Fatal oral anticoagulant-related intracranial hemorrhage: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) is the most feared complication in patients treated with oral anticoagulants due to non-valvular atrial fibrillation. Non-vitamin K oral anticoagulants (NOACs) reduce the risk of ICH compared with vitamin K antagonists (VKAs). We performed a systematic review and meta-analysis to evaluate the risk of fatal NOAC-related ICH compared with VKA-related ICH. METHODS: We calculated the corresponding risk ratios (RRs) in each included study to express the relative risk of fatal ICH amongst all patients receiving oral anticoagulation with either NOACs or VKAs. We additionally evaluated the mortality rates in NOAC-related ICH in patients treated with and without NOAC-specific reversal agents (idarucizumab and factor Xa inhibitors antidote). Case fatality was evaluated at 30-90 days following symptom onset. RESULTS: Our literature search identified six eligible studies (four randomized controlled trials and two open-label trials of NOAC-specific reversal agents). In pairwise analyses, NOACs were found to have a lower risk of fatal ICH compared with VKAs [RR, 0.46; 95% confidence interval (CI), 0.36-0.58] with no heterogeneity (I2 = 0%) across included randomized controlled trials. However, the case fatality rate was similar in NOAC-related and VKA-related (RR, 1.00; 95% CI, 0.84-1.19) ICH with no evidence of heterogeneity (I2 = 0%). In the indirect analysis, the case fatality rate of NOAC-related ICH in patients treated with specific reversal agents was lower compared with the remainder of the patients [17% (95% CI, 11-24%) vs. 41% (95% CI, 34-49%); P < 0.001]. CONCLUSIONS: Non-vitamin K oral anticoagulants halve the risk of fatal ICH in patients with non-valvular atrial fibrillation compared with VKAs, whereas indirect comparisons indicate that NOAC-specific reversal agents may be associated with a lower case fatality rate in NOAC-related ICH.

Quantification of internal carotid artery flow with digital subtraction angiography: validation of an optical flow approach with Doppler ultrasound.

BACKGROUND AND PURPOSE: Digital subtraction angiography is the reference standard technique to evaluate intracranial vascular anatomy and used on the endovascular treatment of vascular diseases. A dedicated optical flow-based algorithm was applied to DSA to measure arterial flow. The first quantification results of internal carotid artery flow validated with Doppler sonography are reported. MATERIALS AND METHODS: We included 22 consecutive patients who underwent endovascular procedures. To assess the sensitivity of the algorithm to contrast agent-blood mixing dynamics, we acquired high-frame DSA series (60 images/s) with different injection rates: 1.5 mL/s (n = 19), 2.0 mL/s (n = 18), and 3.0 mL/s (n = 13). 3D rotational angiography was used to extract the centerline of the vessel and the arterial section necessary for volume flow calculation. Optical flow was used to measure flow velocities in straight parts of the ICAs; these data were further compared with Doppler sonography data. DSA mean flow rates were linearly regressed on Doppler sonography measurements, and regression slope coefficient bias from value 1 was analyzed within the 95% confidence interval. RESULTS: DSA mean flow rates measured with the optical flow approach significantly matched Doppler sonography measurements (slope regression coefficient, b = 0.83 ± 0.19, P = .05) for injection rate = 2.0 mL/s and circulating volumetric blood flow <6 mL/s. For injection rate = 1.5 mL/s, volumetric blood flow <3 mL/s correlated well with Doppler sonography (b = 0.67 ± 0.33, P = .05). Injection rate = 3.0 mL/s failed to provide DSA-optical flow measurements correlating with Doppler sonography because of the lack of measurable pulsatility. CONCLUSIONS: A new model-free optical flow technique was tested reliably on the ICA. DSA-based blood flow velocity measurements were essentially validated with Doppler sonography whenever the conditions of measurable pulsatility were achieved (injection rates = 1.5 and 2.0 mL/s).

Phenotypes in Swiss patients with familial ALS carrying TARDBP mutations.

BACKGROUND: Recently, mutations in the TARDBP gene encoding the TAR DNA-binding protein 43 (TDP-43) have been identified in some familial amyotrophic lateral sclerosis (ALS) and sporadic ALS patients. The phenotype and frequency of TARDBP mutation carriers reportedly varies greatly among European populations. OBJECTIVE: To define the phenotypic spectrum of TARDBP mutations and their frequency in a Swiss population. METHODS: A total of 225 patients diagnosed with ALS (182 sporadic cases, 43 familial cases) were screened for TARDBP mutations. All patients were carefully examined and interviewed for a familial predisposition. Except for 1 patient who was followed at the University of Geneva, all patients were followed at the Kantonsspital St. Gallen. RESULTS: 43 patients (19.5%) had a definite family history for ALS. A TARDBP mutation was identified in 4 of these (9.3%). Two female ALS patients carried the p.Asn352Ser mutation. Both had limb onset and a slowly progressive course of the disease. A novel mutation (p.Gly376Asp) was identified in a 44-year-old female patient. Survival amongst affected family members varied between 6 and 18 months. The patient and also the other siblings affected with ALS had an accessory nipple. A fourth male patient carried the p.Ala90Val mutation. None of the patients had overt cognitive impairment. TARDBP mutations were not found among patients with sporadic forms of ALS. CONCLUSION: In this Swiss population, the frequency of familial ALS is higher than reported earlier in other populations. The novel p.Gly376Asp TARDBP mutation is associated with rapid disease progression and may be associated with an accessory nipple while the p.Asn352Ser mutation is associated with slow disease progression.

Late adult onset of Langerhans cell histiocytosis mimicking glioblastoma multiforme.

Langerhans cell histiocytosis (LCH) with multiple organ involvement is a rare disorder in adults. Extrapituitary involvement of the central nervous system (CNS) is uncommon. We report the unusual case of a 55-year-old woman presenting with a left-sided hemiataxia-hemiparesis, left hemisensory loss and short-lasting episodes of an alien left hand due to lesions of the internal capsule and the right thalamus, extending into the mesencephalon associated with extensive surrounding edema, without pituitary involvement. The neuroradiological image suggested glioblastoma multiforme. Brain biopsy revealed inflammatory tissue and "pseudotumoral" multiple sclerosis was suspected. Biopsy of concomitant lung and bone lesions disclosed Langerhans cell histiocytosis. The treatment with pulsed steroids in association with mycophenolate mofetil led to a sustained, clinical neurological remission.

From amaurosis fugax to asymptomatic bithalamic infarct.

Bilateral paramedian thalamic infarctions are usually associated with impaired consciousness, oculomotor disturbances and neuropsychological changes. A 44-year-old healthy woman presented with amaurosis fugax of the right eye immediately after a Valsalva maneuver. Neurological examination, in particular visual acuity, vigilance and ocular movements, was normal. Blood pressure, ECG and angio-CT of the neck and head vessels were normal, but MRI/DWI and T2 sequences showed recent bi-thalamic ischemic lesions in the paramedian territories. Doppler sonography and transesophageal echocardiography showed a large right-to-left shunt due to an atrial communication, with septum aneurysm. Twenty-four-hours cardiac monitoring was normal but prior to an eventual closure of the cardiac defect she underwent an ambulatory 7-day ECG monitoring which revealed several paroxystic short lasting passages into atrial fibrillation, unnoticed by the patient. The interest in this case is threefold: (1) bilateral paramedian thalamic infarction which usually presents with a devastating clinical picture may occur clinically silent; (2) monocular amaurosis fugax which is usually associated with ipsilateral carotid disease may be the consequence of cardiac embolism, and (3) atrial fibrillation is never completely ruled out, here it was caught only in a 7-days ambulatory R-test, and consequently prevented closure of a possibly asymptomatic patent foramen ovale.

Combined IV-intra-arterial thrombolysis: a color-coded duplex pilot study.

The authors compared the transcranial color-coded duplex pattern of the middle cerebral arteries (MCAs) before and after IV and combined IV-intra-arterial (IV-IA) thrombolysis in consecutive first-ever stroke patients. Patients receiving combined IV-IA thrombolysis showed greater improvement in flow signal and higher incidence of complete MCA recanalization vs those receiving IV thrombolysis, especially when the MCA was occluded or had only minimal flow.

Double dissociation between representational personal and extrapersonal neglect.

BACKGROUND: Although perceptual and representational neglect are frequently associated, the demonstration of a double dissociation between both neglect forms suggests that both rely on different central mechanisms. In addition, perceptual neglect can be selectively observed within personal space or extrapersonal space. However, it is not known whether the latter dissociation also exists in representational neglect. METHODS: The authors investigated this question in two brain-damaged patients with anatomically different lesions sites, using neuropsychological tests specifically designed to assess perceptual and representational neglect in both personal and extrapersonal space. RESULTS: Patients presented a double dissociation with respect to personal and extrapersonal space in representational neglect. CONCLUSIONS: These data suggest that the cerebral networks that process mental space representation use similar principles of space compartmentalization as those used by cerebral networks processing perceived space.

Power Doppler evaluation of revascularization in childhood moyamoya.

Moyamoya disease is generally recognized in young children. One potential treatment is direct extra-intracranial bypass combined with indirect revascularization using encephalo-myo-synangiosis. Standard follow-up to assess neoangiogenesis includes repeat cerebral angiography, which is invasive. The authors studied whether noninvasive power Doppler imaging could evaluate the patency of the bypass and the degree of indirect revascularization. They found that transcranial power Doppler imaging is a valid noninvasive alternative to cerebral angiography.

The exstrophy-epispadias complex in the duplicated lower urinary tract.

PURPOSE: The exstrophy-epispadias complex in combination with a duplicated lower urinary tract is an extremely rare congenital malformation. We describe 2 cases of bladder exstrophy in association with a duplicated lower urinary tract. MATERIALS AND METHODS: We analyzed the case histories of 2 patients. The first case had anteroposterior duplication of the bladder communicating through an isthmus and a duplicate urethra. The anterior system was exstrophic and epispadiac. The second case had a duplicate bladder without epispadias. There was a communication between the anterior exstrophic and posterior normal bladders. No other malformations were present. RESULTS: Both patients underwent excision of the duplicate exstrophic bladder in conjunction with primary closure of the abdominal wall. Postoperative continence was normal. Histological examination confirmed the diagnosed bladder duplication. CONCLUSIONS: Although duplication of the lower urinary tract in combination with the exstrophy-epispadias complex is extremely rare, all children presenting with an exstrophic bladder and a normal urethra alone or in association with an epispadiac anterior urethra should be evaluated for a bladder duplication with possible isthmic communication.

[Comparative study of preliminary and definitive anatomo-pathological diagnoses in 375 autopsies in adults]. / Etude comparative des diagnostics anatomo-pathologiques préliminaires et définitifs de 375 autopsies d'adultes.

For the past 5 years the institute of pathology of the University of Lausanne has been delivering both provisional and final autopsy reports. The provisional reports are based mainly upon macroscopic findings, whereas the final reports include the information provided by supplementary investigations such as microscopy, histochemistry, more rarely electron microscopy, immunohistochemistry and/or microbiology. The reliability and usefulness of the provisional reports were analyzed by systematic comparison between the provisional and final reports of 375 adult post-mortems as well as through an inquiry among requesting physicians. No significant difference was found between the two reports in 77.1% of the cases. In 22.1% the supplementary investigations provided information which had a bearing on the final diagnosis and made it possible to complete or correct the macroscopic diagnosis. In 0.8% the significant difference was due to the omission, in the provisional report, of an obvious macroscopic diagnosis. Finally, 95% of the consulted physicians found the provisional reports useful because of the precise written and particularly rapid information they provided. These results not only demonstrated that the establishment of such provisional reports is fully justified, but further emphasize the fundamental and complementary role played by the final autopsy reports.