Pause for thought? Syncope and sinus arrest as the presenting feature of temporal lobe epilepsy.

Some forms of focal epilepsy, including temporal lobe epilepsy, are rarely associated with ictal bradycardia and sinus node arrest. We report a case of a previously healthy man presenting with syncope in whom telemetry revealed sinus arrest. Initial treatment was with permanent pacemaker implantation and it was only following a subsequent grand mal seizure that other symptoms suggestive of temporal lobe epilepsy were documented. Anti-epileptic medication was subsequently commenced with resolution of all symptoms. There are few previously reported cases of syncope and documented sinus node arrest as the presenting feature of temporal lobe epilepsy.

Determinants of clinical effectiveness and significant neurological diagnoses in an urgent brain cancer referral pathway in the United Kingdom.

BACKGROUND: Cerebral tumours can rapidly progress to life-threatening complications yet referral pathways often result in non-significant diagnoses. We aimed to identify the determinants of referrals resulting in significant neurological diagnoses after specialist review. METHODS: We reviewed all urgent brain cancer referrals to the neurology service at a British district general hospital between January 2009 and September 2013. Time to appointment, frequency of significant neurological diagnoses, appropriateness of referrals and referral heterogeneity across GP practices were measured as determinants of non-significant diagnoses. RESULTS: 31/105 patients received significant neurological diagnoses (29.5%), including ten (9.5%) tumours (7 malignant), although 2 patients were admitted prior to clinic. There was significant heterogeneity between primary care physicians in referral frequency (p = 0.008) and significant diagnoses (p = 0.005). Non-significant diagnoses were more common in inappropriate referrals and if patients were unaware of the potential diagnosis. Seizures or subacute focal symptoms were more likely to result in a significant neurological diagnosis than isolated headache syndromes (odds ratio 3.45, 1.34-18.4, p = 0.008). DISCUSSION: Despite a significant number of important neurological diagnoses and tumours, there were frequent inappropriate or low-risk referrals resulting in non-significant diagnoses, particularly if a headache syndrome was the sole reason for referral.

Platelet size: measurement, physiology and vascular disease.

Platelet volume is a marker of platelet function and activation. It is readily measured as mean platelet volume (MPV) by clinical haematology analysers using sodium citrate as the anticoagulant. Measurement in EDTA can be unreliable since MPV increases significantly in a time-dependent manner. MPV correlates with platelet function and activation, whether measured as aggregation, thromboxane synthesis, beta-thromboglobulin release, procoagulant function, or adhesion molecule expression. MPV is increased in certain vascular risk factor states, including hypercholesterolaemia and diabetes mellitus, but not essential hypertension. It is increased in acute myocardial infarction, acute ischaemic stroke, pre-eclampsia and renal artery stenosis. Importantly, an elevated MPV predicts a poor outcome following myocardial infarction, restenosis following coronary angioplasty, and the development of pre-eclampsia. Research into the epidemiology of MPV is now required to determine whether thrombomegaly is a risk factor for developing vascular disease. Similarly, the physiological mechanisms which regulate MPV within the megakaryocyte need to be elucidated. Whether MPV ever becomes a routinely requested test remains to be seen but changes in methodology will be required first.

Serum S-100 protein, relationship to clinical outcome in acute stroke.

The clinical significance of serum S-100 protein, a protein released by damaged brain tissue, was assessed in patients with acute ischaemic or haemorrhagic stroke and matched controls. Serum S-100 protein concentration was significantly elevated in patients with ischaemic stroke [median (SQR): 0.27 (0.90) microgram/L, n = 68] and haemorrhagic stroke [0.43 (0.23 microgram/L, n = 13] compared to controls [0.11 (0.03) microgram/L, n = 51, P < 0.0001]. Although patients with haemorrhagic stroke had higher serum S-100 concentrations compared to patients with ischaemic stroke, this was not quite statistically significant. Serum S-100 concentrations were related to infarct size, large (total anterior circulation) infarcts concentrations having the highest [0.40 (0.22) microgram/L], and small vessel ('lacunar') infarcts concentrations having the lowest [0.20 (0.60) microgram/L, P < 0.0005] concentrations. S-100 protein concentration was also significantly related to clinical outcome at three months measured using three disability and handicap scales (n = 81): modified Barthel index (rs = -0.285, P = 0.01), modified Rankin score (rs = 0.313, P = 0.004) and Lindley score (rs = 0.262, P = 0.018) with high values associated with poor clinical outcome. Similarly high values of serum S-100 protein were observed in patients who died or were discharged to an institution [median (SQR): 0.63 (0.29) microgram/L and 0.37 (0.13) microgram/L, respectively compared to those who were discharged home [0.26 (0.11) microgram/L, P = 0.13]. The present study suggests measurement of serum S-100 protein could be a useful prognostic marker of clinical outcome in acute stroke. Whether S-100 concentrations can be altered by therapeutic intervention in acute stroke remains to be elucidated.

Serum S-100 protein, relationship to clinical outcome in acute stroke.

The clinical significance of serum S-100 protein, a protein released by damaged brain tissue, was assessed in patients with acute ischaemic or haemorrhagic stroke and matched controls. Serum S-100 protein concentration was significantly elevated in patients with ischaemic stroke [median (SQR): 0.27 (0.09) microgram/L, n = 68] and haemorrhagic stroke [0.43 (0.23) microgram/L, n = 13] compared to controls [0.11 (0.03) microgram/L, n = 51, P < 0.0001]. Although patients with haemorrhagic stroke had higher serum S-100 concentrations compared to patients with ischaemic stroke, this was not quite statistically significant. Serum S-100 concentrations were related to infarct size, large (total anterior circulation) infarcts concentrations having the highest [0.40 (0.22) microgram/L], and small vessel ('lacunar') infarcts concentrations having the lowest [0.20 (0.06) microgram/L, P < 0.0005] concentrations. S-100 protein concentration was also significantly related to clinical outcome at three months measured using three disability and handicap scales (n = 81): modified Barthel index (rs = -0.285, P = 0.01), modified Rankin score (rs = 0.313, P = 0.004) and Lindley score (rs = 0.262, P = 0.018) with high values associated with poor clinical outcome. Similarly high values of serum S-100 protein were observed in patients who died or were discharged to an institution [median (SQR): 0.63 (0.29) microgram/L and 0.37 (0.13) microgram/L, respectively] compared to those who were discharged home [0.26 (0.11) microgram/L, P = 0.13]. The present study suggests measurement of serum S-100 protein could be a useful prognostic marker of clinical outcome in acute stroke. Whether S-100 concentrations can be altered by therapeutic intervention in acute stroke remains to be elucidated.

Nitric oxide donors (nitrates), L-arginine, or nitric oxide synthase inhibitors for acute ischaemic stroke.

BACKGROUND: Nitric oxide has several effects that may be beneficial in ischaemic stroke and useful in the management of hypertension in acute stroke. Some forms of nitric oxide synthase inhibition may also be beneficial. However, high concentrations of nitric oxide are likely to be toxic to brain tissue. OBJECTIVES: The objective of this review was to assess the effects of nitric oxide donors, L-arginine, or nitric oxide synthase-inhibitors in people with acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (July 1997), Medline (for trials from 1965), Embase (from 1980) and ISI (from 1981). We contacted drug companies and researchers in the field. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing nitric oxide donors, L-arginine, or nitric oxide synthase-inhibitors in patients within one week of onset of confirmed ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the inclusion criteria. MAIN RESULTS: No completed trials were found. One small placebo-controlled trial of glyceryl trinitrate patches is underway. REVIEWER'S CONCLUSIONS: There is currently no evidence from randomised trials on the effects of nitric oxide donors, L-arginine, or nitric oxide synthase-inhibitors in patients with acute ischaemic stroke.

Wound contraction: a review.

A review of research into the role played by contraction in wound healing.

Measuring quality of life in patients with granulating wounds.

A discussion of the potential value of quality of life studies in patients with granulating wounds.

Comparing Allevyn cavity wound dressings and Silastic foam.

An assessment by staff and patients of two cavity wound dressings in the treatment of surgical granulating cavity wounds.

Quantification of cell types in human granulation tissue.

This study is concerned with acute surgical granulating wounds such as those which follow excision of hidradenitis suppurativa. The Wound Healing Research Unit, Cardiff, frequently assesses the effect of new dressing materials on such wounds. The aim was to establish the normal histological findings during healing in these wounds before examining the effects of active agents on them. No detailed information has been found in the literature on histological findings in non-experimental human wounds.

The relationship between mean platelet volume, stroke subtype and clinical outcome.

Platelets play a crucial role in the pathophysiology of atherothrombotic disease and are involved in the early thromboembolic phase of ischaemic stroke. Large platelets are known to be more active. We hypothesized that thrombomegaly would be limited to patients with cortical infarction as compared with patients with lacunar infarcts, and that it would be associated with functional outcome. Mean platelet volume (MPV) and platelet count (PC) were studied in 167 hospitalized patients with stroke within 48 h of symptom onset, and 65 age, gender and race matched controls. Stroke was clinically and radiologically sub-typed. MPV was significantly higher in patients with ischaemic stroke than the control group: mean (SD) 7.35 (1.05) vs 7.09 (0.74) fl, 2 P = 0.04; this difference could be explained by MPV being higher in patients with cortical stroke: 7.46 (1.00) fl, 2 P = 0.039, but not lacunar infarction: 7.14 (1.16) fl, 2 P = 1.0. No difference was seen in PC between ischaemic patients and controls: 231 (82) 10(9)/l vs 236 (54) 10(9)/l, 2 P = 0.63. MPV did not change at 3 months post-stroke in surviving patients with ischaemic stroke: 7.39 (1.03) fl vs 7.34 (0.97) fl, 2 P = 0.53. Patients who were dead or dependent at 3 months had a significantly higher baseline MPV and a tendency to a lower PC than those who returned to independence. MPV and PC were not altered in patients with primary intracerebral haemorrhage. No differences in red cell volume was observed. Platelet volume is elevated in acute ischaemic stroke, a finding that persists at 3 months post-stroke and is limited to patients with cortical infarction. Thrombomegaly is a risk factor for a poor outcome after ischaemic stroke.

Can Crohn's disease be diagnosed at laparotomy?

The typical macroscopic features of Crohn's disease have been well described and are widely regarded as sufficient to diagnose the disease at laparotomy. We report six patients undergoing laparotomy for symptomatic Crohn's disease, shown radiologically, who were found to have macroscopically normal small bowel despite careful examination of the bowel by an experienced surgeon. In four cases resection was deferred, but all subsequently deteriorated and required further surgery. Minor abnormalities found by balloon examination of the terminal ileum prompted resection in two further patients. Histology showed an unusually superficial distribution of inflammation, which could explain the negative findings at laparotomy. We conclude that normal laparotomy findings alone do not exclude a diagnosis of clinically important small bowel Crohn's disease. Crohn's disease should be considered in patients with persisting symptoms after negative laparotomy.

Von Willebrand factor, P-selectin and fibrinogen levels in patients with acute ischaemic and haemorrhagic stroke, and their relationship with stroke sub-type and functional outcome.

Although ischaemic stroke is associated with accentuated platelet function, it remains unclear whether this applies to all sub-types, especially lacunar infarcts, which differ from cortical infarction in their patho-aetiology. Similarly, conflicting evidence suggests that haemorrhagic stroke may, or may not, be associated with a hypothrombotic state. Levels of von Willebrand factor (vWF), fibrinogen, and P-selectin were measured within 48 h of ictus in 163 patients with acute ischaemic stroke and 40 patients with acute primary intracerebral haemorrhage, and 33 age, gender and race matched-controls. vW F (IU/dl) was significantly increased in both cortical and lacunar ischaemic stroke, and haemorrhagic stroke, as compared with controls, median (semiquartile range): 158 (25) vs 144 (19) vs 147 (24) vs 114 (16), respectively. Similarly, fibrinogen (g/litre) was increased: 4.80 (0.90) vs 4.65 (0.70) vs 4.35 (0.83) vs 3.70 (0.70). In contrast, soluble P-selectin (ng/ml) was increased in cortical stroke as compared with lacunar infraction patients or controls: 408 (101) vs 300 (108) vs 324 (121), respectively; P-selectin was not increased in haemorrhagic stroke, 360 (153). Both vW F and fibrinogen correlated with 3-month functional outcome (modified Rankin score): r = 0.371 (2 P = 0.0006), and r = 0.195 (2 P = 0.042), respectively; however, P-selectin was not associated with outcome: r = 0.188 (2 P = 0.084). The results suggest that increases in vW F and fibrinogen in all types of stroke reflect an acute phase response; in contrast, increased soluble P-selectin levels in cortical stroke, but not lacunar infarction, suggest that platelets contribute to the patho-aetiology of some subtypes of ischaemic stroke.

Pathophysiological assessment of nitric oxide (given as sodium nitroprusside) in acute ischaemic stroke.

Acute ischaemic stroke is characterised by reductions in local cerebral blood flow (CBF) and activation of circulating platelets and leucocytes. Nitric oxide is a vasodilator and can inhibit these circulating cells. The aim of this study was to assess the effect of nitric oxide on platelet function and regional CBF in patients with acute ischaemic stroke. Sodium nitroprusside (SNP), a spontaneous nitric oxide donor, was administered at a dose which caused a 10 mm Hg fall in mean arterial blood pressure (MABP) in a pathophysiological study to 22 patients with acute ischaemic stroke and 12 matched control subjects. Platelet function (whole blood aggregation and flow cytometry) was assessed before and during SNP administration. Changes in regional CBF were measured using single photon emission computerised tomography (SPECT) scanning. SNP significantly reduced platelet aggregation in both the patient and control subject groups. Equally, the expression of platelet adhesion molecules P-selectin (CD62) and glycoprotein (GP) GP IIIa (CD61) were significantly reduced in both groups. GP Ia (CDw49b) expression was significantly attenuated in the patient but not in the control group. Four patients underwent SPECT scanning and improvements in local CBF corresponding to the penumbral area of the clinical stroke site were seen in 3 of these patients. A total of 24 regions of asymmetrical perfusion were examined, pre-SNP (median (SQR)), 0.68 (0.14) vs. peri-SNP 0.78 (0.17), 2p = 0.065. SNP, given at a dose which reduced MABP by 10 mm Hg, significantly inhibited platelet aggregation and adhesion molecule expression. Improved regional CBF was seen in some patients. SNP is a candidate therapeutic agent for patients with acute ischaemic stroke and warrants further study.

The King's College Hospital Acute Stroke Unit.

The King's College Hospital (KCH) Acute Stroke Unit (ASU) was set up in January 1994 in order to provide acute management for patients admitted with stroke and to undertake biomedical research. Of 206 patients admitted to KCH with a stroke or suffering an in-hospital stroke, 141 (68%) patients were admitted to the ASU over its first 6 months of operation: 120 (85%) were from the Accident and Emergency Department and 21 (15%) from other wards. Management included resuscitation and medical stabilisation, investigation, prevention of stroke complications (including aspiration, venous thrombosis, and pressure sores), rehabilitation (physiotherapy, occupational therapy, speech and language therapy), nutrition (dietetics) and initiation of secondary prevention measures (aspirin or anticoagulation, blood pressure and lipid lowering, and carotid endarterectomy). All aspects of management are driven by agreed guidelines. Patients remain under the care of the admitting physician but specific stroke management and guidance is provided by two research doctors and the unit's nurses, therapists and dietician. The unit also facilitates research into stroke pathophysiology and acute therapeutic interventions. Our experience suggests that an ASU is relatively easy to set up and may contribute to improved care. Whether ASUs improve patient survival and functional outcome, and are cost-effective, requires further study.

Endovascular treatment of carotid dissecting aneurysms.

BACKGROUND AND PURPOSE: Cervical arterial dissection is a well-recognised cause for acute ischaemic stroke. Dissecting aneurysms commonly occur in the affected vessels contributing to the clinical presentation. Persistence of these aneurysms may provide a source of future embolic events as well as causing local symptoms or even be at risk of spontaneous rupture. METHODS: We describe 4 patients with traumatic internal carotid artery (ICA) dissections with aneurysm formation at the skull base. Three of the 4 patients still had carotid aneurysms on follow-up investigations and so underwent endovascular procedures using stenting and coil techniques. The carotid aneurysm resolved spontaneously in the fourth patient. RESULTS: The endovascular procedures resulted in significant reduction or obliteration of the flow within the carotid aneurysms with restoration of the true lumen diameter in the adjacent ICA in all 3 patients. No perioperative complications were experienced except for transient headache in 2 patients. CONCLUSIONS: In patients with persistent aneurysms the exact risk of subsequent ischaemic events remains unknown and prospective long-term studies are needed to ascertain this risk. If recurrent stroke rates are found to be high, then carotid stenting (with or without coil insertion) is a feasible invasive approach which could be considered in these patients.

Serum neuron-specific enolase, carnosinase, and their ratio in acute stroke. An enzymatic test for predicting outcome?

BACKGROUND AND PURPOSE: Few admission variables adequately predict neuronal damage and prognosis in individual patients after stroke. Therefore, there is a need for a reliable non-invasive surrogate measure of clinical outcome. METHODS: We have developed a surrogate measure of stroke outcome using the ratio of serum neuron-specific enolase (NSE) to human serum carnosinase (HSC) in 124 patients with acute ischemic or hemorrhagic stroke and 61 matched control subjects. Serum NSE is known to rise and HSC to fall after neuronal injury such as cerebral ischemia. RESULTS: Serum NSE levels were significantly higher and HSC levels lower in the patient group. The NSE/HSC ratio was elevated in patients with stroke: median (semiquartile) hemorrhages, 0.072 (0.033); infarcts, 0.039 (0.026); and control subjects, 0.019 (0.014), P = .0001. Patients with a primary intracerebral hemorrhage had nonsignificantly higher ratios than those with an infarct (P = .082). The NSE/HSC ratio was significantly associated with 90-day outcome measured in two out of three disability and handicap scales: modified Barthel Index (rs = -.34, P = .001), modified Rankin Scale (rs = .30, P = .002), and Lindley Score (rs = .19, P = .057). Patients who died or were institutionalized had higher ratios than those who were discharged home: 0.069 (0.043) versus 0.038 (0.024), P = .011. Correlations between the NSE/HSC ratio and outcome were comparable to those between patient age or consciousness level on admission and clinical outcome. CONCLUSIONS: We believe that measurement of NSE, HSC, or their ratio may be useful in the assessment of patients with acute stroke with respect to diagnosis and prediction of clinical outcome.

Investigation of variant Creutzfeldt-Jakob disease and other human prion diseases with tonsil biopsy samples.

BACKGROUND: Prion diseases are associated with the accumulation of an abnormal isoform of cellular prion protein (PrPSc), which is the principal constituent of prions. Prions replicate in lymphoreticular tissues before neuroinvasion, suggesting that lymphoreticular biopsy samples may allow early diagnosis by detection of PrPSc. Variant Creutzfeldt-Jakob disease (variant CJD) is difficult to distinguish from common psychiatric disorders in its early stages and definitive diagnosis has relied on neuropathology. We studied lymphoreticular tissues from a necropsy series and assessed tonsillar biopsy samples as a diagnostic investigation for human prion disease. METHODS: Lymphoreticular tissues (68 tonsils, 64 spleens, and 40 lymph nodes) were obtained at necropsy from patients affected by prion disease and from neurological and normal controls. Tonsil biopsy sampling was done on 20 patients with suspected prion disease. Tissues were analysed by western blot to detect and type PrPSc, by PrP immunohistochemistry, or both. FINDINGS: All lymphoreticular tissues obtained at necropsy from patients with neuropathologically confirmed variant CJD, but not from patients with other prion diseases or controls, were positive for PrPSc. In addition, PrPSc typing revealed a consistent pattern (designated type 4t) different from that seen in variant CJD brain (type 4) or in brain from other CJD subtypes (types 1-3). Tonsil biopsy tissue was positive in all eight patients with an adequate biopsy sample and whose subsequent course has confirmed, or is highly consistent with, a diagnosis of variant CJD and negative in all patients subsequently confirmed to have other diagnoses. INTERPRETATION: We found that if, in the appropriate clinical context, a tonsil biopsy sample was positive for PrPSc, variant CJD could be diagnosed, which obviates the need for a brain biopsy sample to be taken. Our results also show that variant CJD has a different pathogenesis to sporadic CJD.