ABSTRACT
BACKGROUND: Multiple sclerosis (MS) and CADASIL presenting together is exceedingly rare. As more cases of "inflammatory" CADASIL emerge, diagnostic challenges for clinicians increase. We report an individual with MS and CADASIL presenting with cognitive decline at age 25. She presented with gadolinium enhancing lesions on MRI and inflammatory cerebrospinal fluid raising the question of whether these patients should be given a diagnosis of "inflammatory CADASIL" or both MS and CADASIL. METHODS: A literature review was conducted on reports of inflammatory CADASIL or MS and CADASIL, clinical presentations including spinal cord lesions and CSF inflammatory markers. RESULTS: Nine cases in the literature of individuals with CADASIL and inflammatory presentations were found with treatment varying from intravenous steroids to MS immunomodulatory therapy. CONCLUSIONS: If individuals with CADASIL present with immune mediated inflammatory components they may benefit from immunomodulatory therapy. This is discussed with a review of the inflammatory CADASIL/MS cases in the literature and report of a case.
Subject(s)
CADASIL/complications , CADASIL/therapy , Multiple Sclerosis/complications , Multiple Sclerosis/therapy , Adult , Biomarkers/analysis , Brain/immunology , Brain/pathology , CADASIL/diagnosis , Female , Humans , Immunomodulation/immunology , Inflammation/therapy , Magnetic Resonance Imaging/methods , Multiple Sclerosis/diagnosisABSTRACT
The complex interplay between hypernatremic osmotic disturbances and cerebral lesions is yet to be clarified. In this review, we discuss, on the basis of the reported data of hypernatremic CNS challenge in the adult population, the clinical and radiologic features of the condition. Our search captured 20 case studies and 1 case series with 30 patients in total who acquired acute hypernatremia due to different etiologies and developed CNS lesions. We explored the associations between premorbid conditions, clinical presentation, hypernatremic state, correction rate, and radiologic appearance, including the localization of brain lesions and the outcomes. The results revealed that altered mental status was the most commonly reported symptom and osmotic demyelination syndrome in the form of extrapontine myelinolysis was the prevailing radiologic pattern. Finally, we contrasted, when appropriate, clinical and experimental data related to hypernatremic and hyponatremic osmotic insults to aid the understanding of the pathophysiology of CNS osmotic brain injury.
Subject(s)
Brain Diseases/diagnosis , Brain Diseases/etiology , Hypernatremia/complications , Hypernatremia/diagnosis , Neuroradiography , Adult , Demyelinating Diseases/diagnosis , Demyelinating Diseases/etiology , Female , Humans , Male , Statistics as Topic , Symptom Assessment/statistics & numerical data , Syndrome , Young AdultABSTRACT
Extrapontine myelinolysis (EPM) and cortical laminar necrosis (CLN) have rarely been reported in association with severe hypernatremia. We describe a patient with EPM associated with CLN following severe hypernatremia due to hypertonic peritoneal lavage after a ruptured hydatid cyst of the liver. Clinical and neuroimaging findings in acute stage and serial brain MRI at two and five month follow-up are discussed in detail.
ABSTRACT
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.
