Fabrication of Shape Memory Polymer Endovascular Thrombectomy Device for Treating Ischemic Stroke.

Stroke is the second result for death and ischemic stroke constitutes most of all stroke cases. Ischemic stroke takes place when blood clot or embolus blocks cerebral vessel and interrupts blood flow, which often leads to brain damage, permanent disability, or death. There is a 4.5-h (golden hour) treatment window to restore blood flow prior to permanent neurological impairment results. Current stroke treatments consist mechanical system or thrombolytic drug therapy to disrupt or dissolve thrombus. Promising method for stroke treatment is mechanical retrieving of thrombi employing device deployed endovascularly. Advent of smart materials has led to research fabrication of several minimally invasive endovascular devices that take advantage of new materials capabilities. One of these capabilities is shape memory, is capability of material to store temporary form, then activate to primary shape as subjected to stimuli. Shape memory polymers (SMPs) are employed as good materials for thrombectomy device fabrication. Therefore, current review presents thrombectomy device development and fabrication with SMPs. Design, performance, limitations, and in vitro or in vivo clinical results of SMP-based thrombectomy devices are identified. Review also sheds light on SMP's future outlook and recommendations for thrombectomy device application, opening a new era for advanced materials in materials science.

Single Component Polymers, Polymer Blends, and Polymer Composites for Interventional Endovascular Embolization of Intracranial Aneurysms.

Intracranial aneurysm is the abnormal focal dilation in brain arteries. When untreated, it can enlarge to rupture points and account for subarachnoid hemorrhage cases. Intracranial aneurysms can be treated by blocking the flow of blood to the aneurysm sac with clipping of the aneurysm neck or endovascular embolization with embolics to promote the formation of the thrombus. Coils or an embolic device are inserted endovascularly into the aneurysm via a micro-catheter to fill the aneurysm. Many embolization materials have been developed. An embolization coil made of soft and thin platinum wire called the "Guglielmi detachable coil" (GDC) enables safer treatment for brain aneurysms. However, patients may experience aneurysm recurrence because of incomplete coil filling or compaction over time. Unsatisfactory recanalization rates and incomplete occlusion are the drawbacks of endovascular embolization. So, the fabrication of new medical devices with less invasive surgical techniques is mandatory to enhance the long-term therapeutic performance of existing endovascular procedures. For this aim, the current article reviews polymeric materials including blends and composites employed for embolization of intracranial aneurysms. Polymeric materials used in embolic agents, their advantages and challenges, results of the strategies used to overcome treatment, and results of clinical experiences are summarized and discussed.

Differentiation of relapsing-remitting and secondary progressive multiple sclerosis: a magnetic resonance spectroscopy study based on machine learning.

INTRODUCTION: Magnetic resonance imaging (MRI) is the most important tool for diagnosis and follow-up in multiple sclerosis (MS). The discrimination of relapsing-remitting MS (RRMS) from secondary progressive MS (SPMS) is clinically difficult, and developing the proposal presented in this study would contribute to the process. OBJECTIVE: This study aimed to ensure the automatic classification of healthy controls, RRMS, and SPMS by using MR spectroscopy and machine learning methods. METHODS: MR spectroscopy (MRS) was performed on a total of 91 participants, distributed into healthy controls (n=30), RRMS (n=36), and SPMS (n=25). Firstly, MRS metabolites were identified using signal processing techniques. Secondly, feature extraction was performed based on MRS Spectra. N-acetylaspartate (NAA) was the most significant metabolite in differentiating MS types. Lastly, binary classifications (healthy controls-RRMS and RRMS-SPMS) were carried out according to features obtained by the Support Vector Machine algorithm. RESULTS: RRMS cases were differentiated from healthy controls with 85% accuracy, 90.91% sensitivity, and 77.78% specificity. RRMS and SPMS were classified with 83.33% accuracy, 81.81% sensitivity, and 85.71% specificity. CONCLUSIONS: A combined analysis of MRS and computer-aided diagnosis may be useful as a complementary imaging technique to determine MS types.

Diffuse microvascular dysfunction and loss of white matter integrity predict poor outcomes in patients with acute ischemic stroke.

We sought to investigate the relationship between blood-brain barrier (BBB) permeability and microstructural white matter integrity, and their potential impact on long-term functional outcomes in patients with acute ischemic stroke (AIS). We studied 184 AIS subjects with perfusion-weighted MRI (PWI) performed <9 h from last known well time. White matter hyperintensity (WMH), acute infarct, and PWI-derived mean transit time lesion volumes were calculated. Mean BBB leakage rates (K2 coefficient) and mean diffusivity values were measured in contralesional normal-appearing white matter (NAWM). Plasma matrix metalloproteinase-2 (MMP-2) levels were studied at baseline and 48 h. Admission stroke severity was evaluated using the NIH Stroke Scale (NIHSS). Modified Rankin Scale (mRS) was obtained at 90-days post-stroke. We found that higher mean K2 and diffusivity values correlated with age, elevated baseline MMP-2 levels, greater NIHSS and worse 90-day mRS (all p < 0.05). In multivariable analysis, WMH volume was associated with mean K2 ( p = 0.0007) and diffusivity ( p = 0.006) values in contralesional NAWM. In summary, WMH severity measured on brain MRI of AIS patients is associated with metrics of increased BBB permeability and abnormal white matter microstructural integrity. In future studies, these MRI markers of diffuse cerebral microvascular dysfunction may improve prediction of cerebral tissue infarction and functional post-stroke outcomes.

Structural Integrity of Normal Appearing White Matter and Sex-Specific Outcomes After Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Women have worse poststroke outcomes than men. We evaluated sex-specific clinical and neuroimaging characteristics of white matter in association with functional recovery after acute ischemic stroke. METHODS: We performed a retrospective analysis of acute ischemic stroke patients with admission brain MRI and 3- to 6-month modified Rankin Scale score. White matter hyperintensity and acute infarct volume were quantified on fluid-attenuated inversion recovery and diffusion tensor imaging MRI, respectively. Diffusivity anisotropy metrics were calculated in normal appearing white matter contralateral to the acute ischemia. RESULTS: Among 319 patients with acute ischemic stroke, women were older (68.0 versus 62.7 years; P=0.004), had increased incidence of atrial fibrillation (21.4% versus 12.2%; P=0.04), and lower rate of tobacco use (21.1% versus 35.9%; P=0.03). There was no sex-specific difference in white matter hyperintensity volume, acute infarct volume, National Institutes of Health Stroke Scale, prestroke modified Rankin Scale score, or normal appearing white matter diffusivity anisotropy metrics. However, women were less likely to have an excellent outcome (modified Rankin Scale score <2: 49.6% versus 67.0%; P=0.005). In logistic regression analysis, female sex and the interaction of sex with fractional anisotropy, radial diffusivity, and axial diffusivity were independent predictors of functional outcome. CONCLUSIONS: Female sex is associated with decreased likelihood of excellent outcome after acute ischemic stroke. The correlation between markers of white matter integrity and functional outcomes in women, but not men, suggests a potential sex-specific mechanism.

Integrity of normal-appearing white matter and functional outcomes after acute ischemic stroke.

OBJECTIVE: To characterize the effect of white matter microstructural integrity on cerebral tissue and long-term functional outcomes after acute ischemic stroke (AIS). METHODS: Consecutive AIS patients with brain MRI acquired within 48 hours of symptom onset and 90-day modified Rankin Scale (mRS) score were included. Acute infarct volume on diffusion-weighted imaging (DWIv) and white matter hyperintensity volume (WMHv) on T2 fluid-attenuated inversion recovery MRI were measured. Median fractional anisotropy (FA), mean diffusivity, radial diffusivity, and axial diffusivity values were calculated within normal-appearing white matter (NAWM) in the hemisphere contralateral to the acute lesion. Regression models were used to assess the association between diffusivity metrics and acute cerebral tissue and long-term functional outcomes in AIS. Level of significance was set at p < 0.05 for all analyses. RESULTS: Among 305 AIS patients with DWIv and mRS score, mean age was 64.4 ± 15.9 years, and 183 participants (60%) were male. Median NIH Stroke Scale (NIHSS) score was 3 (interquartile range [IQR] 1-8), and median normalized WMHv was 6.19 cm3 (IQR 3.0-12.6 cm3). Admission stroke severity (ß = 0.16, p < 0.0001) and small vessel stroke subtype (ß = -1.53, p < 0.0001), but not diffusivity metrics, were independently associated with DWIv. However, median FA in contralesional NAWM was independently associated with mRS score (ß = -9.74, p = 0.02), along with age, female sex, NIHSS score, and DWIv. CONCLUSIONS: FA decrease in NAWM contralateral to the acute infarct is associated with worse mRS category at 90 days after stroke. These data suggest that white matter integrity may contribute to functional recovery after stroke.

Higher minor hemoglobin A2 levels in multiple sclerosis patients correlate with lesser disease severity.

OBJECTIVE: To define whether minor adult hemoglobin A2 (HbA2, α2δ2) exerts any protective activity in multiple sclerosis (MS). METHODS: HbA2 levels were measured in 146 MS patients with high performance liquid chromatography and association with MS Severity Scores (MSSS) were determined. HbA2 associations with blood count parameters were also studied using blood counts evaluated on the same day of high performance liquid chromatography sampling. Routine biochemical parameters were also determined to rule out elusively influential factors, such as anemia and thyroid disorders. RESULTS: HbA2 levels negatively correlated with MSSS (Spearman correlation, R: -0.186, P=0.025). Exclusion of confounding factors with a generalized linear model revealed an even stronger negative correlation between HbA2 and MSSS (P<0.001). HbA2 positively correlated with red blood cells (RBCs) (R=0.350, P<0.001) and in turn, RBCs negatively correlated with MSSS (R=-0.180, P=0.031). Average HbA2 levels were highest among patients treated with interferon ß1a. CONCLUSION: RBC fragility is increased in MS, and recent data suggest that circulating free Hb contributes to neural injury in MS. HbA2 and its oxidative denaturation product hemichrome A2 enhance RBC membrane stability to a greater extent than do major HbA or hemichrome A. Reductions in ischemic cerebrovascular vascular events are reported in ß-thalassemia carriers and HbA2 levels are considerably higher in this population. Episodic declines of cerebral blood flow were shown in bipolar disorder, and we have recently shown a protective role of HbA2 against postpartum episodes in females with bipolar disorder. HbA2's erythroprotective functions may reduce free Hb and long-term neural injury in MS.

FLAIR Vascular Hyperintensity is a Surrogate of Collateral Flow and Leukoaraiosis in Patients With Acute Stroke Due to Proximal Artery Occlusion.

BACKGROUND: Fluid attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH) is a novel radiographic marker detected in acute ischemic stroke (AIS) patients, which is linked to slow blood flow and potentially salvageable brain tissue. Poor leptomeningeal collateral status in AIS patients with proximal artery occlusion (PAO) is associated with larger final infarct and worse clinical outcomes, which are also affected by severity of white matter hyperintensity (WMH). We sought to evaluate FVH utility as a marker of acute collateral vessel status and its association with WMH burden in AIS patients. METHODS: Consecutive AIS patients with PAO on baseline CT angiography (CTA) were retrospectively selected from a prospectively derived database. FVH was graded by its location, degree, and score on admission MRI obtained immediately after intravenous tissue plasminogen activator administration. Leptomeningeal collateral flow grade was ranked on admission CTA. WMH volume (WMHV) was assessed using a validated volumetric protocol. Relationship between FVH, collateral flow grade, and WMHV were analyzed. RESULTS: Among 39 patients (mean age 70.5 ± 12.7 years; 56% women, mean National Institutes of Health Stroke Scale score 17.2 (± 4.4)), median WMHV was 6.0 cm(3). FVH score and collateral flow grade were significantly correlated (Spearman's ρ = .41, P = .009). In a univariate regression model, FVH degree was inversely associated with WMHV (ß = -.33, P = .04). CONCLUSIONS: FVH score detected on acute MRI can be used as a surrogate of collateral flow grade in AIS patients. FVH degree is inversely associated with WMHV, possibly signifying diffuse disease of cerebral vasculature in patients with severe leukoaraiosis.

Ulnar nerve entrapment neuropathy at the elbow: relationship between the electrophysiological findings and neuropathic pain.

[Purpose] Ulnar nerve neuropathies are the second most commonly seen entrapment neuropathies of the upper extremities after carpal tunnel syndrome. In this study, we aimed to evaluate pain among ulnar neuropathy patients by the Leeds assessment of neuropathic symptoms and signs pain scale and determine if it correlated with the severity of electrophysiologicalfindings. [Subjects and Methods] We studied 34 patients with clinical and electrophysiological ulnar nerve neuropathies at the elbow. After diagnosis of ulnar neuropathy at the elbow, all patients underwent the Turkish version of the Leeds assessment of neuropathic symptoms and signs pain scale. [Results] The ulnar entrapment neuropathy at the elbow was classified as class-2, class-3, class-4, and class-5 (Padua Distal Ulnar Neuropathy classification) for 15, 14, 4, and 1 patient, respectively. No patient included in class-1 was detected. According to Leeds assessment of neuropathic symptoms and signs pain scale, 24 patients scored under 12 points. The number of patients who achieved more than 12 points was 10. Groups were compared by using the χ(2) test, and no difference was detected. There was no correlation between the Leeds assessment of neuropathic symptoms and signs pain scale and electromyographic findings. [Conclusion] We found that the severity of electrophysiologic findings of ulnar nerve entrapment at the elbow did not differ between neuropathic and non-neuropathic groups as assessed by the Leeds assessment of neuropathic symptoms and signs pain scale.

Endovascular therapy of acute ischaemic stroke by interventional cardiologists: single-centre experience from Turkey.

AIMS: We report our single-centre experience with the Solitaire AB self-expanding retrievable stent system in patients with acute ischaemic stroke. METHODS AND RESULTS: Demographic, clinical, and angiographic findings of thirty-eight consecutive patients with acute ischaemic stroke who underwent mechanical thrombectomy were evaluated retrospectively. The mean initial National Institutes of Health Stroke Scale (NIHSS) score was 17.8±4.6. Nearly half of the patients had a middle cerebral artery (MCA) occlusion (45%). Both internal carotid artery and MCA occlusions were detected in five patients. Successful revascularisation (Thrombolysis in Cerebral Infarction [TICI] 2b and 3) was achieved in 34 of 38 (89%) patients; a TICI 3 state was observed in 24 (63%) patients. Almost three quarters of the patients (74.3%) improved by >5 points on the NIHSS at discharge, and 57.9% showed a modified Rankin Scale (mRS) score of ≤2 at 90 days. CONCLUSIONS: This single-centre experience with mechanical thrombectomy devices demonstrated that the procedure could be performed safely with high success rates by experienced interventional cardiologists in suitably equipped cathlabs.

Association between smoking and cognitive impairment in multiple sclerosis.

PURPOSE: Although smoking is known to cause various symptoms in multiple sclerosis (MS) patients, there have been no reports regarding the relationship between smoking and cognitive impairment in MS. Studying the effects of cigarette smoking in MS patients is imperative as there is a high prevalence of cognitive impairment in MS patients. In this study we examined the potentially deleterious effects of heavy smoking on mentation of patients with MS. PATIENTS AND METHODS: MS patients receiving care at the Neurology Clinic at Bezmialem Vakif University, between the ages of 18-65 years who have at least graduated elementary school were included in the study. The Brief Repeatable Battery of Neuropsychological Tests (BRB-N) is a commonly used method to assess cognitive function in MS patients and was utilized in our study. Patients that smoked for at least 10 pack-years were considered heavy smokers. RESULTS: ALL THE PATIENTS WERE STRATIFIED INTO TWO GROUPS: heavy smokers (n=20) and nonsmokers (n=24). For heavy smokers, their cognitive functioning was more impaired than that of nonsmokers (P=0.04, χ (2)=4.227). For patients with cognitive impairment, 78.9% of the Paced Auditory Serial Addition Test and 63.2% of the Symbol Digit Modalities Test scores were found to be lower. CONCLUSION: Previous reports have suggested that smoking increases the frequency of relapse among individuals with relapsing-remitting MS and accelerates disease progression in patients with progressive MS. According to the results of our study, heavy smokers had increased cognitive impairment when compared to nonsmokers. Extensive studies are necessary to further elucidate the relationship between smoking and cognitive impairment in MS patients.

Multiple sclerosis presents with psychotic symptoms and coexists with hypertrophic cardiomyopathy.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. Psychiatric symptoms are not infrequent during MS, yet onset of MS with psychosis is rarely encountered. A 27-year-old Caucasian male was admitted due to numbness in his right arm and difficulty in walking. His clinical and laboratorial exams lead to the MS diagnosis. Nine months earlier, he also developed psychotic disorder, not otherwise specified (PD-NOS). His sudden onset of PD-NOS, his rapid and complete response to antipsychotics, and a relatively short interval between psychiatric and neurological signs indicate a high likelihood that PD-NOS was a manifestation of underlying MS. He also suffers from hypertrophic obstructive cardiomyopathy (HOCM). The patient's neurological complaints were recovered with methylprednisolone (1 g/day, i.v.) given for five days. Glatiramer acetate (1 × 1 tb.s.c.) was prescribed for consolidation and, after nine months of his admission, the patient fully recovered from neurological and psychiatric complaints. Interestingly, very recent studies indicate specific alpha-actinin antibodies in MS and alpha-actinin mutations cause HOCM. Thus, concurrence of MS with HOCM can be even a new syndrome, if further genetic studies prove.

Influences of socio-demographics on depression and anxiety in patients with complex partial and tonic-clonic seizures.

AIM: To compare the levels of anxiety and depression in patients with milder epilepsy characterized by complex partial seizures versus more severe epilepsy comprised of generalized tonic-clonic seizures. METHODS: A total of 60 patients aged between 18 and 80 admitted with seizures were prospectively enrolled. Patients with history of any psychiatric disorders were excluded. Imaging studies were performed to rule out any organic brain lesions that might be responsible for seizures. Patients were divided into two groups according to the type of the seizures: group 1 (n=30) with complex partial seizures without focal and generalized tonic-clonic seizures, and group 2 (n=30) with generalized tonic-clonic seizures. Structured Clinical Interviews for DSM-IV Axis I disorders (SCID-I/ NP) were performed in all patients. Additionally, Hamilton Depression Rating Scale (HAM-D) and Hamilton Anxiety Rating Scale (HAM-A) were administered to the patients where appropriate. All the parameters were statistically compared. RESULTS: Mean age of the patients was 29.66±10.33 years, 38 (63.3%) were females. Both groups were comparable in terms of age, educational status, marital status, occupational status, age of epilepsy onset, and Hamilton scores. Mean HAM-D score (2.11) and mean HAM-A total score (2.31) of the patients employed during the last 6 months were different than the mean HAM-D score (4.76) and mean HAM-A total score (5.66) of the patients unemployed during last 6 months. Patients with no reliable employment within the past 6 months demonstrated significantly higher depression and anxiety scores (p less than 0.05). CONCLUSION: This study clearly demonstrated a relationship among the features of epileptics and levels of depression and anxiety. There was a relationship between employment and depressive and anxiety symptoms of epileptic patients. Also, unemployment may be indicative for treatment compliance.

A 17-year-old female with systemic lupus presents with complex movement disorder: possible relationship with antiribosomal p antibodies.

Complex movement disorder is a relatively rare presentation of neurolupus. Antiphospholipid antibodies are associated with movement disorders likely via aberrant neuronal stimulation. Antiribosomal P antibodies have been previously associated with neuropsychiatric disorders but their correlation with movement disorder was not previously established. Our case report involves a 17-year-old Caucasian female patient positive for only antiribosomal P antibody and lupus anticoagulant who presented with a sudden onset of complex movement disorder. After complete cessation of physical signs with olanzapine, anticardiolipin and anti- ß 2 glycoprotein I antibodies became positive which indicates a likely discordance between movement disorder and antiphospholipid antibodies. This also indicates a potential causal role of antiribosomal P antibodies in inducing movement disorder.