(1) Objective: The objective was two-fold: (a) test a protocol of combined interventions; (b) administer this combined protocol within the framework of a six-month, intensive, long-duration program. The array of interventions was designed to target the treatment-resistant impairments underlying persistent mobility dysfunction: weakness, balance deficit, limb movement dyscoordination, and gait dyscoordination. (2) Methods: A convenience sample of eight chronic stroke survivors (>4 months post stroke) was enrolled. Treatment was 5 days/week, 1–2.5 h/day for 6 months, as follows: strengthening exercise, balance training, limb/gait coordination training, and aerobic exercise. Outcome measures: Berg Balance Scale (BBS), Fugl-Meyer Lower Limb Coordination (FM), gait speed, 6 Minute Walk Test (6MWT), Timed up and Go (TUG), Functional Independence Measure (FIM), Craig Handicap Assessment Rating Tool (CHART), and personal milestones. Pre-/post-treatment comparisons were conducted using the Permutation Test, suitable for ordinal measures and small sample size. (3) Results: For the group, there was a statistically (p ≤ 0.04) significant improvement in balance, limb movement coordination (FM), gait speed, functional mobility (TUG), and functional activities (FIM). There were measurable differences (minimum detectible change: MDC) in BBS, FM, gait speed, 6MWT, and TUG. There were clinically significant milestones achieved for selected subjects according to clinical benchmarks for the BBS, 6MWT, gait speed, and TUG, as well as achievement of personal milestones of life role participation. Effect sizes (Cohen’s D) ranged from 0.5 to 1.0 (with the exception of the (6MWT)). After six months of treatment, the above array of gains were beyond that reported by other published studies of chronic stroke survivor interventions. Personal milestones included: walking to mailbox, gardening/yardwork, walking a distance to neighbors, return to driving, membership at a fitness center, vacation trip to the beach, swimming at local pool, returning to work, housework, cooking meals. (4) Conclusions: Stroke survivors with mobility dysfunction were able to participate in the long-duration, intensive program, with the intervention array targeted to address impairments underlying mobility dysfunction. There were either clinically or statistically significant improvements in an array of measures of impairment, functional mobility, and personal milestone achievements. Full article

Background: MLC601/MLC901 (NeuroAiD™) is a combination of natural products shown to be safe and to aid neurological recovery after brain injuries, especially ischemic stroke. Few studies have investigated NeuroAiD in primary intracerebral hemorrhage (ICH). The NeuroAiD Safe Treatment (NeST) Registry explores NeuroAiD use in the real-world setting. This cohort study aimed to assess its use and safety in ICH. Methods: The online NeST Registry of subjects with ICH given NeuroAiD prospectively collected clinical data at baseline and monthly visits (V) 1 to 3. Outcome measures included compliance, side effects, Glasgow Coma Scale (GCS), National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Short Orientation-Memory-Concentration Test (SOMCT). Results: Sixty-six subjects were included. NeuroAiD was well-tolerated with fair compliance over three months. Two non-serious side effects were reported. Mean scores significantly improved on all outcome scales. The proportion of subjects with favorable outcomes significantly improved from baseline to V3: NIHSS 0–4, from 12% to 59% (p < 0.0001); GCS 13–15, from 64% to 88% (p = 0.007); mRS 0–1, from 9% to 37% (p = 0.004); and SOMCT score 0–8, from 44% to 68% (p = 0.029). Conclusions: NeuroAiD in the real-world setting was safe and showed potential for a sustained positive effect on neurological recovery after ICH. Full article

After a stroke, forward head posture occurs, resulting in swallowing dysfunction. Neuromuscular electrical stimulation (NMES) combined with upper cervical spine mobilization has demonstrated enhanced recovery of the swallowing function in stroke patients. This study investigated the therapeutic effects of NMES in conjunction with upper cervical mobilization in stroke patients with dysphagia. Thirty-four stroke patients were recruited (in a randomized controlled clinical trial) and divided into an experimental group (n = 17; NMES plus upper cervical spine mobilization) and a control group (n = 17; NMES plus sham mobilization). Forward head posture was measured by craniocervical flexion test (CCFT) and craniovertebral angle (CVA). Swallowing function was measured by variations in video fluoroscopic dysphagia scale (VDS) and penetration–aspiration scale (PAS) scores using the video fluoroscopic swallowing study (VFSS). All measurements were done at baseline and after four weeks of NMES plus mobilization. A significant increase was observed in CCFT, CVA, VDS (total VDS score, oral stage score, pharyngeal stage score), and PAS score in all variations in the experimental group. The CCFT, CVA, pharyngeal stage score, total VDS, and PAS score were significantly higher in the experimental group when compared to the control group. NMES plus upper cervical spine mobilization can be regarded as a promising method to improve swallowing function and forward head posture changes in stroke patients with dysphagia. Full article

Apoptosis in acute stroke is associated with a negative prognosis and is correlated with the severity of the neurological deficit. However, there is no evidence that indicates that, in the subacute phase of the stroke, the apoptosis process might activate neuroplasticity. Therefore, in this study, we investigated the effect of an extremely low frequency electromagnetic field (ELF-EMF) on the molecular mechanism of apoptosis, as used in the rehabilitation of post-stroke patients. Patients with moderate stroke severity (n = 48), 3–4 weeks after incident, were enrolled in the analysis and divided into ELF-EMF and non-ELF-EMF group. The rehabilitation program in both groups involves the following: kinesiotherapy—30 min; psychological therapy—15 min; and neurophysiological routines—60 min. Additionally, the ELF-EMF group was exposed to an ELF-EMF (40 Hz, 5 mT). In order to assess the apoptosis gene expression level, we measured the mRNA expression of BAX, BCL-2, CASP8, TNFα, and TP53. We found that ELF-EMF significantly increased the expression of BAX, CASP8, TNFα, and TP53, whereas the BCL-2 mRNA expression after ELF-EMF exposition remained at a comparable level in both groups. Thus, we suggest that increasing the expression of pro-apoptotic genes in post-stroke patients promotes the activation of signaling pathways involved in brain plasticity processes. However, further research is needed to clarify this process. Full article

Cerebral artery fenestration is a rare variant of the vascular architecture, but its existence is well documented. The common site of fenestration is the vertebra-basilar artery and it may be found incidentally with subarachnoid hemorrhage. However, fenestration-related cerebral infarction is rare. We analyzed the clinical characteristics, stroke etiology, and image findings of fenestration-related cerebral infarction of the vertebrobasilar artery. We reviewed our hospital records and previously published reports to find cases of fenestration-related cerebral infarction. We excluded those with unknown clinical features or radiological findings. We retrieved 4 cases of fenestration-related infarction from our hospital, in which vascular change, headache, vertigo/dizziness, and dissection in stroke etiology were detected. In eight previously reported cases of fenestration-related infarction, similar vascular changes were noted, but they were mainly diagnosed as embolic stroke of undetermined source. However, based on the criteria for dissection in this study, dissection as the stroke etiology was suspected in the previously reported cases. Many hypotheses have been proposed for the development of dissection, thrombus, and aneurysms in fenestration. Although an embryological and morphological study is needed, clinicians must consider basilar artery fenestration-related infarction as a differential diagnosis and intensive non-invasive image study is recommended. Full article

Background: Meta-analysis has found that high baseline red blood cell distribution width (RDW) is associated with increased long-term mortality (mortality at one year or more) in ischemic stroke. The objectives of this study were to determine whether there is an association between RDW and 30-day mortality, and to explore whether RDW during the first week of ischemic stroke could be a 30-day mortality biomarker. Methods: We included patients with malignant middle cerebral artery infarction (MMCAI). RDW at days 1, 4, and 8 of MMCAI were determined. The end-point study was 30-day mortality. Results: We found that survivor (n = 37) in respect to non-survivor patients (n = 37) had lower RDW at days 1 (p < 0.001), 4 (p < 0.001), and 8 (p = 0.02). The area under curve (95% CI) for prediction of 30-day mortality by RDW at days 1, 4, and 8 of MMCAI were 0.80 (0.69–0.89; p < 0.001), 0.79 (0.66–0.89; p < 0.001), and 0.73 (0.58–0.84; p = 0.02). Regression analysis showed an association between RDW (odds ratio = 1.695; 95% CI = 1.230–2.335; p < 0.001) and 30-day mortality. Conclusions: The association between RDW and early mortality, and the potential role of RDW during the first week of MMCAI as a prognostic biomarker of early mortality were the main novelties of our study. Full article

The therapeutic benefits of repetitive transcranial magnetic stimulation (rTMS) combined with rehabilitation therapy on recovery after stroke have not been fully elucidated. This study aimed to explore the therapeutic effects of rTMS followed by aerobic exercise on neuroplasticity and recovery of motor function in a rat model of permanent middle cerebral artery occlusion (MCAO). Rats were randomized into sham operation (N = 10, sham op), MCAO (N = 10, control group), rTMS (N = 10, MCAO and rTMS therapy), and combination groups (N = 10, MCAO and combination therapy). High-frequency rTMS (10 Hz) was applied on the ipsilesional forepaw motor cortex, and aerobic exercise training on the rotarod was performed for two weeks. The rotarod and Garcia tests were conducted to evaluate changes in behavioral function. Motor evoked potentials (MEPs) were used to evaluate electrophysiological changes. Stroke severity was assessed using infarction volume measurement. Neuronal recovery was explored with western blot for brain-derived neurotrophic factor (BDNF) pathway proteins. Compared with control therapy, combination therapy was significantly more effective than rTMS therapy for improving function on the rotarod test (p = 0.08), Garcia test (p = 0.001), and MEP amplitude (p = 0.001) In conclusion, combination therapy may be a potential treatment to promote recovery of motor function and neuroplasticity in stroke patients. Full article

Background: The aim of this prospective, a three-year follow-up study, was to establish the role of high on-treatment platelet reactivity (HTPR) in predicting the recurrence of vascular events in patients after cerebrovascular incidents, particularly in the aspect of stroke etiology. Methods: The study included 101 subjects with non-embolic cerebral ischemia (69 patients with ischemic stroke and 32 patients with transient ischemic attack) treated with 150 mg of acetylsalicylic acid (aspirin) a day. The platelet reactivity was tested in the first 24 h after the onset of cerebral ischemia by impedance aggregometry. Recurrent vascular events, including recurrent ischemic stroke, transient ischemic attack, myocardial infarction, systemic embolism, or sudden death of vascular reason, were assessed 36 months after the onset of cerebral ischemia. Results: Recurrent vascular events occurred between 3 and 9 months after onset in 8.5% of all subjects; in the HTPR subgroup, recurrent vascular events occurred in 17.9%; in the normal on-treatment platelet reactivity (NTPR) subgroup, they occurred in 4.6%. We did not notice early or long-term recurrent events. Aspirin resistant subjects had a significantly higher risk of recurrent vascular events than did aspirin sensitive subjects (Odds ratio (OR) = 4.57, 95% Confidence interval (CI) 1.00–20.64; p = 0.0486). Cox proportional hazard models showed that large-vessel disease (Hazard ratio (HR) 12.04, 95% CI 2.43–59.72; p = 0.0023) and high on-treatment platelet reactivity (HR 4.28, 95% CI 1.02–17.93; p = 0.0465) were independent predictors of recurrent vascular events. Conclusion: Aspirin resistance in the acute phase of cerebral ischemia was associated with a higher risk of recurrent medium-term vascular events, coexisting with large-vessel etiology of stroke. Platelet function-guided personalized antiplatelet treatment should be considered for patients with recurrent strokes, especially when due to large-vessel disease. Full article

Objective: Caspase-cleaved cytokeratin (CCCK)-18 could appear in blood during apoptosis. In two different studies, on day 1 of cerebral infarction and at 72 h of cerebral infarction, respectively, higher circulating CCCK-18 levels were found in non-surviving than in surviving patients. The objective of this study was to analyze the ability of these levels to predict mortality at any time during the first week of cerebral infarction. Methods: Patients with malignant middle cerebral artery infarction (MMCAI) were included and the diagnosis criteria were the presence, observed in a computed tomography, of an acute cerebral infarction in at least 50% of this territory and midline shift, and an acute neurological deterioration with a Glasgow Coma Scale ≤ 8. Serum CCCK-18 levels at days 1, 4 and 8 of MMCAI were determined. Results: Serum concentrations of CCCK-18 at days 1, 4 and 8 of MMCAI were higher in non-surviving (n = 34) than in surviving patients (n = 34). Serum CCCK-18 concentrations at days 1, 4 and 8 of MMCAI had an area under curve (95% CI) used to predict a 30-day mortality of 0.83 (0.72 –0.91; p < 0.001), 0.78 (0.65–0.89; p < 0.001) and 0.82 (0.68–0.92; p < 0.001). Conclusions: The novel finding is that serum levels of CCCK-18 levels at any time after the first week of MMCAI could help predict 30-day mortality. Full article

Dural arteriovenous fistulas involving the cavernous sinus can lead to orbital pain, vision loss and, in the setting of associated cortical venous reflux, intracranial hemorrhage. The treatment of dural arteriovenous fistulas has primarily become the role of the endovascular surgeon. The venous anatomy surrounding the cavernous sinus and venous sinus thrombosis that is often associated with these fistulas contributes to the complexity of these interventions. The current report gives a detailed description of the alternate endovascular routes to the cavernous sinus based on a single center’s experience as well as a literature review supporting each approach. A comprehensive understanding of the anatomy and approaches to the cavernous sinus available to the endovascular surgeon is vital to the successful treatment of this condition. Full article

Background and Importance: Since Trousseau’s initial publication, the development of thromboembolic events related to malignancy has been well established. The pathophysiology of this is understood to be through activation of the coagulation cascade through neoplastic cells themselves or the therapy initiated (chemotherapy or surgery). To date, there have been a variety of studies, such as the OASIS-CANCER trial, which highlight the relationship of hypercoagulability to ischemic stroke. Despite these efforts, clear evidence is lacking for the utilization of antiplatelet or anticoagulation therapy in the secondary prevention of stroke following mechanical thrombectomy in patients with suspected or confirmed malignancy. Clinical Presentation: A 71-year-old female with a history of immune thrombocytopenia, diabetes mellitus, and hypertension who was undergoing an evaluation for a lung nodule, later determined to be adenocarcinoma of the lung, underwent three successful mechanical thrombectomies for acute ischemic stroke with large vessel occlusion over a one month period. This patient had improved National Institutes of Health Stroke Scale (NIHSS) scores following each of her thrombectomies. However, her history of immune thrombocytopenia and underlying malignancy complicated her discharge medication regimen following each of her thrombectomies and may have contributed to her repeat strokes. Conclusion: Clear guidance is lacking regarding the utilization of antiplatelet and anticoagulation therapy in patients with suspected or confirmed malignancy following mechanical thrombectomy. Review of the literature suggests that controlling a patient’s hypercoagulability may lead to improved clinical outcomes, but further clinical trials are warranted. Full article

Stroke is a neurologic disorder considered the first cause of disability worldwide due to motor, cognitive, and sensorial sequels. Balance dysfunctions in stroke survivors increase the risk of falls and physiotherapeutic rehabilitation is essential to reduce it. Virtual reality (VR) seems to be an alternative to conventional physiotherapy (CT), providing virtual environments and multisensorial inputs to train balance in stroke patients. The aim of this study was to assess if immersive VR treatment is more effective than CT to improve balance after stroke. This study got the approval from the Ethics Committee of the University of Almeria. Three chronic ischemic stroke patients were selected. One patient who received 25 sessions of immersive VR intervention for two months was compared with another patient who received equivalent CT and a third patient with no intervention. Balance, gait, risk of falling, and vestibular and visual implications in the equilibrium were assessed. After the interventions, the two patients receiving any of the treatments showed an improvement in balance compared to the untreated patient. In comparison to CT, our results suggest a higher effect of immersive VR in the improvement of balance and a reduction of falls risk due to the active upright work during the VR intervention. Full article

Dysphagia after stroke impacts quality of life and is a risk factor for respiratory infections. Patients frequently require prophylactic measures including nasogastric tube or percutaneous endoscopic gastrostomy. Until recently, therapy for dysphagia was limited to training with a speech and language specialist. Intraluminal pharyngeal electrical stimulation (PES) is a new technique that stimulates the pharyngeal sensory afferents to the higher swallowing center in cortex. The clinical trials published to date involved stimulation for 10 minutes over three days. We present a case of brainstem infarction with severe dysphagia in a 53-year-old woman with preserved cognitive functions. For airway protection, she had a surgical tracheotomy. The initial swallowing training achieved slight improvements, but stagnated after three months so PES was tried. Under good PES tube tolerance, a prolonged and repeated stimulation protocol was administered, with the main purpose of relieving her of the tracheal tube. Although the swallowing improved, she stayed tube-dependent with minimal attempts with puréed food during therapy, and could not be decannulated. Further studies are required to assess the value of this promising approach for the treatment of dysphagia. Full article