Journal of neurology, neurosurgery, and psychiatry
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J. Neurol. Neurosurg. Psychiatr. · Sep 2015
ReviewTransthyretin (ATTR) amyloidosis: clinical spectrum, molecular pathogenesis and disease-modifying treatments.
Transthyretin (ATTR) amyloidosis is a life-threatening, gain-of-toxic-function disease characterised by extracellular deposition of amyloid fibrils composed of transthyretin (TTR). TTR protein destabilised by TTR gene mutation is prone to dissociate from its native tetramer to monomer, and to then misfold and aggregate into amyloid fibrils, resulting in autosomal dominant hereditary amyloidosis, including familial amyloid polyneuropathy, familial amyloid cardiomyopathy and familial leptomeningeal amyloidosis. Analogous misfolding of wild-type TTR results in senile systemic amyloidosis, now termed wild-type ATTR amyloidosis, characterised by acquired amyloid disease in the elderly. ⋯ Recently, the clinical effects of TTR tetramer stabilisers, diflunisal and tafamidis, were demonstrated in randomised clinical trials, and tafamidis has been approved for treatment of hereditary ATTR amyloidosis in European countries and in Japan. Moreover, antisense oligonucleotides and small interfering RNAs for suppression of variant and wild-type TTR synthesis are promising therapeutic approaches to ameliorate ATTR amyloidosis and are currently in phase III clinical trials. These newly developed therapies are expected to be effective for not only hereditary ATTR amyloidosis but also wild-type ATTR amyloidosis.
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J. Neurol. Neurosurg. Psychiatr. · Sep 2015
ReviewChronic inflammatory demyelinating polyradiculoneuropathy: from pathology to phenotype.
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an inflammatory neuropathy, classically characterised by a slowly progressive onset and symmetrical, sensorimotor involvement. However, there are many phenotypic variants, suggesting that CIDP may not be a discrete disease entity but rather a spectrum of related conditions. While the abiding theory of CIDP pathogenesis is that cell-mediated and humoral mechanisms act together in an aberrant immune response to cause damage to peripheral nerves, the relative contributions of T cell and autoantibody responses remain largely undefined. ⋯ In other human inflammatory neuropathies, there is evidence of antibody responses to Schwann cell, compact myelin or nodal antigens. In this review, the roles of the cellular and humoral immune systems in the pathogenesis of CIDP will be discussed. In time, it is anticipated that delineation of clinical phenotypes and the underlying disease mechanisms might help guide diagnostic and individualised treatment strategies for CIDP.
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J. Neurol. Neurosurg. Psychiatr. · Sep 2015
Review Comparative StudyComparative efficacy of interferon β versus glatiramer acetate for relapsing-remitting multiple sclerosis.
Interferon β (INFβ) and glatiramer acetate (GA) are widely used in patients with relapsing-remitting multiple sclerosis (RRMS). However, it is still unclear whether they have different efficacy. We performed a systematic search of head-to-head trials for gaining objective reliable data to compare the two drugs, using the Cochrane Collaboration methodology. ⋯ However, the average reduction in T2-weighted and T1-weighted lesion volume was significantly greater in the INFβ group than in the GA group (mean difference (MD) -0.58, 95% CI -0.99 to -0.18, p 0.004, and MD -0.20, 95% CI -0.33 to -0.07, p 0.003, respectively). The number of participants who dropped out of the studies because of adverse events was similar in the two groups. These data support clinicians in the use of these therapies, based on their similar safety and efficacy in the prevention of disease activity, although the different effect on MRI measures and the different tolerability might have a role in the therapeutic choice at the individual level.