IntroductionAbout 60% of patients with Autoimmune-Paraneoplastic Encephalitis (AIE-PNE) develop a clinical syndrome before malignancy is diagnosed. Tumour screening, early recognition and prompt ...treatment is likely to improve outcomes. Imaging guidelines for the management of these patients have not yet been defined. This study aimed to characterise the current use of imaging in the monitoring and management of people with AIE-PNE.MethodsWe enrolled 23 patients with a diagnosis of suspected or confirmed AES-PNE (Dalmau, 2016). MRI head, whole body CT and PET scans patterns were analysed.ResultsPatients had a diagnosis of suspected or confirmed AIE-PNE. A third had MRI abnormalities at presentation. 81% underwent a body CT at presentation with 20% having abnormalities. 66% had PET scans at presentation with 22% showing an abnormality. Most prevalent antibodies were NMDA (35%), LGI1 (17%) and GABA-B (9%). 14% had lung malignancy.ConclusionBody CT was the commonest imaging investigation performed at presentation and only a little over half had further investigations if initial CT was negative. No patient that responded to initial treatment had further investigations to look for an underlying malignancy. There is an urgent need for follow up studies that will inform future imaging criteria for AIE-PNE.arshiaseddigh@nhs.net|ABN Bursary44
BackgroundNeurological disorders account for 20% of acute medical admissions and 7% of GP consulta- tions. We evaluated our acute neurology service with the catchment area of 3 million people. ...Moreover, we investigated the impact on the service during the COVID19 pandemic.MethodsWe identified 6618 urgent phone calls logged between March 2017 and June 2020. We performed a detailed analysis of 800 referrals: 400 in 10 weeks before and 400 in 11 weeks during the first national lockdown.ResultsReferrals were made by teaching hospitals (43%), district general hospitals (35%) and GPs (22%). The reasons for referrals were similar between hospitals and GPs: epilepsy (33% vs 30%), headache (15% vs 20%), sensory symptoms (10% vs 7%) and weakness (10% vs 8%). The outcomes of these referrals were telephone advice only (64%), neurology ward admission (9%), rapid assessment and other outpatient clinics (8% and 25% respectively). There was a threefold decrease in the number of phone calls during the initial four weeks of national lockdown. However, the patient demographics and the range of diagnoses remained overall unchanged.ConclusionsThis provides important descriptive data on demographics and outcomes for acute neurology referrals, which can be used to guide service provision and training.alexandergrundmann@nhs.net45
Remyelination is a promising strategy to prevent axonal degeneration and progressive disability in people with multiple sclerosis (MS). In animal models, remyelination becomes inefficient with ...advancing age and much preclinical research is focused on interventions to reverse cellular hallmarks of ageing in remyelinat- ing lesions. However, there is currently limited evidence that human remyelination also declines with age.We investigated the effect of patient age on treatment response among participants of the CCMR One trial (ISRCTN14265371): a double-blind, placebo-controlled phase 2a study (n=52) that demonstrated the ability of bexarotene, a retinoid-X receptor agonist, to promote remyelination in people aged 25–50 with relapsing remitting MS. For eyes with chronic optic neuropathy (baseline latency >118ms), bexarotene shortened the full-field visual-evoked potential P100 latency maximally in younger patients. The treatment effect diminished by approximately 0.5ms per year, such that older patients receiving bexarotene had a similar P100 latency change to controls. Furthermore, MRI scans of the same patients demonstrated an age-dependent treatment effect on lesion magnetisation transfer ratio, a radiological correlate of remyelination.These results provide evidence that bexarotene promotes remyelination best in younger patients, rein- forcing the need to address the age-associated decline in remyelination capacity to develop successful remyelinating therapies.cem73@cam.ac.uk|NIHR Bursary
A man with Erb’s disease Leddy, Sara; Jaffer, Fatima; Lipnicka-Khan, Monika ...
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A man, currently aged 72, developed a spastic paraparesis without sensory abnormalities progressing to wheel-chair dependence and late urinary incontinence over 14 years. Apart from a history of type ...2 diabetes mellitus, he was otherwise well. Extensive blood and CSF investigations including screening for HIV, HTLV1, syphilis, and Lyme disease were normal or negative. There was no evidence of neuropathy or denervation on EMG. MRI showed mild non-specific white matter signal change in both cerebral hemi- spheres. A provisional diagnosis of primary lateral sclerosis (PLS) was revised with the finding of elevated Very Long Chain Fatty Acids (VLCFAs). Genetic testing revealed a novel missense variant c.1771C>Gp. (Arg591Gly) in exon 7 of the ABCD1 gene. Mutation in ABCD1 transporter leads to accumulation of VLCFAs in the peroxisomes and cytosol which is toxic, causing oxidative stress and demyelination in the CNS and PNS. Literature review did not reveal reports of AMN mimicking PLS. Our patient highlights the importance of screening VLCFAs (abnormal in ~99% of men with AMN) in suspected PLS, a diagnosis of exclusion. Diagnosis of ALD/AMN allows genetic counselling, screening for adrenal failure, and access to stem cell therapy for children with asymptomatic cerebral onset ALD.sara.leddy1@nhs.net
Long-term seizure-free outcome failure following Antero-Mesial Temporal (AMT) resection in drug-resistant Mesial Temporal Lobe Epilepsy (MTLE) patients may arise from extra-temporal regions termed ...pseudotem- poral epilepsy (pTLE) or alternatively, the epileptogenic zone may extend beyond the AMT termed tem- poral-plus epilepsy (T+E). Insula (INS), Orbito-Frontal (OF) cortex, cingulum (CI), temporo-parieto-occipital junction are Candidate Brain Regions (CBRs) that can be involved.Stereoelectroencephalography (SEEG) can distinguish T+E and pTLE from MTLE if the electrodes are accu- rately placed to sample the CBRs. We study the structural connectivity from the amygdalohippocampal complex (AHC) to sub-segmented parcels of the CBRs to identify differential connectivity that may guide SEEG planning. Whole-brain connectomes were generated in 25 patients with hippocampal sclerosis (12 right) that underwent SEEG. Connectivity of the AHC was calculated as a normalized t-score map and the regions with the greatest connectivity are shown in Table 1.Results suggest parcels of the CBRs show preferential connectivity to the AHC which occasionally differ between the left and right HS. Further studies are required to identify if structural connectivity-based SEEG- targeting can improve the detection of pTLE and T+E.khosropanahpegah7@gmail.com31
IntroductionSORD is a newly described autosomal recessive gene that is emerging as the commonest cause of autosomal recessive CMT (Charcot-Marie-Tooth disease) and hereditary motor neuropathy ...(HMN).MethodsWe present nine cases of SORD-related neuropathy.ResultsNine unrelated patients were found to have biallelic mutations in SORD. Eight were male (89%) and median age of assessment was 34 years (range 18–55 years). Median age of symptom onset was 15 years (range 12–18 years) and all patients initially presented with difficulty walking and/or problems involving distal lower limbs. Only one patient (11%) had sensory symptoms. 5/9 (56%) had distal upper limb weakness and all had distal lower limb weakness. Sensory examination was abnormal to at least one modality in 7/9 cases (78%). The median CMT Examination and CMT Neuropathy Scores were 6 (range 2–12) and 7.5 (range 3–14) respectively. Neurophysiology showed conduction velocities in the axonal or intermediate ranges in all cases. Clinical diagnosis was distal HMN in 5/9 (56%), CMT2 in 2/9 (22%) and CMT intermediate in 2/9 (22%).ConclusionsThe SORD phenotype is typically a slowly progressive, length-dependent motor neuropathy of onset during the second decade. Sensory symptoms are rare and sensory signs minimal.chris.record@ucl.ac.uk
Secondary (acquired) haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome which can occur in the context of infection, malignancy or rheumatological disease and is associated ...with high mortality. Early recognition facilitates access to effective biological therapies and engage- ment with specialist MDTs which focus on managing the underlying trigger. Neurological manifestations are associated with poor prognosis but are not well described.We retrospectively reviewed 40 cases of secondary HLH in UCLH/NHNN; 25 had neurological compli- cations. Median age at onset: 36 years (range 11–79); 8 females. Causes of HLH were haematological malignancy (14), rheumatological disease (3), infection (2) and other/unknown (6). Neurological involve- ment portended higher morbidity and mortality: 21/40 ICU support; 19/40 in hospital death (15/25 and 16/25 with neurology). Neurological presentations included confusion (10) and reduced consciousness (5), headache (7), neuropathy (3) and myopathy (1). Based on symptomatology, radiological, CSF and metabolic and histological information we propose mechanistic causality of neurological manifesta- tions into: disease infiltration (13/25), metabolic (12/25), iatrogenic (2/25). The role of the cytokine storm in metabolic neurological derangement requires further investigation.We designed a minimal neurology dataset to improve prospective data collection instituted via the UK HiHASC (Hyperinflammatory and HLH Across Speciality Collaboration). A management algorithm is in development.rachelbrown@ucl.ac.uk|ABN Bursary86
128 Variety is the splice of life Knight, KAW; McDonald, JJ; Davenport, RJ
Journal of neurology, neurosurgery and psychiatry,
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Case 1: A 42-year-old female presented with progressive exertional breathlessness over 2 years. She was breathless at rest and had bilateral Trendelenburg signs. Pulmonary function testing ...demonstrated a restrictive defect. Serum CK was elevated at 300. EMG demonstrated myotonia. We considered a wide differential, but a very low alpha glucosidase level led to genetic testing revealing GAA heterozygosity (c.-32–13T>G and c.1528G>A; p.(Trp516*) variants), confirming Pompe disease.Case 2: A 35-year-old female presented with a 20-year history of arm and leg weakness. Examination revealed proximal weakness affecting all four limbs but no respiratory involvement. Investigations dem- onstrated a raised CK of 1,000. Neurophysiology confirmed myopathic changes. An alpha glucosidase level was low on two occasions. Genetic testing confirmed GAA heterozygosity: (c.-32–13T>G variant and GAA exon 18 deletion) confirming Pompe disease.Pompe disease is an autosomal recessive condition caused by mutations in the GAA gene. Enzyme deficiency leads to impaired glycogen breakdown, with subsequent body tissue accumulation. GSD-II may present with varying phenotypes which are influenced by genotypic variations and level of enzyme activity, as these cases demonstrate. Diagnosis is important as enzyme replacement therapy is available. The clue is a low alpha-glucosidase level, a simple but crucial test to perform.kawknight@gmail.com89
IntroductionObjective algorithms (OA; Ramanujam, 2020) identify SPMS in those with clinically assigned (CA) RRMS, suggesting SPMS is under-diagnosed in practice. It’s unclear if clinicians are aware ...of this evolution and escalate therapy in response to clinical worsening with highly active (HA) disease modifying treatments (DMT).ObjectiveAssess whether treatment intensity escalates as the disease advances from RRMS to OA-SPMS and from RRMS to CA-SPMS.MethodsMS registries in Czech Republic, Denmark, Germany, Sweden and UK were used. Active DMTs at the date of last visit were classified as highly active (HA) or not, and DMT usage prior to CA-SPMS or OA-SPMS classification.Results3740 SPMS and 9542 OA-SPMS patients were on DMTs. HADMT use was 21.3% prior to OA-SPMS clas- sification in RRMS and 27.9% (p<0.0001) once classified. HADMT use was 23.5% prior to CA-SPMS diagnosis and 36.9% (p<0.0001) once diagnosed. HADMT use in the UK was lower than in other registries for all groups.ConclusionAcross Europe the evolution to clinical SPMS via OA-SPMS is eliciting a response from clini- cians that is not initially reflected in a change of diagnosis. Country variations in HADMT use in transitioning patients should be explored further.r.m.middleton@swansea.ac.uk74
057 Para-herpetic SUNCT syndrome Sim, Nicholas Keyi; Ying, Li; Mowafi, Walied
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Pre and post-herpetic SUNCT syndrome is a rare but previously reported complication of herpes zoster reactivation. We report a case of a zoster associated SUNCT syndrome developing at the same time ...as reactivation.A 79-year-old gentleman was referred to Neurology for refractory right sided facial pain. 7 months prior to presentation he had developed shingles in the right upper face around his forehead area, which was managed by his GP. At the same time, he developed daily attacks of sharp stabbing pain behind his eye, up to 5 a day, lasting up to 5 minutes each. This was associated with injection and lacrimation of the affected eye. The attacks can be triggered by touch, such as a shower. Neurological examination was unremarkable except for allodynia in the right V1 distribution. Plain MRI scan showed cortical atrophy only.He had a good response to lamotrigine. nchlasim@doctors.org.uk
