Validation of the Arabic Rowland Universal Dementia Assessment Scale (A-RUDAS) in elderly with mild and moderate dementia.

OBJECTIVES: Validated screening tests for dementia in Arabic are lacking. Given the low levels of education among elderly in the Middle East and North Africa region, the commonly used screening instrument, the Mini Mental State Examination, is not best suited. Alternatively, the Rowland Universal Dementia Assessment Scale (RUDAS) was especially designed to minimize the effects of cultural learning and education. The aim of this study was to validate the RUDAS in the Arabic language (A-RUDAS), evaluate its ability to screen for mild and moderate dementia, and assess the effect of education, sex, age, depression, and recruitment site on its performance. METHODS: A-RUDAS was administered to 232 elderly aged ≥65 years recruited from the communities, community-based primary care clinics, and hospital-based specialist clinics. Of these, 136 had normal cognition, and 96 had dementia. Clinicians diagnosed dementia according to the Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV) criteria. Interviewers, blind to the cognitive status of participants, administered A-RUDAS. The psychometric properties of A-RUDAS were examined for three cutoffs. RESULTS: At the cutoff of ≤22, A-RUDAS exhibited good sensitivity (83%) and specificity (85%) with an area under the receiver operating characteristic curve of 83.95%. Adjusting for age, sex, education, depression, and recruitment site, A-RUDAS score demonstrated a high level of accuracy in screening for mild and moderate dementia against DSM-IV diagnosis. CONCLUSION: The A-RUDAS is proposed for dementia screening in clinical practice and in research in Arabic-speaking populations with an optimal cutoff of ≤22.

Cranial nerve VI palsy as a rare initial presentation of systemic lupus erythematosus: case report and review of the literature.

A 48-year-old woman presented with isolated sixth cranial nerve palsy. She subsequently developed systemic lupus erythematosus (SLE) based on clinical and laboratory parameters. Three years later, she presented again with sixth cranial nerve palsy affecting the contralateral eye. Within 2 weeks of steroid initiation, complete recovery occurred. The unusual rare presentation of SLE in the current patient, as well as the pathogenesis and treatment of cranial neuropathy in SLE are discussed.

Early neurologic complications following coronary bypass surgery.

BACKGROUND: Coronary artery bypass surgery is associated with central and peripheral nervous system complications in the period following surgery. Recognising these complications may help in their prevention or early treatment. METHODS: We reviewed medical records of all the patients who underwent coronary artery bypass surgery at our institution over a period of two years. We studied their risk factors, reasons for surgery, operative variables, and post operative neurologic complications. RESULTS: Of the 587 coronary artery bypass surgeries performed at our centre over a two year period. We found that 2.04% of these patients developed neurologic complication in the two weeks following the surgery. Fifty percent of these patients suffered from cerebrovascular insults and 50% suffered from cognitive decline. No patients in this group developed seizures or peripheral nerve lesions. Patients with renal failure, carotid stenosis, history of cerebral strokes, and redo coronary bypass surgery were more predisposed to develop neurologic complications after bypass surgery. Furthermore, a longer stay in the coronary care unit and the development of arrhythmias predisposed patients to neurologic complications. Mortality for patients who developed neurologic complications post bypass surgery ranged between 16.7% and 33.4%. CONCLUSIONS: Around 2% of patients who undergo coronary artery bypass surgery develop neurologic complications in the period directly after the surgery. Patients with previous history of cerebral, coronary, or carotid disease are more predisposed for such complications, as well as patients who spend more time in the intensive units after the surgery.

Validation of the Multiple Sclerosis International Quality of Life questionnaire.

This study aims to validate the Multiple Sclerosis (MS) International Quality of Life (MusiQoL) questionnaire, a multi-dimensional, self-administered questionnaire, available in 14 languages, as a disease-specific quality of life scale that can be applied internationally. A total of 1992 patients with different types and severities of MS from 15 countries were recruited. At baseline and day 21 +/- 7, each patient completed the MusiQoL, a symptom checklist and the short-form (SF)-36 QoL questionnaire. Neurologists also collected socio-demographic, MS history and outcome data. The database was randomly divided into two subgroups and analysed according to different patient characteristics. For each model, psychometric properties were tested and the number of items was reduced by various statistical methods. Construct validity, internal consistency, reproducibility and external consistency were also tested. Nine dimensions, explaining 71% of the total variance, were isolated. Internal consistency and reproducibility were satisfactory for all the dimensions. External validity testing revealed that dimension scores correlated significantly with all SF-36 scores, but showed discriminant validity by gender, socio-economic and health status. Significant correlations were found between activity in daily life scores and clinical indices. These results demonstrate the validity and reliability of the MusiQoL as an international scale to evaluate QoL in patients with MS.

Longitudinal myelitis in patient with systemic lupus erythematosus, homozygous prothrombin G20210A and heterozygous MTHFR 677T.

Longitudinal myelitis is an uncommon complication of systemic lupus erythematosus (SLE). We describe an unusual case of longitudinal myelitis and ischemic stroke in the presence of homozygous prothrombin G20210A, heterozygous MTHFR 677T mutations and the absence of antiphospholipid antibodies in a young woman with SLE.

Reversible attenuation of neuropathic-like manifestations in rats by lesions or local blocks of the intralaminar or the medial thalamic nuclei.

BACKGROUND AND AIM: Thalamic somatosensory nuclei have been classified into medial and lateral systems based on their role in nociception. An imbalance between these two systems may result in abnormal somatic sensations and spontaneous pain. This study aims to investigate the effects of transient or permanent block of the medial and intralaminar nuclear groups on the neuropathic-like behavior in a rat model for mononeuropathy. METHODS: Neuropathy was induced on one hind paw in different groups of rats following the spared nerve injury model. When the resulting hyperalgesia and allodynia (tactile and cold) reached a maximum plateau, the rats received either chemical or electrolytic lesion or lidocaine (2%) microperfusion, placed in the various thalamic nuclear groups. RESULTS: All procedures produced transient but significant decrease of neuropathic manifestations. The magnitude and duration of decrease depended on the type and the site of the block. These effects can be ranked in increasing order as follows, electrolytic

Seroprevalence of toxocariasis in Lebanon: a pilot study.

Toxocariasis is a common helminthic infection that has a worldwide distribution. However, data from Lebanon about the prevalence of this infection are non-existent. We conducted a Toxocara seroprevalence study with 150 subjects attending the outpatient clinics at the American University of Beirut Medical Center between May and June 2004. Serum specimens were tested for anti-Toxocara antibodies by enzyme-linked immunosorbent assay and confirmed by Western blot. Multivariate analysis was performed to identify risk factors for infection. The seroprevalence rate of toxocariasis was 19%. Male gender and below high school education were significantly associated with a positive serological test (odds ratios = 3.1 and 2.8, respectively). Higher numbers of persons in the household, and low family income during childhood, were significant on bivariate analysis only. Toxocariasis is common in Lebanon. A large population-based survey is needed to confirm these results.

Transient attenuation of neuropathic manifestations in rats following lesion or reversible block of the lateral thalamic somatosensory nuclei.

BACKGROUND AND AIMS: Nociceptive behavior in animal models for mononeuropathy has been shown to be altered by spinal tract lesions which suggest a possible supraspinal modulation. The thalamus constitutes a chief center for the processing of nociception. We have, therefore, investigated the effects of transient or permanent blocks of the lateral somatosensory thalamic nuclei (the ventrobasal complex) on the neuropathic manifestations in rats. METHODS: Different groups of rats (n = 5-6) were subjected to mononeuropathy, following the spared nerve injury model, known to produce sustained heat hyperalgesia and tactile and cold allodynia which peaked about 2 weeks after nerve injury. This was followed by stereotaxic placement of either electrolytic or chemical lesions or implantation of mini osmotic pump for slow release of lidocaine in the ventrobasal complex. RESULTS: Chronic electrolytic and chemical lesions or reversible block of the lateral somatosensory thalamus produced transient (1-2 weeks) attenuation of neuropathic manifestations along with a persistent decrease of the hot plate latency. The most pronounced effect was observed on heat hyperalgesia, and the least significant and short-lived effect was observed on cold allodynia. CONCLUSION: We conclude that the lateral somatosensory thalamic complex is involved in the processing of neuropathic manifestations but cannot be considered as an obligatory or exclusive relay center for the neuropathic syndromes.

Involvement of substance P, CGRP and histamine in the hyperalgesia and cytokine upregulation induced by intraplantar injection of capsaicin in rats.

Intraplantar (i.pl.) injection of small doses of capsaicin has been shown to produce hyperalgesia and upregulation of the levels of proinflammatory cytokines. The present work aimed at investigating the possible mediation of these effects by sensory neuropeptides and mast cells. Various groups of rats received i.pl. injection of capsaicin alone or preceded by the injection of antagonists to substance P (SP), calcitonin gene-related protein (CGRP) and histamine (H1, H2) or the mast cell blocker ketotifen. All pretreatments prevented, in a dose-related manner, the capsaicin-induced hyperalgesia. The SP, H2 antagonists and ketotifen prevented the upregulation of all cytokines and nerve growth factor (NGF) levels, while the CGRP and H1 antagonists showed only attenuation of the NGF level.

Thymulin reverses inflammatory hyperalgesia and modulates the increased concentration of proinflammatory cytokines induced by i.c.v. endotoxin injection.

The immunomodulatory thymic hormone thymulin has been shown previously to possess anti-inflammatory actions in the periphery. In this study, we have examined the effect of i.c.v. injections of either endotoxin (ET) or thymulin, in separate groups of conscious rats, on pain-related behavior and cytokine levels in different areas of the brain. Furthermore, we investigated the effect of pretreatment with either i.c.v. or i.p. injections of thymulin on endotoxin-induced hyperalgesia and the effect of pretreatment with i.c.v. thymulin on endotoxin-induced up-regulation of cytokine levels. Our results demonstrate that i.c.v. injection of endotoxin (1 microg in 5 microl saline) resulted in a significant decrease in the nociceptive thresholds as assessed by different pain tests, with peak hyperalgesia at 3 h. However, thymulin at different doses, when injected (i.c.v.), had no significant effect on pain related behavior. Pretreatment (i.c.v.) with thymulin (0.1, 0.5 and 1 microg in 5 microl saline) 20 min before endotoxin (i.c.v.) injection (1 microg in 5 microl saline) reduced, in a dose dependent manner, the endotoxin-induced hyperalgesia and exerted differential effects on the up-regulated levels of cytokines in different areas of the brain. The results provide behavioral and immunochemical characterization of a rat model for intracerebral inflammation and indicates a neuroprotective role for thymulin in the CNS.

Attenuation of neuropathic manifestations by local block of the activities of the ventrolateral orbito-frontal area in the rat.

Clinical and recent imaging reports demonstrate the involvement of various cerebral prefrontal areas in the processing of pain. This has received further confirmation from animal experimentation showing an alteration of the threshold of acute nociceptive reflexes by various manipulations in the orbito-frontal cortical areas. The present study investigates the possible involvement of this area in the modulation of neuropathic manifestations in awake rats. Several groups of rats were subjected to mononeuropathy following the spared nerve injury model, known to produce evident tactile and cold allodynia and heat hyperalgesia. The activity of the ventrolateral orbital areas was selectively blocked by using either chronic or acute injection of lidocaine, electrolytic lesion, or chemical lesion with kainic acid or 6-hydroxydopamine (6-OHDA). The effects of these manipulations were compared with those following lesion of the somatic sensorimotor cortical areas. Local injection of lidocaine resulted in a reversible depression of all neuropathic manifestations while electrolytic or chemical lesions elicited transient attenuation affecting mainly the heat hyperalgesia and to a lesser extent the cold allodynia. The magnitude of the observed effects with the different procedures used can be ranked as follows: 6-OHDA

A thymulin analogue peptide with powerful inhibitory effects on pain of neurogenic origin.

The effects of a synthetic peptide analog of thymulin (PAT) were tested on nociceptive behavior in two animal models for peripheral mononeuropathy and in another two models for capsaicin-induced hyperalgesia. Treatment with PAT (0.25-25 microg/rat, i.p.) produced significant reduction of the mechanical allodynia and heat hyperalgesia in rats subjected to either chronic constriction injury (CCI) or spared nerve injury (SNI) models for mononeuropathy. Cold allodynia was moderately reduced in the CCI model. The inhibition of neuropathic manifestations peaked at 1-2 h post-treatment and disappeared in 3-4 h. Daily treatment with PAT, however, produced progressive attenuation of all neuropathic manifestations in the SNI model. On the other hand, pretreatment with similar doses of PAT produced dose-dependent reduction of the hyperalgesia induced by intraplantar injection of capsaicin (10 microg in 50 microl). The highest dose of PAT (50 microg) produced significant reduction of abdominal aversive behavior induced by i.p injection of capsaicin (20 microg in 100 microl). Compared with the effects of treatment with morphine or meloxicam (injected at single doses known to produce analgesia), PAT exerted equal or stronger inhibitory effects on neuropathic manifestations. The reported results suggest a possible direct action of PAT on afferent nerve fibers but its mechanisms remain to be determined.

Practice patterns of antiphospholipid syndrome at a tertiary teaching hospital in Lebanon.

The objective of the study was to describe the practice patterns of the antiphospholipid syndrome (APS) as compared with consensus guidelines for diagnosis and to determine whether practice patterns correlate with patient demographics and physician specialty. A retrospective medical chart review was conducted at the American University Hospital, in Beirut, Lebanon. All adult and pediatric patients admitted to the hospital between 1 January and 31 December 1998 who underwent either anticardiolipin antibodies (aCL) or lupus anticoagulant (LA) testing were included in the study. Work-up of APS syndrome was compared with: (a) the consensus guidelines for clinical diagnosis; (b) physician specialty; and (c) patient demographics (age, gender, ethnicity, health insurance status). Eighty-seven patients fulfilled at least one clinical criterion for APS; 92% were for work-up of thrombosis and 8% for pregnancy morbidities. Fifty-one percent underwent both aCL and LA. Overall 38% (33) of patients had an abnormal test result, however only 18% (6) underwent retesting, of whom only two satisfied a minimum of 6 weeks between test and retest TheAPS diagnostic work-up was requested by 11 different specialties. Rheumatologists were the most consistent in asking for both tests. APS is seen and diagnosed by a variety of medical specialties. Practice patterns as compared with the latest consensus are sub-optimal, and need to be improved. Interventions to help improve this have been discussed and are being implemented.

Upregulation of proinflammatory cytokines and nerve growth factor by intraplantar injection of capsaicin in rats.

Capsaicin-sensitive primary afferents (CSPA) are known to be involved in nociception and neurogenic inflammation. Extensive research has been devoted to the sensory role of these fibres but less attention has been paid to their local effector function. This study aimed at gaining more insight into the molecular mechanisms underlying the neurogenic inflammation induced by this special group of afferent fibres. Different groups of rats (n = 5 in each group), either naive or subjected to selective ablation of their CSPA, received individual intraplantar injections of saline, capsaicin, its vehicle or capsaicin preceded by its antagonist, capsazepine. Acute tests for nociception were used to assess the variations of the nociceptive thresholds. Variations of the levels of proinflammatory cytokines and nerve growth factor (NGF) were measured by enzyme-linked immunosorbent assay (ELISA). Intraplantar injection of capsaicin (10 microg in 50 microl) produced a sustained thermal and mechanical hyperalgesia that peaked at 3-6 h and disappeared 24 h following the injection. Similar capsaicin injection in further groups of rats produced an early upregulation of the proinflammatory cytokines and NGF, which peaked at 30-60 min and returned to control levels within 2-5 h. Similar effects were observed following the application of either capsaicin or intense electrical stimulation on the cut end of the distal portion of the sciatic nerve. The effects of capsaicin were abolished in rats subjected to selective ablation of their CSPA. These results demonstrate that CSPA can simultaneously challenge the immune system through the release of proinflammatory mediators and the central nervous system through nociceptive signalling and can therefore serve as a common afferent pathway to both immune and nervous systems.

The role of the dorsal columns in neuropathic behavior: evidence for plasticity and non-specificity.

Despite conflicting clinical and experimental evidence, textbook description of somatic sensations continues to follow a rigid dichotomy based on the concept that pain sensation is transmitted cephalad primarily through anterolateral pathways, while touch is mediated through the dorsal column pathway. This study provides an example of the dynamic rerouting in the transmission of the nociceptive signals following injuries to the peripheral and central processes of sensory neurons. In two rat models for mononeuropathy, the chronic constriction injury model [Bennett, G.J., Xie, Y.K., Pain 33 (1988) 87-107] and the spared nerve injury model [Decosterd, I., Woolf, C.J., Pain 87 (2000) 149-158], we demonstrate that selective dorsal columns lesion produced significant decrease of tactile and cold allodynias and thermal hyperalgesia which were assessed by the Von Frey hair filaments, the acetone drop test and the heat-induced paw withdrawal, respectively. These manifestations, however, can reappear 2 weeks after bilateral dorsal column lesion in rats subjected to spared nerve injury mononeuropathy and appear also in animals sustaining chronic bilateral dorsal column lesion followed by either model of mononeuropathy. Lesion of the dorsal column on the side opposite to the neuropathic leg did not alter the neuropathic manifestations in both animal models. Changes in the sequence of timing of the dorsal column lesion and induction of mononeuropathy, suggest that the effects of the former last for 1 to 2 weeks. The results of this study show that the dorsal columns are involved in neuropathic manifestations and at the same time are not necessary for their full development and persistence. Furthermore, these results shade doubts on the validity of the concept of segregation of pathways involved in the transmission of neuropathic manifestations. Therefore, principles governing acute pain transmission are not necessarily applicable to chronic pain situations. The latter conditions seem to engage other available pathways to reestablish the pain signaling system.

Attenuation of neuropathic pain by segmental and supraspinal activation of the dorsal column system in awake rats.

In addition to its involvement in the transmission of neuropathic pain, the dorsal column system has been shown to have analgesic effects when electrically stimulated. The segmental or supraspinal origin of the analgesia, however, has not been clearly delineated. The aim of this study is to demonstrate the contribution of supraspinal mechanisms to the inhibition of allodynia and hyperalgesia in two different rat models of mononeuropathy. Mononeuropathy was induced, under deep anesthesia, in several groups of rats (n=7 each) following either the chronic constriction injury or the spared nerve injury model. Mechanical and cold allodynia were assessed by the Von Frey monofilaments and by the acetone drop test, respectively. Thermal hyperalgesia was assessed by the paw withdrawal and hot plate tests. Bipolar electrodes for dorsal column stimulation were implanted chronically in all rats on the dorsal aspect of the medulla at the level of the obex. Selective dorsal column bilateral lesions were performed at the upper cervical level in some groups of rats. Dorsal column nuclear stimulation, rostral to selective dorsal spinal lesions, produced strong inhibitory effects on the allodynia and hyperalgesia observed in both models of mononeuropathy. These effects were comparable to those observed following similar stimulations in rats with an intact spinal cord. Our results demonstrate strong inhibitory effects of dorsal column stimulation on neuropathic pain. This inhibition can be attributed to the activation of brainstem pain-modulating centers via rostral projections of the dorsal column nuclei.

Calcitonin gene-related peptide regulates amino acid absorption across rat jejunum.

The calcitonin gene related peptide (CGRP) is widely distributed in the enteric nervous system and gut afferents. Its role in normal digestion and absorption is not characterised. This study is conducted to elucidate whether CGRP regulates amino acid absorption in the small intestine. In in vivo experiments using the single-pass perfusion technique, intravenous infusion of CGRP (250-750 pmol/kg-min) reduced alanine absorption by 35-40%. The effects were completely blocked by the antagonist hCGRP (8-37). Moreover, intravenous infusion of CGRP antagonist blocked the inhibitory effect of intraluminal capsaicin perfusion on alanine absorption. Similarly, intracerebral injection of CGRP decreased alanine absorption, an effect which was reduced by vagotomy. In vitro experiments using isolated jejunal strips showed that CGRP reduced alanine absorption in a dose-dependent manner. At 6 pM, CGRP decreased alanine absorption by 33%. Similarly, CGRP reduced the absorption of proline and taurine by 20 and 11.5%, respectively. Kinetic studies revealed that CGRP reduces alanine influx into intestinal epithelial cells by inhibiting the affinity of the carriers. It is demonstrated that CGRP is involved in the regulation of jejunal amino acid absorption through intrinsic (enteric) and extrinsic (central) neural mechanisms.

The role of cytokines and prostaglandin-E(2) in thymulin induced hyperalgesia.

We have recently reported that intraperitoneal (i.p.) injection of thymulin at low doses (50 ng) resulted in thermal and mechanical hyperalgesia and upregulation of the level of interleukin-1beta in the liver. In this study, we demonstrate that such injections of thymulin result in a significant elevation in the levels of TNF-alpha (P<0.01), NGF (P<0.01) and PGE(2) (P<0.01) in the liver of the treated rats, in addition to the increase in the levels of IL-1beta. Pretreatment with specific antagonists to each of these factors (polyclonal anti-TNF-alpha, anti-NGF antiserum and IL-1 receptor antagonist) did not result in the abolition of the hyperalgesia as assessed by the paw pressure, hot plate, paw immersion and tail flick tests. However, pretreatment with a combination of the above antagonist and antisera almost completely prevented thymulin-induced hyperalgesia. The cyclooxygenase inhibitor, meloxicam, reversed in a dose dependent manner (0.2, 0.4 and 2 mg/kg) thymulin effects as assessed by the different pain tests. It also abolished the thymulin-induced increase in the level of cytokines and NGF in the liver. Our results indicate that PGE(2) could be the key mediator of the hyperalgesic action of thymulin and the observed upregulation of proinflammatory cytokines and NGF.