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Neoadjuvant chemotherapy (NACT) is routinely administered to subsets of breast cancer patients, including triple negative (TN) or human epidermal growth factor receptor 2-positive (HER2+) cancers. After NACT and subsequent surgical resection, 5% to 30% of patients have no residual invasive carcinoma, termed pathological complete response. Unfortunately, many patients experience little-to-no response after NACT and unnecessarily suffer its side effects. Methods are needed to predict an individual patient’s response to NACT. Core needle biopsies, taken before NACT, consist of tumor cells and the surrounding extracellular matrix. We performed second-harmonic generation (SHG) imaging of fibrillar collagen in core needle biopsy sections as a possible predictor of response to NACT. The ratio of forward-to-backward scattering (F/B) SHG was assessed in the “tumor bulk” and “tumor–host interface” in HER2+ and TN core needle biopsy sections. Patient response was classified post-treatment using the Residual Cancer Burden (RCB) score. In HER2+ biopsies, RCB class was associated with F/B derived from the tumor–stromal interface, but not tumor bulk. F/B was not associated with RCB class in TN biopsies. These findings suggest that F/B from needle biopsy sections may be a useful predictor of which patients will respond favorably to NACT, with the potential to help reduce overtreatment.

Power-frequency magnetic field exposure science as it relates to men and couples have not been explored despite the advantage of this information in the design and interpretation of reproductive health epidemiology studies. This analysis examined the distribution and temporal variability of exposures in men, and the correlation of exposures within couples using data from a longitudinal study of 25 men and their female partners recruited from an infertility clinic. The average and 90th percentile demonstrated fair to good reproducibility, whereas the maximum showed poor reproducibility over repeated sampling days, each separated by a median of 4.6 weeks. Average magnetic field exposures were also strongly correlated within couples, suggesting that one partner's data could be used as a surrogate in the absence of data from the other for this metric. Environment was also an important effect modifier in these explored matters. These issues should be considered in future relevant epidemiology studies.

Background Hyperadrenocorticism is an endocrine disease routinely encountered within primary care practice; however, few studies evaluating survival beyond diagnosis have studied this population. Methods This retrospective cohort study analysed the electronic patient records of 219 cases of hyperadrenocorticism from a sample of dogs attending primary care practices in England. Kaplan-Meier plots examined the cumulative survival and Cox proportional hazard regression modelling identified factors associated with the hazard of all-cause mortality. Results In the analysis, 179/219 (81.7 per cent) hyperadrenocorticism cases died during the study period with a median survival time from first diagnosis of 510 days (95% CI 412 to 618 days). Trilostane was used in 94.1 per cent of cases and differentiation between pituitary-dependent and adrenal-dependent disease was made in 20.1 per cent of cases. In the multivariable analysis, dogs weighing greater than or equal to 15 kg (HR 1.51, 95% CI 1.06 to 2.15, P=0.023) and those diagnosed greater than or equal to 13 years of age (HR 3.74, 95% CI 2.29 to 6.09, P

Skeletal tumour burden is a biomarker of prognosis and survival in cancer patients. This study proposes a novel method based on the linear quadratic model to predict the reduction in metastatic tumour burden as a function of the absorbed doses delivered from molecular radiotherapy treatments. The range of absorbed doses necessary to eradicate all the bone lesions and to reduce the metastatic burden was investigated in a cohort of 22 patients with bone metastases from castration-resistant prostate cancer. A metastatic burden reduction curve was generated for each patient, which predicts the reduction in metastatic burden as a function of the patient mean absorbed dose, defined as the mean of all the lesion absorbed doses in any given patient. In the patient cohort studied, the median of the patient mean absorbed dose predicted to reduce the metastatic burden by 50% was 89 Gy (interquartile range: 83–105 Gy), whilst a median of 183 Gy (interquartile range: 107–247 Gy) was found necessary to eradicate all metastases in a given patient. The absorbed dose required to eradicate all the lesions was strongly correlated with the variability of the absorbed doses delivered to multiple lesions in a given patient (r = 0.98, P

The lack of molecular diagnosis in the field of cancer in Iraq has motivated us to perform a genetic analysis of pediatric acute myelogenous leukemia (AML), including class I and II aberrations. Peripheral blood or bone marrow cells were collected from 134 AML children aged ≤15 years. Flinders Technology Associates (FTA) filter paper cards were used to transfer dried blood samples from five Iraqi hospitals to Japan. DNA sequencing was performed to identify class I mutations. Nested RT-PCR was used to detect class II aberrations, except that MLL rearrangement was detected according to long distance inverse-PCR. NPM1 and FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations were analyzed by GeneScan using DNA template. Among 134 Iraqi pediatric AML samples, the most prevalent FAB subtype was M2 (33.6 %) followed by M3 (17.9 %). Class I mutations: 20 (14.9 %), 8 (6.0 %), and 8 (6.0 %) patients had FLT3-ITD, FLT3-TKD, and KIT mutations, respectively. Class II mutations: 24 (17.9 %), 19 (14.2 %), and 9 (6.7 %) children had PML-RARA, RUNX1-RUNX1T1, and CBFB-MYH11 transcripts, respectively. MLL rearrangements were detected in 25 (18.7 %) patients. NPM1 mutation was detected in seven (5.2 %) cases. Collectively, approximately 30 % of AML children were proved to carry favorable prognostic genetic abnormalities, whereas approximately 10 % had high FLT3-ITD allelic burden and needed a special treatment plan including allogeneic hematopoietic stem cell transplantation. Acute promyelocytic leukemia (APL) was frequent among Iraqi pediatric AML. It is likely that molecular diagnosis using FTA cards in underdeveloped countries could guide doctors towards an appropriate treatment strategy.

BACKGROUND: The benefit of intravenous tissue plasminogen activator (tPA) given within 3 h of acute ischaemic stroke to patients over 80 years of age is uncertain. AIM: To examine the clinical characteristics and complications and the predictors of outcome after intravenous tPA treatment in patients aged > or = 80 years. METHODS: Data (n = 1135) prospectively collected from the Canadian Alteplase for Stroke Effectiveness Study were reviewed and patients aged > or = 80 years (n = 270) treated with intravenous tPA for acute ischaemic stroke were compared with those aged or = 80 years and or = 80 years and in 40% of those or = 80 years than in those aged or = 80 years, stroke severity, baseline Alberta Stroke Program Early CT Score and glucose level were found to be the major independent predictors of outcome. CONCLUSION: In carefully selected elderly patients, the use of intravenous tPA was not found to be associated with an increased risk of symptomatic intracerebral haemorrhage. Age-related differences were seen in the clinical characteristics and outcome in the elderly population.

Background: Previous studies of prognosis after a transient ischaemic attack (TIA) have recruited patients soon after the event, when the risk of stroke is very high. However, the majority of patients survive for many years after a TIA, and the need for continued preventive treatment to lower vascular risk will need to be reassessed at a later date. Obective: To determine the long term risks of stroke and other vascular events in patients with TIA who survive the initial high risk period. Methods: 290 patients were studied who had initially been followed up after a TIA in the Oxford community stroke project and in a contemporaneous hospital based cohort study, and who were alive and stroke-free at the end of planned follow up in 1988. All patients were followed for a further 10 years, and the risks of major vascular events (stroke, myocardial infarction, vascular death) were determined. Standardised mortality ratios (SMR) were calculated from the observed numbers of fatal events and the number expected on the basis of age and sex in the general population. Results: Median time since last TIA was 3.8 years (interquartile range, 2.2 to 5.8 years). The risk of major vascular events was constant through time. The 10 year risk of first stroke was 18.8% (95% confidence interval (CI), 13.6 to 23.7; 45 events). The 10 year risk of myocardial infarction or death from coronary heart disease was 27.8% (95% CI, 21.8 to 33.3; 67 events) and there was a significant excess of fatal coronary events compared with that expected in the general population (SMR = 1.47; 95% CI, 1.10 to 1.93; p = 0.009). A total of 114 patients had at least one major vascular event, with a 10 year risk of any first stroke, myocardial infarction, or vascular death of 42.8% (95% CI, 36.4 to 48.5). Conclusions: The overall risk of major vascular events remains high for 10 to 15 years after a TIA. It is important therefore that preventive treatments are continued in the long term, even in apparently "low risk" patients who have already survived free of stroke for several years.

Pathological examination has been the gold standard for diagnosis in cancer and its role has also included the elucidation of etiology, pathogenesis, clinicopathological correlation, and prognostication. The advent of newer technologies and the realization that breast cancer is heterogeneous has shifted the focus to prognostication, with increased attention being paid to the identification of morphological features and immunohistochemical markers of prognostic relevance. However, despite the massive efforts invested in the identification of immunohistochemical biomarkers in breast cancer the majority have not proven to be of value in multivariate analyses and only estrogen receptor, progesterone receptor, and Her2/neu expression have remained essential components of pathological examination. These 3 markers were initially employed for prognostication but their role in treatment also rendered them of predictive value. Newer molecular methods, especially high-throughput technologies, have shown that even morphologically similar subtypes of breast cancer can show molecular heterogeneity; moreover, infiltrating ductal carcinoma can be separated into at least 4 molecular subtypes designated luminal (ER+, PR+, and Her2/neu–), Her2 overexpressing (ER–, PR–, and Her2/neu+), basal-like (ER–, PR–, Her2/neu–, and CK5/6+, EGFR+), and normal breast-like (ER–, PR–, and Her2/neu–), each with different clinical outcomes. The importance of proliferative gene expression in these subtypes has been demonstrated and surrogate immunohistochemical markers include ER, PR, Her2/neu, and Ki67 for the more expensive molecular tests. Molecular technologies, importantly, have not only provided further insights into the heterogeneity of breast cancer but have also opened new avenues for treatment through the identification of signaling molecules important in the proliferation and survival of the neoplastic cells. The treatment of cancer thus shifts from the conventional approach of ‘one size fits all’ to one of personalized treatment tailored to the specific characteristics of the tumor. Pathologists continue to play their traditional role in diagnosis but, as purveyors of the excised tissue, pathologists now have the additional role of identifying biomarkers responsive to therapeutic manipulation, thus playing an inextricable role as diagnostic oncologists in the management of breast cancer.

Introduction Pancreatic cancer has a poor prognosis with

Background Research suggests that women have higher mortality after acute myocardial infarction (AMI) than men. Potential factors to explain this disparity include delay to presentation, less aggressive interventional strategies, and more severe disease at coronary angiography in women. Methods Consecutive patients (n=663) presenting to coronary care between Jan 2002 and Jan 2005 with ischemic type chest pain and AMI (troponin T >0.09ng/ml) were recruited. Details of the presentation and management were obtained from the medical notes. The primary endpoint was three month all cause mortality. Results Of these patients 31% (205/663) were female. Mean age of women was 70 (SD 11) and 63 (SD 13) for men (p

Objective: To determine whether any common maternal-fetal variable has prenatal predictive value of prosthetic repair in congenital diaphragmatic hernia. Methods: This was a 5-year single-center retrospective review of fetal congenital diaphragmatic hernia referrals. Multiple prenatal variables were correlated with the need for a prosthetic repair. Statistical analyses were by Fisher’s exact and Mann-Whitney U-tests, as appropriate (p < 0.05). Results: Fetal liver position was a predictor of prosthetic repair. The presence or absence of liver herniation was correlated with prosthetic repair rates of 83.3 and 23.1%, respectively (p < 0.001). All patients with moderate/severe liver herniation required a prosthetic patch. Conclusion: Liver herniation has prenatal predictive value for the need for prosthetic repair in congenital diaphragmatic hernia. This finding should be valuable during prenatal counseling for clinical trials of engineered diaphragmatic repair.

Deliberate ingestion of foreign bodies is common amongst prison inmates. The motives behind the ingestion are variable. As the only designated hospital in Northern Ireland treating acute surgical pathologies in the prison population, we reviewed our experience of foreign body ingestion between March 1998 and June 2007. Types of foreign objects, symptomatology, haematological analyses, radiological findings, operative intervention and complications were retrieved from case notes. A literature search was performed using Medline to correlate this clinical data with published evidence to produce therapeutic guidelines to assist the surgical multi-disciplinary team. Eleven prisoners presented with foreign body ingestion over the study period (M=8 and F=3, mean age: 28.1 years, range 21-48). Mean follow-up was 597 days (range 335-3325 days). Although the literature states that most foreign bodies usually pass spontaneously without the need for intervention, this study demonstrates a higher intervention rate of 36% within the Northern Irish prison population in comparison with other prisoners.

Objective: To compare the clinical aspects of peripheral neuropathy associated with Wegener’s granulomatosis (WG), Churg–Strauss syndrome (CSS) and microscopic polyangiitis (MP). Methods: Cohort study conducted in a single university hospital. Patients were included when a definite diagnosis of WG, CSS or MP was made according to the current classification criteria in our hospital, between 1999 and 2006. All patients underwent periodically clinical and electrophysiological screening for peripheral neuropathy, assessment of disability, and clinical and laboratory evaluation during a mean follow-up of 38 months. Results: Sixty-four consecutive patients diagnosed with WG (26 patients), CSS (26 patients) and MP (12 patients) were recruited. Peripheral neuropathy occurred in 27/64 patients: six with WG, 15 with CSS and six with MP. Neuropathy occurred earlier in the disease history in CSS and MP compared with WG. Among patients with WG, those who developed peripheral neuropathy during follow-up were older than those without neuropathy both at the time of onset and of diagnosis of vasculitis. Distal symmetric polyneuropathy was present in 11 patients, and single or multiple mononeuropathy in 16. Patients with WG had a less severe form of mononeuritis multiplex than CSS or MPA patients. Disability and pain were greater in patients with mononeuropathy, although one-third of them were painless. Relapses of neuropathy were extremely infrequent. Conclusions: Peripheral neuropathy in WG occurs less frequently, later in the disease course and in a milder form than in CSS and MP. Single or multiple mononeuropathy associated with these subsets of vasculitis can often be painless.

Background: Measurement of the duration of post-traumatic amnesia (PTA) is common practice, serving as an important index of the severity of traumatic brain injury (TBI) and a predictor of functional outcome. However, controversy exists regarding the nature of PTA; some studies indicate that it is a confusional state with symptoms that extend beyond disorientation and amnesia. Objective: To evaluate the contribution of the severity of acute confusion 1 month after TBI to prediction of employment at 1 year after injury, comparing it with PTA duration. Methods: Prospective study involving 171 participants with complete data, who met the study criteria, from 228 consecutive TBI Model System admissions. Outcome measures included weekly administration of the Delirium Rating Scale-Revised-98 (DelRS-R98) to measure the severity of acute confusion. Evaluations closest to 1 month after injury were used for study purposes. Duration of PTA was defined as the interval from injury until two consecutive Galveston Orientation and Amnesia Test scores of ⩾76 were obtained within a period of 24–72 h. Univariable and multivariable logistic regression were used to predict employment status at 1 year after injury. Results: Age, education and DelRS-R98 were significant predictors accounting for 34% of outcome variance. Individuals with greater confusion severity at 1 month after injury, older age and lower levels of education were less likely to be employed at 1 year after injury. Severity of confusion was more strongly associated with employment outcome (r s = −0.39) than was PTA duration (r s = −0.34). Conclusions: In addition to demographic indices, severity of acute confusion makes a unique contribution to predicting late outcome after TBI.

The issue of when to start treatment in Parkinson's disease (PD) remains controversial. Some favour treatment at diagnosis while others opt for a "wait and watch" policy. The effect of the latter policy on the self reported health status of people with PD is unknown.To record self reported health status through longitudinal use of a validated PD specific questionnaire (PDQ-39) in untreated PD patients in multiple centres in the UK. To compare patients who were left untreated with those who were offered treatment during follow-up.A multicentre, prospective, "real life" observational audit based study addressing patient reported outcomes in relation to self reported health status and other sociodemographic details.198 untreated PD were assessed over a mean period of 18 months. During two follow-up assessments, the self reported health status scores in all eight domains of the PDQ-39 and the overall PDQ-39 summary index worsened significantly (p0.01) in patients left untreated. In a comparative group in whom treatment was initiated at or soon after diagnosis, there was a trend towards improvement in self reported health status scores after treatment was started.This study addresses for the first time self reported health status, an indicator of health related quality of life, in untreated PD. The findings may strengthen the call for re-evaluation of the policy to delay treatment in newly diagnosed patients with PD.

Background: The mismatch between perfusion and diffusion lesions on magnetic resonance perfusion-weighted imaging (PWI)/diffusion-weighted imaging (DWI) may help identify patients for thrombolysis. Evidence underlying this hypothesis was assessed. Methods: All papers describing magnetic resonance PWI/DWI findings in patients with acute ischaemic stroke, and their functional and/or radiological outcome at 1 month, with or without thrombolysis were systematically reviewed. Results: 11 papers fulfilled the inclusion criteria. Among these, there were 5 different mismatch definitions and at least 7 different PWI methods. Only 3 papers including 61 patients with and 18 without mismatch provided data on mismatch, outcome and influence of thrombolysis. Mismatch ( v no mismatch) without thrombolysis was associated with a non-significant twofold increase in the odds of infarct expansion (odds ratio (OR) 2.2, 95% confidence interval (CI) 0.34 to 14.1), which did not change with thrombolysis (OR 2.0, 95% CI 0.37 to 10.9). Half of the patients without mismatch also had infarct growth (with or without thrombolysis). No data were available on functional outcome. Conclusions: Standardised definitions of mismatch and perfusion are needed. Infarct growth may occur even in the absence of mismatch. Currently, data available on mismatch are too limited to guide thrombolysis in routine practice. More data are needed from studies including patients with and without mismatch, and randomised treatment allocation, to determine the role of mismatch.

On the basis of preliminary evidence from patients with subarachnoid haemorrhage (SAH), axonal degeneration is thought to be an underestimated pathological feature.A longitudinal study in 17 patients with aneurysmal SAH. Ventricular CSF was collected daily for up to 14 days. The neurofilament heavy chain(SMI35) (NfH(SMI35), a biomarker for axonal damage) was quantified using a standard ELISA (upper limit of normal 0.73 ng/ml). The primary outcome measure was the Glasgow Outcome Score (GOS) at 3 months.Of 148 samples from patients with SAH, pathologically high NfH levels in the CSF were found in 78 (52.7%) samples, compared with 20 (5%) of 416 samples from the reference population (p0.0001). A pathological increase in NfH was observed in all patients with a bad outcome (GOS 1-3) compared with 8% of those with a good outcome (GOS 4-5, p0.0001). This increase typically became significant 7 days after the haemorrhage (p0.01). The result was confirmed by analysing the individual mean NfH concentrations in the CSF (3.45 v 0.37 ng/ml, p0.01), and was reinforced by the inverse correlation of NfH in the CSF with the GOS (r = -0.65, p0.01). Severity of injury was found to be correlated to NfH(SMI35) levels in the CSF (World Federation of Neurological Surgeons, r = 0.63, p0.01 and Glasgow Coma Score, r = -0.61, p0.01).Patients with SAH thus have secondary axonal degeneration, which may adversely affect their outcome.

Background: Severe head injury (SHI) is one of the most important health, social and economic problems in industrialised countries. Unfortunately, none of the neuroprotection trials for traumatic brain injury have shown efficacy. One of the reasons for this failure could be the inclusion of patients with high probability of early death. A population-based, retrospective study was conducted to develop a prognostic model for identification of these patients. Methods: Between January 1987 and August 1999, a total of 895 patients (⩾15 years of age) with non-missile SHI were studied, in whom a computed tomography scan was carried out within the first 6 h of injury. The association between early death (first 48 h after injury) and independent prognostic factors was determined by logistic regression analysis. A scoring system was also constructed. Results: The early-death rate was 20%. Independent predictors of early mortality after SHI were non-evacuated mass (odds ratio (OR) 65, 95% confidence interval (CI) 11 to 379), diffuse injury IV (OR 25, 95% CI 5 to 112), diffuse injury III (OR 8, 95% CI 3 to 22), flaccidity (OR 7, 95% CI 3 to 15), non-reactive bilaterally mydriasis (OR 6, 95% CI 3 to 12), evacuated mass (OR 4, 95% CI 1 to 11), age ⩾65 years (OR 4, 95% CI 1 to 9), decerebration (OR 3, 95% CI 2 to 7) and shock (OR 3, 95% CI 2 to 6). The prognostic model correctly identified 93% of the patients. Conclusions: This prognostic model is based on simple clinical and radiological data readily available during the first 6 h after injury and is useful for identification of early death after SHI.

Background: Little is known about long term prognosis and course after immune treatments in chronic inflammatory demyelinating polyneuropathy (CIDP). Objective: To study long term outcomes and prognostic factors in patients with CIDP. Methods: Clinical and electrophysiological findings, responses to immune modulating treatments, and outcomes five years after the start of treatment were reviewed in 38 CIDP patients. Results: Patients were treated with corticosteroids (89%), immunoglobulin infusion (45%), or plasmapheresis (34%), and 58% received combined therapy. Five years after treatment was begun, 10 (26%) of the patients had complete remission (lasting >2 years with normal nerve conduction studies), and 23 (61%) had partial remission (able to walk) with (26%) or without (34%) immune treatments. The remaining five patients (13%) still had severe disability (unable to walk) or treatment dependent relapses. Patients with complete remission more often had subacute onset, symmetrical symptoms, good response to initial corticosteroid treatment, and nerve conduction abnormalities predominant in the distal nerve terminals. In contrast, insidious onset, asymmetrical symptoms, and electrophysiological evidence of demyelination in the intermediate nerve segments were associated with refractoriness to treatment or treatment dependent relapse. Conclusions: The long term prognosis of CIDP patients was generally favourable, but 39% of patients still required immune treatments and 13% had severe disabilities. Mode of onset, distribution of symptoms, and electrophysiological characteristics may be prognostic factors for predicting a favourable outcome.

Objective: To present a large series of surgically treated tuberculum sellae meningiomas with particular regard to involvement of the optic canal and visual outcome. Methods: A retrospective analysis was done on 53 patients (40 female) with meningiomas originating from the tuberculum sellae who underwent surgery between 1991 and 2002. The standard surgical approach consisted of pterional craniotomy. Sixteen meningiomas extended posteriorly onto the diaphragma sella, 29 anteriorly to the planum sphenoidale, and 19 to the anterior clinoid process. Thirty seven tumours involved the optic canal, three bilaterally. Follow up ranged from 6 to 108 months (mean 29.9 months). Results: Total macroscopic resection was achieved in 48 patients. Median tumour size was 2.6 cm. Postoperatively, visual acuity improved in 20 patients and deteriorated in seven. Preoperative and postoperative visual acuity worsened with increasing duration of preoperative symptoms and with increasing age. Extension into the intraconal space was a negative predictor. However, tumour size did not influence visual acuity. Recurrence occurred in two cases (21 and 69 months postoperatively). Two patients died from causes unrelated to the tumour. Conclusions: In the majority of patients with tuberculum sellae meningiomas, total resection may be achieved through a pterional approach with minimal complications.

Objectives: Several models for prediction of short term outcome after intracerebral haemorrhage (ICH) have been published, however, these are rarely used in clinical practice for treatment decisions. This study was conducted to identify current models for prediction of short term outcome after ICH and to evaluate their clinical applicability and relevance in treatment decisions. Methods: MEDLINE was searched from 1966 to June 2003 and studies were included if they met predefined criteria. Regression coefficients of multivariate models were extracted. Two neurologists independently evaluated the models for applicability in clinical practice. To assess clinical relevance and accuracy of each model, in a validation series of 122 patients the proportion with a ⩾95% probability of death or poor outcome and the actual 30 day case fatality in these patients were calculated. Receiver operator characteristic (ROC) curves were computed for assessment of discriminatory power. Results: A total of 18 prognostic models were identified, of which 14 appeared easy to apply. In the validation series, the proportion of patients with a ⩾95% probability of death or poor outcome ranged from 0% to 43% (median 23%). The 30 day case fatality in these patients ranged from 75% to 100% (median 93%). The area under the ROC curves ranged from 0.81 to 0.90. Conclusions: Most models are easy to apply and can generate a high probability of death or poor outcome. However, only a small proportion of patients have such a high probability, and 30 day case fatality is not always correctly predicted. Therefore, current models have limited relevance in triage, but can be used to estimate the chances of survival of individual patients.

Objective: To assess risk factors and prognosis in patients with refractory status epilepticus (RSE). Methods: We retrospectively analysed all episodes of status epilepticus (SE) treated between 1993 and 2002 on the neurological intensive care unit (NICU) of the Charite-Universitatsmedizin Berlin. The predictive and prognostic features of RSE were compared with non-RSE (NRSE). All patients with "de novo" SE were followed up to identify the possible development of post-SE symptomatic epilepsy. Results: A total of 83 episodes fulfilled our criteria of SE. Of these 43% were refractory to first line anticonvulsants. The mean age of patients with SE was 53.3 (SD 19) years, with only two patients younger than 18 years. Encephalitis was significantly more often the primary cause in RSE (p

Background: The role of admission blood glucose level on the prognosis of patients with intracerebral haemorrhage has not been elucidated. Objective: To examine this association on the basis of an epidemiologically representative patient material. Methods: 249 500 people living in the catchment area of the Central Hospital of Central Finland. The diagnosis of ICH was established if verified by cranial computed tomography (CT) or autopsy. Results: Of the 416 patients who fulfilled the diagnostic criteria, 30 died before admission and 386 were admitted to the Central Hospital. All 329 patients (290 nondiabetics and 39 diabetics) with both admission blood glucose and cranial CT data were included in the study. The mean blood glucose level was 10.6 mmol/l for nondiabetics who died on the day of onset, 8.6 mmol/l for those dying during days 1 to 28, and 6.8 mmol/l for the 28 day survivors. The corresponding figures for diabetics were 13.9 mmol/l, 12.5 mmol/l, and 9.3 mmol/l. In both nondiabetics and diabetics, patients who died had significantly higher mean glucose than the 28 day survivors (p

Objective: In view of the association of the apolipoprotein E ( APOE ) e4 allele with poor outcome after traumatic brain injury we determined the frequency of cerebral amyloid angiopathy (CAA) and the extent of haemorrhagic pathology in relation to APOE genotype in an autopsy series of 88 head injured cases. Methods: Tissue sections from the frontal and temporal lobes were immunostained for amyloid-β peptide (Aβ) and stained for Congo red to identify vascular amyloid pathology. A semiquantitative assessment of contusions, the total contusion index, was used to estimate the severity of the haemorrhagic pathology. APOE genotypes were determined by polymerase chain reaction of genomic DNA extracted from paraffin embedded tissue sections. Results: CAA was present in 7/40 (18%) e4 carriers compared with 1/48 (2%) non-e4 carriers (p = 0.021, 95% confidence interval (CI) for difference in proportions with CAA 3% to 29%) with 6/40 (4 with CAA) e4 carriers being homozygotes. Thus the risk of having CAA for e4 carriers was 8.4 times that for the non-e4 carriers. However, there was no clear tendency for patients with CAA to have more severe or more numerous contusions (median contusion index 19 (CAA) v 14.5, p = 0.23, 95% CI for difference in medians −5 to 14). Conclusions: Presence of CAA in head injured cases was significantly associated with possession of an APOE e4 allele but not with the severity of contusions.

Objectives: To determine under what circumstances repair of unruptured intracranial aneurysms may be beneficial. Methods: A life expectancy analysis of patients with unruptured aneurysms with and without repair based on prospective data from the International Study of Unruptured Intracranial Aneurysms (ISUIA). Results: Life years are lost at all ages by repairing anterior circulation aneurysms under 7 mm in diameter in patients with no history of a subarachnoid haemorrhage from another aneurysm (incidental). For all other aneurysms the number of life years saved by repair is dependent on the patient’s age at the time when repair is undertaken. Between 2 and 40 years are saved by repairing aneurysms in patients aged 20 years. These benefits fall to 0 when remaining life expectancy falls below 15–35 years, corresponding to the age range of 45–70 years. Conclusions: Repair of unruptured aneurysms benefits patients harbouring them by improving life expectancy except in certain circumstances. The exceptions are patients with remaining life expectancy less than 15–35 years or aged 45–70 (depending on aneurysm size and location) and patients with aneurysms of the anterior circulation under 7 mm in diameter with no history of a previous subarachnoid haemorrhage. These results are based on the findings of the ISUIA and are dependent on their accuracy.

Background: There is limited information about predictors of outcome and recurrence of ischaemic stroke affecting young adults. Objective: To assess the predictive value of the presenting characteristics for both outcome and recurrence in young stroke victims. Methods: Clinical and radiological data for 203 patients aged 16 to 45 years were collected prospectively; they comprised 11% of 1809 consecutive patients with ischaemic stroke. The National Institutes of Health stroke scale (NIHSS), the Bamford criteria, and the trial of ORG 10172 in acute stroke treatment (TOAST) classification were used to define stroke severity, subtype, and aetiology. The clinical outcome of 198 patients (98%) was assessed using the modified Rankin scale (mRS) and categorised as favourable (score 0–1) or unfavourable (score 2–6). Results: Stroke was caused by atherosclerotic large artery disease in 4%, cardioembolism in 24%, small vessel disease in 9%, another determined aetiology in 30%, and undetermined aetiology in 33%. Clinical outcome at three months was favourable in 68%, unfavourable in 29%, and lethal in 3%. Thirteen non-fatal stroke, two fatal strokes, and six transient ischaemic attacks (TIA) occurred during a mean (SD) follow up of 26 (17) months. High NIHSS score, total anterior circulation stroke, and diabetes mellitus were independent predictors of unfavourable outcome or death (p

Neurofilament phosphoforms (Nf) are principal components of the axoskeleton released during axonal injury. Cerebrospinal fluid (CSF) levels of Nf phosphoforms might be useful surrogate markers for disability in multiple sclerosis (MS), aid in distinguishing clinical subtypes, and provide valuable prognostic information.Thirty four patients with MS were included in a three year follow up study along with 318 controls with other non-inflammatory neurological diseases. CSF levels of two Nf heavy chain (NfH) phosphoforms (NfH(SMI35), NfH(SMI34)) were quantified at baseline and three year follow up using new ELISA techniques. Levels of NfH phosphoforms, the degree of phosphorylation (NfH(SMI34):NfH(SMI35) ratio), and changes in NfH levels between baseline and follow up (Delta NfH) were related to the clinical phenotype (RR or SP/PP), to three clinical scales (Kurtzke's EDSS, ambulation index (AI), and nine hole peg test (9HPT)), and to progression of disability.A significantly higher proportion (59%) of patients with SP/PPMS experienced an increase in NfH(SMI35) levels between baseline and follow up compared with those with RRMS (14%, p0.05). CSF NfH(SMI34) levels at baseline were higher in patients with SP/PP (11 pg/ml) compared with RR (7 pg/ml, p0.05) and NfH(SMI35) levels were higher at follow up in SP/PP (129 pg/ml) compared with levels below assay sensitivity in RR (p0.05). NfH(SMI35) correlated with the EDSS (r(s) = 0.54, p0.01), the AI (r(s) = 0.42, p0.05), and the 9HPT (r(s) = 0.59, p0.01) at follow up.The increase in NfH during the progressive phase of the disease together with the correlation of NfH(SMI35) with all clinical scales at follow up suggests that cumulative axonal loss is responsible for sustained disability and that high NfH(SMI35) levels are a poor prognostic sign.

Objective: To identify factors predicting improvement in motor disability in writer's cramp treated with botulinum toxin (BTX). Methods: 47 patients with writer's cramp were treated with BTX and were evaluated by the same neurologists at initial referral, after each BTX injection, and when the effect of BTX was maximal at the time of the study. Patients and examiners simultaneously and independently rated the efficacy of BTX injections. Self assessment was a global clinical impression of the impact of treatment on writing quality, writing speed, writing errors, and legibility of handwriting; for objective assessment, the examiners used the Burke-Fahn-Marsden (BFM) scale. Results: On the BFM scale, there was a significant improvement (p

Objectives: To evaluate the influence of clinical, investigational, surgical, and histopathological factors on postoperative seizure relief in patients with mesial temporal lobe epilepsy (MTLE) due to lesions other than ammonshornsclerosis (AHS). Methods: Of 738 patients operated for TLE, 78 patients underwent limited resections for lesional MTLE (1990–2000). Seventy four patients with a follow up of more than one year were included. The preoperative clinical, neuropsychological, electroencephalogram, and neuroimaging characteristics were prospectively collected in a database. The histopathological material was re-examined. Results: The mean follow up was 49 months. Fifty eight patients were classified as seizure free (78.4% Class I), and six as almost seizure free (8.1% Class II), grouped together as satisfactory seizure control (64 patients, 86.5%). Five patients (6.8%) were categorised in Classes III and IV, respectively. These were grouped as unsatisfactory seizure control (10 patients, 13.5%). Surgical procedures were: 32 amygdalohippocampectomies (AH), 17 partial anterior AH, 15 AH plus polar resection, seven AH plus basal resection, and three AH plus extended temporal lesionectomy. There was no mortality and 2.7% mild permanent morbidity. Seizure relief did neither differ significantly with these approaches, nor with different classes of pathological findings (43 developmental tumours, 12 glial tumours, 10 dysplasias, and nine others). Even operation of dysplasias resulted in 80% satisfactory seizure control. Seizure onset during childhood proved to be a negative predictor for seizure relief (p = 0.020). MRI revealed 73 suspected lesions (98.6%), one dysembryoplastic neuroepithelial tumour was missed, in four cases no structural abnormalities could be confirmed with histopathological exam. Additionally, multifactorial regression revealed the factors “seizure onset after 10 years of age”, “presence of complex partial seizures”, “absence of a neurological deficit”, and a “correlating neuropsychological deficit” as predictive for satisfactory seizure control. Conclusions: “Preoperative tailoring” resulting in limit resections has proven to be safe and to provide a very good chance for satisfactory seizure relief in patients with lesional MTLE.

Background: Although movement disorders that occur following a stroke have long been recognised in short series of patients, their frequency and clinical and imaging features have not been reported in large series of patients with stroke. Methods: We reviewed consecutive patients with involuntary abnormal movements (IAMs) following a stroke who were included in the Eugenio Espejo Hospital Stroke Registry and they were followed up for at least one year after the onset of the IAM. We determined the clinical features, topographical correlations, and pathophysiological implications of the IAMs. Results: Of 1500 patients with stroke 56 developed movement disorders up to one year after the stroke. Patients with chorea were older and the patients with dystonia were younger than the patients with other IAMs. In patients with isolated vascular lesions without IAMs, surface lesions prevailed but patients with deep vascular lesions showed a higher probability of developing abnormal movements. One year after onset of the IAMs, 12 patients (21.4%) completely improved their abnormal movements, 38 patients (67.8%) partially improved, four did not improve (7.1%), and two patients with chorea died. In the nested case–control analysis, the patients with IAMs displayed a higher frequency of deep lesions (63% v 33%; OR 3.38, 95% CI 1.64 to 6.99, p

Objectives: The evolutionary pattern of spontaneous recovery from acute neglect was studied by assessing cognitive deficits and motor impairments. Detailed lesion reconstruction was also performed to correlate the presence of and recovery from neglect to neural substrates. Methods: A consecutive series of right brain-damaged (RBD) patients with and without neglect underwent weekly tests in the acute phase of the illness. The battery assessed neglect deficits, neglect-related deficits, and motor impairment. Age-matched normal subjects were also investigated to ascertain the presence of non lateralised attentional deficits. Some neglect patients were also available for later investigation during the chronic phase of their illness. Results: Partial recovery of neglect deficits was observed at the end of the acute period and during the chronic phase. Spatial attention was impaired in acute neglect patients, while non spatial attentional deficits were present in RBD patients with and without acute neglect. A strong association was found between acute neglect and fronto-parietal lesions. Similar lesions were associated with neglect persistence. In the chronic stage, neglect recovery was paralleled by improved motor control of the contralesional upper limb, thus emphasising that neglect is a negative prognostic factor in motor functional recovery. Conclusions: These findings show that spatial attention deficits partially improve during the acute phase of the disease in less than half the patients investigated. There was an improvement in left visuospatial neglect at a later, chronic stage of the disease, but this recovery was not complete.

Objective: To determine the long term visual and neurological outcome of patients diagnosed with cavernous sinus aneurysms (CCAs). Methods: Prospective follow up for at least five years or until death of 31 retrospectively recruited patients (27 women, 4 men) with treated and untreated CCAs. Results: There were 40 aneurysms in all. Mean age at diagnosis was 60.4 years (range 25 to 86; median 64). The most common symptoms were diplopia (61%), headache (53%), and facial or orbital pain (32%). Fifteen patients (48%) were diagnosed after they developed cranial nerve pareses, four (13%) after they developed carotid–cavernous sinus fistulas (CCFs), and 12 (39%) by neuroimaging studies done for unrelated symptoms. Twenty one patients (68%) had treatment to exclude the aneurysm from circulation, 10 shortly after diagnosis and 11 after worsening symptoms. Immediate complications of treatment occurred in six patients and included neurological impairment, acute ophthalmoparesis, and visual loss. Ten patients (32%) were observed without intervention. Over a mean (SD) follow up period of 11.8 (7.7) years, eight had improvement in symptoms, five remained stable, and eight deteriorated. Among the 10 patients followed without intervention, none improved spontaneously, three remained stable, and seven worsened. Conclusions: Most treated patients in this series improved or remained stable after treatment, but none improved without treatment. The long term prognosis for treated cases is relatively good, with most complications occurring immediately after the procedure. Endovascular surgery has decreased the morbidity and mortality of treatment so should be considered for any patient with a CCA.

Objectives: Little is known about the long term outcome of patients with periventricular nodular heterotopia (PNH) and epilepsy, particularly the course of seizures. This study investigated the electroclinical and prognostic features of 16 patients with PNH. Methods: Of 120 patients with epilepsy and malformations of cortical development, 16 had PNH. Of these, eight patients had periventricular nodules only (simple PNH) and eight also presented with other cortical or cerebral malformations (subcortical heterotopia; polymicrogyria; focal dysplasia; schizencephaly; cortical infolding; agenesis of the corpus callosum; mega cisterna magna and cerebellar atrophy) (PNH plus). All patients underwent clinical, neurophysiological, and MRI investigation. The mean follow up was 17.3 years (2–40 years). Results: Two electroclinical patterns emerged: (1) The first pattern, associated with simple PNH, was characterised by normal intelligence and seizures, usually partial, which began during the second decade of life. The seizures never became frequent and tended to disappear or become very rare. The EEG showed focal abnormalities. (2) The second pattern, associated with PNH plus, was characterised by mental retardation and seizures that began during the first decade of life. The seizures were very frequent in most cases and sudden drops were observed in six patients. Seizures were medically refractory in four patients. The EEG showed focal and bisynchronous abnormalities. Conclusions: Two groups of PNH patients with different electroclinical and neuroradiological features can be identified after a long term follow up. The presence of other types of cortical or cerebral malformations, in addition to periventricular nodules, determines a poor prognosis.

Objective: To explore the use and interpretation of self reported on/off diary data for assessment of daily motor fluctuations in Parkinson’s disease. Methods: 26 consecutive non-demented patients with fluctuating Parkinson’s disease received standardised training on how to fill out the four category CAPSIT-PD on/off diary, followed by four hours of clinical observation and four weeks of daytime on/off diaries every 30 minutes at home. Results: Overall patient–clinician agreement in diary entries was good ({kappa} = 0.62; weighted {kappa} = 0.84). Agreement for individual diary categories was good for "off" and "on with dyskinesias" ({kappa} = >=0.72), but moderate for "partial off" and "on" ({kappa} = 0.49). The overall validity of patient kept diaries was supported by expected symptom severity variability across diary categories, as assessed in the clinic. One day’s home diary data failed to predict outcomes from the full four weeks for all diary categories, and data from three days failed to yield good prediction (predefined as R2 = >=~0.7) for the time spent in "off" and "partial off". Data from one week yielded good prediction (R2 = >=0.74) in all instances except "partial off", which could not be well predicted even when two weeks’ home diary data were considered (R2 = 0.52). Conclusions: The data provide support for the overall accuracy and validity of the four category CAPSIT-PD on/off diary, but suggest that a three category diary format may improve accuracy and validity. Interpretation of diary data beyond the assessed time frame should be made with caution unless diaries have been kept for sufficiently long periods.

Objectives: Hepatitis C virus (HCV) infection is often associated with cryoglobulinaemia (CG). Peripheral neuropathy (PN) is a comparatively common complication of CG associated with HCV infection and it is thought to be attributable to nerve ischaemia. Only few HCV CG patients with PN have been reported. The recent finding of HCV RNA in nerve biopsy specimens has suggested a possible direct role of HCV in the pathogenesis of PN. The authors studied 51 HCV patients to determine the prevalence of CG and to clarify the possible mechanism by which HCV determines the PN. Methods: All the patients were studied clinically, by laboratory tests and electrophysiologically. Twenty eight patients underwent sural nerve biopsy where both morphological and morphometric evaluation of the biopsy specimen was performed, as well as statistical analysis. Results: CG was found in 40 of 51 cases (78%). Polyneuropathy was significantly prevalent in CG+ patients compared with CG- (18 of 40 compared with 1 of 11 patients; p=0.01). HCV CG- patients more frequently developed well defined mononeuropathy or multiple neuropathy when compared with HCV CG+ (10 of 11 compared with 22 of 40; p

Background: The presence of Lewy bodies (LB) in the neocortex and limbic system in patients with Parkinson's disease (PD) is commonly thought to be linked with cognitive impairment. The authors present here a series of patients with diagnosis of PD in life and no significant cognitive impairment who, at necropsy, satisfied the current neuropathological criteria for dementia with Lewy bodies (DLB). Methods: Two hundred and seventy six brains with PD pathology were examined at the Queen Square Brain Bank in London between 1993 and 1999. The neuropathological diagnosis was PD, but 117 patients also had sufficient LB involvement above the brain stem to satisfy the current neuropathological criteria for DLB (50 patients had a neuropathological picture consistent with the limbic category of DLB and 67 with neocortical DLB). Forty eight cases were excluded who developed early cognitive impairment together with motor features of parkinsonism, 12 cases for lack of detailed clinical history, and 19 cases with coexistent features of advanced Alzheimer's disease changes. Thirty eight patients (13.8% of the total with PD pathology and 32.5 % of the total with DLB pathology) were found where there was no or very late cognitive impairment reported in the clinical records. Results: Selected cases were 24 men and 14 women, with a mean (SD) age at onset of parkinsonian symptoms of 60.1 (10.1) years and a mean disease duration of 15.3 (5.5) years. At some time during the evolution of the disease 21 patients developed different degrees of cognitive impairment (after a mean disease duration of 12.2 (4.8) years). Clinical diagnosis at death was PD in 10 cases and PD with dementia in 11. In the remaining 17 patients no history of cognitive impairment was ever recorded in life and all of them had a clinical diagnosis of PD at death; in this subgroup, nine patients later revealed a neuropathological picture consistent with limbic (or transitional) category of DLB and eight with neocortical DLB. Interestingly, in all these patients the parkinsonian features including the response to dopaminergic drugs were indistinguishable from classic brain stem PD. Conclusions: The authors demonstrate that the classic pathology of DLB can commonly be seen outside the generally accepted clinical spectrum for DLB and that important factors other than the absolute number of LB in the neocortex and limbic system influence the development of cognitive impairment in PD. Furthermore, the pathology of PD may be indistinguishable from that reported in DLB, suggesting that the two clinicopathological syndromes may be attributable to the same biological abnormality.

Objectives: To investigate (1) the prevalence of various aspects of cognitive and psychosocial dysfunction, including post-traumatic stress symptoms, over nine months after subarachnoid haemorrhage (SAH); (2) whether SAH is preceded by increased life stress; (3) to what extent adverse outcomes may be predicted from preillness life stress, early neurological impairment, age, and sex; and (4) relations between emotional and functional outcomes. Methods: 52 patients with good neurological recovery after surgery for SAH were each matched for age, sex, and occupation with a healthy control participant. SAH patients were assessed three and nine months postdischarge on measures of cognitive functioning, mood, and social functioning. Objective stressors and subjective life change during the preceding year were rated retrospectively. Controls completed measures of mood and social functioning once only. Results: Compared with controls, SAH patients showed increased mood disturbance, subtle cognitive impairment, and abnormally low independence and participation on measures of social functioning. 60% showed clinically significant post-traumatic stress symptomatology (intrusive thoughts or avoidance of reminders) at three months and 30% at nine months. Independence in activities of daily living was greatly reduced in half to a third of the sample at both three and nine months. Productive employment was below the 10th percentile of the control group for 75% of patients at three months and for 56% at nine months; this outcome could not be predicted from selected demographic, premorbid, or clinical variables but dependence on others for organisational activities was predicted by impaired prose recall. Mood at nine months was strongly predicted by prior mental health problems, poor physical health, dysphasia, and impaired prose recall at three months. There was no evidence of an abnormally high level of stressful life events in the year before SAH, although patients rated their subjective level of stress in this period slightly more highly than did the control participants. Conclusions: These findings highlight the need for structured support and treatment after surgery for SAH to reduce persisting mood disturbance and increase independence and participation.

Objectives: To determine whether the extent of white matter high intensity lesions (WML) on magnetic resonance imaging (MRI) is an independent predictor of risk for stroke from arteriolosclerosis, and whether serial evaluation of WML can be used to identify patients who are at risk of strokes. Methods: Prospective follow up with serial MRI scans was done in 89 patients who were either diagnosed as having symptomatic lacunar infarcts or were stroke-free, neurologically normal individuals with headache or dizziness. None had significant stenosis of major cerebral arteries or atrial fibrillation. Multivariable analysis with the Cox proportional hazards model was used to test the predictive value for subsequent stroke of risk factor status at entry and during follow up, lacunar infarction, and the extent of WML (scored from 0 to 16) on the baseline scans. Results: During follow up (mean (SD), 51 (19) months), seven strokes occurred (five lacunar infarcts and two haemorrhages): four in nine patients with severe WML (score 9–16), and three in 40 patients with mild WML (score 1–8) (log-rank test; p < 0.005). None of 40 patients without WML experienced stroke. The extent of WML was an independent predictor of subsequent stroke (relative risk for a 1 point score increase, 1.60; 95% confidence interval, 1.02 to 2.54; p < 0.05). In three strokes among 80 patients without severe WML, two occurred in four patients with an increase in WML score during follow up, and one occurred in the other 76 patients without an increased score (p < 0.0001). Conclusions: Severe WML at baseline is an independent predictor of risk for stroke from arteriolosclerosis, while progression of WML during follow up may be associated with subsequent stroke in patients with initially mild WML.

Background: Information collected at baseline can be useful in predicting patient outcome after head injury. The appearance of the CT brain scan may add useful baseline information. The aim of this study was to evaluate which features on the admission CT scan might add significantly to other baseline clinical information for predicting survival in patients with head injury. Methods: Baseline CT scans were reviewed for patients with all grades of traumatic head injury in a head injury registry, in which baseline demographic and injury status and outcome at 1 year were recorded. Details from the CT scan on haemorrhage, brain swelling, and focal or diffuse damage were noted blind to clinical or outcome information and the scans classified according to the simple seven point grading (normal, mild, moderate, or severe focal injury, mild, moderate, or severe diffuse injury). An existing CT scoring system, the trauma coma databank (TCDB) classification, was also used. Logistic regression modelling was used to test the value of the CT appearance, in addition to the other baseline clinical characteristics, in predicting survival at 1 year. Results: 425 CT scans were read from patients with all severities of injury. Significant independent outcome predictors were age, Glasgow coma score (GCS), pupil reaction, presence of subarachnoid blood, and the simple grading of the overall appearance of the scan (all p

Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a heterogeneous disorder having a wide clinical range, and is characterised by multifocal demyelination that can involve the distal nerve terminals, intermediate nerve segments, and nerve roots. Objective: To investigate whether the distribution patterns of demyelination along the course of the nerve correlate with clinical profiles in patients with CIDP. Methods: Motor nerve conduction studies were carried out on 42 consecutive patients. According to the physiological criteria for demyelination, the presence of a demyelinative lesion was determined in the distal nerve segments (distal pattern) or intermediate nerve segments (intermediate pattern), or in both (diffuse pattern). The serum concentration of tumour necrosis factor (TNF)-α was measured by immunoassay. Results: Patients were classified as having a distal (n=10), intermediate (n=13), or diffuse (n=15) pattern, or were unclassified (n=4). Patients with the distal or diffuse pattern had common clinical features such as subacute onset, symmetric symptoms, and weakness involving proximal as well as distal muscles. Patients with the distal pattern had a good response to treatment and a monophasic remitting course, but the diffuse pattern was associated with a treatment dependent relapsing course, reflecting longer disease activity. The serum TNF-α concentrations increased only in the “diffuse” subgroup of patients, and this might be associated with breakdown of the blood-nerve barrier and therefore, involvement of the intermediate segments. The intermediate pattern was characterised by a chronic course, asymmetric symptoms, less severe disability, and refractoriness to treatments. Conclusions: CIDP consists of subtypes with varying predilections for lesions along the course of the nerve. The distribution patterns of conduction abnormalities may be useful in the prediction of outcome of patients with CIDP.

Background Krabbe disease (KD) is an inherited lysosomal storage disease (LSD) caused by the deficiency of galactocerebrosidase (GALC) and is characterized by a severe and progressive leukodystrophy with death frequently before one year of life in the classical early-onset form. As a consequence of the enzyme defect, globoid cells containing undigested galactosylceramide are observed and are characteristic of the disease. Hematopoietic stem cell transplantation is the current treatment for this disease, with some success in the classical cases if performed very early in life. Definitive diagnosis of KD is generally accessed by determination of GALC in leukocytes or fibroblasts. For the last few years, dried-blood filter paper (DBFP) samples have been increasingly used for lysosomal enzyme assays. Originally, some lysosomal enzymes could not be tested in DBFP samples using fluorometric assays, including GALC, heparan-sulfamidase and a few others. Recently, we reported successful results using dried-leukocytes filter paper (DLFP) samples for heparan sulfamidase and β-galactosidase. Extending these studies, we present now a new GALC assay on these type of samples. Methods Adapted leukocyte fluorometric assay was used for the evaluation of GALC in DLFP samples. Results Our results using this method showed a clear discrimination between GALC levels observed in KD patients and healthy controls. Conclusions The assay is robust and reliable and could be adopted by reference laboratories for diagnosis of LSDs. It is expected that the use of DLPF would make it possible to diagnose patients living in isolated areas, where liquid samples usually have to be transported over several days and sometimes across country borders before reaching reference laboratories.

A system to provide surveillance, diagnosis, and protocolized management of surgical intensive care unit (SICU) sepsis was undertaken as a performance improvement project. A system for sepsis management was implemented for SICU patients using paper followed by a computerized system. The hypothesis was that the computerized system would be associated with improved process and outcomes.A system was designed to provide early recognition and guide patient-specific management of sepsis including (1) modified early warning signs-sepsis recognition score (MEWS-SRS; summative point score of ranges of vital signs, mental status, white blood cell count; after every 4 hours) by bedside nurse; (2) suspected site assessment (vascular access, lung, abdomen, urinary tract, soft tissue, other) at bedside by physician or extender; (3) sepsis management protocol (replicable, point-of-care decisions) at bedside by nurse, physician, and extender. The system was implemented first using paper and then a computerized system. Sepsis severity was defined using standard criteria.In January to May 2012, a paper system was used to manage 77 consecutive sepsis encounters (3.9 ± 0.5 cases per week) in 65 patients (77% male; age, 53 ± 2 years). In June to December 2012, a computerized system was used to manage 132 consecutive sepsis encounters (4.4 ± 0.4 cases per week) in 119 patients (63% male; age, 58 ± 2 years). MEWS-SRS elicited 683 site assessments, and 201 had sepsis diagnosis and protocol management. The predominant site of infection was abdomen (paper, 58%; computer, 53%). Recognition of early sepsis tended to occur more using the computerized system (paper, 23%; computer, 35%). Hospital mortality rate for surgical ICU sepsis (paper, 20%; computer, 14%) was less with the computerized system.A computerized sepsis management system improves care process and outcome. Early sepsis is recognized and managed with greater frequency compared with severe sepsis or septic shock. The system has a beneficial effect as a clinical standard of care for SICU patients.Therapeutic study, level III.

Title Encapsulating peritoneal sclerosis – A 5 year experience Aim Encapsulating peritoneal sclerosis (EPS) is a rare, life-threatening condition, characterised by a progressive, intra-abdominal inflammatory process resulting in fibrotic visceral constriction. We report the aetiology, management, and outcome of EPS in Belfast. Method All patients diagnosed with EPS in Belfast over the past 5 years are included. Presentation, aetiology, imaging, pathology, and outcome are retrospectively analysed and reported. Results 7 patients (4 males) were identified with EPS with a mean age 54 years (range 33–69). Aetiology included peritoneal dialysis (3), radiation enteritis (1), peritoneal dialysis and radiation enteritis (1), tuberculosis, cirrhosis, and beta-blocker use (1), infected aorto-bifemoral graft (1). Of the 7 patients, 5 underwent definitive surgery. Bowel conserving surgery (laparotomy, division of adhesions, excision of membrane) was performed in 4 patients. One patient required an ileocaecal resection for radiation enteritis. Median pre-operative and post-operative hospital stay were 25 and 62 days respectively. Three patients required total parenteral nutrition (TPN) pre-operatively, 3 patients post-operatively; with 4 of the 7 patients discharged on TPN. 5 out of 7 patients are alive at median follow-up of 24 months. There was no 30-day in-hospital mortality. Conclusions Patients with EPS often require parenteral nutrition before and after surgery. Peritoneal dialysis is a major risk factor for the development of EPS but other aetiologies should be considered. These patients have multiple co-morbidities, and operations for EPS are challenging with a high risk of peri-operative complications. Therefore these patients are best managed in a specialised unit with experience in intestinal failure surgery and access to a multi-disciplinary nutrition support team.

BackgroundPersistent infection with high-risk (HR) human papillomavirus (HPV) is a well-recognized cause of cervical cancer, but little is known about the situation in Laos. The aims of the study were to determine the prevalence of HR-HPV among Lao women and to evaluate the use of a filter paper card (FTA Elute Micro Card) for collection of cervical cells in the humid tropical climate.MethodsThis is a cross-sectional study including 1922 women from 3 provinces in Laos. During a gynecological examination, cervical cells were collected and applied to the FTA card followed by HPV typing using a real-time polymerase chain reaction (PCR)-based assay.ResultsOverall, 213 of the 1922 women were positive for HR-HPV (11%). The most common type was the group HPV33/52/58 (3%), followed by the single type 16 (2%) and the group 18/45 (1%), respectively. Only 11 cards (0.6%) did not contain a sufficient amount of genomic DNA for polymerase chain reaction–based analysis.ConclusionsThe prevalence of HR-HPV infections in Laos is similar to other Asian countries, and 40% of the women with an HR-HPV infection will be target of the present HPV vaccines. The FTA card is suitable for collection of cervical cells for HR-HPV typing in tropical conditions. This information is important for planning and establishing primary and secondary prevention of cervical cancer in Laos.

The investigation of male infertility is assuming greater importance, with male factors implicated as a causal factor in up to half of infertile couples. Following routine history, examination and blood tests, imaging is frequently utilised in order to assess the scrotal contents for testicular volume and morphology. Additionally, this may give indirect evidence of the presence of possible reversible pathology in the form of obstructive azoospermia. Further imaging in the form of transrectal ultrasound and MRI is then often able to categorise the level of obstruction and facilitate treatment planning without resort to more invasive imaging such as vasography. Ultrasound guidance of therapy such as sperm or cyst aspiration and vasal cannulation may also be performed. This article reviews the imaging modalities used in the investigation of male infertility, and illustrates normal and abnormal findings that may be demonstrated.

Retinal vascular disease is the most common cause of macular edema (ME). While there are several etiologies of vascular compromise and subsequent macular leakage, diabetic retinopathy is the most prevalent and continues to challenge ophthalmologists and frustrate patients due to its refractory nature. In response to this epidemic, diabetic ME (DME) along with cystoid ME (CME) have been areas of active investigation both in the clinic and the laboratory. Several decades of basic science research have revealed a growing and complex array of cytokine growth factors and proinflammatory mediators which are capable of inciting the cellular changes that result in accumulation of fluid within the retina. Much of this new molecular foundation provides the current and fundamental scaffold for understanding the pathologic process of ME while simultaneously identifying potential therapeutic targets. Whereas CME has classically been treated with corticosteroids and nonsteroidal antiinflammatory drugs, recent clinical studies have demonstrated improved visual outcomes for DME treatment with light focal/grid laser, corticosteroids and anti-vascular endothelial growth factor antibodies. Yet, each of these treatments has differential effects on the multifactorial mechanisms of ME. This article reviews the anatomical, cellular and molecular derangements associated with ME and highlights specific pathways targeted by current treatments.

Objective To investigate the effect of font size and paper thickness on the response to, and completion of, a self-completion postal questionnaire among older people with joint pain. Study Design and Setting Randomized trial. People aged 50 years and older with joint pain who consulted a general practitioner at one of five general practices in Central Cheshire were sent a postal questionnaire. Questionnaire format (large or small font size, thick or thin paper) was randomly allocated using a 2 × 2 factorial design. Results Questionnaires were received from 502 out of 650 participants (crude response 77%). Response was significantly higher for participants receiving questionnaires with a larger font size (79.3% vs. 75.2%; hazard ratio 1.26, 95% confidence interval: 1.02, 1.56). Paper thickness had no significant effect on response. Completion (measure by assessing double-page turnover error) was increased in participants receiving questionnaires printed on thicker paper (3.2% vs. 7.1%; P = 0.049) but was not affected by font size. Conclusion This study demonstrates that questionnaires in larger font and on thicker paper may produce higher and more complete responses than surveys using standard size font and standard thickness paper, and should therefore be considered in studies among older people.

Background and aim: Inflammation has been extensively implicated in the pathogenesis of Alzheimer’s disease (AD). Although there is evidence of a key role for cytokines in neuroinflammation processes, so far the proinflammatory cytokine interleukin (IL)-18 has not been associated with AD. The aim of this study was to investigate the impact of two polymorphisms of the human IL-18 gene promoter at positions −607 (C/A) and −137 (G/C) on both susceptibility to and progression of AD. Results: The results revealed that the genotype distribution of the −607 (C/A) polymorphism was different between patients with AD and control subjects (χ 2 = 7.99, df = 2, p = 0.0184). In particular, carriers of the CC genotype were at increased risk of developing AD (OR 2.33; 95% CI 1.29 to 4.22; p = 0.0052). The observed genotypes were in Hardy–Weinberg equilibrium, as for the −607 polymorphism, whereas the −137 polymorphism appeared in Hardy–Weinberg disequilibrium only in the patient group (p = 0.0061). Finally, in a 2 year follow-up study, the −137 CC genotype was strongly and specifically associated with a faster cognitive decline (F = 4.024; df = 4,192; p = 0.0037 for time by IL-18 −137 G/C group interaction) with no interaction effect with the apolipoprotein E e4/non-e4 allele presence. Conclusion: As IL-18 cytokine promoter gene polymorphisms have been previously described to have functional consequences on IL-18 expression, it is possible that individuals with a prevalent IL-18 gene variant have a dysregulated immune response, suggesting that IL-18 mediated immune mechanisms may play a crucial role in AD.

Progression rates in primary progressive multiple sclerosis (PPMS) vary widely and brain magnetisation transfer imaging (MTI) has potential as an early prognostic indicator. We investigated the predictive value of MTI and the longitudinal changes developing over 1 year in early PPMS.To determine (1) whether baseline brain MTI parameters in early PPMS predict clinical changes over 1 year, independent of brain volume and (2) whether a change in magnetisation transfer (MT) parameters occurs over 1 year, independent of atrophy.30 patients with PPMS within 5 years of symptom onset and 15 controls underwent MT and volumetric imaging studies, at baseline and at 1 year. Patients underwent clinical assessment using the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC), including the timed walk subtest (TWT). Normalised MT histograms were generated for whole brain, normal appearing brain tissue (NABT) and normal appearing white and grey matter (NAWM and NAGM) segments. Multiple regression analyses were performed to investigate whether baseline MTR parameters predicted clinical change over 1 year, adjusting for baseline brain volume. MTR changes over 1 year were assessed using paired t tests.In patients, lower baseline NAWM MTR predicted greater deterioration in EDSS and MSFC, particularly in walking ability measured by the TWT, independent of NAWM baseline volume (p = 0.001). NAGM MTR mean (p0.001), and to a lesser extent NAWM mean (p = 0.011) and lesion MTR (p = 0.03), decreased over 1 year.NAWM MTR may provide information on short term clinical prognosis in early PPMS. MTI is sensitive to brain tissue changes over 1 year in early PPMS, which were primarily seen in the NAGM.