Electrophysiological features and prognosis of Guillain-Barré syndrome in Israel: A single-center's 20 years' experience.

INTRODUCTION: We previously reported on 40 patients with Guillain-Barré syndrome (GBS) identified 1999-2005 at our center, and showed that a higher proportion had an axonal pattern, compared to Europe and North America. METHODS: Retrospective chart review of 100 adult patients with GBS between 2006 and 2018 at Shamir Medical Center. RESULTS: 46.8% of those with an abnormal EMG had an axonal pattern. Of the 60 patients who presented with mild disease (defined as Hughes score 1-2), walking deteriorated in 35 (58%, considering any worsening of Hughes score). 20 patients (33%) lost the ability to walk independently (Hughes score 3), 8 reached a point they could not walk (Hughes 4), and 2 needed mechanical ventilation. Ninety-four of 100 patients (94%) were treated with intravenous immunoglobulins (IVIg). Using ECG monitoring and DVT prophylaxis, IVIg-related adverse reactions were rare. CONCLUSIONS: This study demonstrated a higher proportion of axonal GBS patients in Israel, compared to European and North American patients, replicating the findings in the 1999-2005 patients. Due to the progressive nature of the disease, with more than half of patients presenting with mild disease deteriorating and needing inpatient rehabilitation - we advocate initiation of treatment once a clinical diagnosis of GBS is made.

CT-guided thrombolytic treatment of patients with wake-up strokes.

BACKGROUND: Observational studies of thrombolysis outcomes in wake-up acute ischemic stroke patients selected based on non-contrast brain CT criteria suggested that treated patients did as well as or better than those not treated, after adjustment for baseline characteristics. We began offering thrombolytic treatment (IVTPA) to patients presenting with wake-up strokes and normal non-contrast brain CTs, who could be treated within 4.5 h of being found. DESIGN/METHODS: A retrospective chart review was performed in patients presenting with AIS between November 2014 and December 2017 who received IVTPA. A planned subgroup analysis compared patients with wake-up strokes and normal non-contrast brain CTs to patients with witnessed stroke treated within 4.5 h of being found, or of witnessed onset, respectively. RESULTS: Three hundred and six patients were treated, 279 with witnessed-onset and 27 with wake-up strokes. The latter were not candidates for endovascular intervention. Efficacy and safety were similar in both groups. Discharges home, respectively, were 143(53%) and 13(48%); facility discharges were 112(40.1%) and 11(40.7%) and in-hospital mortality was 19 (6.8%) and 3 (11%). Treatment-related symptomatic bleeds were: 5(1.8%) and 1 (3.7%), respectively. CONCLUSIONS: The findings affirm, in a new clinical series reflecting routine practice, that it is safe to treat with IVTPA patients with wake-up strokes and a normal brain CT scan, who are not candidates for endovascular intervention. We hypothesize, that when the non-contrast brain CT scan is normal, it may be safe to extend beyond 4.5 h the IVTPA treatment eligibility window in similar patients with witnessed-onset stroke.

Active transport on disordered microtubule networks: the generalized random velocity model.

The motion of small cargo particles on microtubules by means of motor proteins in disordered microtubule networks is investigated theoretically using both analytical tools and computer simulations. Different network topologies in two and three dimensions are considered, one of which has been recently studied experimentally by Salman [Biophys. J. 89, 2134 (2005)]. A generalization of the random velocity model is used to derive the mean-square displacement of the cargo particle. We find that all cases belong to the class of anomalous superdiffusion, which is sensitive mainly to the dimensionality of the network and only marginally to its topology. Yet in three dimensions the motion is very close to simple diffusion, with sublogarithmic corrections that depend on the network topology. When details of the thermal diffusion in the bulk solution are included, no significant change to the asymptotic time behavior is found. However, a small asymmetry in the mean microtubule polarity affects the corresponding long-time behavior. We also study a three-dimensional model of the microtubule network in living animal cells. Three first-passage-time problems of intracellular transport are simulated and analyzed for different motor processivities: (i) cargo that originates near the nucleus and has to reach the membrane, (ii) cargo that originates from the membrane and has to reach the nucleus, and (iii) cargo that leaves the nucleus and has to reach a specific target in the cytoplasm. We conclude that while a higher motor processivity increases the transport efficiency in cases (i) and (ii), in case (iii) it has the opposite effect. We conjecture that the balance between the different network tasks, as manifested in cases (i) and (ii) versus case (iii), may be the reason for the evolutionary choice of a finite motor processivity.