Statins and the risk of bleeding in patients taking dabigatran.

OBJECTIVES: Dabigatran etexilate is a direct thrombin inhibitor that clinicians increasingly prescribe to prevent stroke in patients with non-valvular atrial fibrillation (NVAF). Clinicians also commonly prescribe statins for primary and secondary prevention of cardiovascular diseases. Little is known about the bleeding risk in patients taking a statin and dabigatran together. The aim of this study was to evaluate the safety and persistence of dabigatran after co-medication with statins. MATERIALS AND METHODS: We performed a prospective, multicenter registry study of stroke patients with NVAF who initiated dabigatran therapy within 3 months after a clinically evident ischemic cerebrovascular event between 2013 and 2017. The main outcome measure was symptomatic bleeding after 90, 180, and 360 days. RESULTS: In total, 652 patients (336 statin users, 316 non-users) were followed for 1 year after dabigatran therapy. Cox multivariate analysis demonstrated that male sex, prior use of aspirin, and concurrent use of an antiarrhythmic drug were associated with a higher risk of bleeding at 360 days. After adjusting time-dependent covariates, statin users had a significantly lower bleeding risk (adjusted hazard ratio: 0.11, P < 0.001) than non-users. Kaplan-Meier analysis indicated that patients prescribed with statins had a higher rate of bleeding-free survival (P = 0.028). CONCLUSION: For secondary prevention of stroke in patients with NVAF who are taking dabigatran etexilate, co-prescription with a statin was associated with a lower risk of bleeding complications. Future research is needed to determine the pharmacological mechanism underlying this effect.

Fusarium Brain Abscess in a Patient with Diabetes Mellitus and Liver Cirrhosis.

PURPOSE: Invasive mycosis caused by the Aspergillus, Fusarium, and Mucor can be fetal, especially in the immunocompromised patients with central nervous system (CNS) involvement. Here we present a case of CNS Fusarium infection, and this is the first reported case of Fusarium brain abscess in Taiwan. CASE REPORT: A 65-year-old woman presented with fever and conscious disturbance for 3 days. Neurological examination showed stupor consciousness, neck stiffness, multiple cranial nerves palsy, and bilateral Babinski signs. Magnetic resonance imaging showed multifocal lesions involving medulla oblongata, pons, bilateral cerebral peduncles, and bilateral cerebellar peduncles. Cerebrospinal fluid (CSF) study revealed neutrophil predominant pleocytosis, but both blood and CSF culture were negative. We treated patient with ceftriaxone and vancomycin initially as empiric therapy for suspected bacterial meningoencephalitis. However, chronic sinusitis with fungal ball and brain abscess were later found. Despite antifungal treatment and surgical intervention, patient expired 3 months after admission. Fungal culture of the brain abscess disclosed Fusarium species 2 weeks after her death. CONCLUSION: CNS Fusarium infection should be considered when an immunocompromised patient presenting with fever, conscious change, cranial nerve palsies, and angioinvasion suggested by brain imaging. To properly manage the disease, early effective antifungal therapy and neurosurgical intervention are important.

Recurrent nonconvulsive status epilepticus in a patient with progressive left hemispheric leukoencephalopathy after a remote viral meningoencephalitis.

Nonconvulsive status epilepticus (NCSE), defined as changes in behavior and/or mental processes from baseline with continuous epileptiform discharges, remains a diagnostic and treatment challenge. Here, we present a 68-year-old female who developed 3 episodes of NCSE 10 years after a viral meningoencephalitis which gradually progressed to left hemispheric leukoencephalopathy. In this case, we hypothesize that immune-mediated mechanisms and perhaps genetic predisposition played a role in epileptogenesis, and these will be discussed. This article is part of a Special Issue entitled "Status Epilepticus".

Cervical spinal epidural hematoma mimics acute ischemic stroke.

Spinal epidural hematoma is an accumulation of blood in the epidural space that can mechanically compress the spinal cord. It is an uncommon condition, and most cases occur spontaneously. Detailed evaluation of neurologic deficit and detailed history taking are important tools for early diagnosis, and magnetic resonance imaging is currently the diagnostic method of choice. Prompt surgical intervention is important in achieving positive clinical outcomes. Spinal epidural hematoma usually comes with acute, severe pain with radiation to the extremities and may be accompanied with severe neurologic deficit. Common neurologic signs include paraparesis and quadriparesis. Here, we report 2 cases of cervical spinal epidural hematoma with sudden onset of neck pain, followed by the development of unilateral limbs weakness and respiratory distress. Both patients were initially suspected to have acute ischemic stroke and were considered using intravenous thrombolytic therapy with recombinant tissue plasminogen activator as treatment. Cervical spinal epidural hematoma was confirmed after obtaining magnetic resonance imaging. Patients with this uncommon presentation must be carefully distinguished from acute stroke. This article aimed to highlight the potential pitfalls in diagnosing acute hemiparesis with no cranial nerves deficits and the importance of clinical suspicion.

The prescribing patterns of antithrombotic agents for prevention of recurrent ischemic stroke.

OBJECTIVES: Antithrombotic agents are effective in the secondary prevention of ischemic strokes. In the present study, we sought to determine the antithrombotic prescribing patterns of neurologists in patients with first-ever ischemic stroke and also to identify the factors influencing the choice of a specific agent and what changes are made when a recurrent stroke occurs in these patients. METHODS: We retrospectively reviewed the medical records of neurology patients who were diagnosed with first-ever ischemic stroke and were antithrombotic naive from January 1, 2000 to December 31, 2000. Patients' antithrombotic agents at discharge and during the follow-up period were reviewed to identify factors affecting the choice of antithrombotic agents. RESULTS: A total of 376 patients experienced non-fatal first-ever ischemic stroke. Of these, 351 were prescribed antithrombotic agents at discharge, while the remaining 25 were not on antithrombotic treatment. Low-dose aspirin was the most commonly prescribed agent (65%). The most important determinant for the choice of other antiplatelet agents was aspirin intolerance. Not surprisingly, only 36% of the patients with atrial fibrillation were treated with oral anticoagulants at the time of hospital discharge. CONCLUSION: Aspirin remains the most commonly used antithrombotic agent for the prevention of recurrent stroke among antithrombotic naive patients with a first-ever ischemic stroke in our institution. Our results demonstrate that current recommendations find their way into clinical practice, but to a limited extent. We aim that all patients discharged from our hospital after strokes must receive appropriate antithrombotic drugs for prevention of recurrent strokes provided if there are no contraindications to therapy.

Persistent Klüver-Bucy syndrome after bilateral temporal lobe infarction.

Klüver-Bucy (KBS) syndrome is a rare and complicated neurobehavioral syndrome in humans resulting from damage of bilateral anterior temporal portion, especially the amygdala. It can be seen in association with a variety of etiologies. Stroke is a rarely reported. Here we present a 50-year-old right handed man who developed persistent KBS after cardioembolic stroke involving bilateral lateral temporal lobes. He exhibited all clinical features of KBS including visual agnosia, hypersexuality, placidity, hyperorality and hypermetamorphosis. The anatomical basis of pathophysiolgy, clinical course and possible treatment are discussed.

A case of bow hunter's stroke caused by non-dominant vertebral artery.

Rotational movements in the territory of vertebrobasilar artery of the head and neck can induce vertebrobasilar insufficiency (VBI) or infarction. The term "bow hunter's stroke" or "rotational VBI" has been used to describe this clinical syndrome. In most cases, symptoms were provoked because of involvement of a dominant vertebral artery (VA) with hypoplasia or occlusion of the contralateral VA. The author presented a case in which bow hunter's stroke was caused by occlusion of a non-dominant VA ending in the posterior inferior cerebellar artery (PICA). Diagnosis of rotational VBI was based on stereotypical clinical symptoms related to head rotation and hemodynamic study of the effects of head rotation. VA compression was documented in dynamic ultrasonography including the disappearance of end-diastolic flow in extracranial portion of VA and marked reduction in blood flow velocity (more than 50%) in the intracranial portion of VA upon head rotation. We emphasize that rotational occlusion of this anatomical variation is an important cause of VBI. This may cause permanent neurological deficits if left undiagnosed.

Transcranial Doppler studies on cerebral autoregulation suggest prolonged cerebral vasoconstriction in a subgroup of patients with orthostatic intolerance.

We studied the cerebral autoregulation in a subgroup of patients with orthostatic intolerance, who exhibited excessively decreased middle cerebral artery flow velocity (MCAFV) on transcranial Doppler sonography (TCD) during head-up tilt (HUT) test but without orthostatic hypotension or postural tachycardia. Twenty patients and 20 age- and sex-matched controls underwent Valsalva maneuver (VM) and HUT test with simultaneous monitoring of MCAFV by TCD and blood pressure, heart rate recordings. The pulsatility index (PI), cerebrovascular resistance (CVR) and autoregulatory indices were calculated. During HUT, patients had marked MCAFV reduction (-29.0 ± 5.25% vs. -8.01 ± 4.37%), paradoxically decreased PI (0.68 ± 0.17 vs. 0.96 ± 0.28) but increased CVR (45.7 ± 16.7% vs. 14.3 ± 12.6%). The MCAFV decreased similarly during early phase II of VM in both groups but did not recover to baseline in patients during late phase II, phase III and less overshoot in phase IV (-11 ± 16.7% vs. +2.2 ± 17.9 %; -15.4 ± 16.5% vs. -2.4 ± 17.8% and 16.7 ± 22.9% vs. 38.7 ± 26.5%, respectively). We concluded that in these patients, cerebrovascular vasoconstriction in response to physiologic stimulation was normal but relaxation during and after stimulation were impaired, indicating prolonged cerebral vasoconstriction.

Isolated thunderclap headache during sex: Orgasmic headache or reversible cerebral vasoconstriction syndrome?

Orgasmic headache (OH) is an "explosive" headache that occurs at orgasm. Historically, it was considered benign with no treatment needed. Reversible cerebral vasoconstriction syndrome (RCVS) refers to a group of disorders characterized by recurrent thunderclap headache (TCH) and multifocal vasoconstriction. Patients who have RCVS often recover completely, but some may have persistent neurological deficits. We report a 34-year-old woman who presented with isolated and recurrent TCH at orgasm, which fulfilled the diagnosis of OH. However, she was post-partum and had recent exposure to ecstasy, making her symptoms highly suggestive of RCVS. Brain magnetic resonance angiography showed segmental vasoconstriction. We concluded that she could be considered to have either OH or RCVS. This patient suggests the theory that OH could be a presentation of RCVS. Given that RCVS is potentially treatable, early recognition by clinicians is vital in order to prevent devastating complications.

Jugular venous hemodynamic changes with aging.

Cerebral venous outflow insufficiency via the internal jugular vein (IJV) is associated with several neurological disorders. However, a normal reference set of IJV hemodynamic parameters derived from a large, healthy population over a wide range of age has, until now, been lacking. Color-coded duplex sonography was performed on the IJVs of 349 subjects (55.60 ± 17.49,16 to 89 y; 167 M/182 F). With increasing age, increased lumen area and decreased time-averaged mean velocity of bilateral IJV and a decreased proportion of total flow volume, drainage in the left IJV were found. The frequency of left jugular venous reflux (JVR) also increased with aging. We report IJV hemodynamic parameters across a large population, which could be used as a normal reference for clinical and research purposes. Furthermore, we found a decreased proportion of venous drainage, increased JVR prevalence, dilated lumen and slowed flow velocity in the left IJV, all of which suggest increased left IJV outflow impedance with aging.

Pathophysiology of neuropathic pain in type 2 diabetes: skin denervation and contact heat-evoked potentials.

OBJECTIVE: Neuropathic pain due to small-fiber sensory neuropathy in type 2 diabetes can be diagnosed by skin biopsy with quantification of intra-epidermal nerve fiber (IENF) density. There is, however, a lack of noninvasive physiological assessment. Contact heat-evoked potential (CHEP) is a newly developed approach to record cerebral responses of Aδ fiber-mediated thermonociceptive stimuli. We investigated the diagnostic role of CHEP. RESEARCH DESIGN AND METHODS: From 2006 to 2009, there were 32 type 2 diabetic patients (20 males and 12 females, aged 51.63 ± 10.93 years) with skin denervation and neuropathic pain. CHEPs were recorded with heat stimulations at the distal leg, where skin biopsy was performed. RESULTS: CHEP amplitude was reduced in patients compared with age- and sex-matched control subjects (14.8 ± 15.6 vs. 33.7 ± 10.1 µV, P < 0.001). Abnormal CHEP patterns (reduced amplitude or prolonged latency) were noted in 81.3% of these patients. The CHEP amplitude was the most significant parameter correlated with IENF density (P = 0.003) and pain perception to contact heat stimuli (P = 0.019) on multiple linear regression models. An excitability index was derived by calculating the ratio of the CHEP amplitude over the IENF density. This excitability index was higher in diabetic patients than in control subjects (P = 0.023), indicating enhanced brain activities in neuropathic pain. Among different neuropathic pain symptoms, the subgroup with evoked pain had higher CHEP amplitudes than the subgroup without evoked pain (P = 0.011). CONCLUSIONS: CHEP offers a noninvasive approach to evaluate the degeneration of thermonociceptive nerves in diabetic neuropathy by providing physiological correlates of skin denervation and neuropathic pain.