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Cerebral venous sinus thrombosis is a challenging condition because of its variability of clinical symptoms and signs. It is very often unrecognised at initial presentation. All age groups can be affected. Large sinuses such as the superior sagittal sinus are most frequently involved. Extensive collateral circulation within the cerebral venous system allows for a significant degree of compensation in the early stages of thrombus formation. Systemic inflammatory diseases and inherited as well as acquired coagulation disorders are frequent causes, although in up to 30% of cases no underlying cause can be identified. The oral contraceptive pill appears to be an important additional risk factor. The spectrum of clinical presentations ranges from headache with papilloedema to focal deficit, seizures and coma. Magnetic resonance imaging with venography is the investigation of choice; computed tomography alone will miss a significant number of cases. It has now been conclusively shown that intravenous heparin is the first-line treatment for cerebral venous sinus thrombosis because of its efficacy, safety and feasability. Local thrombolysis may be indicated in cases of deterioration, despite adequate heparinisation. This should be followed by oral anticoagulation for 3-6 months. The prognosis of cerebral venous sinus thrombosis is generally favourable. A high index of clinical suspicion is needed to diagnose this uncommon condition so that appropriate treatment can be initiated. [ABSTRACT FROM AUTHOR]

Background: Whole genome sequencing is increasingly being used for the diagnosis of patients with rare diseases. However, the diagnostic yields of many studies, particularly those conducted in a healthcare setting, are often disappointingly low, at 25-30%. This is in part because although entire genomes are sequenced, analysis is often confined to in silico gene panels or coding regions of the genome., Methods: We undertook WGS on a cohort of 122 unrelated rare disease patients and their relatives (300 genomes) who had been pre-screened by gene panels or arrays. Patients were recruited from a broad spectrum of clinical specialties. We applied a bioinformatics pipeline that would allow comprehensive analysis of all variant types. We combined established bioinformatics tools for phenotypic and genomic analysis with our novel algorithms (SVRare, ALTSPLICE and GREEN-DB) to detect and annotate structural, splice site and non-coding variants., Results: Our diagnostic yield was 43/122 cases (35%), although 47/122 cases (39%) were considered solved when considering novel candidate genes with supporting functional data into account. Structural, splice site and deep intronic variants contributed to 20/47 (43%) of our solved cases. Five genes that are novel, or were novel at the time of discovery, were identified, whilst a further three genes are putative novel disease genes with evidence of causality. We identified variants of uncertain significance in a further fourteen candidate genes. The phenotypic spectrum associated with RMND1 was expanded to include polymicrogyria. Two patients with secondary findings in FBN1 and KCNQ1 were confirmed to have previously unidentified Marfan and long QT syndromes, respectively, and were referred for further clinical interventions. Clinical diagnoses were changed in six patients and treatment adjustments made for eight individuals, which for five patients was considered life-saving., Conclusions: Genome sequencing is increasingly being considered as a first-line genetic test in routine clinical settings and can make a substantial contribution to rapidly identifying a causal aetiology for many patients, shortening their diagnostic odyssey. We have demonstrated that structural, splice site and intronic variants make a significant contribution to diagnostic yield and that comprehensive analysis of the entire genome is essential to maximise the value of clinical genome sequencing., (© 2023. Crown.)

Background: Nitrous oxide (N 2 O) is the second most common recreational drug used by 16- to 24-year-olds in the UK. Neurological symptoms can occur in some people that use N 2 O recreationally, but most information comes from small case series., Methods: We describe 119 patients with N 2 O-myeloneuropathy seen at NHS teaching hospitals in three of the UK's largest cities: London, Birmingham and Manchester. This work summarises the clinical and investigative findings in the largest case series to date., Results: Paraesthesia was the presenting complaint in 85% of cases, with the lower limbs more commonly affected than the upper limbs. Gait ataxia was common, and bladder and bowel disturbance were frequent additional symptoms. The mid-cervical region of the spinal cord (C3-C5) was most often affected on MRI T2-weighted imaging. The number of N 2 O canisters consumed per week correlated with methylmalonic acid levels in the blood as a measure of functional B 12 deficiency (rho (ρ)=0.44, p=0.04)., Conclusions: Preventable neurological harm from N 2 O abuse is increasingly seen worldwide. Ease of access to canisters and larger cylinders of N 2 O has led to an apparent rise in cases of N 2 O-myeloneuropathy in several areas of the UK. Our results highlight the range of clinical manifestations in a large group of patients to improve awareness of risk, aid early recognition, and promote timely treatment., Competing Interests: Competing interests: DM leads a medical student-run unpaid campaign - ‘N2O: Know The Risks’ - which provides educational teaching sessions on the risks of nitrous oxide in East London., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Long-term electroencephalogram monitoring is often used to help distinguish epileptic from dissociative (non-epileptic) seizures. Home video telemetry now offers many of the benefits in diagnosis previously available only with inpatient video telemetry, which is usually regarded as the 'gold standard'. Here, we describe recent developments in home video telemetry and how we undertake this procedure in our unit., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

A 19-year-old woman presented with a 4-week history of headache, ataxia, vertigo, confusion, intermittent blurred vision in the right eye and intermittent hearing loss. MRI revealed white matter lesions and 'pepper pot' lesions of the corpus callosum. The cerebrospinal fluid had raised protein and lymphocytes. Fundal examination revealed multiple peripheral arterial occlusions in the both eyes confirmed with fundus fluorescein angiography (FFA). A diagnosis of Susac's syndrome was made. The patient was initially treated with steroids, followed by azathioprine and intravenous immunoglobulins (IVIg). Clinical improvement was noted, associated with improvement of the retinal circulation on FFA., (2014 BMJ Publishing Group Ltd.)

Background and Purpose: Overviews of randomized patch trials by the Cochrane Collaboration suggest that a policy of routine patching is preferable to routine primary closure. However, there is no systematic evidence that patch type, whether prosthetic or vein, influences outcome after carotid endarterectomy (CEA)., Methods: Two hundred seventy-three patients were randomized to vein or thin-walled Dacron patch (Hemashield Finesse) closure of the arteriotomy after 276 CEA procedures. Patients were reviewed clinically and with duplex ultrasound scanning at 1, 6, 12, 24, and 36 months or until death. No patients were lost to follow-up. Cumulative statistical analyses are presented for the 264 patients (269 CEAs) who actually received a randomized treatment allocation., Results: Cumulative freedom from death or ipsilateral stroke at 3 years (including operative events) was 93.0% in the Dacron patch group and 95.5% in the vein group P =.42). Cumulative freedom from death or any stroke was 91.5% after Dacron patch closure and 93.9% after vein closure (P =.46). Cumulative freedom from recurrent stenosis greater than 70% or occlusion at 3 years was 92.9% for patients randomized to the Dacron patch group and 98.4% for patients randomized to the vein group (P =.03). At 3 years the incidence of stroke in the carotid territory not operated on was 1.0% in 93 patients with no contralateral internal carotid artery disease at randomization, and increased to 1.3% in 78 patients with 1% to 69% stenosis, and 2.0% in 51 patients with contralateral 70% to 99% stenosis. No late strokes occurred distal to 42 occluded contralateral internal carotid arteries., Conclusions: Patch type has no influence on early operative risk, no association with enhanced patterns of thrombogenicity in the early postoperative period, and no influence on risk for ipsilateral or any stroke at 3 years. Dacron patches were, however, associated with a significantly higher incidence of recurrent stenosis at 3 years, with most occurring within 6 to 12 months of surgery. However, the higher incidence of recurrent stenosis was not associated with a parallel increase in late stroke, and in this study a program of serial ultrasound surveillance could not have prevented one ipsilateral stroke.

Purpose: A recent overview indicated that although routine patching is safer than routine primary closure after carotid endarterectomy (CEA), there is no systematic evidence that patch type influences outcome. However, most surgeons still believe that prosthetic patches are probably more thrombogenic than vein patches. This study tested the hypothesis that there was no difference in thrombogenicity between the different patch types., Methods: A total of 274 patients undergoing 276 CEAs were randomized to either Dacron-patch closure (n = 137) or vein-patch closure (n = 139). All patients with an accessible cranial window were monitored for 3 hours postoperatively with transcranial Doppler scanning (TCD). The number of emboli and rate of embolization were quantified with the requirement for selective dextran therapy to control high rates of postoperative embolization. All patients were assessed postoperatively and again at 30 days by a neurologist, and all patients underwent a duplex examination at 30 days., Results: The 30-day death/any stroke rate was 2.2% for patients in the Dacron-patch group and 3.6% for patients in the vein-patch group (P =.72). Patients in the Dacron-patch group had a higher incidence of postoperative emboli (median, 5; interquartile range, 0-10.5) than patients in the vein-patch group (median, 3; interquartile range, 1-17; P =.028). However, the incidence of detecting more than 50 emboli was virtually identical, and patch type had no effect on the incidence of high-rate, sustained embolization that required dextran therapy (5.3% for Dacron, 3.7% for vein). No patient had a carotid thrombosis at 30 days., Conclusion: Sustained, high-rate embolization, previously shown to be highly predictive of progression to carotid thrombosis, appears to be patient dependent, rather than related to patch type.

Background and Purpose: The current risk of stroke after carotid endarterectomy may be worse than reported in the international trials. Because studies have suggested that most operative strokes follow surgeon error, the aim of the current study was to audit the impact of introducing a strategy of perioperative monitoring and quality control assessment on outcome., Methods: A total of 500 patients underwent carotid endarterectomy with intraoperative transcranial Doppler scan monitoring, completion angioscopy, and 3 hours of postoperative transcranial Doppler scan monitoring. The last of these guided selective dextran therapy in patients with high rates of postoperative embolization, which in previous series has been shown to be highly predictive of progression to thromboembolic stroke., Results: Intimal flaps were repaired in 3% of patients and luminal thrombus removed in 4% of patients. The rate of intraoperative stroke was 0.2%. A total of 313 patients had more than one embolus detected postoperatively (96% within 2 hours of flow restoration), but only 22 patients had sustained embolization requiring dextran. Embolization ceased in all but one patient receiving dextran, although the dose had to be increased in seven patients (36%). One patient was unable to receive adequate dextran therapy because of severe cardiac failure. Overall, the 30-day death/stroke rate was 2.2%, no patient had a perioperative stroke because of carotid thrombosis, and the rate of ipsilateral embolic stroke was 0.8%. Most complications resulted from cardiac pathology or intracranial hemorrhage., Conclusions: A program of monitoring and quality control assessment has been associated with a 60% decrease in the operative risk in comparison with that observed before implementation of the protocol.

Whether exercise causes right ventricular ischemia severe enough to depress right ventricular function is still controversial. Therefore, right ventricular function was evaluated in 44 patients with isolated coronary artery disease of either the proximal left anterior descending or right coronary artery during exercise (n = 22) or balloon occlusion during percutaneous transluminal coronary angioplasty (PTCA) (n = 22). Central hemodynamics and right ventricular volumes were determined using a new thermodilution Swan-Ganz catheter. Exercise increased right ventricular end-diastolic volume index [from 89 (66-127) to 101 (70-130) ml m-2, p = 0.00005; median (range)] and stroke volume index [from 44 (27-68) to 53 (36-75) ml m-2, p = 0.0005]. During PTCA, right ventricular end-diastolic volume index remained unchanged, while stroke volume index decreased from 49 (38-60) to 40 (26-49) ml m-2 (p = 0.00005). The decrease in right ventricular ejection fraction during exercise from 56 (41-64) to 52% (39-64) reached only borderline significance (p = 0.06) and was significantly (p = 0.02) smaller than during angioplasty [from 53 (44-62) to 41% (25-66; p = 0.0008)]. Right ventricular ejection fraction did not differ between left anterior descending or right coronary artery obstruction and did not depend on right ventricular afterload. In comparison to exercise angioplasty caused a decreased systolic pressure-volume ratio and a leftward shift of the diastolic pressure-volume curve. In conclusion, exercise has only little effect on right ventricular ejection fraction, whereas inadequate oxygen supply during balloon angioplasty induces severe depression of right ventricular function.

Only few data exist concerning right ventricular function in the chronic stage after cardiac transplantation. Therefore, we investigated hemodynamic and right ventricular volumetric data by a computerized thermodilution Swan-Ganz catheter in 17 patients (median age: 53, range: 18-63 yr) at a median of 24 (4 to 44) months after cardiac transplantation during rest and supine bicycle exercise. Myocardial biopsy showed grade one or less according to the classifications of Billingham. Sixteen patients with coronary artery disease, but without prior myocardial infarction, served for comparison. While angiographic left ventricular ejection fraction was nearly identical in transplant recipients [77 (60-92)%, median (range)] and in patients with coronary artery disease [78 (64-94)%], right ventricular ejection fraction was lower (p < 0.001) in patients after cardiac transplantation [37 (16-58)%] as compared to patients with coronary artery disease [56 (46-62)%]. In transplant recipients right atrial pressure was significantly higher both at rest [10 (2-18) mmHg] and exercise [18 (8-30) mmHg] than in patients with coronary artery disease [5 (1-11) and 8 (3-18) mmHg]. Pulmonary capillary wedge pressure behaved similar in both groups. To further evaluate reasons for right ventricular impairment, a correlation analysis was performed. This showed a negative correlation between right ventricular ejection fraction and the time interval after transplantation (p < 0.0002). However, there was no correlation between right ventricular ejection fraction and acute rejection or a rejection score. In conclusion, right ventricular function may be severely altered in transplant recipients, in contrast to an only slight impairment of left ventricular function.

In 29 patients with stable ischaemic heart disease, right heart catheterization was performed to assess the effect of exercise and nitroglycerin on right ventricular volumes, which were determined by a new computerized thermodilution system. The coefficient of variation for the determination of right ventricular ejection fraction averaged 11.0 +/- 6.2% (mean +/- standard deviation) at rest and 14.6 +/- 8.1% during exercise. End-diastolic volume index increased from 90 (65-127) ml/m2 [median (range)] at rest to 101 (81-130) ml/m2 (P less than or equal to 0.0001) during exercise. Nitroglycerin reduced this parameter at rest to 77 (44-121) ml/m2 (P less than or equal to 0.05), without affecting exercise values. Resting right ventricular ejection fraction (55 [44-64]%) was diminished by both exercise (to 52 [39-62]%, P less than or equal to 0.05) and nitroglycerin (to 53 [40-65]%, P less than or equal to 0.05). Additionally, nitroglycerin reduced the exercise induced decrease of right ventricular ejection fraction from -3 (-20-10)% to -1 (-15-14)% (P less than or equal to 0.01). Nitroglycerin diminished the left-to-right interventricular end-diastolic pressure gradient, which was estimated from the difference between pulmonary capillary wedge pressure and right atrial pressure, at rest from 6 (1-17) mmHg to 5 (2-14) mmHg (P less than or equal to 0.05) and during exercise from 17 (6-31) mmHg to 14 (1-33) mmHg (P less than or equal to 0.001). It is concluded, that both exercise and nitroglycerin cause significant changes in right ventricular volumes.(ABSTRACT TRUNCATED AT 250 WORDS)