Foot Drop: Looking Beyond Common Peroneal Nerve Palsy: A Neurophysiology Centre Experience.

Foot drop is a complex symptom with a considerable range in aetiology, severity and prognosis. We aim to characterise the aetiologies of foot drop and assess the diagnostic contribution of neurophysiologic testing (NCS/EMG). Retrospective review of consecutive referrals of foot drop to the Neurophysiology Department in Cork University Hospital was performed over a two year period (January 2012 to December 2013). Of a total of 59 referrals, common peroneal nerve (CPN) palsy comprised only slightly more than half of cases; 3(5%) have central origin; 3(5%) have motor neuron disease. Six (10%) have diabetes; 7(12%) have cancer; 5(8%) were bilateral. NCS/EMG altered initial working diagnosis in 14 out of 52 (27%) cases whereby initial diagnosis was provided. However one-third of all cases revealed additional coexistent pathology in an anatomic location remote to that of the primary diagnosis. Foot drop with central and proximal localisations are important and under recognised. NCS/EMG is valuable and also reveals additional pathology which warrants investigation.

An unusual presentation of Guillain-Barré syndrome in a young man with bilateral upper extremity weakness.

A 30-year-old man attended the emergency department with a 4-day history of progressive, bilateral upper limb weakness. He had mild shortness of breath and occasional swallowing difficulties. One month prior to presentation, he had flu-like symptoms and diarrhoea. Examination revealed upper limb hypotonia, symmetrical distal arm weakness and hyporeflexia. Power and reflexes in the lower limbs were normal. Nerve conduction studies and lumbar puncture demonstrated features consistent with Guillain-Barré syndrome (GBS). The patient was treated with a 5-day course of intravenous immunoglobulins. He improved significantly over the next 2 weeks. Breathing and swallow function did not deteriorate and required no further intervention. He had a sustained improvement, and remained at baseline 1 year later. Work-up for underlying structural, infectious, inflammatory and paraneoplastic aetiologies were negative. Serum antiganglioside antibodies were positive for the anti-GT1a IgG isotype supporting the clinical diagnosis of the pharyngeal-cervical-brachial variant of GBS.

Profound and persistent painful paclitaxel peripheral neuropathy in a premenopausal patient.

The authors herein report the case of a 35-year-old woman undergoing adjuvant therapy for node positive breast cancer, who presented with short and rapidly progressive history of bilateral lower limb symptoms of peripheral neuropathy following therapy with paclitaxel. MRI of her neural axis revealed no leptomeningeal enhancement or focal metastatic lesions. Neurophysiological tests favoured toxic sensory axonal polyneuropathy. She remains symptomatic following discontinuation of therapy 20 months ago, and is under review with pain management.

Unusual paraneoplastic syndromes of breast carcinoma: a combination of cerebellar degeneration and Lambert-Eaton Myasthenic Syndrome.

INTRODUCTION: Paraneoplastic neurological disorders are rare complications of breast carcinoma. Lambert-Eaton Myasthenic Syndrome (LEMS) is most commonly associated with small cell lung cancer. However, a combination of LEMS and subacute cerebellar degeneration as paraneoplastic syndromes is extremely rare, and has never been described in association with breast cancer. CASE: We report for the first time an unusual association of LEMS and paraneoplastic subacute cerebellar degeneration with breast carcinoma. CONCLUSION: In patients with atypical LEMS, when there is no evidence of respiratory malignancy, breast cancer should be included in the differential diagnosis.

A review of nerve conduction studies in cases of suspected compression neuropathies of the upper limb.

INTRODUCTION: Entrapment neuropathies, particularly those affecting upper limbs, are common reasons for referral for nerve conduction studies (NCS). However, concordance between clinical findings and NCS findings, especially in patients being considered for intervention including decompressive surgery, has not been assessed. METHODS: We conducted a retrospective study using records from a tertiary referral centre's neurophysiology database. We aimed to establish the proportions of agreement between the suspected clinical diagnosis as defined by the referring clinician and NCS findings in the setting of an upper limb entrapment neuropathy. RESULTS: Of the 571 referrals for NCS, suspected bilateral carpal tunnel syndrome was the commonest reason for referral (30.5%). In total, there was 51.5% concordance between suspected clinical diagnosis and NCS findings. Patients with NCS evidence of an entrapment neuropathy (n = 437) were more likely to be older compared to those with normal studies (54.0 +/- 15.6 years vs. 45.9 +/- 13.4 years, p < 0.001). Those with normal NCS findings were more likely to be female (72%, p = 0.001). An alternative or additional diagnosis was found in 14%. CONCLUSION: This study raises concerns regarding the appropriateness of referral for decompressive surgery based on clinical diagnosis alone as many have an additional or alternative diagnosis as suggested by NCS findings.

Vacuolar leucoencephalopathy and pulvinar sign in association with coeliac disease.

Several neurological disorders have been associated with coeliac disease, including epilepsy, ataxia and neuropathy. Here we report a rare case of white matter disease in a 55-year-old man with coeliac disease. He presented with anxiety, headache and left upper limb jerking. He subsequently developed epilepsy and brain MRI revealed diffuse white matter abnormality. He died 6 months after presentation due to status epilepticus and sepsis. Brain biopsy demonstrated vacuolar leucoencephalopathy with no evidence of vCJD. An extensive clinical screen excluded infectious, inflammatory and para-neoplastic causes for this condition. Coeliac disease may be causally associated with vacuolar leucoencephalopathy in this case.

Non-traumatic brachial plexopathies, clinical, radiological and neurophysiological findings from a tertiary centre.

OBJECTIVE: To establish the clinical characteristics, aetiology, neuro-physiological characteristics, imaging findings and other investigations in a cohort of patients with non-traumatic brachial plexopathy (BP). METHODS: A 3-year retrospective study of patients with non-traumatic BP identified by electromyography (EMG) and nerve conduction studies (NCS). Clinical information was retrieved from patients' medical charts. RESULTS: Twenty-five patients were identified. Causes of BP included neuralgic amyotrophy (NA) (48%), neoplastic (16%), radiation (8%), post infectious (12%), obstetric (4%), rucksack injury (4%), thoracic outlet syndrome (4%) and iatrogenic (4%). Patients with NA presented acutely in 50%. The onset was subacute in all others. Outcome was better for patients with NA. All patients with neoplastic disease had a previous history of cancer. MRI was abnormal in 3/16 patients (18.8%). PET scanning diagnosed metastatic plexopathy in two cases. CONCLUSIONS: NA was the most common cause of BP in our cohort and was associated with a more favourable outcome. The authors note potentially discriminating clinical characteristics in our population that aid in the assessment of patients with brachial plexopathies. We advise NCS and EMG be performed in all patients with suspected plexopathy. Imaging studies are useful in selected patients.

Who receives specialist palliative care in Western Australia--and who misses out.

OBJECTIVES: To describe the characteristics of Western Australian (WA) people who received, and did not receive, specialist palliative care (SPC) during their last 12 months of life. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: People who died between 1 July 2000 and 31 December 2002 in WA, and whose cause of death was from cancer or selected non-cancer conditions. MAIN OUTCOME MEASURES: Use of SPC in the last 12 months of life. RESULTS: There were 27,971 deaths from all causes in WA over the study period. Two-thirds (68%) of people who died of cancer received SPC, but less than one in ten (8%) who died of selected non-cancer conditions received SPC. Those who died of cancer were significantly less likely to receive SPC if they were single or widowed, aged > 85 years or lived in a region other than a major city. Of those who died of selected noncancer conditions, people other than those who were married were significantly less likely to have accessed SPC. Indigenous people were less likely to have accessed SPC, although this was not statistically significant (OR = 0.70, 95% CI: 0.36-1.34). CONCLUSIONS: Within a WA context, this study confirms established international evidence for problems of access to SPC by non-cancer patients and other disadvantaged groups. Importantly, this evidence is provided at a population level, thus documenting the extent of inequities in palliative care service provision. By pointing to the areas of most critical need, this study assists in health service policy and planning.

Estimating the size of a potential palliative care population.

OBJECTIVES: To develop a method for estimating the population who could potentially benefit from receiving palliative care in the last year of their lives, and then apply the estimates to the Western Australian population to ascertain characteristics of these people. METHODS: Three estimates of the potential palliative care population, Minimal, Mid-range and Maximal, were developed through focus groups, interviews and the literature. These estimates were applied to the cohort of people who died in Western Australia between 1 July 2000 and 31 December 2002 by linking death records with hospital morbidity data through the Western Australian Data Linkage System. RESULTS: Between 0.28% and 0.50% of people in the Western Australian population in any one year could potentially benefit from palliative care, many of whom die from conditions other than neoplasms. While neoplasms accounted for 59.5% of all underlying causes of deaths in the Minimal Estimate, heart failure (21.0%), renal failure (9.8%), chronic obstructive pulmonary disease (9.6%), Alzheimer's disease (4.0%), liver failure (3.2%), Parkinson's disease (1.3%), motor neurone disease (0.9%), HIV/AIDS (<0.01%) and Huntington's disease (<0.01%) accounted for other conditions in this estimate. The study was expanded to include Mid-range and Maximal Estimates. Characteristics of the Western Australian population in these three estimates are described. CONCLUSIONS: Unlike traditional palliative care estimates that focus on malignant disease, this study included nonmalignant conditions in a set of three estimates of a potential palliative care population. By using population-based data to describe characteristics of people who compose palliative care populations, these results offer a tool for planning equitable healthcare services.

The heating of gas in a galaxy cluster by X-ray cavities and large-scale shock fronts.

Most of the baryons in galaxy clusters reside between the galaxies in a hot, tenuous gas. The densest gas in their centres should cool and accrete onto giant central galaxies at rates of 10-1,000 solar masses per year. No viable repository for this gas, such as clouds or new stars, has been found. New X-ray observations, however, have revealed far less cooling below X-ray temperatures than expected, altering the previously accepted picture of cooling flows. As a result, most of the gas must be heated to and maintained at temperatures above approximately 2 keV (ref. 3). The most promising heating mechanism is powerful radio jets emanating from supermassive black holes in the central galaxies of clusters. Here we report the discovery of giant cavities and shock fronts in a distant (z = 0.22) cluster caused by an interaction between a radio source and the hot gas surrounding it. The energy involved is approximately 6 x 10(61) erg, the most powerful radio outburst known. This is enough energy to quench a cooling flow for several Gyr, and to provide approximately 1/3 keV per particle of heat to the surrounding cluster.

Video-EEG recording: a four-year clinical audit.

In the setting of a regional neurological unit without an epilepsy surgery service as in our case, video-EEG telemetry is undertaken for three main reasons; to investigate whether frequent paroxysmal events represent seizures when there is clinical doubt, to attempt anatomical localization of partial seizures when standard EEG is unhelpful, and to attempt to confirm that seizures are non-epileptic when this is suspected. A clinical audit of all telemetry performed over a four-year period was carried out, in order to determine the clinical utility of this aspect of the service and to determine means of improving effectiveness in the unit. Analysis of the data showed a high rate of negative studies with no attacks recorded. Of the positive studies approximately 50% showed non-epileptic attacks. Strategies for improving the rate of positive investigations are discussed.

Role of EspF in host cell death induced by enteropathogenic Escherichia coli.

Enteropathogenic Escherichia coli (EPEC) causes diarrhoea in children in developing countries. Many EPEC genes involved in virulence are contained within the locus of enterocyte effacement (LEE), a large pathogenicity island. One of the genes at the far righthand end of the LEE encodes EspF, an EPEC secreted protein of unknown function. EspF, like the other Esps, is a substrate for secretion by the type III secretory system. Previous studies found that an espF mutant behaved as wild type in assays of adherence, invasion, actin condensation and tyrosine phosphorylation. As EPEC can kill host cells, we tested esp gene mutants for host cell killing ability. The espF mutant was deficient in host cell killing despite having normal adherence. The addition of purified EspF to tissue culture medium did not cause any damage to host cells, but expression of espF in COS or HeLa cells caused cell death. The mode of cell death in cells transfected with espF appeared to be pure apoptosis. EspF appears to be an effector of host cell death in epithelial cells; its proline-rich structure suggests that it may act by binding to SH3 domains or EVH1 domains of host cell signalling proteins.

Translocated EspF protein from enteropathogenic Escherichia coli disrupts host intestinal barrier function.

The mechanisms by which enteropathogenic Escherichia coli (EPEC), an important cause of diarrhea among infants in developing countries, induce symptoms are not defined. EPEC have a type III secretion system required for characteristic attaching and effacing changes that modify the cytoskeleton and apical surface of host cells. Infection of polarized intestinal epithelial cell monolayers by EPEC leads to a loss of transepithelial electrical resistance, which also requires the type III secretion system. We demonstrate here that EspF, a protein that is secreted by EPEC via the type III secretion system, is not required for quantitatively and qualitatively typical attaching and effacing lesion formation in intestinal epithelial cells. However, EspF is required in a dose-dependent fashion for the loss of transepithelial electrical resistance, for increased monolayer permeability, and for redistribution of the tight junction-associated protein occludin. Furthermore, the analysis of EPEC strains expressing EspF-adenylate cyclase fusion proteins indicates that EspF is translocated via the type III secretion system to the cytoplasm of host cells, a result confirmed by immunofluorescence microscopy. These studies suggest a novel role for EspF as an effector protein that disrupts intestinal barrier function without involvement in attaching and effacing lesion formation.

Rapid activation of basolateral potassium transport in human colon by oestradiol.

1. We investigated the effect of oestradiol on basolateral potassium channels in human colonic epithelium. 2. Ion transport was quantified using short circuit current (I:(sc)) measurements of samples mounted in Ussing chambers. Serosal K transport was studied using nystatin permeabilization of the apical membrane. Intracellular pH changes were quantified using spectroflouresence techniques. 3. Experiments were performed with either 10 nM or 1 microM Ca(2+) in the apical bathing solution. With 10 nM Ca(2+) in the apical bathing solution addition of oestradiol (1 nM) to the basolateral bath produced a rapid increase in current (delta I(K)=11.2+/-1.2 microA.cm(-2), n=6). This response was prevented by treatment of the serosal membrane with tolbutamide (1 microM). With 1 microM Ca(2+) in the apical bathing solution addition of oestradiol produced a rapid fall in current (delta I(K)=-12.8+/-1.4 microA.cm(-2)), this response was prevented by treatment of the basolateral membrane with tetra-pentyl-ammonium (TPeA). These responses were rapid and occurred independently of protein synthesis. 4. Inhibition of basolateral Na(+)/H(+) exchange with either amiloride or a low sodium bathing solution prevented this response. These responses were prevented by inhibition of protein kinase C (PKC) with bis-indolyl-maleimide. 5. Oestradiol (1 nM) produced a rapid intracellular alkanization (mean increase=0.11 pH units; n=6; P<0.01). 6. These results suggest that oestradiol rapidly modulates serosal K transport in human colon. These effects depend upon intact Na(+)/H(+) exchange and protein kinase C. We propose a non-classical, possibly membrane linked, mechanism for oestradiol action in human colonic epithelium.

Bone-marrow micrometastases in patients with brain metastases from epithelial cell tumours.

Carcinoma that has metastasized to the central nervous system (CNS) poses a particular clinical problem regarding confirmation of the diagnosis and subsequent management. Prior to excision, thorough evaluation for coexisting systemic disease is essential, but current imaging techniques are limited by their spatial resolution and under-stage many patients. We evaluated the potential utility of bone-marrow evaluation for micrometastatic cells in patients with CNS metastasis. Bone-marrow aspirates were examined for cytokeratin-positive cells in 12 consecutive patients who presented with symptomatic space-occupying lesions of the CNS. These patients had previously undergone surgical excision of either gastrointestinal or breast cancers. All twelve had micrometastases in their bone marrow at the time of presentation with the CNS disease and all had a fatal outcome within 13 months. In nine of the 12 patients, bone-marrow micrometastases were the only evidence for systemic spread. Three patients had elevated serum tumour markers and two of these had radiologically detectable recurrence elsewhere. Bone-marrow micrometastases indicate concurrent systemic involvement and a poor prognosis. The results suggest that bone-marrow evaluation for systemic spread is a useful diagnostic adjunct and should be performed before considering diagnostic biopsy or excision.

Role of EspB in experimental human enteropathogenic Escherichia coli infection.

Enteropathogenic Escherichia coli (EPEC), a leading cause of diarrhea among infants in developing countries, induces dramatic alterations in host cell architecture that depend on a type III secretion system. EspB, one of the proteins secreted and translocated to the host cytoplasm via this system, is required for numerous alterations in host cell structure and function. To determine the role of EspB in virulence, we conducted a randomized, double-blind trial comparing the ability of wild-type EPEC and an isogenic DeltaespB mutant strain to cause diarrhea in adult volunteers. Diarrhea developed in 9 of 10 volunteers who ingested the wild-type strain but in only 1 of 10 volunteers who ingested the DeltaespB mutant strain. Marked destruction of the microvillous brush border adjacent to adherent organisms was observed in a jejunal biopsy from a volunteer who ingested the wild-type strain but not from two volunteers who ingested the DeltaespB mutant strain. Humoral and cell-mediated immune responses to EPEC antigens were stronger among recipients of the wild-type strain. In addition, four of the volunteers who ingested the wild-type strain had lymphoproliferative responses to EspB. These results demonstrate that EspB is a critical virulence determinant of EPEC infections and suggest that EspB contributes to an immune response.

Palliative care in a multicultural society: perceptions of health care professionals.

This study assesses the perceived competence of 191 Australian palliative care professionals in delivering crosscultural care. The relationship between the perceived competence levels of professionals and their experience and training is examined. Strategies to improve crosscultural palliative care, as suggested by palliative care providers, are also presented. Information about perceived competence and the kinds of difficulties encountered in crosscultural palliative care interactions form the basis of suggested guidelines for proposed education programmes. The results of this study suggest that specific education, rather than individual experience of crosscultural interactions, which may not always be positive, is needed to improve the competence of palliative care professionals. Education, therefore, is the key to the provision of culturally appropriate care to patients and their families from all cultural backgrounds.