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
Delayed and disorganised brain activation detected with magnetoencephalography after mild traumatic brain injury.
Awareness to neurocognitive issues after mild traumatic brain injury (mTBI) is increasing, but currently no imaging markers are available for mTBI. Advanced structural imaging recently showed microstructural tissue changes and axonal injury, mild but likely sufficient to lead to functional deficits. Magnetoencephalography (MEG) has high temporal and spatial resolution, combining structural and electrophysiological information, and can be used to examine brain activation patterns of regions involved with specific tasks. ⋯ Patients with mTBI showed significant delays in the activation of important areas involved in executive function. Also, more regions of the brain are involved in an apparent compensatory effort. Our study suggests that MEG can detect subtle neural changes associated with cognitive dysfunction and thus, may eventually be useful for capturing and tracking the onset and course of cognitive symptoms associated with mTBI.
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J. Neurol. Neurosurg. Psychiatr. · Sep 2015
Randomized Controlled TrialPer cent of patients with chronic migraine who responded per onabotulinumtoxinA treatment cycle: PREEMPT.
The approved use of onabotulinumtoxinA for prophylaxis of headaches in patients with chronic migraine (CM) involves treatment every 12 weeks. It is currently unknown whether patients who fail to respond to the first onabotulinumtoxinA treatment cycle will respond to subsequent treatment cycles. To help inform decisions about treating non-responders, we examined the probability of treatment cycle 1 non-responders responding in cycle 2, and cycle 1 and 2 non-responders responding in cycle 3. ⋯ A meaningful proportion of patients with CM treated with onabotulinumtoxinA who did not respond to the first treatment cycle responded in the second and third cycles of treatment.
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J. Neurol. Neurosurg. Psychiatr. · Sep 2015
Randomized Controlled TrialDantrolene for cerebral vasospasm after subarachnoid haemorrhage: a randomised double blind placebo-controlled safety trial.
Dantrolene is neuroprotective in animal models and may attenuate cerebral vasospasm (cVSP) in human aneurysmal subarachnoid haemorrhage (aSAH). We evaluated safety, feasibility and tolerability of intravenous dantrolene (IV-D) in patients with aSAH. ⋯ In this small trial, IV-D after aSAH was feasible, tolerable and safe.
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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.