Neurology

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https://hdl.handle.net/20.500.14709/76

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HCB-12 Multiple motor proteins regulate the ALS-linked TDP-43 anterograde transport
(Taylor and Francis, 2025-11-12) Feole, Monica; Devoto, Victorio; Dragisic, Neda; Zaragoza, Alba; Lall, Deepti; Carna, Maria; Forte, Giancarlo; Smith, Richard; Stokin, Gorazd Bernard; Svendsen; Stokin, Gorazd Bernard; Medical and Dental
No abstract available
New-onset refractory status epilepticus (NORSE) in a 23-year-old female
(Elsevier, 2020-11-25) Morrison, Hamish; Morgan, Catherine; Urankar, Kathryn; Wylde, John; O'Beirne, Martin; Kroklikowski, Konrad; Wakerley, Benjamin; Morrison, Hamish; Wylde, John; O'Bierne, Martin; Wakerley, Benjamin; Medical and Dental
No abstract available
Clinical and Genetic Features in a Series of Eight Unrelated Patients with Neuropathy Due to Glycyl-tRNA Synthetase (GARS) Variants
(SAGE Publications, 2020-01-24) Forrester, Natalie; Rattihalli, Rohini; Horvath, Rita; Maggi, Lorenzo; Manzur, Adnan; Fuller, Geraint; Gutowski, Nicholas; Rankin, Julia; Dick, David; Buxton, Christopher; Greenslade, Mark; Majumdar, Anirban; Fuller, Geraint; Medical and Dental
Pathogenic variants in the Glycyl-tRNA synthetase gene cause the allelic disorders Charcot-Marie-Tooth disease type 2D and distal hereditary motor neuropathy type V. We describe clinical features in 8 unrelated patients found to have Glycyl-tRNA synthetase variants by Next Generation Sequencing. In addition to upper limb predominant symptoms, other presentations included failure to thrive, feeding difficulties and lower limb dominant symptoms. Variability in the age at testing ranged from 14 months to 59 years. The youngest being symptomatic from 3 months and ventilator-dependent. Sequence variants were reported as pathogenic, p.(Glu125Lys), p.(His472Arg); likely pathogenic, p.(His216Arg), p.(Gly327Arg), p.(Lys510Gln), p.(Met555Val); and of uncertain significance, p.(Arg27Pro). Our case series describes novel Glycyl-tRNA synthetase variants and demonstrates the clinical utility of Next Generation Sequencing testing for patients with hereditary neuropathy. Identification of novel variants by Next Generation Sequencing illustrates that there exists a wide spectrum of clinical features and supports the newer simplified classification of neuropathies.
Improving liaison neurology services
(BMJ Publishing Group, 2020-09-02) Fuller, Geraint; Fuller, Geraint; Medical and Dental
Liaison neurology (consulting with inpatient ward referrals) is the main way that most patients admitted with neurological disease will access neurology services. Most liaison neurology services are responsive, seeing referrals on request, but they also can be proactive, with a regular neurology presence in the acute medical unit. Fewer than half of hospitals in England have electronic systems, yet these can facilitate the process-allowing electronic responses to advise on investigations before seeing the patient, and arranging follow-up after-as well as prioritising referrals and documenting the process. In this time of COVID-19, there are additional benefits in providing prompt remote advice. Improving the way liaison neurology is delivered can improve patient outcomes and save money by shortening admissions. This hidden work of the neurologists needs to be recorded and recognise
Recommendations for the Organization of Multidisciplinary Clinical Care Teams in Parkinson’s Disease
(SAGE Publications, 2020-05-16) Radder, Danique; Nonnekes, Jorik; van Nimwegen, Marlies; Eggers, Carsten; Abbruzzese, Giovanni; Alves, Guido; Browner, Nina; Ray, Chaudhuri; Ebersbach, Georg; Ferreira, Joaquim; Fleisher, Jori; Fletcher, Peter; Frazzitta, Giuseppe; Giladi, Nir; Guttman, Mark; Iansek, Robert; Khandhar, Suketa; Klucken, Jochen; Lafontaine, Anne-louise; Fletcher, Peter; Medical and Dental
Background: Optimal management in expert centers for Parkinson’s disease (PD) usually involves pharmacological and non-pharmacological interventions, delivered by a multidisciplinary approach. However, there is no guideline specifying how this model should be organized. Consequently, the nature of multidisciplinary care varies widely. Objective: To optimize care delivery, we aimed to provide recommendations for the organization of multidisciplinary care in PD. Methods: Twenty expert centers in the field of multidisciplinary PD care participated. Their leading neurologists completed a survey covering eight themes: elements for optimal multidisciplinary care; team members; role of patients and care partners; team coordination; team meetings; inpatient versus outpatient care; telehealth; and challenges towards multidisciplinary care. During a consensus meeting, outcomes were incorporated into concept recommendations that were reviewed by each center’s multidisciplinary team. Three patient organizations rated the recommendations according to patient priorities. Based on this feedback, a final set of recommendations (essential elements for delivery of multidisciplinary care) and considerations (desirable elements) was developed. Results: We developed 30 recommendations and 10 considerations. The patient organizations rated the following recommendations as most important: care is organized in a patient-centered way; every newly diagnosed patient has access to a core multidisciplinary team; and each team has a coordinator. A checklist was created to further facilitate its implementation. Conclusion: We provide a practical tool to improve multidisciplinary care for persons with PD at the organizational level. Future studies should focus on implementing these recommendations in clinical practice, evaluating their potential applicability and effectiveness, and comparing alternative models of PD care.
Idiopathic intracranial hypertension: Update on diagnosis and management
(Elsevier, 2020-07) Wakerley, Benjamin; Mollan, Susan; Sinclair, Alexandra; Wakerley, Benjamin; Medical and Dental
Idiopathic intracranial hypertension is a condition of raised intracranial pressure of unknown cause. Features include new onset headache, which is frequently non-specific; papilloedema is present, visual disturbances are common; and there may be sixth nerve palsy. Diagnosis includes brain imaging with venography to exclude structural causes and venous sinus thrombosis. Lumbar puncture reveals pressure greater than 250 mmCSF with normal constituents. Treatments aim to modify the disease, prevent permanent visual loss and manage headaches. These include weight loss. For those with rapid visual decline, urgent surgical intervention is essential. For most, this is a chronic condition characterised by significantly disabling headaches.
New horizons for idiopathic intracranial hypertension: advances and challenges
(Oxford University Press, 2020-12-15) Mollan, Susan; Grech, Olivia; Alimajstorovic, Zerin; Wakerley, Benjamin; Sinclair, Alexandra; Wakerley, Benjamin; Medical and Dental
Introduction: Idiopathic intracranial hypertension (IIH) is becoming a recognized condition due to the increasing incidence linked to a global obesity epidemic. Sources of data: All English papers on PubMed, Cochrane and Scholar between inception until 1 March 2020 were considered. Areas of agreement: Studies suggest central adiposity has a pathogenic role. Recent weight gain is a risk factor and weight loss has a key role in management. Areas of controversy: Interpretation of abnormal lumbar puncture opening pressure is debated. There is an increasing recognition of obesity stigma and how this should be approached. Growing points: Further evidence is required for the choice of surgical intervention for fulminant IIH. Education regarding IIH should be evidence based. Areas timely for developing research: Novel research of the pathology of IIH is influencing development of therapies such as glucagon-like peptide-1 receptor agonists and targeting unique androgen signatures. The newly discovered cardiovascular risk requires further attention.
Emerging themes in idiopathic intracranial hypertension
(Soringer, 2020-07-22) Grech, Olivia; Mollan, Susan; Wakerley, Benjamin; Alimajstorovic, Zerin; Lavery, Gareth; Sinclair, Alexandra; Wakerley, Benjamin; Medical and Dental
Purpose Idiopathic intracranial hypertension (IIH) is a rare disorder characterised by raised intracranial pressure. The underlying pathophysiology is mostly unknown and effective treatment is an unmet clinical need in this disease. This review evaluates key emerging themes regarding disease characteristics, mechanisms contributing to raised intracranial pressure and advances in potential therapeutic targets. Findings IIH is becoming more common, with the incidence rising in parallel with the global obesity epidemic. Current medical management remains centred around weight management, which is challenging. Metabolic investigations of patients have identified specific androgen profiles in cerebrospinal fluid (CSF), which suggest an endocrine dysfunction impacting CSF secretion in IIH. Glucagon-like peptide-1 (GLP-1) and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) have been found to play a role in CSF dynamics in IIH and have formed the basis of the first clinical trials looking at new treatments. Conclusions Identification of novel molecular targets thought to underlie IIH pathology is now being translated to clinical trials.
Drug-induced meningitis: A review of the literature and comparison with an historical cohort of viral meningitis cases
(Elsevier, 2020-04-05) Kalmi, Galith; Javeri, Florian; Vanjak, Anthony; Kirren, Quentin; Green, Andrew; Jarrin, Irene; Lloret-Linares, Celia; Green, Andrew; Medical and Dental
Background: Drug-induced aseptic meningitis (DIAM) is potentially insufficiently considered by clinician, being of rare etiology, with there being no previously published exhaustive study describing its clinical and biological features. Methods: Two independent academic clinicians searched all the case reports of DIAM from 1995 until 15th April, 2017. The search was limited to studies performed in humans, published in English or French. Clinical and biological data of subjects were compared with those of patients with documented viral meningitis. Results: One hundred and fifty-one case reports fulfilled our inclusion criteria. Non-steroidal anti-inflammatory drugs were the commonest drug cause of AM n=49, followed by antibiotics n=46, biotherapy n=19 and finally immunomodulators n=15. The clinical and biological presentation of DIAM varies according to the causative etiological drug, especially with respect to the interval between exposure and presentation and cerebrospinal fluid (CSF) pleiocytosis. Clinical symptoms associated with meningitis were more prevalent in viral meningitis than in DIAM, except for fever and signs of encephalitis. Cerebrospinal fluid examination in DIAM reveals an increased CSF white cell count and an increased proportion of neutrophils and protein, compared with viral meningitis. Discussion: We present an extensive review of the DIAM case reports, and highlight their clinical and biological characteristics according to the drugs involved. While comparing for the first time their characteristics with those of viral meningitis, this review hopes in facilitate earlier diagnosis and management of DIAM in clinical practice.
Guillain-Barré syndrome in Eastern China: A study of 595 patients
(Wiley, 2021-05-04) Song, Yan; Zhang, Yong; Yuki, Nobuhiro; Wakerley, Benjamin; Liu, Chen; Song, Jin; Wang, Min; Feng, Xungang; Hao, Yanlei; Wang, Yuzhong; Wakerley, Benjamin; Medical and Dental
Background and purpose: This study aimed to investigate geographical differences in the clinical features of Guillain-Barré syndrome (GBS) between patients from our region in Eastern China and patients from other areas. Methods: A total of 595 patients fulfilling the diagnostic criteria for GBS or its variants were included from two large hospitals located in Eastern China. Data collection included demographics, antecedent events, clinical presentation and signs, electrophysiological subtypes, treatment, complications during hospitalization, clinical severity at nadir, and outcome at 12 months, and these data were compared to data from a study conducted in Southern China and the Europe/Americas section of the International GBS Outcome Study. Results: The median (interquartile range) age of patients was 50 (36-61) years, the ratio of men to women was 1.2, and 49% of patients had antecedent events. Patients in our region of Eastern China had pure motor predominant GBS (158/340, 46%) and 30% (103/340) had complications during hospitalization. Patients aged over 60 years had a lower frequency of antecedent infections and single, axonal subtypes, but higher disability scores at entry, nadir, and 12 months. When compared with the Europe/Americas data, our patients had a lower frequency of antecedent infection (46% vs. 63%), cranial nerve involvement (43% vs. 49%), sensory deficits (45% vs. 69%), pain (19% vs. 57%) and mechanical ventilation (11% vs. 17%), but a higher frequency of axonal subtype (35% vs. 6%). There was a higher frequency of patients with antecedent gastroenteritis (16% vs. 8%), mechanical ventilation (11% vs. 8%) and axonal subtypes (35% vs. 19%) in our region in Eastern China than in Southern China. Conclusions: Patients with GBS in Eastern China showed significant clinical heterogeneity and differences when compared to other geographic areas.
Effectiveness of Bariatric Surgery vs Community Weight Management Intervention for the Treatment of Idiopathic Intracranial Hypertension A Randomized Clinical Trial
(American Medical Association, 2021-04-26) Mollan, Susan; Mitchell, James; Ottridge, Ryan; Aguiar, Magda; Yiangou, Andreas; Alimajstorovic, Zerin; Cartwright, David; Grech, Olivia; Lavery, Gareth; Westgate, Connar; Vijay, Vivek; Scotton, William; Wakerley, Benjamin; Matthews, Tim; Ansons, Alec; HIckman, Simon; Benzimra, James; Rick, Caroline; Singhal, Rishi; Tahrani, Abd; Brock, Kristian; Frew, Emma; Sinclair, Alexandra; Wakerley, Benjamin; Medical and Dental
Importance: Idiopathic intracranial hypertension (IIH) causes headaches, vision loss, and reduced quality of life. Sustained weight loss among patients with IIH is necessary to modify the disease and prevent relapse. Objective: To compare the effectiveness of bariatric surgery with that of a community weight management (CWM) intervention for the treatment of patients with active IIH. Design, setting, and participants: This 5-year randomized clinical trial (Idiopathic Intracranial Hypertension Weight Trial) enrolled women with active IIH and a body mass index (calculated as weight in kilograms divided by height in meters squared) of 35 or higher at 5 National Health Service hospitals in the UK between March 1, 2014, and May 25, 2017. Of 74 women assessed for eligibility, 6 did not meet study criteria and 2 declined to participate; 66 women were randomized. Data were analyzed from November 1, 2018, to May 14, 2020. Interventions: Bariatric surgery (n = 33) or CWM intervention (Weight Watchers) (n = 33). Main outcomes and measures: The primary outcome was change in intracranial pressure measured by lumbar puncture opening pressure at 12 months, as assessed in an intention-to-treat analysis. Secondary outcomes included lumbar puncture opening pressure at 24 months as well as visual acuity, contrast sensitivity, perimetric mean deviation, and quality of life (measured by the 36-item Short Form Health Survey) at 12 and 24 months. Because the difference in continuous outcomes between groups is presented, the null effect was at 0. Results: Of the 66 female participants (mean [SD] age, 32.0 [7.8] years), 64 (97.0%) remained in the clinical trial at 12 months and 54 women (81.8%) were included in the primary outcome analysis. Intracranial pressure was significantly lower in the bariatric surgery arm at 12 months (adjusted mean [SE] difference, -6.0 [1.8] cm cerebrospinal fluid [CSF]; 95% CI, -9.5 to -2.4 cm CSF; P = .001) and at 24 months (adjusted mean [SE] difference, -8.2 [2.0] cm CSF; 95% CI, -12.2 to -4.2 cm CSF; P < .001) compared with the CWM arm. In the per protocol analysis, intracranial pressure was significantly lower in the bariatric surgery arm at 12 months (adjusted mean [SE] difference, -7.2 [1.8] cm CSF; 95% CI, -10.6 to -3.7 cm CSF; P < .001) and at 24 months (adjusted mean [SE] difference, -8.7 [2.0] cm CSF; 95% CI, -12.7 to -4.8 cm CSF; P < .001). Weight was significantly lower in the bariatric surgery arm at 12 months (adjusted mean [SE] difference, -21.4 [5.4] kg; 95% CI, -32.1 to -10.7 kg; P < .001) and at 24 months (adjusted mean [SE] difference, -26.6 [5.6] kg; 95% CI, -37.5 to -15.7 kg; P < .001). Quality of life was significantly improved at 12 months (adjusted mean [SE] difference, 7.3 [3.6]; 95% CI, 0.2-14.4; P = .04) and 24 months (adjusted mean [SE] difference, 10.4 [3.8]; 95% CI, 3.0-17.9; P = .006) in the bariatric surgery arm. Conclusions and relevance: In this randomized clinical trial, bariatric surgery was superior to a CWM intervention in lowering intracranial pressure. The continued improvement over the course of 2 years shows the impact of this intervention with regard to sustained disease remission.
Clinical Features and Genetic Risk of Demyelination Following Anti-TNF Treatment
(Oxford University Press, 2020-05-04) Lin, Simeng; Green, Harry; Hendy, Peter; Heerasing, Neel; Chanchlani, Neil; Hamilton, Benjamin; Walker, Gareth; Heap, Graham; Hobart, Jeremy; Martin, Roswell; Coles, Alasdair; Martin, Roswell; Medical and Dental
Background: Anti-TNF exposure has been linked to demyelination events. We sought to describe the clinical features of demyelination events following anti-TNF treatment and to test whether affected patients were genetically predisposed to multiple sclerosis [MS]. Methods: We conducted a case-control study to describe the clinical features of demyelination events following anti-TNF exposure. We compared genetic risk scores [GRS], calculated using carriage of 43 susceptibility loci for MS, in 48 cases with 1219 patients exposed to anti-TNF who did not develop demyelination. Results: Overall, 39 [74%] cases were female. The median age [range] of patients at time of demyelination was 41.5 years [20.7-63.2]. The median duration of anti-TNF treatment was 21.3 months [0.5-99.4] and 19 [36%] patients were receiving concomitant immunomodulators. Most patients had central demyelination affecting the brain, spinal cord, or both. Complete recovery was reported in 12 [23%] patients after a median time of 6.8 months [0.1-28.7]. After 33.0 months of follow-up, partial recovery was observed in 29 [55%] patients, relapsing and remitting episodes in nine [17%], progressive symptoms in three [6%]: two [4%] patients were diagnosed with MS. There was no significant difference between MS GRS scores in cases (mean -3.5 × 10-4, standard deviation [SD] 0.0039) and controls [mean -1.1 × 10-3, SD 0.0042] [p = 0.23]. Conclusions: Patients who experienced demyelination events following anti-TNF exposure were more likely female, less frequently treated with an immunomodulator, and had a similar genetic risk to anti-TNF exposed controls who did not experience demyelination events. Large prospective studies with pre-treatment neuroimaging are required to identify genetic susceptibility loci.
Autologous haematopoietic stem cell transplantation for immune-mediated neurological diseases: what, how, who and why?
(BMJ Publishing Group, 2022-09-26) Brittain, Gavin; Coles, Alasdair; Muraro, Paolo; Palace, Jacqueline; Petrie, Jennifer; Roldan, Elisa; Scolding, Neil; Snowden, John; Sharrack, Basil; Scolding, Neil; Medical and Dental
In carefully selected patients, autologous haematopoietic stem cell transplantation (HSCT) is a safe, highly effective and cost-saving treatment modality for treatment-resistant, and potentially treatment-naïve, immune-mediated neurological disorders. Although the evidence base has been growing in the last decade, limited understanding has led to confusion, mistrust and increasing use of health tourism. In this article, we discuss what autologous HSCT is, which immune-mediated conditions can be treated with it, how to select patients, what are the expected outcomes and potential adverse effects, and how cost-effective this treatment is.
Orthostatic dysarthria in myasthenia gravis
(BMJ Publishing Group, 2022-10-18) Cleaver, Jonathan; Silva, Mark; Martin, Roswell; Cleaver, Jonathan; Silva, Mark; Martin, Roswell; Medical and Dental
No abstract available
Cost-effectiveness of bariatric surgery versus community weight management to treat obesity-related idiopathic intracranial hypertension: evidence from a single-payer healthcare system
(Elsevier, 2021-03-30) Elliot, Laura; Frew, Emma; Mollan, Susan; Mitchell, James; Yiangou, Andreas; Alimajstorovic, Zerin; Ottridge, Ryan; Wakerley, Benjamin; Thaller, Mark; Grech, Olivia; Singhal, Rishi; Tahrani, Abd; Harrison, Mark; Sinclair, Alexandra; Aguiar, Magda; Wakerley, Benjamin; Medical and Dental
Background: Idiopathic intracranial hypertension (IIH) is associated with significant morbidity, predominantly affecting women of childbearing age living with obesity. Weight loss has demonstrated successful disease-modifying effects; however, the long-term cost-effectiveness of weight loss interventions for the treatment of IIH has not yet been established. Objectives: To estimate the cost-effectiveness of weight-loss treatments for IIH. Setting: Single-payer healthcare system (National Health Service, England). Methods: A Markov model was developed comparing bariatric surgery with a community weight management intervention over 5-, 10-, and 20-year time horizons. Transition probabilities, utilities, and resource use were informed by the IIH Weight Trial (IIH:WT), alongside the published literature. A probabilistic sensitivity analysis was conducted to characterize uncertainty within the model. Results: In the base case analysis, over a 20-year time horizon, bariatric surgery was "dominant," led to cost savings of £49,500, and generated an additional 1.16 quality-adjusted life years in comparison to the community weight management intervention. The probabilistic sensitivity analysis indicated a probability of 98% that bariatric surgery is the dominant option in terms of cost-effectiveness. Conclusion: This economic modeling study has shown that when compared to community weight management, bariatric surgery is a highly cost-effective treatment option for IIH in women living with obesity. The model shows that surgery leads to long-term cost savings and health benefits, but that these do not occur until after 5 years post surgery, and then gradually increase over time.
Predicting the risk of long-term relapse in MOGAD
(SAGE Publications, 2022-10-12) Francis, Anna; Gomez, Enrique; Chen, Bo; Woodhall, Mark; Blain, Camilla; Cooper, Sarah; Dobson, Ruth; Fisniku, Leonora; Halfpenny, Christopher; Hobart, Jeremy; Martin, Roswell; Martin, Roswell; Medical and Dental
Introduction: Approximately half of patients with MOG-antibody associated disease (MOGAD) relapse. It is not clear whether early relapsing activity (within 1 year of initial attack) indicates risk of chronic disease. We aimed to identify whether early relapse, along with predictors of early relapses, predicts relapse beyond one year. Methods: A prospective cohort of 192 MOGAD patients from 5 UK centres with at least 2 years’ disease duration and no long-term immunosuppressive treatment during the first year were included. One hundred and eighteen (61%) experienced relapses at any stage. Univariate Cox regressions for time-to-relapse after the first year were performed with covariates including the presence and number of early relapses, the timing of early relapse (categorized in three-month epochs), decision to treat with corticosteroid and duration of taper (days), age at onset, self-identified race, onset phenotype and seroconversion to MOG antibody-negative. Multivariate Cox-regression models included all previously significant variables, as well as MOG-antibody seroconversion. Results: Out of 118 relapsing MOGAD patients, we found 49 (25.5%) patients with early relapses with a median number of 1 (range 1-4) relapses. Univariate analysis revealed an increased risk of long-term relapse with any early relapse (Hazard Ratio [HR] 1.60, CI 1.16-1.89), relapses in the first (HR 2.24, CI 1.27-3.92) or the last 3-month epoch (HR 2.66, 1.22-5.78), higher numbers of early relapses (HR 1.48, CI 1.16-1.89) and non-white race (HR 1.94, CI 1.08-3.48). Longer duration of early corticosteroid treatment (HR 0.99days, CI 0.996-0.999, p=0.035) was protective. Following multivariate regression analysis, the number of early relapses and relapse in the first (HR 2.51, CI 1.19-5.27) and third 3-month epochs (HR 3.71, CI 1.52-9.06) were significant, as were days on corticosteroid treatment (HR 0.99days, CI 0.99-0.99; HR 30 days 0.74) and non-white race (HR 2.69, CI 1.45-5.11). There was an 84% and 99% specificity for long-term relapses in the first 5 years in those with ⩾1 and ⩾2 early relapses respectively, with low sensitivity (20% and 5%). Conclusion: Our results suggest that early relapses are associated with increased risk of long-term relapsing disease and may indicate a need for long-term immunosuppression as they do not appear to solely reflect early inflammatory phase. Early corticosteroid treatment may have a protective role in preventing relapses beyond one year.
053 Intracranial pressure determines headache morbidity in idiopathic intracranial hypertension
(BMJ Publishing Group, 2022-05-29) Mollan, Susan; Wakerley, Benjamin; Alimajstorovic, Zerin; Mitchell, James; Ottridge, Ryan; Yiangou, Andreas; Thaller, Mark; Grech, Olivia; Brock, Kristian; Sinclair, Alex; Wakerley, Benjamin; Medical and Dental
No abstract available
Acute paraparesis during surfing: the perils of riding the wave
(Elsevier, 2022-08-26) Cleaver, Jonathan; Boehm, Miriam; Faulkner, Howard; Cleaver, Jonathan; Medical and Dental
No abstract available
Terminal Choking in Parkinson's Disease
(Elsevier, 2022-01-22) Ling, Andrea; Herbert, Fiona; Wright, Bethany; Richfield, Edward; Herbert, Fiona; Medical and Dental
No abstract available
Myasthenic syndromes: mistaking genetic for acquired
(BMJ Publishing Group, 2025-07-22) Henehan, Leighann; Rossini, Elena; Platt, Sarah; Dong, Yin Yao; Beeson, David; Fuller, Geraint; Leite, Maria; Palace, Jacqueline; Fuller, Geraint; Medical and Dental
Congenital myasthenic syndromes (CMS) are a rare, heterogeneous group of disorders caused by pathogenic variants in genes encoding proteins essential for neuromuscular transmission. DOK7 variants are among the most common causes of CMS and one of the subtypes that may worsen with pyridostigmine. We report two patients who presented in adulthood with fatigable limb girdle weakness, initially diagnosed with seronegative myasthenia gravis, who slowly progressed over time despite escalating treatment and eventually needed intensive care admission. Revisiting the history led to the diagnosis of DOK7 CMS. Both patients improved after stopping immunosuppressants and pyridostigmine and starting salbutamol. These cases highlight the importance of considering CMS in patients with seronegative myasthenia gravis.

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