Consensus recommendations for the diagnosis and treatment of multiple sclerosis in Kuwait.

OBJECTIVES: We aim to develop consensus recommendations to guide neurologists in the community for the diagnosis and treatment of Multiple Sclerosis (MS). METHODS: After reviewing the available literature, a group of neurologists with expertise in MS met to discuss the evidence and develop consensus recommendations for the diagnosis and treatment of MS. RESULTS: The revised 2010 McDonald criteria is the established diagnostic criteria for MS and has wide international acceptance among international MS experts. Several red flags in the history and examination, along with certain laboratory tests were pointed out to exclude MS mimickers in the diagnostic phase. The available approved disease modifying therapies (DMTs) were listed in an algorithmic fashion based on initial assessment of disease severity and subsequent disease breakthrough while on DMTs. Risk stratification based on the benefit versus risk ratio was used to help choosing the appropriate therapy to MS patients using an "individualized therapy" approach. The requirements for initiation and monitoring of treated MS patients were highlighted with emphasis on early identification of disease breakthrough, adverse events, and safety concerns. The role of multi-disciplinary MS clinics was discussed and a guide for referral to specialized MS clinics was developed. CONCLUSIONS: Consensus recommendations have been developed to guide local neurologists on the diagnosis and treatment of patients with MS. Implementation of the revised 2010 McDonald diagnostic criteria was advised while a personalized treatment approach was recommended using a treatment algorithm based on risk stratification and patient-centered outcomes.

A case of community-onset meningitis caused by hospital methicillin-resistant Staphylococcus aureus successfully treated with linezolid and rifampicin.

OBJECTIVE: To report a relatively rare presentation of methicillin-resistant Staphylococcus aureus (MRSA) meningitis in a previously healthy boy in Kuwait. CLINICAL PRESENTATION AND INTERVENTION: A 14-year-old boy presented with a 2 weeks' history of headache and fever with increasing severity. He developed photophobia and double vision 2 days prior to his hospital visit and received ceftriaxone for 6 days prior to admission to the hospital. There was no history of head trauma or neurosurgical operation. Lumbar puncture revealed a slightly turbid cerebrospinal fluid with pleocytosis and greatly reduced glucose, elevated protein level and on culture grew MRSA. Staphylococcal chromosome cassette mec (SCCmec) typing revealed that it belonged to SCCmec type III and sequence type 238 (ST238-SCCmec-III). Polymerase chain reaction screening for the presence of Panton-Valentine leukocidin (PVL) genes yielded a negative result; all these findings were consistent with hospital-acquired MRSA. He was treated with intravenous linezolid and rifampicin for 2 weeks, made good response and was discharged home fully recovered and well. CONCLUSION: Hospital MRSA should be considered in the differential diagnosis of the causative agents of community-onset meningitis in healthy patients even without predisposing factor.

Apolipoprotein E polymorphism and clinical disease phenotypes in Arab patients with schizophrenia.

BACKGROUND: Apolipoprotein E (APOE) is polymorphic, and may be involved in the pathogenesis and clinical expression of schizophrenia. This study aimed to investigate the frequency of specific APOE genotypes and alleles in a schizophrenic Arab population and evaluate the association of specific APOE types with clinical phenotypes of the disease. SUBJECTS AND METHODS: Two age-matched groups of subjects were studied: (1) healthy controls, n = 165; (2) patients with schizophrenia (SZ), n = 207. Each subject was evaluated for age and mode of onset of disease, family history of psychosis, disease severity and outcome over the years of illness. APOE genotyping was performed by a validated PCR-RFLP technique. RESULTS AND DISCUSSION: Genotype E3E2 and allele E2 were less frequent in the patients with schizophrenia (p = 0.04), and both APOE types tended to be more common in male than female schizophrenic patients (p = 0.08). Schizophrenic patients with a positive family history of psychosis had lower frequencies of genotype E3E2 and allele E2 (both p = 0.04). Genotype E3E4 and allele E4 were least common in patients with an age at onset of disease >31 years (OR: 5.5, 95% CI: 1.1-27.4), particularly in males. CONCLUSION: APOE genetic polymorphism potentially influences susceptibility to schizophrenia and may be associated with aspects of its phenotypic expression, particularly gender, age of onset and family history of psychotic illness. This relationship of APOE with schizophrenia is likely to be race- and gender-specific.

Biosimilars: opinion of an expert panel in the Middle East.

BACKGROUND: Several biotechnology-derived drugs are reaching the end of their patent lives. As a result, so-called biosimilar products are in development, and a few have already gained approval in Europe and other countries such as the USA. Biosimilars, unlike generic versions of conventional drugs, are not identical to their reference product, and their production is complex and sensitive to even slight changes in the manufacturing and storage process. Therefore, the registration of these products requires more stringent evaluation than that for conventional generics. METHODS AND SCOPE: A consensus group of experts from the Near and Middle East discussed the currently available guidelines for registration of biosimilars--including those produced by the European Medicines Agency (EMEA)--and their application in this region. To inform this report, a literature search was also conducted on PubMed in January 2008, using the search terms 'biosimilar' and 'follow-on biologic'. This paper provides an overview of the issues in the development and registration of biosimilars, a description of the EMEA guidelines and the recommendations of the consensus group for the registration of biosimilars in the Middle East. FINDINGS: Because of the complex nature of biosimilars and their potential immunogenicity, these products cannot undergo the abbreviated approval process used for generic agents. Instead demonstration of their quality, safety and efficacy, in comparison with their reference biological product, is required. CONCLUSIONS: The consensus group recommended the implementation of the EMEA guidelines as the basis of Regional guidelines for the registration of biosimilars in the Near and Middle East. Registration would, therefore, require demonstration of the robustness of the manufacturing process and quality-control methods, the comparability of pharmacokinetics, pharmacodynamics, efficacy and safety between the biosimilar and reference product and plans for post-marketing surveillance of the long-term risks and immunogenicity of new biosimilars.

Associations of blood homocysteine concentrations in Arab schizophrenic patients.

BACKGROUND: This study aimed to evaluate the blood homocysteine concentration in Arab patients with schizophrenia and assess its associations with clinical phenotypes of the disease. SUBJECTS AND METHODS: Two age-matched groups of subjects were studied: (1) Healthy Controls, HC, n=165; (2) patients with schizophrenia, SZ: n=207. Each subject was evaluated with a standard questionnaire for age at disease onset, family history, disease severity and outcome. Plasma homocysteine levels (Hcys) were measured by immunoassay and serum levels of other biochemical parameters were measured by routine Autoanalyzer techniques. RESULTS AND DISCUSSION: Group HC was heavier (body mass index, BMI) while SZ had greater waist-hip ratio (WHR) and plasma Hcys levels. In SZ, there were significant correlations between Hcys and BMI, triglycerides and HDL. Hcys levels in SZ were highest in the younger male patients. CONCLUSION: Schizophrenic patients have increased blood Hcys levels which correlate with components of the metabolic syndrome. Hcys levels were highest in the younger male patients and were not influenced by prognostic features of the disease.

HLA determinants of susceptibility to multiple sclerosis in an Arabian Gulf population.

BACKGROUND: An association between HLA antigens and susceptibility to multiple sclerosis (MS) has been established, especially in Caucasian populations. Such associations have not been as clearly defined in many Arab populations, where even the frequencies of specific HLA antigens remain unclear OBJECTIVE: The study was designed to (i) investigate the frequencies of HLA Class I and II antigens in Kuwaiti Arabs with MS, and; (ii) assess possible inter-relationships between HLA Class II antigens and such clinical phenotypic variables in MS as age at onset, gender, disease subtype and scale of disability. SUBJECTS AND METHODS: HLA Class I (A, B, C) and Class II (DR, DQ) antigens' tissue-typing was performed by the standard complement-dependent microlymphocytotoxicity technique in two groups of age- and sex-matched Kuwaiti subjects: (i) 67 patients with definite MS (48 relapsing remitting, 19 relapsing-progressive) and (ii) 145 unrelated healthy controls. The frequencies of specific HLA types were then compared between patients with controls, and in the former, related to specified clinical parameters. RESULTS: The frequencies for the Class I antigens: A9, A10, A19, A33, B5 and CW4 appeared higher with the presence of MS, although the numbers of positive subjects were rather low. For the Class II antigens, frequencies of DR4, DQ5, DQ6, DQ7 and DQ8 were increased while those for DR6 and DR1 were decreased in the patients with MS. HLA types DR15 and DR4 were present at higher frequencies in patients with a younger age at disease onset; DR15 also appeared more frequent in the female patients. CONCLUSION: There is a trend towards an association between HLA Class II antigens (DR4, DQ6, DQ7 and DQ8) and MS in Kuwaiti subjects. Additionally, it appeared that DR4 and DR15 were more frequent in females and those with an early onset of the disease. These patterns of HLA Class II determinants of susceptibility to MS differ from reports in some other populations, and may reflect the recognized variability in genetic influence on HLA and disease expression.

Confirmation of brain death using brain radionuclide perfusion imaging technique.

OBJECTIVE: To determine the reliability of radionuclide cerebral blood perfusion imaging in confirming brain death irrespective of continued heartbeat. SUBJECTS AND METHODS: Twenty-eight patients (19 male and 9 female, aged 17-63 years) with severe brain injury and fully supported until the final cardiac asystole were included in the study. Two sets of clinical tests aimed at ascertaining brain death in each subject were performed separately for each case within an interval of 24 h. Dynamic, planar and single photon emission computed tomographic (SPECT) brain scintigraphy were also performed after intravenous administration of 550 MBq (15 mCi) technetium-99m hexamethyl propyleneamine oxime. RESULTS: Following the clinical diagnosis of brain death, none of the patients was withdrawn from cardiopulmonary support or had any organ harvested. Dynamic, planar and SPECT imaging performed thereafter did not reveal any intracranial cerebral perfusion in any of the subjects, except in 1 patient where the initial scan showed posterior fossa activity that ceased, in a subsequent scan obtained after 24 h. All of the patients were declared dead only after the emergence of cardiac asystole. CONCLUSION: The findings indicate that radionuclide brain perfusion imaging is reliable, reproducible, noninvasive and simple to perform for the confirmation of brain death and as such we recommend it as an alternative to exhaustive neurophysiological tests and invasive catheter angiography.

Risk factors, subtypes and outcome of ischaemic stroke in Kuwait--a hospital-based study.

OBJECTIVE: To report on stroke subtypes, associated risk factors and outcome in Kuwait. METHODS: The records of 62 patients (30 male, 32 female) admitted with diagnosis of stroke to Kuwait Oil Company Hospital, Kuwait, a tertiary care hospital, during a 5-year period (1995-1999), were retrospectively reviewed. RESULTS: Small artery infarction was the most common subtype and occurred in 37 subjects (59.7%); less common were atherosclerotic large artery strokes (19 patients, 30.6%) and strokes of cardio-embolic origin (6 patients, 9.7%). Identifiable risk factors or associated morbidities were hypertension (72.5%), diabetes mellitus (69.4%), ischaemic heart disease (14.5%), history of migraine (8.1%), lone atrial fibrillation (5.0%), and valvular heart disease (1.6%). The most important determinants of a deleterious 30-day outcome, as indicated by severe disability or death, were female gender, lack of use of anti-platelet drugs, presence of a large artery infarction stroke subtype, and cardio-embolic stroke. CONCLUSION: Prevalence of hypertension and diabetes is high among patients with stroke in Kuwait, with rates higher than those found in any previous reports from the Gulf region. Two unusual observations were that women had a rather high frequency of stroke, and infarction of the small artery was more common than that of the large artery. Outcome, as indicated by severe disability or death, was worse among women, elderly patients, and those with large artery atherosclerotic and cardio-embolic strokes. There is some evidence that such a deleterious outcome might be ameliorated with use of anti-platelet drugs.

Survival of cardiac function after brain death in patients in Kuwait.

BACKGROUND: Persistent cessation of all cerebral and brainstem function (brain death) is accepted in most countries as legal evidence of death. It is presumed that cardiac function will cease within a short time after brain death has occurred. In some countries, such as Kuwait, tradition and practice discourage application of the brain death criteria despite legal acceptance. OBJECTIVE: The study was designed to assess the duration of persistence of cardiac function in patients after the diagnosis of brain death had been made on the basis of generally accepted criteria. METHODS: We evaluated how long cardiac function persisted after brain function had ceased in 40 patients in Kuwait who were admitted to hospital and died during the 10-year period 1992-2001. RESULTS: It was found that the mean persistence of cardiac function after brain death was 8.20 days and the median survival time was 6 days. Two thirds of the patients survived longer than a week, but none had cardiac function for longer than 30 days. CONCLUSION: The study confirms that brain death is not automatically followed immediately by cessation of all other body functions. It may be speculated therefore that whole-body homeostasis is not as intimately associated with brain function as has hitherto been thought.

Neuroblastoma and fetal exposure to phenytoin in a child without dysmorphic features.

Despite the fact that the teratogenic effects of phenytoin have been suggested in several case reports, the evidence for a possible oncogenic potential of phenytoin has not been widely recognized. Recently, neuroblastoma as well as other neuroectodermal and non-ectodermal tumors has been seen in several children exposed to phenytoin prenatally. Previous cases have been almost uniformly associated with the features of "fetal hydantoin syndrome" and none have been developmentally normal. We report a developmentally-normal boy of 21/2 years with an abdominal neuroblastoma whose mother had been on phenytoin (as well as carbamazepine) throughout gestation. We review the various neoplasms which have been reported in the offspring of mothers receiving phenytoin.