A failure of protein degradation may underpin Lewy body disease (LBD) where α-synuclein is assimilated into the pathognomic Lewy bodies and Lewy neurites. We investigated histological alterations in lysosomes and autophagosomes in the substantia nigra (SN) and cingulate gyrus (CG) in 34 patients with LBD employing antibodies against phosphorylated α-synuclein and lysosomal (lysosomal associated membrane proteins 1 and 2 (LAMP-1 and LAMP-2), cathepsin D (CTSD)) and autophagosomal (microtubule-associated protein light chain 3α (LC3A)) proteins. Immunostained sections were qualitatively and semi-quantitatively assessed for the appearance, distribution and intensity of staining. Four LBD patients had mutations in GBA1. There was significantly less LAMP-1, LAMP-2 and CTSD immunostaining in neurons of the SN in LBD cases compared to control cases and marginally less LAMP-1 in patients with GBA1 mutations compared to those without. Loss of LAMP-1 and CTSD immunoreactivity correlated with cell loss from the SN. There were no changes in LC3A immunoreactivity in the SN, nor any major changes in the CG, or glial cell activity in the SN and CG, for any of the markers. A proportion of amyloid plaques in both the LBD and control cases was immunoreactive for LAMP-1 and LAMP-2, but not CTSD or LC3A proteins. These immunohisochemical features were seen in glial cells, which were negative for amyloid-β. Alterations in lysosomal structure or function, but not macroautophagy, may underpin the pathogenesis of LBD.
Frontal lobe seizures can be difficult to distinguish from non-epileptic seizures or sleep disorders. Addition- ally, the ictal EEG is often normal. To illustrate the challenging semiology and frequent misdiagnosis of FLE we discuss two patients, accompanied by video-EEG from the Chalfont Centre for Epilepsy.Case 1, a 41-year-old man with right frontal lobe focal cortical dysplasia presented with stereotyped nocturnal focal motor seizures that were associated with right frontal epileptic discharges. Seizures manifested as contralateral head version and tonic posturing of the upper limbs; the characteristic “fencing posture” described in seizures involving the supplementary motor area. In some, these evolved to hyperkinetic seizures.Case 2, a 23-year-old woman with multiple cavernous haemangiomas secondary to KRIT1 gene mutation, presented with stereotyped bipedal cycling movements of the lower limbs and loss of awareness, without associated ictal EEG change. These episodes were previously mis-diagnosed as non-epileptic but were confirmed as epileptic seizures from a right frontal lobe cavernoma.The unusual semiology of FLE represents a diagnostic challenge, which cannot always be resolved with ictal EEG recordings. FLE should be considered with episodes which are nocturnal, brief, stereotyped, motor predominant with, or without, awareness, and often with bilateral upper limb posturing or hyper- kinetic movements.rowangurney1@nhs.net30
In 2016, a hospital approved guideline on first line immunosuppression was introduced. This included evidence-based guidance on consent, prescription, dosing, safety and efficacy monitoring of corticos- teroid, azathioprine, methotrexate, mycophenolate, IVIg, SCIg, rituximab and cyclophosphamide use in common inflammatory neuromuscular diseases. It was accompanied by drug-specific patient information booklets and disease-specific clinical outcome measurement tools. The centre for neuromuscular diseases has not recorded any serious adverse events associated with these medications since its introduction.With junior doctors rotating in 3-6 monthly cycles, we identified the need for recurrent implementation efforts to maintain guideline impact. With an iterative process of four sequential cycles we:1) performed a survey of adequacy of admission/discharge documentation,2) created electronic patient record (EPR) proformas for admission/discharge,3) included a training session at changeover hospital induction,4) added a training session to mid-rotation peer-led teaching rota.This process resulted in optimal admission/discharge documentation (as per guidelines) of: Cycle 2) 61%/96%; Cycle 3) 100%/70%; Cycle 4) 86%/100%.Here we highlight the potential for loss of compliance with guideline use by junior medical staff over multiple changeovers, demonstrate the need for ongoing implementation efforts and underline the benefit of integrated electronic proformas (content in poster).
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