Copper-Mediated N-Trifluoromethylation of O-Benzoylhydroxylamines.

The use of trifluoromethyl containing compounds is well established within medicinal chemistry, with a range of approved drugs containing C-CF3 and O-CF3 moieties. However, the utilisation of the N-CF3 functional group remains relatively unexplored. This may be attributed to the challenging synthesis of this unit, with many current methods employing harsh conditions or less accessible reagents. A robust methodology for the N-trifluoromethylation of secondary amines has been developed, which employs an umpolung strategy in the form of a copper-catalysed electrophilic amination. The method is operationally simple, uses mild, inexpensive reagents, and has been used to synthesise a range of novel, structurally complex N-CF3 containing compounds.

Stroke with large vessel occlusion in the posterior circulation: IV thrombolysis plus thrombectomy versus IV thrombolysis alone.

Efficacy and safety of mechanical thrombectomy (MT) for stroke with posterior circulation large vessel occlusion (LVO) is still under debate. We aimed to compare the outcomes of stroke patients with posterior circulation LVO treated with intravenous thrombolysis (IVT) (< 4.5 h after symptom onset) plus MT < 6 h after symptom onset with those treated with IVT alone (< 4.5 h after symptom onset). Patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) and in the Italian centers included in the SITS-ISTR were analysed. We identified 409 IRETAS patients treated with IVT plus MT and 384 SITS-ISTR patients treated with IVT alone. IVT plus MT was significantly associated with higher rate of sICH (ECASS II) compared with IVT alone (3.1 vs 1.9%; OR 3.984, 95% CI 1.014-15.815), while the two treatments did not differ significantly in 3-month mRS score ≤ 3 (64.3 vs 74.1%; OR 0.829, 95% CI 0.524-1.311). In 389 patients with isolated basilar artery (BA) occlusion, IVT plus MT was significantly associated with higher rate of any ICH compared with IVT alone (9.4 vs 7.4%; OR 4.131, 95% CI 1.215-14.040), while two treatments did not differ significantly in 3-month mRS score ≤ 3 and sICH per ECASS II definition. IVT plus MT was significantly associated with higher rate mRS score ≤ 2 (69.1 vs 52.1%; OR 2.692, 95% CI 1.064-6.811) and lower rate of death (13.8 vs 27.1%; OR 0.299, 95% CI 0.095-0.942) in patients with distal-segment BA occlusion, while two treatments did not differ significantly in 3-month mRS score ≤ 3 and sICH per ECASS II definition. IVT plus MT was significantly associated with lower rate of mRS score ≤ 3 (37.1 vs 53.3%; OR 0.137, 0.009-0.987), mRS score ≤ 1 (22.9 vs 53.3%; OR 0.066, 95% CI 0.006-0.764), mRS score ≤ 2 (34.3 vs 53.3%; OR 0.102, 95% CI 0.011-0.935), and higher rate of death (51.4 vs 40%; OR 16.244, 1.395-89.209) in patients with proximal-segment BA occlusion. Compared with IVT alone, IVT plus MT was significantly associated with higher rate of sICH per ECASS II definition in patients with stroke and posterior circulation LVO, while two treatment groups did not differ significantly in 3-month mRS score ≤ 3. IVT plus MT was associated with lower rate of mRS score ≤ 3 compared with IVT alone in patients with proximal-segment BA occlusion, whereas no significant difference was found between the two treatments in primary endpoints in patients isolated BA occlusion and in the other subgroups based on site occlusion.

Use of fluorescein sodium-assisted intraoperative sample validation to maximize the diagnostic yield of stereotactic brain biopsy: progress toward a new standard of care?

OBJECTIVE: In patients with contraindication to open resection, histological diagnosis is obtained through a stereotactic biopsy (SB). Missed diagnoses and sampling errors are important limitations of SB; therefore, various ways have been proposed to increase the diagnostic yield (DY). Intraoperative histopathology can obtain a DY exceeding 98% but with several drawbacks, namely prolonged operative times and logistic concerns. The objective of this study was to evaluate whether intraoperative validation of samples with fluorescein sodium can obtain a high DY with the same ease of use as standard SB. METHODS: One hundred three consecutive cases of frameless neuronavigated SB performed at the authors' center from May 2013 to June 2021 were included. Two groups were compared: 46 patients underwent standard nonassisted SB (nSB), and 57 patients underwent fluorescein sodium-assisted SB (fSB). Data were collected retrospectively before 2017 and prospectively thereafter. DY, operative time, and rate of complications were compared between the two groups. The surgical technique for fSB was standardized, and a novel classification system for intraoperative fluorescence findings was developed. RESULTS: Statistically significant differences between the two groups were identified. The DY of the fSB group (100%, 95% CI 93.73%-100%) was significantly greater than that of the nSB group (89.13%, 95% CI 80.14%-98.13%) (p = 0.0157). No statistically significant differences were observed in terms of mean operative time (p = 0.7104), intraoperative complications (p = 0.999), or postoperative complications (p = 0.5083). CONCLUSIONS: Compared with standard nSB, fSB showed a significantly higher DY and similar surgical time and rate of complications. The ease of use, wide diagnostic spectrum, and low cost make fluorescein sodium preferable to other fluorophores. The present study strengthens the limited data in the literature indicating routine use of fSB. The proposed workflow suggests that fSB should be the standard of care for contrast-enhanced cases. Intraoperative histopathology should be limited to nonenhancing cases, and nSB should be avoided. Future prospective multicenter studies will be useful for further validation of our findings.

Neurological emergency at the COVID-19 pandemic: report from a referral hospital in Eastern Piedmont, Italy.

BACKGROUND: The pandemic implied dramatic changes in public health assets. In Italy, some Stroke Units were transformed into sub-intensive COVID-19 Units, making the management of neurological patients demanding. We described how the flow of neurological emergencies was affected by the pandemic impact. METHODS: We analyzed accesses to the Emergency Department (ED) of the "Maggiore della Carità" Hospital, Piedmont, Italy, during a period of 8 months (COVID time; March to May 2020 and October 2020 to February 2021) and analyzed the admissions to the Neurology Unit and the underlying diagnosis. We also evaluated potential changes in the treatment of acute ischemic stroke in the same period. These variables were compared with two equivalent periods of time (2019-2020; 2018-2019). RESULTS: During the COVID time, there was a clear-cut reduction of the total ED accesses compared to NoCOVID times. However, admissions for acute neurological conditions showed a mild but non-significant decrease (6.3%vs.7.3%). The same applied to acute ischemic stroke, which represented the most common condition (47.7%). The proportion of patients who underwent emergent reperfusion therapies remained unchanged. Furthermore, no difference was found in door-to-needle and door-to-groin intervals between COVID time and NoCOVID times. On the contrary, the onset-to-door interval was significantly longer during the COVID time (p value: 0.001). DISCUSSION: While the percentage of admissions following an ED access grew dramatically, those to the Neurology Unit showed overall only a slight non-significant decrease. This finding implicitly reflects the serious and urgent nature of many neurological diseases, compelling people to access EDs at any time.

Flash-evoked high-frequency EEG oscillations in photosensitive epilepsies.

OBJECTIVE: To determine the feasibility of measuring scalp-recorded, flash-evoked, high-frequency EEG oscillations (F-HFOs) using a relatively simple technique. Furthermore, to assess whether F-HFOs are enhanced in photosensitive epileptic patients and if they might be proposed as a putative non-provocative biomarker of photosensitivity. METHODS: We studied 19 photosensitive patients with idiopathic generalized epilepsy, and 22 controls matched for demographic features. We extracted F-HFOs from the broadband scalp flash-visual evoked potential (b F-VEP) through appropriate filtering. We measured F-HFO amplitude, number and latency. Also, we carried out a time-frequency domain spectral F-HFO analysis. Inter-group statistics was performed. Within-groups, F-HFO features were correlated to the b F-VEP. RESULTS: The N3-N3I wave of the b F-VEP was significantly (p = 0.01) larger in patients compared to controls. The same was true for the inter-group F-HFO amplitude (p = 0.01). F-HFOs showed two main spectral peaks (∼88 and ∼125 Hz), whose power was greater (p = 0.001) in patients than in controls. The ∼88 Hz peak power exceeded the upper normal range in 15/19 patients. Patients showed a significant (p = 0.04) correlation between the ∼88 Hz peak power and the size of the N3-N3I wave. SIGNIFICANCE: A simplified F-HFO measurement proved feasible. In patients, F-HFOs were enhanced in terms of both size and spectral power, suggesting a role in the generation of the photoparoxysmal response. Some spectral features of the F-HFOs may be proposed as a putative non-provocative marker of epileptic photosensitivity.

Antiphospholipid Syndrome and the Neurologist: From Pathogenesis to Therapy.

Antiphospholipid syndrome (APS) is an autoimmune antibody-mediated condition characterized by thrombotic events and/or pregnancy morbidity in association with persistent positivity to antiphospholipid antibodies (aPL). The nervous system is frequently affected, as intracranial vessels are the most frequent site of arterial pathology. Over the course of years, many other neurological conditions not included in the diagnostic criteria, have been associated with APS. The pathogenic mechanisms behind the syndrome are complex and not fully elucidated. aPL enhance thrombosis, interfering with different pathways. Nevertheless, ischemic injury is not always sufficient to explain clinical features of the syndrome and immune-mediated damage has been advocated. This may be particularly relevant in the context of neurological complications. The reason why only a subgroup of patients develop non-criteria nervous system disorders and what determines the clinical phenotype are questions that remain open. The double nature, thrombotic and immunologic, of APS is also reflected by therapeutic strategies. In this review we summarize known neurological manifestations of APS, revisiting pathogenesis and current treatment options.

Treatment of chronic inflammatory demyelinating polyneuropathy: from molecular bases to practical considerations.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease of the peripheral nervous system, in which both cellular and humoral immune responses are involved. The disease is clinically heterogeneous with some patients displaying pure motor form and others also showing a variable degree of sensory dysfunction; disease evolution may also differ from patient to patient, since monophasic, progressive, and relapsing forms are reported. Underlying such clinical variability there is probably a broad spectrum of molecular dysfunctions that are and will be the target of therapeutic strategies. In this review we first explore the biological bases of current treatments and subsequently we focus on the practical management that must also take into account pharmacoeconomic issues.

Immunity and inflammation in neurodegenerative diseases.

Immune reactions inside the central nervous system are finely regulated, thanks to the presence of several checkpoints that have the fundamental purpose to preserve this fragile tissue form harmful events. The current knowledge on the role of neuroinflammation and neuro-immune interactions in the fields of multiple sclerosis, Alzheimer's disease and Parkinson's disease is reviewed. Moreover, a focus on the potential role of both active and passive immunotherapy is provided. Finally, we propose a common perspective, which implies that, under pathological conditions, inflammation may exert both detrimental and protective functions, depending on local factors and the timing of immune activation and shutting-off systems.

In-home continuing care services for substance use affected families.

The role of in-home work with substance use affected family members has great potential for addressing family and personal issues that are often not well addressed by continuing care interventions that involve limited contact with the family and the impact alcohol and other drug "abuse" has on the family environment. This article reviews the importance of involving the family in the recovery process and offers comparative advantages of an in-home visitation approach for assisting the substance user with maintaining substance use avoidance, reintegrating with the family, and addressing unresolved family issues affecting children and spousal relationships.