Developing a framework for utilizing adjunct rehabilitation therapies in motor recovery of upper extremity post stroke.

INTRODUCTION: Standardization of first principles has transformed stroke rehabilitation in developed countries and helped guide the appropriate allocation of resources to ensure better outcomes for patients. There have been challenges in incorporating new evidence into stroke rehabilitation practices. The sheer number of RCTs can be daunting to the average clinician, made worse by the lack of a framework for their application. OBJECTIVES: To develop a framework for the introduction of adjunct practices for the motor recovery of the upper extremity post stroke into clinical practice. METHODOLOGY: A literature search following PRISMA guidelines revealed 1,307 RCTs involving rehabilitation interventions for the hemiparetic upper extremity post stroke. RESULTS: Therapies were divided into three categories of therapies: (1) Basic Conventional Therapy Approaches (<15% of interventions), (2) Adjunct Therapies Designed to Enhance Conventional Therapies (>85% of interventions), and (3) Treatment to Manage Complications (~9% of interventions). Adjunct Therapies, despite having a spectacular evidence base, are often not employed clinically. To encourage their clinical use, we have developed a framework that divides adjunct therapies into two categories: (1) Treatments that Stimulate the Brain (i.e. rTMS, mental practice, and virtual reality) and (2) Treatments that Peripherally Facilitate the Hemiparetic Upper Extremity (i.e. robotics, EMG Biofeedback, and Constraint-induced Movement Therapy). CONCLUSION: To allow stroke rehabilitation to continue to improve upper extremity recovery and outcomes, we propose a new intuitive framework that is based on a strong evidence base to guide clinicians and improve stroke rehabilitation.

Perspective of an International Online Patient and Caregiver Community on the Burden of Spasticity and Impact of Botulinum Neurotoxin Therapy: Survey Study.

BACKGROUND: Patient- and caregiver-reported data are lacking on the burden of spasticity, and the impact of botulinum neurotoxin type A (BoNT-A) treatment for this condition, on patients' daily lives. As recommended in recent guidance from the US Food and Drug Administration, online patient communities can represent a platform from which to gather specific information outside of a clinical trial setting on the burden of conditions experienced by patients and caregivers and their views on treatment options in order to inform evidence-based medicine and drug development. OBJECTIVE: The objective of our study is to characterize spasticity symptoms and their associated burdens on Western European and US patients and caregivers in the realms of work, daily activities, quality of life (QoL), as well as the positive and negative impacts of treatment with BoNT-A (cost, time, QoL) using Carenity, an international online community for people with chronic health conditions. METHODS: We performed a noninterventional, multinational survey. Eligible participants were 18 years old or older and had, or had cared for, someone with spasticity who had been treated with BoNT-A for at least 1 year. Patients and caregivers were asked to complete an internet-based survey via Carenity; caregivers reported their own answers and answered on behalf of their patients. Questions included the burden of spasticity on the ability to work, functioning, daily-living activities, and QoL, the impact of BoNT A therapy on patients' lives, and the potential benefits of fewer injections. RESULTS: There were 615 respondents (427 patients and 188 caregivers). The mean age of patients and caregivers was 41.7 years and 38.6 years, respectively, and the most commonly reported cause of spasticity was multiple sclerosis. Caregivers were most often the parents (76/188, 40%) or another family member (51/188, 27%) of their patients. Spasticity had a clear impact on patients' and caregivers' lives, including the ability to work and injection costs. For patients, spasticity caused difficulties with activities of daily living and reduced QoL indices. The median number of BoNT-A injections was 4 times per year, and 92% (393/427) of patients reported that treatment improved their overall satisfaction with life. Regarding the BoNT-A injection burden, the greatest patient-reported challenges were the cost and availability of timely appointments. Overall, 86% (368/427) of patients believed that a reduced injection frequency would be beneficial. Caregivers answering for their patients gave largely similar responses to those reported by patients. CONCLUSIONS: Spasticity has a negative impact on both patients' and caregivers' lives. All respondents reported that BoNT A treatment improved their lives, despite the associated challenges. Patients believed that reducing the frequency of BoNT-A injections could alleviate practical issues associated with treatment, implying that a longer-acting BoNT-A injection would be well received.

Predictors of Neurological and Functional Recovery in Patients with Moderate to Severe Ischemic Stroke: The EPICA Study.

BACKGROUND: Improving our knowledge about the impact of restorative therapies employed in the rehabilitation of a stroke patient may help guide practitioners in prescribing treatment regimen that may lead to better post-stroke recovery and quality of life. AIMS: To evaluate the neurological and functional recovery for 3 months after an acute ischemic stroke occurred within previous 3 months. To determine predictors of recovery. DESIGN: Prospective observational registry. Population. Patients having suffered acute moderate to severe ischemic stroke of moderate to severe intensity within the previous 3 months with National Institutes of Health Stroke Scale (NIHSS) score from 10 to 20, 24 hours after arrival at emergency room (ER). METHODS: All prespecified variables (sociodemographic and clinical data, lifestyle recommendations, rehabilitation prescription, and neurological assessments) were assessed at three visits, i.e., baseline (D0), one month (M1), and three months (M3). RESULTS: Out of 143 recruited patients, 131 could be analysed at study entry within 3 months after stroke onset with a mean acute NIHSS score of 14.05, decreased to 10.8 at study baseline. Study sample was aged 64.9 ± 13.8 years, with 49.2% of women. Neurorehabilitation treatment was applied to 9 of 10 patients from the acute phase and for three months with different intensities depending on the centre. A large proportion of patients recovered from severe dependency on activities of daily living (ADL) at D0 to a mild or moderate disability requiring some help at M3: mean NIHSS = 10.8 to 5.7; median modified Rankin Scale (mRS) = 4 to 3; Barthel index (BI) = 40 to 70; all p values < 0.001. Multivariate analyses integrating other regression variables showed a trend in favour of rehabilitation and revascularization therapies on recovery although did not reach statistical significance and that the positive predictors of recovery improvement were baseline BI score, time to treatment, and dietary supplement MLC901 (NurAiD™II). A larger percentage of patients with more severe stroke (NIHSS > 14) who received MLC901 showed above median improvements on mRS compared to control group at M1 (71.4% vs. 29.4%; p = 0.032) and M3 (85.7% vs. 50%; p = 0.058). Older subjects and women tend to have less improvement by M3. CONCLUSIONS: Our study in patients with moderate to severe stroke shows overall recovery on neurological and functional assessments during the 3 months of study observation. Apart from demonstrating traditional "non-modifiable" predictors of outcome after stroke, like age, sex, and stroke severity, we also detected association between the use of dietary supplement MLC901 and recovery.

An international survey of patients living with spasticity.

PURPOSE: To better understand patient perspectives on the life impact of spasticity. METHODS: Global Internet survey (April 2014-May 2015) of 281 people living with spasticity. RESULTS: Respondents indicated that spasticity has a broad impact on their daily-life: 72% reported impact on quality of life, 44% reported loss of independence and 44% reported depression. Most respondents (64%) were cared for by family members, of whom half had stopped working or reduced their hours. Overall, 45% reported dissatisfaction with the information provided at diagnosis; main reasons were "not enough information" (67%) and "technical terminology" (36%). Respondents had high treatment expectations; 63% expected to be free of muscle spasm, 41% to take care of themselves and 36% to return to a normal routine. However, 33% of respondents had not discussed these expectations with their physician. The most common treatments were physiotherapy (75%), botulinum neurotoxin (BoNT, 73%) and oral spasmolytics (57%). Of those treated with BoNT, 47% waited >1 year from spasticity onset to treatment. CONCLUSIONS: This survey emphasises the broad impact of spasticity and highlights unmet needs in the patient journey. Improvements with regards to communication and the therapeutic relationship would be especially welcomed by patients, and would help manage treatment expectations. Implications of Rehabilitation Spasticity has broad impact on the lives of patients and their families that extends beyond the direct physical disability. Patients with spasticity need to be well informed about their condition and treatments available and should be given the opportunity to discuss their expectations. Physicians need to be aware of the patient's individual needs and expectations in order to better help them achieve their therapeutic goals.

The next revolution in stroke care.

Stroke is the second leading cause of death and disability worldwide. Initiatives to decrease the burden of stroke have largely focused on prevention and acute care strategies. Despite considerable resources and attention, the focus on prevention and acute care has not been successful in changing the clinical trajectory for the majority of stroke patients. While efforts to prevent strokes will continue to have an impact, the total burden of stroke will increase due to the aging population and decreased mortality rates. There is strong evidence for the effectiveness of rehabilitation in better managing stroke and its related disabilities. The time has come to shift the attention in stroke care and research from prevention and cure to a greater focus and investment in the rehabilitation and quality of life of stroke survivors. The rebalancing of stroke care and research initiatives requires a reinvestment in rehabilitation and community reintegration of stroke survivors.

Recent onset disequilibrium mimicking acute vestibulopathy in early multiple sclerosis.

The differential diagnosis of patients with acute unilateral vestibulopathy rests in the proper clinical assessment and use of selected tests of vestibular function. In case of a central nervous system lesion as in Multiple Sclerosis, the case shown here, it is of particular importance to observe congruency between severity of symptoms and signs and, of topographic diagnosis. We report a case of a 37-year-old woman with recent onset disequilibrium that after careful analysis of the different test results several incongruences were found; this prompted a radiological study that provided the clue to diagnosis. After treatment the patient recovered completely not only clinically but also in vestibular deficit.

[What is the optimal dose for the prophylactic treatment of chronic migraine patients?]. / Realmente es beneficioso usar las dosis de OnabotulinumtoxinA del estudio PREEMPT?

INTRODUCTION: OnabotulinumtoxinA (OnabotA) is indicated for headache prophylaxis in patients with chronic migraine. However, there is some controversy about what is the minimum effective dose for treating chronic migraine patients. AIM: To determine the optimal dose of OnabotA for the prophylactic treatment of patients with chronic migraine. DEVELOPMENT: We performed a literature review of the randomized, double blind, placebo-controlled studies that have evaluated the safety and efficacy of OnabotA as headache prophylactic treatment in migraine patients. In the studies conducted before the PREEMPT clinical programme, a variety of dose ranges and infiltration paradigms were used. Initial phase II studies of OnabotA in chronic daily headache showed that those patients treated with 150 U had significant mean reductions from baseline in headache frequency compared with placebo, and this benefit was not observed for patients treated with 75 U. The experience from previous studies allowed to define an injection paradigm and dose range (155-195 U) that was used in the PREEMPT clinical trials. PREEMPT studies demonstrate that OnabotA is a safe an effective prophylactic treatment for chronic migraine. CONCLUSIONS: Available evidence to date supports that the optimal dose for the treatment of chronic migraine patients is the use of at least 150 U of OnabotA, that should be administered according to the PREEMPT injection paradigm.

TITLE: Realmente es beneficioso usar las dosis de OnabotulinumtoxinA del estudio PREEMPT?Introduccion. La OnabotulinumtoxinA (OnabotA) esta indicada para el tratamiento preventivo de los pacientes con diagnostico de migraña cronica. Existe cierta controversia acerca de cual es la dosis minima eficaz de OnabotA. Objetivo. Determinar cual es la dosis mas adecuada de OnabotA para el tratamiento de la migraña cronica. Desarrollo. Se revisan los estudios controlados frente a placebo, que han evaluado la eficacia y seguridad de OnabotA para el tratamiento de la migraña, prestando especial atencion a las dosis de toxina utilizadas. En los diferentes ensayos clinicos llevados a cabo antes del año 2010 se utilizaron distintos protocolos de infiltracion. La experiencia obtenida de los estudios previos permitio definir un protocolo de infiltracion que se utilizo en el programa PREEMPT, y que demostro que el tratamiento con OnabotA es seguro y eficaz en pacientes con migraña cronica. La dosis elegida en los ensayos PREEMPT 1 y 2 fue de 155-195 U, al observarse en los estudios en fase II que la dosis de 75 U no era eficaz y que la utilizacion de 150-200 U aumentaba la eficacia sin incrementar los efectos adversos. Ademas de la dosis, el paradigma de inyeccion PREEMPT tambien establece de manera detallada los puntos de inyeccion y la metodologia de infiltracion. Conclusiones. La evidencia cientifica disponible hasta la fecha sustenta que la dosis mas adecuada para el tratamiento de la migraña cronica es la utilizacion de al menos 150 U de OnabotA, y que la infiltracion debe realizarse con la metodologia definida en el paradigma de inyeccion PREEMPT.

¿Realmente es beneficioso usar las dosis de OnabotulinumtoxinA del estudio PREEMPT? / What is the optimal dose for the prophylactic treatment of chronic migraine patients?

Introducción. La OnabotulinumtoxinA (OnabotA) está indicada para el tratamiento preventivo de los pacientes con diagnóstico de migraña crónica. Existe cierta controversia acerca de cuál es la dosis mínima eficaz de OnabotA. Objetivo. Determinar cuál es la dosis más adecuada de OnabotA para el tratamiento de la migraña crónica. Desarrollo. Se revisan los estudios controlados frente a placebo, que han evaluado la eficacia y seguridad de OnabotA para el tratamiento de la migraña, prestando especial atención a las dosis de toxina utilizadas. En los diferentes ensayos clínicos llevados a cabo antes del año 2010 se utilizaron distintos protocolos de infiltración. La experiencia obtenida de los estudios previos permitió definir un protocolo de infiltración que se utilizó en el programa PREEMPT, y que demostró que el tratamiento con OnabotA es seguro y eficaz en pacientes con migraña crónica. La dosis elegida en los ensayos PREEMPT 1 y 2 fue de 155-195 U, al observarse en los estudios en fase II que la dosis de 75 U no era eficaz y que la utilización de 150-200 U aumentaba la eficacia sin incrementar los efectos adversos. Además de la dosis, el paradigma de inyección PREEMPT también establece de manera detallada los puntos de inyección y la metodología de infiltración. Conclusiones. La evidencia científica disponible hasta la fecha sustenta que la dosis más adecuada para el tratamiento de la migraña crónica es la utilización de al menos 150 U de OnabotA, y que la infiltración debe realizarse con la metodología definida en el paradigma de inyección PREEMPT (AU)

Introduction. OnabotulinumtoxinA (OnabotA) is indicated for headache prophylaxis in patients with chronic migraine. However, there is some controversy about what is the minimum effective dose for treating chronic migraine patients. Aim. To determine the optimal dose of OnabotA for the prophylactic treatment of patients with chronic migraine. Development. We performed a literature review of the randomized, double blind, placebo-controlled studies that have evaluated the safety and efficacy of OnabotA as headache prophylactic treatment in migraine patients. In the studies conducted before the PREEMPT clinical programme, a variety of dose ranges and infiltration paradigms were used. Initial phase II studies of OnabotA in chronic daily headache showed that those patients treated with 150 U had significant mean reductions from baseline in headache frequency compared with placebo, and this benefit was not observed for patients treated with 75 U. The experience from previous studies allowed to define an injection paradigm and dose range (155-195 U) that was used in the PREEMPT clinical trials. PREEMPT studies demonstrate that OnabotA is a safe an effective prophylactic treatment for chronic migraine. Conclusions. Available evidence to date supports that the optimal dose for the treatment of chronic migraine patients is the use of at least 150 U of OnabotA, that should be administered according to the PREEMPT injection paradigm (AU)

Rethinking the continuum of stroke rehabilitation.

Suffering a stroke can be a devastating and life-changing event. Although there is a large evidence base for stroke rehabilitation in the acute and subacute stages, it has been long accepted that patients with stroke reach a plateau in their rehabilitation recovery relatively early. We have recently published the results of a systematic review designed to identify all randomized controlled trials (RCTs) where a rehabilitation intervention was initiated more than 6 months after the onset of the stroke. Of the trials identified, 339 RCTs met inclusion criteria, demonstrating an evidence base for stroke rehabilitation in the chronic phase as well. This seems at odds with the assumption that further recovery is unlikely and the subsequent lack of resources devoted to chronic stroke rehabilitation and management.

Carotid intima-media thickness changes with Mediterranean diet: a randomized trial (PREDIMED-Navarra).

OBJECTIVE: Observational studies have reported inverse associations between adherence to the Mediterranean diet (MedDiet) and atherosclerotic disease. We tested the effect of two types of MedDiet on progression of subclinical carotid atherosclerosis. METHODS: We randomized 187 high-cardiovascular-risk asymptomatic subjects (51% women, mean age 67 years) to three treatment arms: MedDiet with supplemental virgin olive oil (VOO), n=66; MedDiet with supplemental nuts, n=59; and control diet, n=62. Participants received nutrition behavioral counseling in quarterly group and individual educational sessions. Free supplemental foods were provided to the MedDiet groups. Changes in mean intima-media thickness (IMT) were measured ultrasonographically in the far wall of bilateral common carotid arteries after 1 year. RESULTS: Overall, no significant between-group differences in IMT progression were observed after 1-year. However, a significant interaction (p=0.03) between baseline IMT and treatment effect was apparent. Among participants with baseline IMT≥0.9 mm, 1-year IMT changes versus control showed significant differences of -0.079 mm (95% confidence interval, -0.145 to -0.012) for the MedDiet with VOO and -0.072 mm (-0.140 to -0.004) for the MedDiet with nuts. No IMT changes occurred in any intervention group among participants with lower baseline IMT values (<0.9 mm). CONCLUSIONS: MedDiets enhanced with VOO or nuts were not effective in inducing ultrasonographic regression of carotid atherosclerosis after 1 year intervention. However, they were effective among subjects with elevated baseline IMT, suggesting that subclinical atherosclerosis may respond to dietary intervention within a relatively short time frame only among subjects with a high initial atherosclerotic burden.

Acute management of acquired brain injury part II: an evidence-based review of pharmacological interventions.

PRIMARY OBJECTIVE: To review the research literature on pharmacological interventions used in the acute phase of acquired brain injury (ABI) to manage ICP and improve neural recovery. MAIN OUTCOMES: A literature search of multiple databases (CINAHL, EMBASE, MEDLINE and PSYCHINFO) and hand searched articles covering the years 1980-2008 was performed. Peer reviewed articles were assessed for methodological quality using the PEDro scoring system for randomized controlled trials (RCTs) and the Downs and Black tool for RCTs and non-randomized trials. Levels of evidence were assigned and recommendations were made. RESULTS: In total, 11 pharmacological interventions used in the acute management of ABI were evaluated. These included propofol, barbiturates, opioids, midazolam, mannitol, hypertonic saline, corticosteroids, progesterone, bradykinin antagonists, dimethyl sulphoxide and cannabinoids. Of these interventions, corticosteroids were found to be contraindicated and cannabinoids were reported as ineffective. The other nine interventions demonstrated some benefit for treatment of acute ABI. However, rarely did these benefits result in improved long-term patient outcomes. CONCLUSIONS: Substantial research has been devoted to evaluating the use of pharmacological interventions in the acute management of ABI. However, much of this research has focused on the application of individual interventions in small single-site trials. Future research will need to establish larger patient samples to evaluate the benefits of combined interventions within specific patient populations.

Acute management of acquired brain injury part I: an evidence-based review of non-pharmacological interventions.

PRIMARY OBJECTIVE: To review the literature on non-pharmacological interventions used in acute settings to manage elevated intracranial pressure (ICP) and minimize cerebral damage in patients with acquired brain injury (ABI). MAIN OUTCOMES: A literature search of multiple databases (CINAHL, EMBASE, MEDLINE and PSYCHINFO) and hand-searched articles covering the years 1980-2008 was performed. Peer reviewed articles were assessed for methodological quality using the PEDro scoring system for randomized controlled trials (RCTs) and the Downs and Black tool for RCTs and non-randomized trials. Levels of evidence were assigned and recommendations made. RESULTS: Five non-invasive interventions for acute ABI management were assessed: adjusting head posture, body rotation (continuous rotational therapy and prone positioning), hyperventilation, hypothermia and hyperbaric oxygen. Two invasive interventions were also reviewed: cerebrospinal fluid (CSF) drainage and decompressive craniectomy (DC). CONCLUSIONS: There is a paucity of information regarding non-pharmacological acute management of patients with ABI. Strong levels of evidence were found for only four of the seven interventions (decompressive craniectomy, cerebrospinal fluid drainage, hypothermia and hyperbaric oxygen) and only for specific components of their use. Further research into all interventions is warranted.

Acute management of acquired brain injury Part III: an evidence-based review of interventions used to promote arousal from coma.

PRIMARY OBJECTIVE: To review the literature regarding techniques used to promote arousal from coma following an acquired brain injury. MAIN OUTCOMES: A literature search of multiple databases (CINAHL, EMBASE, MEDLINE and PsycINFO) and hand searched articles covering the years 1980-2008 was performed. Peer reviewed articles were assessed for methodological quality using the PEDro scoring system for randomized controlled trials and the Downs and Black tool for RCTs and non-randomized trials. Levels of evidence were assigned and recommendations were made. RESULTS: Research into coma arousal has generally focused on the stimulation of neural pathways responsible for arousal. These pathways have been targeted using pharmacological and non-pharmacological techniques. This review reports the evidence surrounding agents targeting dopamine pathways (amantadine, bromocriptine and levodopa), sensory stimulation, music therapy and median nerve electrical stimulation. Each of these interventions has shown some degree of benefit in improving consciousness, but further research is necessary. CONCLUSIONS: Despite numerous studies, strong evidence was only found for one intervention (Amantadine use in children) and this was based on a single study. However, each of the interventions showed promise in some aspect of arousal and warrant further study. More methodologically rigorous study is needed before any definitive conclusions can be drawn.

Sleep structure in patients with periodic limb movements and obstructive sleep apnea syndrome.

Periodic limb movements (PLM) and obstructive sleep apnea syndrome (OSAS) are two frequent sleep disorders which often occur in the same patient. The goal of this study was to know the influence of the presence of PLM in the sleep architecture in patients with and without OSAS. Two hundred twenty consecutive patients (69 women and 151 men) participated in this transversal study. They were patients with clinical suspicion of dysomnia, including snoring, OSAS, and PLM. All of them underwent a full polysomnography and were interviewed using questionnaires about the sleep quality. The sleep parameters (percentage of sleep stages, rapid eye movement latency, sleep efficiency, awakenings, PLM presence, apnea-hypopnea index) were calculated and compared between groups. Descriptive statistics and nonparametric distribution techniques were used for the analysis. Patients with PLM when compared with patients with OSAS had lower sleep efficiency and less rapid eye movement percentage. The presence of PLM in patients with sleep apnea was less relevant being responsible only for an increase in the rapid eye movement latency and a decrease in the duration of the three to four sleep stages. However, the presence of OSAS was related to a better sleep efficiency (patients with PLM plus OSAS had a better sleep efficiency than patients with only PLM). PLM alters the structure of sleep. In patients with sleep apnea, the presence of PLM is less relevant.

Stroke rehabilitation: an international perspective.

There is a revolution underway in stroke rehabilitation. International comparative studies coupled with an impressive evidence base have provided a platform from which an ideal system for stroke rehabilitation can be envisioned. Using the concepts of structure and process of care, different systems of stroke rehabilitation can be compared and evaluated against best evidence. Two structures of care are examined: specialized interdisciplinary stroke rehabilitation units and outpatient programs. Although specialized interdisciplinary stroke rehabilitation units remain the "gold standard" of care, access to them is often limited. Outpatient programs are essential to stroke rehabilitation systems of care; however, while some countries are investing in outpatient programs, others are scaling back. Even though structures of care have been shown to affect processes of care, it is the processes of care that have proven to be more influential in altering patient outcomes. Four key processes of care are examined: time to admission, intensity of therapy, task-specific therapy, and discharge planning. Within international stroke rehabilitation systems, differences in these processes have resulted in significant differences in outcomes. This allows for "real-world" comparisons of how differing processes affect patient outcomes. Those systems whose structures and processes of care best reflect current best evidence appear to achieve better outcomes.

Carotid intima-media thickness is inversely associated with olive oil consumption.

BACKGROUND: Intima-media thickness (IMT) is a valid marker for generalized vascular disease whose main risk factors are associated with food habits and lifestyle. A Mediterranean food pattern may have a protective effect on cardiovascular mortality. OBJECTIVE: To assess the relationship between carotid IMT and olive oil consumption. METHODS: One hundred and ninety nine patients were randomly extracted from 1055 asymptomatic high cardiovascular risk participants at the AP-UNAV recruitment center of the PREDIMED (PREvención con DIeta MEDiterránea) project. Demographic and clinical variables were collected, and a validated semiquantitative food frequency questionnaire (137 items) was administered at the inclusion interview. A B-mode ultrasound imaging technique was used to measure the mean common carotid IMT. RESULTS: The mean age was 67.3 years and 53.3% were women. Energy-adjusted olive oil consumption quintiles were assessed as the main exposure after adjusting for potential dietary and non-dietary confounders. Using continuous carotid IMT as the outcome in an ANCOVA analysis, the adjusted IMT means throughout quintiles showed an inverse association with a plateau after the second quintile, with statistical differences when the adjusted IMT mean of the merged four upper quintiles were compared with the lowest quintile (p<0.05). The averaged (both sides) mean IMT of the common carotid was dichotomised and values above the median (0.804 mm) were used to identify carotid atherosclerotic damage. We also found an inverse association of olive oil consumption with high IMT, throughout the second to the fifth quintile as compared with the lowest quintile. The adjusted OR was of 0.08 (95% confidence interval, CI, of 0.02-0.37; p=0.001) after merging the four upper quintiles. CONCLUSION: The inverse association between the olive oil consumption and the carotid IMT could suggest a protective role of olive oil against the development of carotid atherosclerosis in persons at high cardiovascular risk.

Diagnostic accuracy of retinal abnormalities in predicting disease activity in MS.

OBJECTIVES: To assess the association between the thickness of the retinal nerve fiber layer (RNFL), assessed by optical coherence tomography (OCT), retinal periphlebitis (RP), and multiple sclerosis (MS) disease activity. METHODS: We studied a prospective cohort of 61 patients and 29 matched controls for 2 years, performing a neurologic assessment every 3 months and an ophthalmologic evaluation, including OCT scans, every 6 months. Baseline MRI studies were also carried out from which brain volume and lesion load were assessed. RESULTS: We found that the RNFL thickness in patients with MS was thinner than in controls, particularly in the temporal quadrant (p = 0.004). Although RNFL atrophy was greater in patients who also had optic neuritis (p = 0.002), it also augmented in MS patients who did not have optic neuritis compared with controls (p = 0.014). RNFL atrophy was correlated with greater disability (r = -0.348, p = 0.001) and longer disease duration (r = -0.301, p = 0.003). Furthermore, baseline temporal quadrant RNFL atrophy was associated with the presence of new relapses and changes in the Expanded Disability Status Scale by the end of the study (p < 0.05 in all cases). Indeed, RNFL thickness was correlated with white matter volume (r = 0.291, p = 0.005) and gray matter volume (r = 0.239, p = 0.021). The presence of RP was a risk factor for having new relapses in the next 2 years (odds ratio = 1.52, p = 0.02), and patients with RP had larger gadolinium-enhancing lesions volume (p = 0.003). CONCLUSION: Retinal nerve fiber layer atrophy and the presence of retinal periphlebitis are associated with disease activity, suggesting that retinal evaluation can be used as biomarkers of multiple sclerosis activity.

Total remission of thymus carcinoma after treatment with intravenous immunoglobulin.

We report the case of a 42 year-old woman with myasthenia gravis associated with a malignant thymoma. Despite surgery, chemotherapy and radiotherapy, the thymoma showed soft tissues, pleural and mediastinic progression. Unexpectedly, a complete remission of the thymoma was confirmed by FDG-PET after four cycles of immunoglobulins, administered as treatment for a myasthenic crisis. To our knowledge this is the first case report of complete remission of a malignant thymoma with immunoglobulin therapy.

Neuroprotection in vascular dementia.

Vascular dementia (VaD) is the second most common form of dementia after Alzheimer's disease (AD), and one of the major causes of mental and physical disability in developed countries. As such, the identification and implementation of strategies which prevent the development of the condition or enable improvements in patients with VaD are healthcare objectives of the first order. VaD is now regarded as a combined group of clinical-pathological entities rather than one disease, that is, multiple pathogenic mechanisms and lesion types underlie a cognitive impairment of vascular origin. The clinical diagnosis of VaD is complex and difficult because of the heterogeneous nature of its clinical presentation and progression and the low sensitivity of existing clinical criteria. Moreover, there is growing evidence of the epidemiological significance of mixed forms of dementia, and that ischemic processes may precipitate and exacerbate cognitive impairment in AD. Numerous compounds have been proposed as potentially useful in the treatment of patients with VaD, comprising vasodilatative, antithrombotic, hemorrheological, nootropic, antiserotoninergic and, most recently, antiglutamatergic and cholinergic approaches. In spite of some initially favorable reports based on the use of memantine, donepezil and galantamine, there is as yet no conclusive evidence of a definitive treatment for VaD. Unsatisfactory results from VaD drug trials may be attributed in part to the diversity of the patients included (underlying pathogenic mechanisms, number, type, and location of vascular lesions), and to methodological limitations in the design of the trials (outcome measures, end-points, size, follow-up period). The treatment of modifiable vascular risk factors - hypertension, diabetes mellitus, hypercholesterolemia and heart disease - is an important strategy for the reduction of the risk of dementia, and is likely to slow the progress of cognitive decline.