Abdullah Al-Asmi

The detection of mood and anxiety in people with epilepsy using two-phase designs: Experiences from a tertiary care centre in Oman

BACKGROUND The detection of mood and anxiety disorders is of great clinical importance in patients with chronic disease but data on the occurrence of affective dysfunction is lacking among people with epilepsy (PWE) in non-western populations. Further compounding such situation, the validity of some of the common assessment measures has not been examined. OBJECTIVE The study aims to investigate the application of the Hospital Anxiety and Depression Scale (HADS) by identifying patients with comorbid affective dysfunctions in an Omani population. The semi structured interview, Composite International Diagnostic Interview (CIDI) will be used to establish the psychometric property of HADS in the Omani population. METHODS PWE (n=150) were screened with the semi-structured, (CIDI) and the HADS. A receiver operating characteristics (ROC) curve was calculated to discriminate the power of the HADS for every possible threshold score. RESULTS The semi-structured interview revealed the prevalence rate of 27% for depressive disorder and 45% for anxiety disorder. The best compromise using, the cut-off score of 7 or 8, gave a sensitivity of 99% for depression and 83-91% for anxiety and a specificity of 87.5-100% for depression and 85-94% for anxiety. CONCLUSIONS Findings suggest that HADS is a useful screening tool for this particular population. This finding is discussed from the socio-cultural perspective of Omani society.

Neuromyelitis optica: an overview

Neuromyelitis optica (NMO) is a relapsing inflammatory disorder of the central nervous system that closely resembles multiple sclerosis. This review discusses recent understanding of NMO with reference to epidemiology, clinical spectrum, immunopathology, diagnostic evaluation, clinical course and management. Within the clinical spectrum of NMO, the classical form (with relapsing opticomyelitis) and limited forms (either recurrent myelitis or optic neuritis), as well as its association with other autoimmune disorders, have been recognised in recent years. Further, symptomatic or asymptomatic cerebral lesions may be present, and such brain lesions do not necessarily exclude the diagnosis. In the appropriate clinical context, the diagnosis is supported by longitudinally extensive myelitis on spinal MRI. Overwhelming evidence strongly indicates that aquaporin 4 antibody has a pathogenetic role in the development of NMO and serves as a useful diagnostic and prognostic marker. Detection of this autoantibody has led to the categorisation of NMO as an autoimmune channelopathy. NMO can be distinguished from multiple sclerosis by a combination of clinical, radiological and laboratory studies. However, the nosological position of Asian opticospinal multiple sclerosis is not settled. In NMO, acute attacks usually result in moderate to severe functional impairment, and, in the absence of a secondary progressive course (unlike relapsing–remitting multiple sclerosis), prevention of relapses is of crucial importance in the management of the disease. Indeed, relapse prevention with long-term immunosuppressive medication remains the cornerstone of therapy in this otherwise debilitating disease!

Pomegranate from Oman Alleviates the Brain Oxidative Damage in Transgenic Mouse Model of Alzheimer’s Disease

Oxidative stress may play a key role in Alzheimer′s disease (AD) neuropathology. Pomegranates (石榴 Shí Liú) contain very high levels of antioxidant polyphenolic substances, as compared to other fruits and vegetables. Polyphenols have been shown to be neuroprotective in different model systems. Here, the effects of the antioxidant-rich pomegranate fruit grown in Oman on brain oxidative stress status were tested in the AD transgenic mouse. The 4-month-old mice with double Swedish APP mutation (APPsw/Tg2576) were purchased from Taconic Farm, NY, USA. Four-month-old Tg2576 mice were fed with 4% pomegranate or control diet for 15 months and then assessed for the influence of diet on oxidative stress. Significant increase in oxidative stress was found in terms of enhanced levels of lipid peroxidation (LPO) and protein carbonyls. Concomitantly, decrease in the activities of antioxidant enzymes was observed in Tg2576 mice treated with control diet. Supplementation with 4% pomegranate attenuated oxidative damage, as evidenced by decreased LPO and protein carbonyl levels and restoration in the activities of the antioxidant enzymes [superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione (GSH), and Glutathione S transferase (GST)]. The activities of membrane-bound enzymes [Na+ K+-ATPase and acetylcholinesterase (AChE)] were altered in the brain regions of Tg2576 mouse treated with control diet, and 4% pomegranate supplementation was able to restore the activities of enzymes to comparable values observed in controls. The results suggest that the therapeutic potential of 4% pomegranate in the treatment of AD might be associated with counteracting the oxidative stress by the presence of active phytochemicals in it.

Long-term (15 mo) dietary supplementation with pomegranates from Oman attenuates cognitive and behavioral deficits in a transgenic mice model of Alzheimer's disease

OBJECTIVE Transgenic (Tg) mice, which possess an amyloid precursor protein (APP) gene mutation, develop extracellular amyloid β (Aβ) deposition in the brain, and severe memory and behavioral deficits with age. These mice serve as an important animal model for testing the efficacy of novel drug candidates for the treatment and management of symptoms of Alzheimers disease (AD). Several reports have suggested that oxidative stress is the underlying cause of Aβ neurotoxicity in AD. Pomegranates contain very high levels of antioxidants and several medicinal properties that may be useful for improving quality of life in individuals with AD. The aim of this study was to investigate the effect of dietary supplementation of Omani pomegranate extract on memory, anxiety, and learning skills in an AD mouse model possessing the double Swedish APP mutation (APPsw/Tg2576). METHODS The experimental groups of APP-Tg mice from the age of 4 mo were fed a custom mixed diet (pellets) containing 4% pomegranate. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in Tg and wild-type mice at the age of 4 to 5 mo and 18 to 19 mo using the Morris water maze test, rotarod performance test, elevated plus-maze test, and open field test. RESULTS APPsw/Tg2576 mice that were fed a standard chow diet without pomegranates showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial learning ability, position discrimination learning ability, and motor coordination compared with the wild-type mice on the same diet, at the age of 18 to 19 mo. In contrast, APPsw/Tg2576 mice that were fed a diet containing 4% pomegranates showed significant improvements in memory, learning, locomotor function, as well as reduction in anxiety, compared with APPsw/Tg2576 mice fed the standard chow diet. CONCLUSION Our results suggest that dietary supplementation with pomegranates may slow the progression of cognitive and behavioral impairments in AD.

Neuroprotective Effects of a Variety of Pomegranate Juice Extracts against MPTP-Induced Cytotoxicity and Oxidative Stress in Human Primary Neurons

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is an environmental toxin which selectively induces oxidative damage and mitochondrial and proteasomal dysfunctions to dopaminergic neurons in the substantia nigra leading to Parkinsonian syndrome in animal models and humans. MPTP is one of the most widely used in vitro models to investigate the pathophysiology of Parkinsons disease (PD) and, screen for novel therapeutic compounds that can slow down or ameliorate this progressive degenerative disease. We investigated the therapeutic effect of pomegranate juice extracts (PJE), Helow, Malasi, Qusum, and Hamadh against MPTP-induced neurotoxicity in primary human neurons by examining extracellular LDH activity, intracellular NAD+ and ATP levels, and endogenous antioxidant levels including lipid peroxidation products, catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, and reduced glutathione (GSH) levels. MPTP induced a reduction in SOD and GPx activities and intracellular NAD+, ATP, and GSH levels parallel to an increase in extracellular LDH and CAT activities, although lipid peroxidation was not altered. We report that helow and malasi can ameliorate MPTP-induced neurotoxicity by attenuating the observed changes in redox function to a greater extent than qusum and hamedh. Selected PJE varieties may exhibit properties which may be of therapeutic value to slow down age-related degeneration and neurodegeneration in particular.

Effect of dietary supplementation of dates in Alzheimer's disease APPsw/2576 transgenic mice on oxidative stress and antioxidant status

Abstract Oxidative stress may play a key role in Alzheimers disease (AD) neuropathology. Changes in the oxidative stress, antioxidants, and membrane-bound enzymes were investigated in the cerebral cortex and hippocampus of AD transgenic mice model after long-term dietary supplementation of date palm fruits from Oman. The 4-month-old mice with double Swedish APP mutation (APPsw/Tg2576) were purchased from Taconic Farm, NY, USA; mice were fed two different doses of dates (such as 4 and 2%) or control diet for 15 months and then assessed for the influence of diet on oxidative stress. Significant increase in oxidative stress in terms of enhanced levels of lipid peroxidation (LPO) and protein carbonyls and parallel decrease in the activity of antioxidant enzymes were observed in control diet-treated Tg2576 AD mice. Dates (4 and 2%) treated APPsw/Tg2576 AD mice exhibited significantly attenuated oxidative damage, evidenced by decreased LPO and protein carbonyl levels and restoration in the activities of the antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione, and glutathione reductase). The activities of membrane-bound enzymes (Na+, K+-ATPase and acetyl cholinesterase) were altered in control diet-treated APPsw/Tg2576 AD mice brain regions. Meanwhile, both the percentages of date supplementation were able to restore the activity of enzymes to comparable values observed in controls. In summary, we have shown that chronic dietary supplementation of date palm fruits grown in Oman showed possible beneficial effects concomitant with oxidative stress reduction and increased antioxidant enzymes in AD transgenic mice model. These results warrant further exploration of how anti-reactive oxygen species properties of dates offer such beneficial effects on the AD-like brain.

Lymphocytic infundibulo-neurohypophysitis: An unusual cause of recurrent optic neuropathy in a child

Lymphocytic infundibulo-neurohypophysitis (LINH), a rare autoimmune disease, is distinct from lymphocytic hypophysitis and is characterized by lymphocytic and plasma cell infiltration of the posterior lobe of the pituitary and the pituitary stalk.(1) We report the case of a young boy who presented with recurrent, steroid-responsive optic nerve dysfunction and diabetes insipidus. T1-weighted magnetic resonance imaging scans of the brain showed an isointense soft tissue mass within the sella turcica and a thickened pituitary stalk. Tissue specimen resected at transsphenoidal surgery revealed chronic inflammation with infiltration of lymphocytes and no granulomatosis or necrosis, establishing the diagnosis of LINH.(2) This is the first report of optic neuropathy in association with LINH in a child.

Consumption of fig fruits grown in Oman can improve memory, anxiety, and learning skills in a transgenic mice model of Alzheimer's disease

Alzheimer disease (AD) is one of the most common forms of dementia in the elderly. Several reports have suggested neurotoxic effects of amyloid beta protein (Aβ) and role of oxidative stress in AD. Figs are rich in fiber, copper, iron, manganese, magnesium, potassium, calcium, vitamin K, and are a good source of proanthocyanidins and quercetin which demonstrate potent antioxidant properties. We studied the effect of dietary supplementation with 4% figs grown in Oman on the memory, anxiety, and learning skills in APPsw/Tg2576 (Tg mice) mice model for AD. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in Tg and wild-type mice at the age of 4 months and after 15 months using the Morris water maze test, rota-rod test, elevated plus maze test, and open-field test. Tg mice that were fed a control diet without figs showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial, position discrimination learning ability, and motor coordination compared to the wild-type control mice on the same diet, and Tg mice fed on 4% fig diet supplementation for 15 months. Our results suggest that dietary supplementation of figs may be useful for the improvement of cognitive and behavioral deficits in AD.

Diet rich in date palm fruits improves memory, learning and reduces beta amyloid in transgenic mouse model of Alzheimer's disease

Background: At present, the treatment options available to delay the onset or slow down the progression of Alzheimer′s disease (AD) are not effective. Recent studies have suggested that diet and lifestyle factors may represent protective strategies to minimize the risk of developing AD. Date palm fruits are a good source of dietary fiber and are rich in total phenolics and natural antioxidants, such as anthocyanins, ferulic acid, protocatechuic acid and caffeic acid. These polyphenolic compounds have been shown to be neuroprotective in different model systems. Objective: We investigated whether dietary supplementation with 2% and 4% date palm fruits (grown in Oman) could reduce cognitive and behavioral deficits in a transgenic mouse model for AD (amyloid precursor protein [APPsw]/Tg2576). Materials and Methods: The experimental groups of APP-transgenic mice from the age of 4 months were fed custom-mix diets (pellets) containing 2% and 4% date fruits. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in all the animals at the age of 4 months and after 14 months of treatment using the Morris water maze test, rota-rod test, elevated plus maze test, and open-field test. We have also analyzed the levels of amyloid beta (Aβ) protein (1-40 and 1-42) in plasma of control and experimental animals. Results: Standard diet-fed Tg mice showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial learning ability, position discrimination learning ability and motor coordination when compared to wild-type on the same diet and Tg mice fed 2% and 4% date supplementation at the age of 18 months. The levels of both Aβ proteins were significantly lowered in date fruits supplemented groups than the Tg mice without the diet supplement. The neuroprotective effect offered by 4% date fruits diet to AD mice is higher than 2% date fruits diet. Conclusions: Our results suggest that date fruits dietary supplementation may have beneficial effects in lowering the risk, delaying the onset or slowing down the progression of AD.

Extrapontine myelinolysis as presenting manifestation of adrenal failure: A case report

BACKGROUND Hyponatremia is a fairly common metabolic disorder. Hyponatremic myelinolysis is a relatively rare, life threatening complication with poorly understood pathophysiology, varied clinical manifestations and uncertain treatment. This case report highlights the range of clinical and imaging phenomena associated with hyponatremic myelinolysis. METHODS Case report. RESULT A middle aged lady presented with an acute delirious state, hypotension and severe hyponatremia on a background of skin hyper-pigmentation and weight loss. Her clinical course evolved to an akinetic-rigid state and later to parkinsonism. Extensive investigations for recognizing a primary neurologic disorder, including brain MRI and CSF analysis were normal, though she had disseminated miliary tuberculosis involving multiple organs. Brain MRI changes characteristic of extrapontine myelinolysis appeared two weeks after the onset of symptoms. The patient recovered completely over several weeks. CONCLUSION This case of hyponatremic extrapontine myelinolysis occurred as the presenting manifestation of adrenal failure secondary to disseminated tuberculosis. Extraponine myelinolysis is difficult to diagnose in the context of delayed brain MRI changes and can have a favorable outcome with modern management.