Shaokuan Fang

Magnetic resonance diffusion tensor imaging for occult lesion detection in multiple sclerosis

It remains challenging to locate occult lesions in patients with multiple sclerosis (MS). Diffusion tensor imaging (DTI) has been demonstrated to have the potential to identify occult changes in MS lesions. The present study used 3.0T magnetic resonance DTI to investigate the characteristics of different stages of MS lesions. DTI parameters, fractional anisotropy (FA), mean diffusivity (MD), λ// and λ┴ values of lesions were compared at the different stages of 10 patients with MS with 10 normal controls. The results demonstrated that FA and λ// values of MS silent and subacute lesions are decreased and MD and λ┴ values are increased, as compared with those of normal appearing white matter (NAWM) and normal controls. NAWM FA values were lower, and MD, λ//, and λ┴ values were higher than those of normal controls. It was also indicated that MS lesions had reduced color signals compared with the controls, and the lesion area appeared larger using DTI as compared with diffusion-weighted imaging. Furthermore, fiber abnormalities were detected in MS lesions using DTT, with fewer fibers connected to the lesion side, as compared with the contralateral side. FA, MD, λ// and λ┴ values in the thalamus were increased, as compared with those of normal controls (P<0.05); whereas MD, λ// and λ┴ values were significantly increased and FA values significantly decreased in the caudate nucleus and deep brain gray matter (DBGM) of patients with MS, as compared with the controls (P<0.05). λ// and λ┴ values were also significantly increased in the DBGM of patients with MS as compared with normal controls (P<0.05). The present findings demonstrate that DTI may be useful in the characterization of MS lesions.

Short-term efficacy and tolerability of venlafaxine extended release in adults with generalized anxiety disorder without depression: A meta-analysis

Background Although efficacy of venlafaxine extended release (XR) for generalized anxiety disorder (GAD) has been reported in previous analyses in 2002 and 2004, the sample size was rather small and estimate of safety or tolerability was not clear. The present analysis had the advantage of large sample size and provided evidence for tolerability. Methods Literature databases were searched, including Pubmed, Embase, Cochrane Central Register of Controlled Trials, Web of science and clinical trials. 10 eligible articles were finally selected and data was extracted and logged into the Review Manager 5.3 by two independent authors. The risk of bias was evaluated by the Cochrane Collaboration’s Risk of Bias Tool and the stability of the results was assessed by sensitivity analysis. The publication bias was assessed by funnel plot and Egger’s/Begg’s test using Stata Version 12.0 software. Results In the current meta-analysis, 10 articles (14 studies) satisfying the inclusion criteria were analyzed. As efficacy outcomes, our findings indicated venlafaxine XR was significantly more effective than placebo according to mean change of the Hamilton Rating Scale for Anxiety total scores [mean difference = 3.31, 95% confidence interval(CI) 1.44–5.18, P = 0.0005], response [odds ratio(OR) = 1.83, 95%CI 1.58–2.12, P<0.00001], and remission (OR = 2.55, 95%CI 1.36–4.78, P = 0.003). In terms of tolerability, the most frequently reported treatment-emergent adverse events were nausea, dry mouth, dizziness, insomnia, somnolence, and headache. In addition, discontinuation due to all-cause (OR = 1.17, 95%CI 0.92–1.49, P = 0.19) was not significantly different between the two groups, whereas discontinuation due to adverse events was statistically higher in the venlafaxine XR group compared with the placebo treatment (OR = 2.80, 95%CI 2.21–3.54, P<0.00001) and discontinuation due to inefficacy was lower in venlafaxine than placebo treatment (OR = 0.26, 95%CI 0.17–0.40, P<0.00001). There was no significant publication bias and sensitivity analysis showed that our analysis exhibited high stability. Conclusion We concluded that venlafaxine XR (75–225 mg/day) is an effective and well-tolerated pharmacological treatment option for adult patients with GAD.

A case of bacterial meningitis complicated by venous sinus thrombosis.

As a result of preventive measures, the annual incidence of bacterial meningitis has decreased in the past two decades [1]. Predisposing risk factors include parameningeal infection; previous head trauma; sinus, ear, or neurosurgical procedure; malignancy, alcoholism and diabetes mellitus [2]. The morbidity and mortality rates associated with bacterial meningitis remain high with no significant change in outcome despite advances in antimicrobial therapy and improvements in intensive care [2, 3]. Although vascular complications are common in bacterial meningitis, venous sinus thrombosis account for simply a small portion. Unlike the complications of increased intracranial pressure, hydrocephalus, cranial nerve palsies, and vascular complications are often irreversible and may be associated with unfavorable outcomes [3, 4]. Mortality is high, whereas those who survive are often left with severe neurologic sequelae [4]. Herein we report a case of bacterial meningitis complicated by venous sinus thrombosis.

Rare cerebellar lesions in a carbon monoxide poisoning case.

Carbon monoxide (CO) is a highly toxic gas produced by the incomplete combustion of carbon-containing compounds. The brain is one of the most severely affected organs in CO poisoning. The use of brain imaging is increasingly being used in the acute phase of CO poisoning to establish a diagnosis. Symmetrical globus pallidus and white matter changes are well-known findings in studies of CO poisoning. Damage to cerebellum in patients with CO poisoning is rare. In this report, we share a less widely known magnetic resonance imaging (MRI) pattern in the acute setting of CO intoxication with damage to cerebellum.

Is plasma homocysteine related to severity and outcome of atherothrombotic stroke? Comment on: acute phase homocysteine related to severity and outcome of atherothrombotic stroke.

In this issue of the European Journal of Internal Medicine Wu and colleagues [1] reported a very important information that acute phase elevated plasma homocysteine (HCY) correlated with severity and prognosis in patients with atherothrombotic stroke. Although the data were analyzed by statistical methods, the data should be interpreted with caution. Stroke, amajor cause ofmorbidity andmortality, has a plethora of risk factors. One emerging risk factor is an increased level of plasma HCY, a sulfur-containing amino acid that is formed during methionine metabolism [2]. The effectiveness of plasma HCY level on severity and outcome of atherothrombotic stroke is still unclear. Positive correlation between total homocysteine (tHCY) and severity of small vessel disease (SVD) has been reported [3–7], while there are negative studies as well [8]. Although randomized controlled epidemiological trials have yielded mixed findings, a multicenter trial did not show any beneficial effect [9]. The VISP trial showed moderate reduction of tHCY level after nondisabling cerebral infarction had no effect on vascular outcomes during the 2 years of follow-up. The very high stroke risk associated with hyperhomocystinemia involves total homocysteine levels in the hundreds of micromoles per liter [10]. At levels approaching the normal range, there is a steep relationship between the total homocysteine and stroke risk: a prospective study in Norway showed that levels of total homocysteine above 20 μmol/l carried a 9-fold increase in stroke risk [11], whereas the European Concerted Action Project showed that levels above 10.2 μmol/l were associated with a doubling of stroke risk [12]. In Wus group analysis, on the basis of plasma HCY levels, the participants were divided into 2 groups: hHCY (HCY > 15 μmol/l) and nhHCY (HCY ≤ 15 μmol/l). We are wondering why Wu and colleagues had selected 15 μmol/l as the critical point. This might lead to a selection bias, resulting in illegibility of the conclusion on account that the relationship between plasma HCY level and stroke risk is complex. In our opinion, we need to classify subjects into four groups according to the interquartile range of plasma HCY level in order that we might come to actual conclusion on whether acute phase HCY is related to severity and outcome of atherothrombotic stroke. In summary, we need to stratify the patients thoroughly according to their plasma HCY levels so that we could be aware of the association between plasma HCY levels and clinical outcome comprehensively.

What if a patient with atrial fibrillation and anticoagulant treatment is suffering from acute ischemia stroke

Accessible online at: www.karger.com/ced Atrial fibrillation (AF) is responsible for about 25% of all ischemic strokes [1] , and the risk of stroke attributed to AF increases with age [2] . AF was associated with increased stroke severity, high frequency of complications and poor outcome [3–5] . Thrombolytic therapy with intravenous tissue plasminogen activator (tPA) is of net benefit in patients with acute ischemic stroke [6] . Approximately 50–60% of ischemic strokes in patients with AF are definitely or probably cardioembolic in origin [7, 8] . In patients with cardioembolic stroke, cerebral arteries are mostly occluded by red thrombi [9] . Red thrombi, which contain erythrocytes and some fibrin, were found to be more vulnerable to tPA with a resultant higher chance of recanalization in an animal study [10] . This finding is reflected in clinical observations that successful tPA-induced recanalization often occurred in cardioembolic strokes [11, 12] . Because ischemic stroke in patients with AF mostly depends on embolism, a primary preventive approach treatment with oral anticoagulants is mandatory [13–16]. What if a patient with AF and anticoagulant treatment is suffering from acute ischemia stroke? Marrone and Marrone [17] reported a case of a 73-year-old man with a history of AF who was submitted to intravenous thrombolysis while under treatment with new classes of anticoagulants. In the guidelines of almost all countries, AF in isolation is not regarded as a contraindication for thrombolytic therapy. However, a patient who could be treated with tPA must, according to the guideline, not take an oral anticoagulant or if an anticoagulant has been taken, the INR must be 1.7 or if the patient has received heparin in the previous 48 h, the APTT must be in the normal range. This patient’s INR and APTT did not meet this criterion. I believe that the neurologist was unaware of the patient’s use of dabigatran. Fortunately, the patient did not develop cerebral hemorrhage. In my opinion, we should prefer intra-arterial thrombolysis to lessen the effect on the coagulation time. Cerebrovasc Dis 2013;35:89–90 DOI: 10.1159/000346078

Efficacy and tolerability of short-term duloxetine treatment in adults with generalized anxiety disorder: A meta-analysis

Objective To investigate the efficacy and tolerability of duloxetine during short-term treatment in adults with generalized anxiety disorder (GAD). Methods We conducted a comprehensive literature review of the PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials databases for randomized controlled trials(RCTs) comparing duloxetine or duloxetine plus other antipsychotics with placebo for the treatment of GAD in adults. Outcome measures were (1) efficacy, assessed by the Hospital Anxiety and Depression Scale(HADS) anxiety subscale score, the Hamilton Rating Scale for Anxiety(HAM-A) psychic and somatic anxiety factor scores, and response and remission rates based on total scores of HAM-A; (2) tolerability, assessed by discontinuation rate due to adverse events, the incidence of treatment emergent adverse events(TEAEs) and serious adverse events(SAEs). Review Manager 5.3 and Stata Version 12.0 software were used for all statistical analyses. Results The meta-analysis included 8 RCTs. Mean changes in the HADS anxiety subscale score [mean difference(MD) = 2.32, 95% confidence interval(CI) 1.77–2.88, P<0.00001] and HAM-A psychic anxiety factor score were significantly greater in patients with GAD that received duloxetine compared to those that received placebo (MD = 2.15, 95%CI 1.61–2.68, P<0.00001). However, there was no difference in mean change in the HAM-A somatic anxiety factor score (MD = 1.13, 95%CI 0.67–1.58, P<0.00001). Discontinuation rate due to AEs in the duloxetine group was significantly higher than the placebo group [odds ratio(OR) = 2.62, 95%CI 1.35–5.06, P = 0.004]. The incidence of any TEAE was significantly increased in patients that received duloxetine (OR = 1.76, 95%CI 1.36–2.28, P<0.0001), but there was no significant difference in the incidence of SAEs (OR = 1.13, 95%CI 0.52–2.47, P = 0.75). Conclusion Duloxetine resulted in a greater improvement in symptoms of psychic anxiety and similar changes in symptoms of somatic anxiety compared to placebo during short-term treatment in adults with GAD and its tolerability was acceptable.

Prevalence and geographical variation of Factor V Leiden in patients with cerebral venous thrombosis: A meta-analysis

Background Previous results regarding the prevalence of Factor V Leiden (FVL) in patients with cerebral venous thrombosis (CVT) varied remarkably. Therefore, we performed a meta-analysis to evaluate the potential association between FVL and CVT. Methods The PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science were searched for relevant case-control studies. The data were pooled for analysis of the association between FVL and CVT with a random-effects model. Subgroup and sensitivity analyses were performed to evaluate the robustness of the results. Publication bias was assessed by funnel plot and the Egger’s test. Results A total of 39 case-control studies including 1807 cases of CVT and 7699 control cases were included. FVL was more common in patients with CVT (195/1822) than in controls(369/7795), [odds ratio(OR) = 2.70, 95% confidence interval(CI) 2.16–3.38, P < 0.00001]. Results of subgroup analyses indicated that the association between FVL and CVT varied according to geographic regions. The associations between FVL and CVT were significant in studies from Germany (OR = 2.42, 95%CI 1.70–3.45, P < 0.00001), Brazil(OR = 2.82, 95%CI 1.24–6.42, P = 0.01), France (OR = 5.44, 95%CI 1.35–21.92, P = 0.02), Iran (OR = 6.61, 95%CI 1.83–23.93, P = 0.004), and Tunisia (OR = 6.54, 95%CI 2.89–14.82, P < 0.00001), but not in those from Italy (OR = 1.49, 95%CI 0.59–3.78, P = 0.40) or the US (OR = 2.37, 95%CI 0.59–9.42, P = 0.22). Conclusion FVL may be more common in patients with CVT. However, the association between FVL and CVT varied depending on the geographic origin of the studies.

Thrombophilia with an onset symptom of intracranial venous thrombosis: A case report and review of the literature

Thrombophilia may be hereditary or acquired and is associated with a high risk of thrombosis. The diagnosis rate for thrombophilia is low, particularly for patients with non-specific symptoms. The present study describes a patient with thrombophilia, presenting with onset symptoms for intracranial venous thrombosis. The patient had increased serum homocysteine and anticardiolipin immunoglobulin G antibodies and decreased protein S activities. In addition, the patient was obese and had a one-week history of fatigue, immobilization and insufficient water intake. Radiological findings identified multiple venous thrombosis. Since the patient had multiple risk factors for thrombosis, the diagnosis of thrombophilia was made. No mutations with definite clinical significance were identified in the assessments for mutations of the protein S-α (PROS1) gene. The current case highlights the importance of correct diagnosis for thrombophilia in patients who present with the onset symptoms of intracranial venous thrombosis.

Dystrophia myotonica type 1 presenting with dysarthria: A case report and literature review

Dystrophia myotonica (DM) type 1 is an autosomal dominant disorder, caused by a trinucleotide CTG repeat expansion in the 3′ untranslated region of the dystrophia myotonica protein kinase (DMPK) gene (chromosome 19q13.3). The disorder affects different organ systems, including the skeletal muscles, ocular lens, lungs, heart and gastrointestinal tract, as well as the endocrine and central nervous systems. The skeletal muscles are most frequently involved, whereby the disorder manifests as myotonia, muscle weakness and amyotrophy. However, DM type 1 presenting with dysarthria is rare. The current study presents a case of a 28-year-old male with DM type 1 presenting with dysarthria and associated multifocal hyperintense lesions in the white matter. Although electromyogram measurements identified myotonic discharges in all extremities, a muscle biopsy failed to detect the characteristic pathological features of DM type 1. A lack of a positive family history for DM type 1 also obscured diagnosis. However, genetic analysis detected a single allele in the P12 segment of the DMPK gene that included a CTG expansion of 13 repeats and a three-base gradient fragment in the P134 segment that included a CTG expansion of >600 repeats. According to the characteristics of dysarthria, multifocal hyperintense lesions in the white matter, electromyogram measurement results and genetic testing results, a diagnosis of DM type 1 was confirmed.