Dementia prevalence, care arrangement, and access to care in Lebanon: A pilot study.

INTRODUCTION: In North Africa and the Middle East, studies about dementia prevalence are scarce. A pilot study was conducted in Lebanon to assess dementia prevalence, using the Arabic-validated 10/66 Dementia Research Group (DRG) diagnostic assessment for case ascertainment. The study also examined care arrangement and access to care. METHODS: A random sample of 502 persons older than 65 years and their informant were recruited from Beirut and Mount Lebanon governorates through multistage cluster sampling. RESULTS: The crude and age-standardized dementia prevalences were 7.4% and 9.0%, respectively. People with dementia were mainly cared for by relatives at home. Access to formal care was very limited. DISCUSSION: Dementia prevalence in Lebanon ranks high within the global range of estimates. These first evidence-based data about disease burden and barriers to care serve to raise awareness and call for social and health care reform to tackle the dementia epidemic in Lebanon and in North Africa and the Middle East.

Deciphering glycomics and neuroproteomic alterations in experimental traumatic brain injury: Comparative analysis of aspirin and clopidogrel treatment.

As populations age, the number of patients sustaining traumatic brain injury (TBI) and concomitantly receiving preinjury antiplatelet therapy such as aspirin (ASA) and clopidogrel (CLOP) is rising. These drugs have been linked with unfavorable clinical outcomes following TBI, where the exact mechanism(s) involved are still unknown. In this novel work, we aimed to identify and compare the altered proteome profile imposed by ASA and CLOP when administered alone or in combination, prior to experimental TBI. Furthermore, we assessed differential glycosylation PTM patterns following experimental controlled cortical impact model of TBI, ASA, CLOP, and ASA + CLOP. Ipsilateral cortical brain tissues were harvested 48 h postinjury and were analyzed using an advanced neuroproteomics LC-MS/MS platform to assess proteomic and glycoproteins alterations. Of interest, differential proteins pertaining to each group (22 in TBI, 41 in TBI + ASA, 44 in TBI + CLOP, and 34 in TBI + ASA + CLOP) were revealed. Advanced bioinformatics/systems biology and clustering analyses were performed to evaluate biological networks and protein interaction maps illustrating molecular pathways involved in the experimental conditions. Results have indicated that proteins involved in neuroprotective cellular pathways were upregulated in the ASA and CLOP groups when given separately. However, ASA + CLOP administration revealed enrichment in biological pathways relevant to inflammation and proinjury mechanisms. Moreover, results showed differential upregulation of glycoproteins levels in the sialylated N-glycans PTMs that can be implicated in pathological changes. Omics data obtained have provided molecular insights of the underlying mechanisms that can be translated into clinical bedside settings.

Performance of the 16-Item Informant Questionnaire on Cognitive Decline for the Elderly (IQCODE) in an Arabic-Speaking Older Population.

BACKGROUND/AIM: The North African and Middle Eastern region has high illiteracy rates among older people, making direct cognitive testing challenging. Validated screening instruments for dementia in Arabic are lacking. We aimed to validate the Arabic version of the 16-item Informant Questionnaire on Cognitive Decline for the Elderly (A-IQCODE 16) for screening for dementia through an informant. METHODS: 236 Lebanese participants older than 65 years, 143 with normal cognition and 93 with mild-to-moderate dementia according to the DSM-IV criteria, and their informants were recruited. Half of the participants had no formal education. Interviewers blinded to the cognitive status of the participants administered the A-IQCODE 16 to the informants. The ability of the A-IQCODE 16 to screen for dementia was evaluated against the DSM-IV diagnoses. RESULTS: The A-IQCODE 16 had excellent overall predictive power (area under the receiver operator characteristic curve = 0.96). A cutoff point of >3.34 yielded the best sensitivity (92.5%) and specificity (94.4%) for dementia screening. At this cutoff point, the discriminatory ability of the A-IQCODE 16 was comparable between participants with and those without formal education. CONCLUSION: The A-IQCODE 16 is not biased by education and is therefore useful as a brief screening tool for dementia among Arabic-speaking older adults with low education.

Validation of the 10/66 Dementia Research Group diagnostic assessment for dementia in Arabic: a study in Lebanon.

OBJECTIVES: In the North Africa and Middle East region, the illiteracy rates among older people are high, posing a great challenge to cognitive assessment. Validated diagnostic instruments for dementia in Arabic are lacking, hampering the development of dementia research in the region. The study aimed at validating the Arabic version of the 10/66 Dementia Research Group (DRG) diagnostic assessment for dementia to determine whether it is suitable for case ascertainment in epidemiological research. METHODS: A total of 244 participants older than 65 years were included, 100 with normal cognition and 144 with mild to moderate dementia. Dementia was diagnosed by clinicians according to Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria. Depression was diagnosed using the Geriatric Mental State. Trained interviewers blind to the cognitive status of the participants administered the 10/66 DRG diagnostic assessment to the participants and interviewed the caregivers. The discriminatory ability of the 10/66 DRG assessment and its subcomponents were evaluated against the clinical diagnoses. RESULTS: Half of the participants had no formal education and 49% of them were depressed. The 10/66 DRG diagnostic assessment showed excellent sensitivity (92.0%), specificity (95.1%), positive predictive value (PPV, 92.9%), and low false-positive rates among controls with no formal education (8.1%) and depression (5.6%). Each subcomponent of the 10/66 DRG diagnostic assessment independently predicted dementia diagnosis. The predictive ability of the 10/66 DRG assessment was superior to that of its subcomponents. CONCLUSION: The 10/66 DRG diagnostic assessment for dementia is well suited for case ascertainment in epidemiological studies among Arabic-speaking older population with high prevalence of illiteracy.

Predicting the occurrence of thrombocytopenia from free valproate levels: A prospective study.

PURPOSE: The likelihood of valproate (VPA) induced thrombocytopenia increases with higher VPA levels. In critically ill patients, the biological active free VPA level cannot be predicted from the total serum level. In this study, we evaluated the relationship between trough free VPA serum levels and concomitant platelet counts and assessed risk factors for the development of thrombocytopenia with the aim of generating a formula specifying the probabilities of developing thrombocytopenia based on trough free serum VPA levels. METHODS: Trough free VPA levels and concomitant platelet counts were collected from a large cohort of patients who participated in a prospective VPA monotherapy trial. Significant variables associated with thrombocytopenia in a univariate analysis were evaluated in a multivariate model. A receiver operator curve was performed to compute the trough free VPA levels with the greatest discriminating power in predicting thrombocytopenia. RESULTS: 844 trough free VPA levels and concomitant platelet counts obtained from 264 patients were analyzed. In a multivariate analysis, trough free VPA levels, gender, and baseline platelet counts were significantly associated with thrombocytopenia. Using stepwise regression and multivariate logistic regression analyses, we generated gender-specific formulas for predicting platelet counts and probabilities of developing thrombocytopenia. The trough free VPA with the greatest discriminating power to predict platelet values ≤ 100,000/µL was 16.65 µg/mL. CONCLUSIONS: The generated model was based on trough free VPA levels and achieved high sensitivity and specificity. Our results are therefore generalizable and can be applied to estimate the probability of developing thrombocytopenia in critically ill patients.

A patient with headache, right upper extremity and right hemithorax hypothermalgesia.

We present a case of partial Wallenberg syndrome also called partial lateral medullary syndrome, a hemorrhagic or ischemic stroke of the area fed by the posterior inferior cerebellar artery and the clinical manifestation depends on the extension of the lesion: dorsal-ventral, medial-lateral and rostrocaudal. Five types have been described. Our patient had headache, hoarseness, right upper extremity, right hemithorax and right upper gluteal hypothermalgesia implicating the involvement of the cervical, the thoracic and part of lumbar fibers of the left lateral spinothalamic tract and the ambiguous nucleus; an entity not described before. The imaging done to our patient disclosed the dissection of the left vertebral artery. He was treated with anticoagulation with gradual improvement in his symptoms.

Emerging drugs for partial onset seizures.

IMPORTANCE OF THE FIELD: Patients with epilepsy have recurrent unproved seizures. Epilepsy is common, with a prevalence range that centers at around 1%. Patients with epilepsy can have a poor quality of life and suffer significant social stigma. Despite the availability of a large number of antiepileptic drugs (AEDs) including standard and newer ones, a significant percentage of patients with epilepsy remain poorly controlled. AREAS COVERED IN THIS REVIEW: In this review, we briefly summarize data on the available AEDs, then present current information on the emerging AEDs, including their chemical structure, pharmacology, mechanism of action, and efficacy and adverse event profile in clinical trials. The AEDs included are rufinamide, lacosamide, eslicarbazepine, retigabine, brivaracetam, ganaxolone, stiripentol and carisbamate. Most of the literature related to these AEDs was published in the past 5 years. WHAT THE READER WILL GAIN: The reader will become familiar with the pharmacology of emerging AEDs and the results of clinical trials with these AEDs. The reader will also be able to assess the advantages of AEDs and their potential respective places in the treatment of epilepsy. TAKE HOME MESSAGE: The emerging AEDs offer predominantly improved pharmacokinetics and tolerability and occasionally new mechanisms of action. They will probably have a modest impact on drug-resistant epilepsy.

Toxocara infection in the differential diagnosis of multiple sclerosis in the Middle East.

A critical step in the diagnosis of multiple sclerosis is to rule out a heterogeneous variety of multiple sclerosis mimickers, which is crucial in the era of powerful immune-modulator treatments. In this review, we discuss the background of toxocariasis in general, present central nervous system Toxocara infection as one of the multiple sclerosis mimickers in the Middle East, and share our experience about the diagnosis and management of this condition. This entity seems very relevant in a region such as the Middle East, where displacement of populations and conflict can result in non-hygienic food and water management bundles. The diagnosis should be entertained, especially when assessing patients with myelopathy. The presence of a single lesion in the spinal cord with inflammatory features should prompt serological testing for Toxocara IgG and IgM in serum and the cerebrospinal fluid. This infection is treatable, with the regimen of high-dose albendazole being one of the most accepted treatments. Although most cases exhibit a good prognosis, some have residual deficits localized to the affected spinal cord level.

Coma With Absent Brainstem Reflexes and a Burst Suppression on EEG Secondary to Baclofen Toxicity.

Baclofen, a muscle relaxant prescribed for the alleviation of symptoms of spasticity acts primarily at the spinal level but with high doses, it penetrates the blood-brain barrier and can result in prominent central nervous depression. Baclofen toxicity has been associated with a variety of symptoms ranging from dizziness to deep coma. We report the clinical course, management, and outcome of a case of baclofen overdose who presented in deep coma with loss of brainstem reflexes and a burst suppression (BS) pattern on his electroencephalogram (EEG). In addition, we reviewed the presentation and outcomes of all reported cases of baclofen toxicity with a BS pattern on EEG to evaluate if those cases share a common clinical presentation and for the presence of signs and symptoms that would help the clinician to consider this diagnosis. There appears to be a common clinical picture associated with severe baclofen toxicity consisting of deep coma associated with loss of all brainstem reflexes including pupillary reactivity, frequent association with seizures/myoclonic jerks, and a BS pattern on EEG. The outcome is generally good, and serial EEGs are recommended to document a reversal of the abnormal electrographic features.

A case of Kleine-Levin syndrome with a complete and sustained response to carbamazepine.

We describe a patient with Kleine-Levin syndrome who was initially misdiagnosed as having epilepsy and who achieved complete remission on carbamazepine treatment. A drug effect was established when symptoms recurred after carbamazepine taper and disappeared after reintroduction of the drug. Carbamazepine, a safer drug than lithium, can be a highly effective treatment in some patients with Kleine-Levin syndrome. This syndrome can sometimes be confused with epilepsy because of the episodic nature of the symptoms and the occasional response to anticonvulsants.

Mental health research in the Arab region: challenges and call for action.

Although mental disorders are a leading cause of disability in the Arab region, which includes 5·54% of the global population, Arab countries produce only 1·0% of the global output of peer-reviewed publications in mental health research. Various stakeholders, including Arab mental health researchers, institutional and funding agency officials, and international research collaborators, convened to identify challenges faced by Arab mental health researchers and propose an evidence-informed call for action. Challenges identified include prevalent stigma and low awareness, conflict and war, scarce institutional and funding resources, inadequate publishing opportunities, insufficient training in mental health research, and shortage of reliable and valid assessment tools. The proposed action plan includes ways of addressing stigma and spreading awareness, increasing collaborative efforts, building research infrastructure, strengthening the mental health workforce, and translating research findings into a call to action on societal and governmental levels. The proposed action plan could provide a roadmap for Arab mental health researchers and research institutions, which might ultimately increase research productivity in the Arab region and close the gap between Arab countries and the rest of the world.

Determinants of free serum valproate concentration: A prospective study in patients on divalproex sodium monotherapy.

PURPOSE: To evaluate variables affecting the valproate (VPA) free fraction and develop an equation for computing free VPA concentration from total VPA concentration. METHODS: Trough total and free VPA concentrations were collected from patients who participated in a prospective VPA monotherapy trial. All available paired data of trough total and free VPA concentrations were included. Significant variables from the univariate analysis were evaluated in a multivariate model. RESULTS: A total of 902 concomitant total and free VPA concentrations were available. Multivariate analysis showed that total VPA concentration, age and gender were significantly associated with VPA free fraction. However, the effect size of total VPA concentration was substantially higher than that of gender and age. VPA free fraction remained stable at around 10% for total VPA concentration between 20 and 60 µg/mL with subsequent linear increases for higher concentration. A scatter plot correlating total and free VPA concentrations showed that a quadratic equation best fitted the data, accounting for 88% of the free VPA concentration variance. CONCLUSIONS: An increase in the total VPA concentration results in corresponding linear and non-linear rise in the VPA free fraction and free VPA concentration, respectively. The total daily dose of VPA should be increased in smaller increments whenever a total VPA concentration of 60 µg/mL is reached. When drug monitoring is needed, we recommend measuring the free VPA concentration. If this test is unavailable, and for patients with normal albumin levels, it can be predicted from the total VPA concentration using the generated equation.

Frequency and Stratification of Epileptogenic Lesions in Elderly With New Onset Seizures.

Objective: To evaluate prospectively the frequency of epileptogenic lesions in a consecutive cohort of elderly patients presenting with new onset unprovoked seizures, and who underwent a complete evaluation including dedicated epilepsy protocol MRI. Methods and materials: We included all consecutive patients 60 years or older who participated in a prospective study on new onset epilepsy. The work-up included the acquisition of a dedicated epilepsy protocol MRI and a 3 h video/EEG recording. We evaluated the frequency and types of epileptogenic lesions in the whole cohort and stratified those variables by age, gender, types and number of seizures at presentation. We also correlated the EEG findings with the clinical characteristics and neuroimaging results. Results: Of the 101 patients enrolled in the study and who underwent an epilepsy protocol MRI, an epileptogenic lesion was identified in 67% of cases. The most common etiologies were vascular events, followed by tumoral causes and traumatic brain injuries. Epileptogenic lesions were more likely to be identified in patients who presented with only focal aware and impaired awareness seizures. In addition, patients with tumoral epilepsy were significantly more likely to only experience those seizure types compared to patients with other pathological substrates. Interictal/ictal discharges were detected in the EEG of 21% of patients. Epileptiform discharges were significantly more frequent in patients with an epileptogenic lesion on brain MRI, especially in those with a brain tumor. Conclusions: Our results stress the importance of obtaining a dedicated epilepsy protocol MRI in elderly patients with new onset seizures. An epileptogenic lesion will be identified in approximately two thirds of patients with important implications regarding initiation of treatment. In addition, the data underscore the value of distinguishing the types of seizures experienced at presentation as this will apprise the treating physician on the likelihood of identifying an epileptogenic lesion and on the probable etiologies.

Socio-demographic and cardiovascular disease risk factors associated with dementia: Results of a cross-sectional study from Lebanon.

Little evidence from the Arab region is available on dementia and its associated risk factors. This study is the first in Lebanon to examine the association between community older adults' socio-demographics and cardiovascular disease risk factors (CVDRF) and dementia in the aim of closing the knowledge gap. A cross-sectional household survey was conducted in 2013 in Beirut and two districts of Mount Lebanon with 502 older adults (65 years and above) and their informants. Data was collected on CVDRF and socio-demographics using structured questionnaires and dementia was assessed using the 10/66 Dementia Research Group validated tools. Multivariable analysis was done using a generalized estimating equation to account for cluster effect. Being older and perceiving personal income as insufficient significantly increased the odds of dementia [OR75-84 years = 4.00 (95%CI = 1.46, 10.95); OR85 + years = 7.07 (1.84, 27.03); ORinsufficient income = 3.90 (1.58, 9.60)]. Having uncontrolled hypertension (versus no hypertension) was the only significant CVDRF that increased the odds of dementia [OR = 6.35 (1.60, 25.10)]. Interventions targeting uncontrolled hypertension that aim to increase awareness about proper management of this chronic condition would contribute to the needed preventive efforts against CVDRFs in response to dementia risk. Further research on the association between income sufficiency - one indicator of low socio-economic status - and dementia is warranted.

Dementia and family burden of care in Lebanon.

The burden on and mental well-being of family carers for the elderly, especially those with dementia, has been well studied in high-income countries and to a lesser extent in the Arab region. Our study of Lebanese carers highlights the importance of considering the psychological well-being of the family carer, and the role of dementia and depression in increasing the burden of care. Psychosocial interventions have produced equivocal results and therefore customised and contextualised interventions need to be researched. Greater understanding of the coping mechanisms used by carers is required and an examination of the positive aspects of caring is warranted.

Moyamoya syndrome with intraventricular hemorrhage in an adult with factor V Leiden mutation.

OBJECTIVE: To report a case of proximal occlusion of 2 major cerebral vessels associated with moyamoya network circulation that manifested by spontaneous intraventricular hemorrhage. DESIGN: Case report. PATIENT AND RESULTS: A 36-year-old Syrian man presented with symptoms of sudden-onset headache, neck stiffness, and confusion. The computed tomography scan of his brain showed intraventricular bleeding, and the subsequent 4 vessel angiographies revealed occlusion of the left middle and anterior cerebral arteries with moyamoya appearance in the terminal branches. The coagulation profile showed the presence of heterozygous factor V Leiden mutation. The patient was treated conservatively until resolution of his blood clot, and later he was started on oral anticoagulation. CONCLUSION: Factor V Leiden mutation may cause large cerebral vessel occlusion with moyamoya syndrome in adults.

Chronic thalamotomy increases pain-related behavior in rats.

The thalamus has been traditionally considered as the 'chief organ' by which pain is perceived (Head H, Holmes G. Sensory disturbances from cerebral lesions. Brain 1911;34:102-254). However, several clinical and experimental observations led to a challenge of this traditional view. In this report, we demonstrate that chronic thalamic lesions, instead of producing hypoalgesia, increased pain reactivity in rats. Different groups of rats were subjected to either subtotal, lateral or medial thalamic lesions. Their reactions to nociceptive stimuli were then assessed for a period of 1-2 months. Rats in the different groups showed an increased reactivity to acute mechanical and thermal nociceptive stimuli and an increase in the pain scores of the formalin test. These results suggest an important role of the thalamus in pain modulation in addition to that of nociceptive transmission.

Effects of chronic dizocilpine on acute pain and on mRNA expression of neuropeptides and the dopamine and glutamate receptors.

The mesocorticolimbic circuitry has been implicated in the pathophysiology of several neuropsychiatric syndromes like chronic pain and addiction. The aim of this study was to evaluate the effects of dizocilpine (MK-801), a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, on sensorimotor behaviors and the consequent changes in the dopamine, glutamate, and opiate systems in rats. Five groups of rats were subjected to acute tests for nociception (hot plate and paw pressure) before and after MK-801 (0.05, 0.1, 0.2 and 0.4 mg/kg, i.p.) or saline. Another two groups received daily i.p. saline or MK-801 (0.4 mg/kg) for 15 days. The nociceptive tests were performed on days 1, 7, and 14. On day 15 the rats received the last injection and were immediately sacrificed. We measured the mRNA expression, by in situ hybridization (ISH), of various dopamine and glutamate receptors, and enkephalin (Enk), dynorphin (Dyn), and substance P (SP) in the striatum, nucleus accumbens (NAC), piriform and cingulate cortex. Acute MK-801, dose-dependently, resulted in hyperalgesia. The chronic effects of 0.4 mg/kg MK-801 showed an extinction of the acute hyperalgesic effects especially with the hot plate test. The ISH studies revealed a decrease in mRNA expression of Enk and SP in the striatum and NAC. Our results indicate that the reversal of acute MK-801-induced hyperalgesia, with repeated exposure to systemic MK-801, is not directly related to changes in dopamine and glutamate receptors and might involve alteration of the striatal neuropeptide system.

Continuous perfusion with morphine of the orbitofrontal cortex reduces allodynia and hyperalgesia in a rat model for mononeuropathy.

Recent imaging reports demonstrate the activation of the orbitofrontal cortical (OFC) area during acute and chronic pain. The aim of this study was to compare the effects of chronic perfusion of this area with morphine on nociception in control rats and in rats subjected to mononeuropathy. Chronic perfusion of morphine, using miniosmotic pumps, produced significant and naloxone-reversible depression of tactile and cold allodynias and thermal hyperalgesia, observed in neuropathic rats, while it produced significant elevation and naloxone insensitive increase of acute nociceptive thresholds in control rats. The observed results support the idea that this area is a component of a flexible cerebral network involved in pain processing and perception.