Journal of neurology, neurosurgery, and psychiatry
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J. Neurol. Neurosurg. Psychiatr. · Mar 2014
ReviewPharyngeal-cervical-brachial variant of Guillain-Barre syndrome.
The pharyngeal-cervical-brachial (PCB) variant of Guillain-Barré syndrome is defined by rapidly progressive oropharyngeal and cervicobrachial weakness associated with areflexia in the upper limbs. Serial nerve conduction studies suggest that PCB represents a localised subtype of Guillain-Barré syndrome characterised by axonal rather than demyelinating neuropathy. Many neurologists are unfamiliar with PCB, which is often misdiagnosed as brainstem stroke, myasthenia gravis or botulism. ⋯ Half of patients with PCB carry IgG anti-GT1a antibodies which often cross-react with GQ1b, whereas most patients with Fisher syndrome carry IgG anti-GQ1b antibodies which always cross-react with GT1a. Significant overlap between the clinical and serological profiles of these patients supports the view that PCB and Fisher syndrome form a continuous spectrum. In this review, we highlight the clinical features of PCB and outline new diagnostic criteria.
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J. Neurol. Neurosurg. Psychiatr. · Mar 2014
Hereditary myopathy with early respiratory failure: occurrence in various populations.
Several families with characteristic features of hereditary myopathy with early respiratory failure (HMERF) have remained without genetic cause. This international study was initiated to clarify epidemiology and the genetic underlying cause in these families, and to characterise the phenotype in our large cohort. ⋯ We report an extensive collection of families with HMERF with five different mutations in exon 343 of TTN, which establishes this exon as the primary target for molecular diagnosis of HMERF. Our relatively large number of new families and mutations directly implies that HMERF is not extremely rare, not restricted to Northern Europe and should be considered in undetermined myogenic respiratory failure.
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J. Neurol. Neurosurg. Psychiatr. · Mar 2014
Titin founder mutation is a common cause of myofibrillar myopathy with early respiratory failure.
Titin gene (TTN) mutations have been described in eight families with hereditary myopathy with early respiratory failure (HMERF). Some of the original patients had features resembling myofibrillar myopathy (MFM), arguing that TTN mutations could be a much more common cause of inherited muscle disease, especially in presence of early respiratory involvement. ⋯ Mutations in TTN are a cause of MFM, and titinopathy is more common than previously thought. The finding of the p.C30071R mutation in 3.9% of our study population is likely due to a British founder effect. The occurrence of novel FN3 domain variants, although still of uncertain pathogenicity, suggests that other mutations in this domain may cause MFM, and that the disease is likely to be globally distributed. We suggest that HMERF due to mutations in the TTN gene be nosologically classified as MFM-titinopathy.
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J. Neurol. Neurosurg. Psychiatr. · Mar 2014
Grammatical comprehension deficits in non-fluent/agrammatic primary progressive aphasia.
Grammatical comprehension difficulty is an essential supporting feature of the non-fluent/agrammatic variant of primary progressive aphasia (naPPA), but well-controlled clinical measures of grammatical comprehension are unavailable. ⋯ These findings emphasise a distinct grammatical comprehension deficit in naPPA and associate this with interruption of a frontal-temporal neural network.
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J. Neurol. Neurosurg. Psychiatr. · Mar 2014
Meta AnalysisAPOE associations with severe CAA-associated vasculopathic changes: collaborative meta-analysis.
Cerebral amyloid angiopathy (CAA) is associated with lobar intracerebral haemorrhage (ICH). While only the ε4 allele of the apolipoprotein E (APOE) gene is associated with the presence of CAA, both APOE-ε4 and ε2 are associated with lobar ICH. The generally accepted explanation is that APOE-ε4 promotes vascular amyloid deposition, while APOE-ε2 promotes progression to severe CAA with associated vasculopathic changes that cause vessel rupture and ICH. We assessed the evidence for these allele-specific effects. ⋯ We found a possible association of severe CAA with APOE-ε4 but not APOE-ε2. However, our findings do not exclude a biologically meaningful association between APOE-ε2 and severe CAA. Further work is needed to elucidate fully the allele-specific associations of APOE with CAA and their mechanisms.