A Rare Case of Extensive Cerebral Venous Sinus Thrombosis Complicated by Heparin-Induced Thrombocytopenia.

Cerebral venous sinus thrombosis (CVST) is a rare but potentially life-threatening cause of stroke. Several risk factors have been identified including hypercoagulable state, malignancy, use of oral contraceptives, pregnancy, head injury, infection, and prothrombotic states such as heparin-induced thrombocytopenia (HIT). HIT is a prothrombotic state leading to thrombosis in several distinct locations including CVST requiring prompt discontinuation of heparin and initiation of nonheparin anticoagulation to prevent catastrophic consequences. Very rarely, HIT can complicate the ongoing CVST leading to worsening thrombosis and clinical deterioration. We here report an exceedingly rare case of CVST complicated by HIT in a 22-year-old female patient who showed remarkable clinical improvement after discontinuation of heparin and initiation of argatroban.

When does postural instability appear in monogenic parkinsonisms? An individual-patient meta-analysis.

BACKGROUND: Postural instability is a disease milestone signaling advanced disease. OBJECTIVES: To estimate the onset of postural instability in monogenic parkinsonisms. METHODS: We systematically reviewed studies (PubMed 1996-2017) in SNCA, PRKN, PINK1, DJ-1, LRRK2, ATP13A2, FBXO7, VPS35, DNAJC6, or SYNJ1-related monogenic parkinsonisms, with documented postural instability. Genes with ≥ 15 patients were included in an individual-patient meta-analysis and compared with a retrospectively collected sporadic Parkinson's disease cohort from our center. The primary outcome measure was the progression-free survival from postural instability using Kaplan-Meier survival curves. Cox proportional hazards analyses were summarized using hazards ratio (HR). RESULTS: Of 2085 eligible studies, 124 met full criteria (636 patients) for the systematic review, whereas a total of 871 subjects (270 from sporadic cohort, 601 monogenic parkinsonisms) were included in the individual-patient meta-analysis. Postural instability was reported in 80% of DJ-1, 40% of PRKN, 39% of PINK1, 34% of ATP13A2, 31% of LRRK2, and 29% of SNCA patients. Progression-free survival from postural instability at 10 years after disease onset was longest in ATP13A2 (97%) and shortest in SNCA (50%). Halfway between these two extremes were PRKN (88%), PINK1 (87%), and LRRK2 (81%), similar to sporadic Parkinson's disease (72%). Higher risk of postural instability was observed in SNCA (HR = 3.2, p = 0.007) and DJ-1 (HR = 3.96, p = 0.001) compared to sporadic Parkinson's disease. Young age at onset in PINK1 and female sex in LRRK2 were associated with a decreased risk of postural instability. CONCLUSIONS: Monogenic parkinsonisms exhibit differential timelines to postural instability, informing prognostic counseling and interpretation of future genotype-specific treatment trials.

RETRACTED ARTICLE: The Novel Effects of a Hydrolyzed Polysaccharide Dietary Supplement on Immune, Hepatic, and Renal Function in Adults with HIV in a Randomized, Double-Blind Placebo-Control Trial.

The primary objective of the study was to evaluate the effects of a hydrolyzed polysaccharide, rice bran arabinoxylan compound (RBAC), on immune, hepatic, and renal function in HIV + individuals. A six-month randomized double-blind placebo-controlled trial was utilized to conduct the intervention. Forty-seven HIV + participants on stable antiretroviral therapy were enrolled and randomly assigned to one of the two study conditions (n = 22 RBAC and n = 25 placebo) and consumed 3 gram/day of either compound for six months. Participants were assessed at baseline and 3 and 6 months follow-up for CD4+ and CD8+, liver enzymes, and kidney function. No side effects were reported, and liver and kidney markers nearly remained completely within normal limits. The percentage change in CD4+ was similar for the placebo (+2.2%) and RBAC (+3.1%) groups at 6 months follow-up. The percentage change in CD8+ count significantly decreased from baseline to 6 months in the RBAC group (-5.2%), whereas it increased in the placebo group (+57.8%; p = 0.04). The CD4+/CD8+ ratio improved clinically in the RBAC group from 0.95 (SD =0.62) at baseline to 1.07 (SD =0.11) at 6 months, whereas it declined in the placebo group from 0.96 (SD =0.80) at baseline to 0.72 (SD =0.59) at 6 months. Our results showed a statistically significant decrease in CD8+ count and a clinically significant increase in CD4+/CD8+ ratio for the RBAC group compared to the placebo group. Thus, the results of this study suggest that the immunomodulatory and antisenescent activities of RBAC are promising for the HIV population.

Cardiovascular, endothelial function, and immune markers in response to treatment with a polysaccharide in HIV+ adults in a randomized, double-blind placebo-controlled trial.

BACKGROUND AND AIM: Given the ongoing problems of hypertension and endothelial dysfunction in the HIV population, the primary objective of the study was to assess the cardiovascular, endothelial function, and immune markers in response to rice bran arabinoxylan compound (RBAC) treatment in a sample of HIV+ adults on antiretroviral therapy (ART). STUDY DESIGN: A randomized, double-blind placebo-controlled trial of 6 months was used to execute the study. MATERIALS AND METHODS: Forty-seven subjects were enrolled and randomly assigned to one of two study conditions (n=22 RBAC and n=25 placebo) for 6 months with assessments at baseline and 3 and 6 months. A multivariate repeated measures analysis of variance model was used to assess the differences between RBAC and placebo groups in cardiovascular (systolic blood pressure), endothelial function (skin blood flow in response to nitric oxide), and immune (CD4+ cell count) markers from baseline to 6 months. RESULTS: The effect of treatment (RBAC versus placebo) was significant (Wilks' λ=0.92, F[3, 102]=3.07, P=0.03). The effect of time was significant (Wilks' λ=0.10, F[2, 103]=474.6, P<0.001). The overall interaction between treatment and time was significant (Wilks' λ=0.92, F[2, 103]=4.58, P=0.01). Time contrasts showed that a difference in the overall dependent variable did not occur from baseline to 3 months (F[1, 104]=2.7, P=0.10), marginally occurred from baseline to 6 months (F[1, 104]=3.2, P=0.08), and was significant from 3 to 6 months (F[1, 104]=6.43, P=0.01). CONCLUSIONS: The overall significant interaction suggests varying responses in the dependent variables between RBAC and placebo over time, which is being driven by systolic blood pressure, as it decreased in the RBAC group, but increased in the placebo group. In addition, CD4+ manifested a non-significant increase from baseline to 3 months then decreased from 3 to 6 months in the RBAC group, whereas it decreased at 3 months followed by a slight increase at 6 months in the placebo group. Skin blood flow in response to nitric oxide improved non-significantly overall in both groups, but worsened from 3 to 6 months in the placebo group. Thus, RBAC treatment may contribute to modest short-term improvements in systolic blood pressure, endothelial function, and CD4+ cell count, which could help improve the overall health profile of HIV+ adults. RELEVANCE FOR PATIENTS: Persons with HIV on ART suffer disproportionately from hypertension and endothelial dysfunction compared to the non-infected population, and conventional medical therapy does not alleviate these issues. RBAC is a safe, low-risk alternative that may help to improve the overall quality of life of these patients through modest improvements in these biomarkers plus CD4+ cell count.

Thyrotoxicosis-Induced Cardiogenic Shock with Encephalopathy and Acute Respiratory Distress: A Case Report and Literature Review.

Thyrotoxicosis-induced cardiomyopathy and cardiogenic shock (CS) can lead to sudden mortality in adults. Hemodynamic instability and collapse occur due to functional alterations in both peripheral circulation and myocardium. Thyroid storm (TS) increases preload and decreases afterload along with an increase in cardiac contractility and heart rate leading to high output acute failure. We present a case of a 30-year-old female who presented with a complaint of watery diarrhea and dehydration for almost a week. At her visit to the emergency room, she was unresponsive with hemodynamic collapse leading to altered mental status and tachycardia. The computed tomography (CT) scan of head was non-contributory. The condition worsened with respiratory distress, and eventually, mechanical ventilation with intubation was completed. Further, laboratory workup showed acute thyrotoxicosis. The severe cardiomyopathy on echocardiography with compromised left ventricle function and diffuse pulmonary congestion led to acute respiratory distress syndrome (ARDS). The multi-organ failure, impending ARDS and CS with encephalopathy led to the sudden death of a patient within 24 hours of intensive care unit (ICU) stay before even extracorporeal membrane oxygenation (ECMO) could be started.

Corrigendum to "The Effect of a Hydrolyzed Polysaccharide Dietary Supplement on Biomarkers in Adults with Nonalcoholic Fatty Liver Disease".

[This corrects the article DOI: 10.1155/2018/1751583.].

Developmental vascular anomaly associated hemi facial spasms and botox injections therapy.

Hemifacial spasm (HFS) is characterized by involuntary synchronous contractions or spasms of one side of the face, usually beginning around the eye. They are typically brief, irregular clonic movements but are occasionally tonic. We present a case of a 41-year-old female who presented to the neurology clinic with complaints of recurrent right facial spasms. These involuntary spontaneous movements had affected her quality of life. The neuroimaging revealed the vascular malformation right cranial nerves (CN) VII/VIII complex. It was considered to be responsible for the patient's HFSs. The patient responded well symptomatically to the botox injections without any neurovascular decompression.

The Novel Effects of a Hydrolyzed Polysaccharide Dietary Supplement on Immune, Hepatic, and Renal Function in Adults with HIV in a Randomized, Double-Blind, Placebo-Control Trial.

The primary objective of the study was to evaluate the effects of a hydrolyzed polysaccharide, rice bran arabinoxylan compound (RBAC), on immune, hepatic, and renal function in HIV + individuals. A 6-month randomized double-blind placebo-controlled trial was utilized to conduct the intervention. Forty-seven HIV + individuals on stable antiretroviral therapy were enrolled and randomly assigned to one of the 2 study conditions (n = 22 RBAC and n = 25 placebo) and consumed 3 gram/day of either compound for 6 months. Participants were assessed at baseline and 3 and 6 months follow-up for CD4+ and CD8+, liver enzymes, and kidney function. No side effects were reported, and liver and kidney markers remained nearly completely within normal limits. The percentage change in CD4+ was similar for the placebo (+2.2%) and RBAC (+3.1%) groups at 6 months follow-up. The percentage change in CD8+ count significantly decreased from baseline to 6 months in the RBAC group (-5.2%), whereas it increased in the placebo group (+57.8%; p = 0.04). The CD4+/CD8+ ratio improved clinically in the RBAC group from 0.95 (SD = 0.62) at baseline to 1.07 (SD = 0.11) at 6 months, whereas it declined in the placebo group from 0.96 (SD = 0.80) at baseline to 0.72 (SD = 0.59) at 6 months. Our results showed a statistically significant decrease in CD8+ count and a clinically significant increase in CD4+/CD8+ ratio for the RBAC group compared to the placebo group. Thus, the results of this study suggest that the immunomodulatory and antisenescent activities of RBAC are promising for the HIV population.

The Effect of a Hydrolyzed Polysaccharide Dietary Supplement on Biomarkers in Adults with Nonalcoholic Fatty Liver Disease.

The primary objective of the study was to evaluate the effect of a hydrolyzed polysaccharide, Rice Bran Arabinoxylan Compound (RBAC), on biomarkers in adults with nonalcoholic fatty liver disease (NAFLD). A 90-day randomized double-blind placebo-controlled trial examined the effect of RBAC on complete blood count, liver enzymes, lipids, oxidative stress markers, cytokines, and growth factors. Twenty-three adults with NAFLD were enrolled and randomly assigned to one of the two study conditions (n = 12 RBAC and n = 11 placebo) and consumed 1 gram/day of either compound for 90 days. Subjects were assessed at baseline and 45 and 90 days. No adverse effects were reported. Alkaline phosphatase significantly decreased (-3.1%; SD = 19.9; F[1,19] = 5.1, p = 0.03) in the RBAC group compared to placebo. Percent monocytes (17.9%; SD = 18.3; F[1,19] = 5.9, p = 0.02) and percent eosinophils (30.6%; SD = 30.5; F[1,19] = 12.3, p < 0.01) increased in the RBAC group. IFN-γ (156%; SD = 131.8; F[1,19] = 4.2, p = 0.06) and IL-18 (29.1%; SD = 64; F[1,19] = 5.3, p = 0.03) increased in the RBAC group compared to placebo. Other improvements were noted for platelets, neutrophils, neutrophil-lymphocyte ratio, γ-glutamyl transferase, and 4-hydroxynonenal. RBAC had beneficial effects on several biomarkers that add to the known immunomodulatory activities of RBAC, which may be promising for people with NAFLD.

Deep brain stimulation in uncommon tremor disorders: indications, targets, and programming.

BACKGROUND: In uncommon tremor disorders, clinical efficacy and optimal anatomical targets for deep brain stimulation (DBS) remain inadequately studied and insufficiently quantified. METHODS: We performed a systematic review of PubMed.gov and ClinicalTrials.gov. Relevant articles were identified using the following keywords: "tremor", "Holmes tremor", "orthostatic tremor", "multiple sclerosis", "multiple sclerosis tremor", "neuropathy", "neuropathic tremor", "fragile X-associated tremor/ataxia syndrome", and "fragile X." RESULTS: We identified a total of 263 cases treated with DBS for uncommon tremor disorders. Of these, 44 had Holmes tremor (HT), 18 orthostatic tremor (OT), 177 multiple sclerosis (MS)-associated tremor, 14 neuropathy-associated tremor, and 10 fragile X-associated tremor/ataxia syndrome (FXTAS). DBS resulted in favorable, albeit partial, clinical improvements in HT cases receiving Vim-DBS alone or in combination with additional targets. A sustained improvement was reported in OT cases treated with bilateral Vim-DBS, while the two cases treated with unilateral Vim-DBS demonstrated only a transient effect. MS-associated tremor responded to dual-target Vim-/VO-DBS, but the inability to account for the progression of MS-associated disability impeded the assessment of its long-term clinical efficacy. Neuropathy-associated tremor substantially improved with Vim-DBS. In FXTAS patients, while Vim-DBS was effective in improving tremor, equivocal results were observed in those with ataxia. CONCLUSIONS: DBS of select targets may represent an effective therapeutic strategy for uncommon tremor disorders, although the level of evidence is currently in its incipient form and based on single cases or limited case series. An international registry is, therefore, warranted to clarify selection criteria, long-term results, and optimal surgical targets.

Acute Confusional Migraine: Distinct Clinical Entity or Spectrum of Migraine Biology?

The goal of this review is to explore the literature reports of acute confusional migraine (ACM) including patient characteristics, migraine symptomatology, and proposed diagnostic criteria. A literature review was conducted using PubMed, Scopus and Web of Science using the terms "confusional migraine" and "confusional state in migraine". All the relevant articles from 1970 to 2016 were included. A total of 120 patients were found in the literature. Most of the cases were seen in the pediatric population with a slight male predominance. Personal or family history of migraine was common. Most patients had a headache prior to the confusional state. In addition to confusion and agitation, some developed visual (32.5%) and/or sensory symptoms (19%) and/or speech problems (39%) either prior to or during the confusional state. Data on treatment outcomes is lacking. Patients with most common forms of migraine report attention and cognitive disturbances but awareness remains intact as opposed to patients with ACM. ACM is a distinct entity and should be included as part of the appendix of International Classification of Headache Disoders-3 beta version (ICHD-3ß) criteria. Prospective studies are needed to further study this disorder and its association with other migraine forms.

Intravenous infusion of magnesium sulfate is not associated with cardiovascular, liver, kidney, and metabolic toxicity in adults.

BACKGROUND: Magnesium (Mg) deficiency contributes to the pathophysiology of numerous diseases. The therapeutic use of Mg has steadily increased over time. The increased in-hospital use of intravenous (IV) magnesium sulfate (MgSO4) warrants more extensive investigation regarding the safety of the therapy. The aim of this study was to determine the safety of IV MgSO4 infusion on cardiovascular, liver, kidney, and metabolic markers in adults. METHODS: Twelve volunteers were randomized to one of two cross-over conditions: (a) IV infusion of MgSO4 in 5% dextrose followed by IV infusion of 5% dextrose 1 week later or (b) IV infusion of 5% dextrose followed by IV infusion of MgSO4 in 5% dextrose 1 week later. An electrocardiogram was recorded continuously during the infusions. Blood was drawn pre- and post-infusion for blood count (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides). Results: Serum Mg increased from pre- to post-infusion in the MgSO4 + 5% dextrose group (p < 0.0001). The QRS interval length increased from pre- to post-infusion in the MgSO4 + 5% dextrose group (p < 0.04). Additionally, serum glucose concentration increased in the MgSO4 + 5% dextrose group (p = 0.04). These significant findings were modeled with gender and age as covariates. No other significant differences were found. CONCLUSIONS: The administration of IV infusion of MgSO4 (4 g/100 mL) in 5% dextrose over a 4-hour treatment period poses no significant deleterious effects on cardiovascular, liver, kidney, or metabolic function. RELEVANCE FOR PATIENTS: IV infusion of MgSO4 may be used for certain treatment indications without significant concern for systemic or organ toxicity.

Anti-cancer effects of aloe-emodin: a systematic review.

BACKGROUND: Anthraquinones are a possible treatment option for oncological patients due to their anti-cancer properties. Cancer patients often exhaust a plethora of resources that ultimately fail to provide fully curative measures. Alternative treatments are subsequently sought in the hope of finding a therapeutic remedy. Po¬tential regimens include aloe-emodin and its related derivatives. This review therefore summarizes the effects of aloe-emodin and other aloe components in light of their anti-proliferative and anti-carcinogenic properties. METHODS: A systematic search was performed in PubMed for aloe-emodin and cancer in humans. Sixty abstracts of in vitrostudies were selected and reviewed with subsequent screening of the full text. Thirty-eight articles were summarized. RESULTS: Aloe-emodin possesses multiple anti-proliferative and anti-carcinogenic properties in a host of human cancer cell lines, with often multiple vital pathways affected by the same molecule. The most notable effects include inhibition of cell proliferation, migration, and invasion; cycle arrest; induction of cell death; mitochondrial membrane and redox perturbations; and modulation of immune signaling. The effects of aloe-emodin are not ubiquitous across all cell lines but depend on cell type. CONCLUSIONS: On the basis of this systematic review, the multiple consistent effects of aloe-emodin in hu¬man-derived cancer cell lines suggest that aloe-emodin is a potential anti-cancer agent that acts on cancer cells in a pleiotropic manner. RELEVANCE FOR PATIENTS: Cancer patients often utilize alternative therapies as a result of suboptimal efficacy of conventional treatments. Aloe-emodin might become a therapeutic option for cancer patients if the basic research is confirmed in clinical trials.

New method of sudomotor function measurement to detect microvascular disease and sweat gland nerve or unmyelinated C fiber dysfunction in adults with retinopathy.

BACKGROUND: Diabetes-associated microvascular complications such as retinopathy and neuropathy often lead to end-organ and tissue damage. Impaired skin microcirculation often precedes the detection of other advanced diabetic complications. The ANS-1 system contains a redesigned sympathetic skin response (ANS-1 SSR) device that measures sudomotor function, a photoplethysmography sensor, and a blood pressure device to comprehensively assess cardiac autonomic neuropathy and endothelial dysfunction. The purpose of this study was to determine the relationships between the ANS-1 SSR amplitude measured at the: (a) negative electrode (Nitric Oxide [NO] Sweat Peak) with microvascular diseases and associated vascular blood markers and (b) positive electrode (iSweat Peak) with C fiber function. METHODS: All participants (healthy controls n = 50 and retinopathy patients n = 50) completed the ANS-1 system evaluation and a basic sociodemographic and medical history questionnaire, including a quality of life measure (SF-36). A small sample of blood was drawn to determine levels of homocysteine, blood urea nitrogen (BUN), C-reactive protein (CRP), and fibrinogen. Symptoms of peripheral foot neuropathy were assessed with a scale from 1 (none) to 10 (the worst). We used Spearman rank correlations, independent samples t-tests, and receiver operating characteristic curves to determine the specificity and sensitivity of the NO Sweat Peak as a potential screening marker of retinopathy. RESULTS: The ANS-1 System Cardiometabolic Risk Score and all indicators of quality of life on the SF-36, other than Emotional Role Functioning, were significantly worse in the retinopathy patients. The sudomotor response marker NO Sweat Peak had a sensitivity of 88% and a specificity of 68% (Area Under the Curve = 0.81, p < 0.0001) to detect retinopathy. The NO Sweat Peak response marker inversely correlated with BUN (ρ = -0.41, p < 0.0001), homocysteine (ρ = -0.44, p < 0.0001), fibrinogen (ρ = -0.41, p < 0.0001), the Cardiac Autonomic Neuropathy score (ρ = -0.68, p < 0.0001), and the heart rate variability Total Power (ρ = -0.57, p < 0.0001), and it positively correlated with the Photoplethysmography Index (PTGi; ρ = 0.53 p < 0.0001). The ANS-1 system sudomotor response marker iSweat Peak inversely correlated with the severity of symptoms on the peripheral neuropathy scale (ρ = -0.56, p < 0.0001). CONCLUSION: The results of the study show that this new method of measuring sympathetic skin response should be useful for detecting the earliest manifestations of microvascular disease and symptoms of C fiber dysfunction.

Double-blind, randomized crossover study of intravenous infusion of magnesium sulfate versus 5% dextrose on depressive symptoms in adults with treatment-resistant depression.

AIM: Treatment-resistant depression patients are more likely to suffer from comorbid physical and mental disorders, experience marked and protracted functional impairment, and incur higher health-care costs than non-affected individuals. Magnesium sulfate is a treatment option that may offer great potential for patients with treatment-resistant depression based on prior work in animals and humans. METHODS: Twelve subjects with mild or moderate treatment-resistant depression were randomized into a double-blind crossover trial to receive an infusion of 4 g of magnesium sulfate in 5% dextrose or placebo infusion of 5% dextrose with a 5-day washout in between the 8-day intervention period. Subjects were assessed before and after the intervention for serum and urine magnesium, lipid panel, the Hamilton Rating Scale for Depression, and the Patient Health Questionnaire-9. RESULTS: We found a difference in serum magnesium from day 2 to 8 (pre-infusion) (P < 0.002) and from baseline to day 8 (P < 0.02). No changes were noted on the Hamilton Rating Scale for Depression or the Patient Health Questionnaire-9 24 h post-treatment, but as serum magnesium increased from baseline to day 7, the Patient Health Questionnaire-9 decreased from baseline to day 7 (P = 0.02). CONCLUSION: Magnesium sulfate did not significantly affect depression 24 h post-infusion, but other results were consistent with the literature. The association between changes in serum magnesium and the Patient Health Questionnaire-9 supports the idea that magnesium sulfate may be used to address treatment-resistant depression, an ongoing medical challenge.