BackgroundHow do we show that neurological services and neurological practice are safe? We aimed to identify the range of safety practices in neurology, develop a means of measuring safety practice ...activity at individual, service and national levels, assess safety culture across UK neuroscience centres and create benchmarks to allow future comparison of safety practice. We intend that this will provide information for service improvement and individual revalidation.MethodsItems assessing safety practice were collated from medical literature and direct experience of ABN Quality and Service Committee members. These were combined into a pilot survey for distribution to ABN Advisory Groups and ABN Committee members.Results18 questions on individual practice and 15 service-level questions were identified for the pilot. Results of the pilot will be presented and delegates will be asked for feedback during the meeting on the safety questions and their use in appraisal and revalidation.ConclusionA suite of individual metrics can be combined to evidence safety practice at a personal and service level in neurology.
BackgroundWe present baseline data on the first 50 participants recruited to the UK MS Pregnancy Register.MethodsData collected via questionnaires from consenting participants until 20th December ...2021 were included.Results50 participants (all with relapsing remitting MS; mean age at diagnosis 28.0 years; mean age at recruitment 33.0 years) were included. Median EDSS was 2.5 (n=16). Gestation at recruitment ranged from 2 to 40 weeks. 78% had discussed their pregnancy in advance with their MS team. 90% of patients had ever taken DMT. Of the patients that stopped DMT (n=23), 16 reported stopping for pregnancy-related reasons. Of these, 39% stopped before pregnancy and 30% following conception. 15 women are continuing DMT during their current pregnancy, taking the following DMT: Glatiramer acetate (n=5), natalizumab (n=7), Peginterferon beta-1a (n=2), not recorded (n=1). In those with prior pregnancies, 61% (14/23) reported pregnancy loss with 1 case of a rare genetic condition in the baby. None of the prior pregnancy losses happened whilst on DMT. One participant reported previous PPH and foetal macrosomia and another reported previous pre-eclampsia.ConclusionsThese results show that a patient-facing pregnancy MS registry is feasible and can collect previous adverse pregnancy outcomes. Future results will inform clinicians and women about the safety of DMT and adjunctive medication during pregnancy and postpartum.
RationaleFenfluramine substantially reduces rates of sudden unexplained death in epilepsy (SUDEP) in Dravet syndrome (Cross JH et al, AES 2020). Fenfluramine reduces respiratory arrest in the DBA/1 ...SUDEP mouse model (Tupal and Faingold, Epilepsia. 2019). Spreading depolarisation (SD) is a pathophysiologic event linked to cardiorespiratory collapse in SUDEP models. We report that fenfluramine inhibits SD, and explore its potential inhibitory mechanisms.MethodsWe examined the effects of fenfluramine on SD evoked by KCl or oxygen glucose deprivation (OGD) in cortical brain slices of adult C57Bl/6 mice. We also measured the effect on GABAAR-mediated inhibitory postsynaptic currents (sIPSC) in vitro.ResultsFenfluramine increased the threshold for SD events at clinically relevant concentration ranges (~10 µM). Blocking GABAARs with gabazine did not fully occlude SD inhibition by fenfluramine, suggesting that GABAAR potentiation is not involved in the inhibitory SD mechanism of fenfluramine.ConclusionOur results demonstrate that fenfluramine directly inhibits SD generation without acting via a neurovascular mechanism suggesting that SD inhibition could account for the decrease in expected rates of SUDEP in patients treated with fenfluramine.
PurposeOptic neuritis (ON) is a common feature of Multiple Sclerosis (MS). DARC is an intravenous fluo- rescent-tagged annexin V (ANX776) identifying cell stress and apoptosis with retinal imaging. ...We aimed to differentiate DARC spots in ON from healthy subjects using descriptive measures (DM) of DARC spots identified by a convolutional neural network-aided algorithm (CNN-AA).MethodsDARC spots were identified from anonymised DARC images obtained from ON (n=12; mean age=46) and healthy (n=68; mean age=48) participants after ANX776 administration using the CNN-AA (ISRCTN10751859). DM characteristics: mean, standard deviation (std), skew, kurtosis, coefficient of variation (cv), Euclidean distance from the nearest blood vessel (bvdist) and the 7Hu moments, were analysed on ON (n = 357) and healthy (n = 2457) eyes using two-tailed student t-tests. Distributions of spot metrics were analysed using two-sample Kolmogorov-Smirnov test.ResultsThe mean, cv and kurtosis (p £ 0.0001) and hu1 and std (p £ 0.001) were found to be significantly different between DARC spots in ON and healthy controls. Distributions of the individual DM metrics analysed, showed a significant difference (p £ 0.0001) between ON and healthy spots for the same variables (mean, cv, kurtosis, hu1 and std).ConclusionDM of DARC spots distinguish ON and healthy subjects. Further studies with larger ON groups are needed to replicate this finding.
GNE myopathy is an adult-onset autosomal recessive distal myopathy uniquely characterised by quadri- ceps sparing. It was previously described in Japanese patients and a large ethnic cluster was ...identified in Jews originating from Iran. Since then, it is recognised to have a worldwide prevalence with multiple pathogenic variants. While compound heterozygous c.830G>A GNE myopathy has previously been reported, homozygous disease has only previously been reported in a non-Jewish Iranian cohort and the Indian subcontinent. Here we report a case of apparent homozygous c.830G>A GNE myopathy in a non-Jewish Iraqi patient.
ObjectiveTo calculate the efficiency index (EI), a recently described metric based on test accuracy and inaccuracy, for dementia diagnosis using the mini-Addenbrooke’s Cognitive Examination (MACE), ...and to compare this with balanced EI (BEI) and unbiased EI (UEI), based on balanced and unbiased accuracy and inaccuracy measures respectively. All efficiency indexes have boundary values of 0 and ∞; inflection point at 1; where value >1 indicates correct diagnostic classification and <1 indicates incorrect classification.ResultsUsing the dataset from a large (N = 755) prospective pragmatic study of MACE, in which 114 patients received criterion diagnosis of dementia, EI was 2.81 at the optimal MACE cut-off (≤20/30, deter- mined by maximal Youden index). BEI was 4.24 and UEI was 0.61 at this cut-off. Plotting values of EI, BEI, and UEI across the range of MACE cut-offs (≤11/30 to ≤29/30), UEI values were lowest, EI values were highest at lower cut-offs and BEI values were highest at higher cut-offs. Adjusting for dementia prevalence (fixed BEI), both EI and UEI values increased with dementia prevalence, with EI>UEI.ConclusionsEfficiency indexes are easily calculatedThese unitary metrics may have greater utility than others in communicating risk of correct diagnosis versus misdiagnosis of test outcomes.
Visual deterioration in Idiopathic Intracranial Hypertension (IIH) warrants surgical intervention. All patients with IIH admitted to St. George’s, London for 10-years from 2010 were identified and ...those with shunts were analyzed retrospectively. Of 1234 IIH patients, 27 had shunts, 12/27 were aged 19-30 and 24 were females. The most common indication for a shunt was quantifiable visual impairment (52%). Majority had lumboperitoneal shunts (67%). The average length of stay was 16 days (2SD+/-8 days). In the first 3 years, neurologists were not involved in the care of 11/27 patients but all since. The number of shunts per year peaked at 6 in 2013 and is now 1-2. At first follow-up, vision and headache improved in 84% and 85% of patients, respectively. 40% had recurrence of symptoms despite a functioning shunt due to coexisting migraine (36%), functional neurological disorder (9%) or both (18%). The most common complication was shunt obstruction (single-revision; 30%; multiple-revisions; 19%), followed by low-pressure symptoms (26%), requiring readmissions in 81% of patients. Shunting is not without risks but is currently indicated in those with deteriorating visual function; hence, the decision to proceed with shunting in IIH should be made with vigilance in accordance with the 2018 consensus guidelines.
A 23-year-old female was admitted to ED two weeks after delivery with severe migrainous headaches and a painful pupil-sparing partial right third nerve palsy presenting as diplopia on upward and ...lateral gaze and a partial ptosis. This was the third such presentation for her as she was diagnosed with oph- thalmoplegic migraine (OM) since 8 years old. A second episode at the 18 years of age required steroid treatment due to a delayed recovery for few months.Repeat orbit MRI confirmed slightly grown lesion on the right oculomotor nerve compared scans 4 years apart appearing as a thickened nodular enhancement between the P1 segment and superior cerebel- lar artery. Multiple neuro-oncology and neuro-radiology MDTs confirmed this lesion to be an oculomotor nerve schwannoma. She had to be treated with steroids due to deficits and 2 months later while migrain- ous headache was fully resolved, she was still left with subtle upward and lateral gaze diplopia. She will have surveillance imaging and follow up.Recurrent Painful Ophthalmoplegic Neuropathy (RPON) is replacing OM and expected to be associated with a resolution of the enhancement. Schwannomas on the other hand are known to be growing during pregnancy and affected by hormonal changes. Transient or recurrent oculomotor nerve deficits may be the primary manifestations of cranial nerve schwannoma and we hypothesise this tumour being the cause of her RPON which must be considered in OM.
Background and AimsCurrent diagnostic criteria for TIA/minor stroke disqualify several atypical clinical presentations, but pre-date DWI-MRI use. We investigated the proportion of DWI-positive ...patients with atypical presentations, identifying clinical factors predicting DWI positivity.MethodsWe retrospectively reviewed consecutive patients with suspected TIA/minor stroke (NIHSS<5) undergoing MRI at our comprehensive stroke centre from March 2020-February 2021. We identified pre- dictors of DWI positivity using logistic regression.ResultsOf 1615 patients, 442 DWI-positive, 39% had atypical presentations including 20% with progres- sive symptom onset. Atypical symptoms common in DWI-positive patients included headache(17%), unsteadiness(15%), positive sensory symptoms(11%), presyncope(10%), confusion(9%) and vertigo(8%). Symptoms independently associated with DWI-positivity included weakness(OR 1.30, 95% CI 1.01-1.67), dysarthria(OR 2.06, CI 1.56-2.70), and ataxia (OR 3.75, CI 2.27-6.20). Fluctuating symptoms(22%) predicted DWI positivity(OR 1.37, CI 1.00-1.81), but sudden onset(80%) did not (OR 1.05, CI 0.80-1.38). Risk factors associated with DWI positivity included increasing age(OR 1.01/year, CI 1.01-1.02), hypertension (OR 1.70, CI 1.30-2.22), diabetes(OR 1.44, CI 1.07-1.93), and smoking(OR 1.68, CI 1.19-2.39). DWI-positive patients had significantly more risk factors (mean 2.65 vs 1.95 p=<0.001).ConclusionsOver one-third with DWI-confirmed TIA/minor stroke present atypically. The value of atypical symptoms in excluding ischaemia, particularly in patients with vascular risk factors, appears limited.
Posterior reversible encephalopathy syndrome (PRES) is a syndrome characterised by reduced GCS/confusion, seizures and visual disturbance along with characteristic MRI findings. Autoimmune disorders ...have been identified in one third of patients with PRES.Here we discuss a 33-year-old female with SLE, who presented with reduced GCS and arm weakness. She had an AKI and metabolic acidosis and was admitted to ICU. Although the patients GCS improved, ongoing upper limb weakness remained. MRI imaging to rule out cerebral lupus, showed high T2 and FLAIR signal within the deep white matter of the occipital, frontal and parietal lobes. This was suggestive of PRES. Whilst in ICU the patient developed hypertension and was started on amlodipine. The patient also had a long history of immunosuppression with mycophenolate, hydroxychloroquine and rituximab. A neurology referral was sent for further advice.Although the name suggests, PRES is often not completely reversible and is not limited to the posterior cerebral cortex, as seen here. It still remains unclear whether it is the autoimmune condition or treatment of these conditions with immunosuppressant’s that is the primary association. Case reports linking PRES with immunosuppressant therapy have shown an early onset of symptoms following treatment, rather than years.
