NFL and GFAP in (pre)symptomatic RVCL-S carriers: a monogenic cerebral small vessel disease.

BACKGROUND: Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have emerged as biomarkers for cerebral small vessel disease (SVD). We investigated their role in a hereditary SVD model, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S). METHODS: NfL and GFAP levels of 17 pre-symptomatic, 22 symptomatic RVCL-S mutation carriers and 69 controls were measured using a Simoa assay. We assessed the association of serum and cerebrospinal fluid (CSF) levels of NfL and GFAP with RVCL-S symptomatology and neuropsychological functioning. RESULTS: Serum and CSF NfL levels were higher in symptomatic RVCL-S compared to controls ≥ 45 years (33.5 pg/mL vs. 9.2 pg/mL, p < 0.01; 8.5*102 pg/mL vs. 3.9*102 pg/mL, p < 0.01, respectively). Serum NfL levels were higher in symptomatic RVCL-S than pre-symptomatic carriers (33.5 pg/mL vs. 5.9 pg/mL, p = 0.02). Pre-symptomatic RVCL-S carriers had increased CSF NfL levels compared to controls < 45 years (5.2*102 pg/mL vs. 1.9*102 pg/mL, p < 0.01). No differences were found in GFAP levels across groups, but in RVCL-S carriers higher serum levels of both NfL and GFAP were linked to poorer global cognitive functioning (ß[95%CI] = - 2.86 [- 5.58 to - 0.13], p = 0.04 and ß[95%CI] = - 6.85 [- 11.54 to - 2.15], p = 0.01, respectively) and prolonged psychomotor test times (ß[95%CI] = 6.71 [0.78-12.65], p = 0.03 and ß[95%CI] = 13.84 [3.09-24.60], p = 0.01). DISCUSSION: Higher levels of serum NfL and GFAP are associated with worse cognitive functioning in RVCL-S carriers and may serve as marker for disease progression. CSF NfL levels may serve as early marker as pre-symptomatic RVCL-S patients already show differences compared to young controls.

Cerebrovascular reactivity to hypercapnia in patients with migraine: A dual-echo arterial spin labeling MRI study.

OBJECTIVE: This study aimed to compare cerebrovascular reactivity between patients with migraine and controls using state-of-the-art magnetic resonance imaging (MRI) techniques. BACKGROUND: Migraine is associated with an increased risk of cerebrovascular disease, but the underlying mechanisms are still not fully understood. Impaired cerebrovascular reactivity has been proposed as a link. Previous studies have evaluated cerebrovascular reactivity with different methodologies and results are conflicting. METHODS: In this single-center, observational, case-control study, we included 31 interictal patients with migraine without aura (aged 19-66 years, 17 females) and 31 controls (aged 22-64 years, 18 females) with no history of vascular disease. Global and regional cerebrovascular reactivities were assessed with a dual-echo arterial spin labeling (ASL) 3.0 T MRI scan of the brain which measured the change in cerebral blood flow (CBF) and BOLD (blood oxygen level dependent) signal to inhalation of 5% carbon dioxide. RESULTS: When comparing patients with migraine to controls, cerebrovascular reactivity values were similar between the groups, including mean gray matter CBF-based cerebrovascular reactivity (3.2 ± 0.9 vs 3.4 ± 1% ΔCBF/mmHg CO2 ; p = 0.527), mean gray matter BOLD-based cerebrovascular reactivity (0.18 ± 0.04 vs 0.18 ± 0.04% ΔBOLD/mmHg CO2 ; p = 0.587), and mean white matter BOLD-based cerebrovascular reactivity (0.08 ± 0.03 vs 0.08 ± 0.02% ΔBOLD/mmHg CO2 ; p = 0.621).There was no association of cerebrovascular reactivity with monthly migraine days or migraine disease duration (all analyses p > 0.05). CONCLUSION: Cerebrovascular reactivity to carbon dioxide seems to be preserved in patients with migraine without aura.

Neuroimaging Findings in Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic Manifestations.

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations is caused by TREX1 mutations. High-quality systematic follow-up neuroimaging findings have not been described in presymptomatic and symptomatic mutation carriers. We present MR imaging findings of 29 TREX1 mutation carriers (20-65 years of age) and follow-up of 17 mutation carriers (30-65 years of age). Mutation carriers younger than 40 years of age showed a notable number of punctate white matter lesions, but scan findings were generally unremarkable. From 40 years of age onward, supratentorial lesions developed with long-term contrast enhancement (median, 24 months) and diffusion restriction (median, 8 months). In these lesions, central susceptibility artifacts developed, at least partly corresponding to calcifications on available CT scans. Some lesions (n = 2) additionally showed surrounding edema and mass effect (pseudotumors). Cerebellar punctate enhancing lesions developed mainly in individuals older than 50 years of age. These typical neuroimaging findings should aid neuroradiologic recognition of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, which may enable early treatment of manifestations of the disease.

Systemic features of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations: a monogenic small vessel disease.

BACKGROUND: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a small vessel disease caused by C-terminal truncating TREX1 mutations. The disease is typically characterized by vascular retinopathy and focal and global brain dysfunction. Systemic manifestations have also been reported but not yet systematically investigated. METHODS: In a cross-sectional study, we compared the clinical characteristics of 33 TREX1 mutation carriers (MC+) from three Dutch RVCL-S families with those of 37 family members without TREX1 mutation (MC-). All participants were investigated using personal interviews, questionnaires, physical, neurological and neuropsychological examinations, blood and urine tests, and brain MRI. RESULTS: In MC+, vascular retinopathy and Raynaud's phenomenon were the earliest symptoms presenting from age 20 onwards. Kidney disease became manifest from around age 35, followed by liver disease, anaemia, markers of inflammation and, in some MC+, migraine and subclinical hypothyroidism, all from age 40. Cerebral deficits usually started mildly around age 50, associated with white matter and intracerebral mass lesions, and becoming severe around age 60-65. CONCLUSIONS: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations is a rare, but likely underdiagnosed, systemic small vessel disease typically starting with vascular retinopathy, followed by multiple internal organ disease, progressive brain dysfunction, and ultimately premature death.

Recurrent coma and fever in familial hemiplegic migraine type 2. A prospective 15-year follow-up of a large family with a novel ATP1A2 mutation.

Background Familial hemiplegic migraine (FHM) is a rare monogenic migraine subtype characterised by attacks associated with transient motor weakness. Clinical information is mainly based on reports of small families with only short follow-up. Here, we document a prospective 15-year follow-up of an extended family with FHM type 2. Patients and methods After diagnosing FHM in a patient with severe attacks associated with coma and fever, we identified eight more family members with FHM and one with possible FHM. All family members were prospectively followed for 15 years. In total 13 clinically affected and 21 clinically non-affected family members were genetically tested and repeatedly investigated. Results A novel p.Arg348Pro ATP1A2 mutation was found in 14 family members: 12 with clinical FHM, one with psychomotor retardation and possible FHM, and one without FHM features. In 9/12 (75%) family members with genetically confirmed FHM, attacks were severe, long-lasting, and often associated with impaired consciousness and fever. Such attacks were frequently misdiagnosed and treated as viral meningitis or stroke. Epilepsy was reported in three family members with FHM and in the one with psychomotor retardation and possible FHM. Ataxia was not observed. Conclusion FHM should be considered in patients with recurrent coma and fever.

Are atraumatic spinal needles as efficient as traumatic needles for lumbar puncture?

The most frequent complication of lumbar puncture is post lumbar puncture headache (PLPH). Recent studies confirmed that the use of atraumatic spinal needles significantly reduces the risk of PLPH. However, the majority of neurologists still use traumatic needles, possibly caused by misconceptions and beliefs about practical performance of atraumatic spinal needles. Therefore, we investigated the practical characteristics of atraumatic and traumatic spinal needles. An experimental setup with a fluid column was used with (1) a physiological NaCl 0.9 % solution and (2) a high protein content solution. Flow rates and duration of pressure measurements were measured using a traumatic needle and an atraumatic needle. The average flow rate differed less than 10 % between the two needle types with NaCl solution, and for the high protein solution the difference was even smaller. Time taken to perform accurate pressure measurements did not differ between the two needle types using NaCl 0.9 %, and was even slightly shorter for the atraumatic needle when using the high protein solution. Average flow rates and duration of pressure measurements are comparable between atraumatic spinal needles and traumatic needles. Therefore, these performance characteristics are no reason to favor traumatic needles over atraumatic needles.

One- vs 4-week stent placement after laparoscopic and robot-assisted pyeloplasty: results of a prospective randomised single-centre study.

OBJECTIVES: To determine whether 1-week stenting of the pelvi-ureteric anastomosis of laparoscopic or robot-assisted pyeloplasty is as effective as 4-week stenting, based on their respective success rates. PATIENTS AND METHODS: A total of 100 patients with pelvi-ureteric junction obstruction were treated by Anderson-Hynes pyeloplasty and the anastomosis was stented using a 6-F JJ catheter for either 1 week (1W series) or 4 weeks (4W series), based on a randomisation protocol. Postoperative follow-up was performed at 3 months using intravenous urography (IVU), at 6 months using diuretic renography and at 1, 3 and 5 years using ultrasonography. Statistical analysis was performed using a one-sided Z-test, Pearsons's chi-squared test and a Wilcoxon rank sum test. RESULTS: The primary outcome measure, success rate, which was defined as no obstruction on IVU and diuretic renography, was 100% in the 1W series and not inferior to the success rate of 98% in the 4W series (P = 0.006). The following secondary outcome measures were not significantly different between the 1W and the 4W series with regard to residual symptoms (10 vs 6%; P = 0.48), rate of complications (4 vs 6%; P = 0.65), need for synchronous robot-assisted pyelolithotomy (4 vs 8%; P = 0.47), improvement in split renal function (1 vs 0%; P = 0.59) and duration of surgery (200 vs 192 min; P = 0.87). Only length of hospital stay was significantly different; this was shorter in the 1W series (5 vs 6 days; P = 0.01). CONCLUSIONS: Stenting of the pelvi-ureteric anastomosis after laparoscopic or robot-assisted pyeloplasty for 1 week is as effective as stenting for 4 weeks. Both procedures, laparoscopic or robot-assisted pyeloplasty have an excellent success rate.

Library use and information-seeking behavior of veterinary medical students revisited in the electronic environment.

Veterinary medical students at Iowa State University were surveyed in January of 1997 to determine their general use of the Veterinary Medical Library and how they sought information in an electronic environment. Comparisons were made between this study and one conducted a decade ago to determine the effect of the growth in electronic resources on student library use and information-seeking behavior. The basic patterns of student activities in the library, resources used to find current information, and resources anticipated for future education needs remained unchanged. The 1997 students used the library most frequently for photocopying, office supplies, and studying coursework; they preferred textbooks and handouts as sources of current information. However, when these students went beyond textbooks and handouts to seek current information, a major shift was seen from the use of print indexes and abstracts in 1987 towards the use of computerized indexes and other electronic resources in 1997. Almost 60% of the students reported using the Internet for locating current information. Overall use of electronic materials was highest among a group of students receiving the problem-based learning method of instruction. Most of the students surveyed in 1997 indicated that electronic resources would have some degree of importance to them for future education needs. The electronic environment has provided new opportunities for information professionals to help prepare future veterinarians, some of whom will be practicing in remote geographical locations, to access the wealth of information and services available on the Internet and Web.

Distribution of Acinetobacter species on human skin: comparison of phenotypic and genotypic identification methods.

At least 19 genomic species are recognized as constituting the genus Acinetobacter. However, little is known about the natural reservoirs of the various members of the genus. An epidemiological study was therefore performed to investigate the colonization with Acinetobacter spp. of the skin and mucous membranes of 40 patients hospitalized in a cardiology ward and 40 healthy controls. Single samples were obtained once from each of nine different body sites, i.e., forehead, ear, nose, throat, axilla, hand, groin, perineum, and toe web. Identification of Acinetobacter isolates was achieved by using phenotypic properties and was compared to identification by amplified ribosomal DNA restriction analysis. Selected isolates were further investigated with sodium dodecyl sulfate-polyacrylamide gel electrophoresis, ribotyping, and DNA-DNA hybridization. Plasmid profile analysis was used for epidemiological typing. Thirty patients (75%) and 17 controls (42.5%) were found to be colonized with Acinetobacter spp., and the colonization rates of patients increased during their hospital stay. The most frequently isolated species were Acinetobacter lwoffii (47%), A. johnsonii (21%), A. radioresistens (12%), and DNA group 3 (11%). In contrast, A. baumannii and DNA group 13TU, the most important nosocomial Acinetobacter spp., were found only rarely on human skin (0.5 and 1%, respectively) and their natural habitat remains to be defined. A good correlation between phenotypic and genotypic methods for identification of Acinetobacter spp. was observed, and only two isolates could not be assigned to any of the known DNA groups.

Use of information resources by veterinary practitioners.

Veterinary practitioners are often isolated from easy access to information in medical or hospital libraries, making necessary the use of a variety of information resources. A survey was conducted to assess the extent to which various information resources were used within the veterinary profession. Most responding veterinarians were small-animal practitioners who used the veterinary literature, colleagues, diagnostic laboratories, continuing education courses, association meetings, and pharmaceutical representatives as sources of information. Books and other practitioners were the preferred information source in critical-care situations, followed closely by diagnostic laboratories and journals. For keeping up-to-date with current advances in veterinary medicine, journals, books, other practitioners, and continuing education were used. University extension services, veterinary medical libraries, and computer applications to information use were not important resources ot most of the respondents. Many veterinarians indicated that they would use library services if they knew more about them. With the trend toward computerization in veterinary practice, it is possible for libraries to help reduce the information isolation of many veterinary practices.

Library use and information-seeking behavior of veterinary medical students.

Veterinary medical students at Iowa State University were assessed for general use of the veterinary library and for their information-seeking behavior. The library was most frequently used for studying and for making photocopies of materials. The typical respondent relied on course textbooks and handouts for current information on unfamiliar topics, instead of using indexes or abstracts for guidance to recent literature. Light use of library information resources raises the concern that students are developing an inadequate base of retrieval skills for finding information on new procedures, diseases and drugs. No differences were found between students with and without formal bibliographic instruction in their approaches to seeking information or in library use.

Absence of glucoprivic feeding after stress suggest impairment of noradrenergic neuron function.

Feeding in response to 2-deoxy-D-glucose (2DG), a quantifiable behavior which appears to depend on noradrenergic (NE) neuron function, was used in these experiments to evaluate the functional capabilities of NE neurons after stress exposure. Depletion of hypothalamic NE after footshock or hypothermic stress was directly correlated with impairment of glucoprivic feeding. When NE depletion was prevented by prior exposure to chronic stress, no impairment of feeding was observed. After hypothermic stress, repletion of NE proceeded more rapidly in the telencephalon than in the hypothalamus and reappearance of a normal feeding response precisely paralleled the time course of repletion in the hypothalamus. Drinking in response to cell dehydration, a behavior not directly dependent on brain catecholamines, was not impaired after either footshock or hypothermic stress, despite similar NE depletions. Presence of a normal drinking response assured that deficits observed in the 2DG test were not due to nonspecific behavioral suppression resulting from stress. These data suggest that NE neuron function may be impaired or temporarily abolished after severe stress exposure. In addition, these results demonstrate that behavioral pathology need not be the result of massive neurotransmitter depletion but may result from relatively subtle alterations of specific neurotransmitter pools.