Duchenne muscular dystrophy (DMD) is a devastating, life-limiting neuromuscular disorder that has a global prevelance of 21.4 cases per 100,000 live male births. DMD is caused by mutations in the dystrophin gene, which is integral to muscle membrane stability. Mutations in the dystrophin gene lead to inflammation and muscle fibrosis. Current standard-of-care treatments include the use of chronic (or classic) corticosteroids, which can cause significant side effects. Vamorolone is a first-in-class dissociative steroid that acts as a partial agonist to glucocorticoid receptors but as an antagonist to mineralocorticoid receptors, leading to a more favourable side effect profile. Clinical data has shown that vamorolone has similar anti-inflammatory benefits to classic corticosteroids but an improved side effect profile.
Background: Natalizumab is a widely used anti-α4 integrin inhibitor for treating highly active multiple sclerosis. Although clinical and radiological relapses were observed in the pivotal natalizumab trials, severe disease activity after initiation of the drug is a rare phenomenon and has been reported only in isolated cases. Objective: To present a case of a patient who experienced a paradoxical increase in disease activity after the second dose of natalizumab. Methods: We describe the case, review the literature concerning similar cases and suggest possible mechanisms for this phenomenon. Results: Our case involves a patient who developed extensive tumefactive demyelinating lesions and multiple gadolinium-enhancing lesions detected on magnetic resonance imaging after receiving the second dose of natalizumab. A brain biopsy confirmed the presence of demyelination, and the patient’s condition improved after treatment with intravenous methylprednisolone, intravenous immunoglobulin and plasma exchange. Tests for anti-natalizumab antibodies were negative. Conclusions: Paradoxical worsening can occur in the setting of natalizumab treatment, which warrants careful attention and should prompt anti-natalizumab antibody testing. We discuss potential mechanisms. Further research is needed to better understand the mechanisms and risk factors for paradoxical worsening and to develop strategies for mitigating this adverse effect with significant patient impact.
Proton pump inhibitors (PPIs) are commonly used for gastroesophageal reflux disease. Previous studies have raised concerns about the impact of PPIs on cognition in older adults, but the evidence supporting this concern is lacking. This article aims to analyse the available data regarding the impact of long-term PPI use on cognition in older adults. We searched PubMed for relevant studies conducted between 2015 and 2022. Seventeen such studies were identified. Limitations to available research data include the fact that studies are mainly observational, use heterogeneous study methods and do not account for confounding variables such as B12 deficiency, Helicobacter pylori infection, and thyroid dysfunction. Overall, this search did not find a compelling association between PPI use and cognitive decline.
On 6 January 2023, the amyloid beta-targeting antibody lecanemab was approved by the US Food and Drug Administration for the treatment of mild cognitive impairment due to Alzheimer’s disease (AD) and mild AD dementia via its Accelerated Approval pathway. However, two important questions need to be highlighted: What is the appropriate patient population to receive treatment? How much should healthcare systems be prepared to pay for the drug? The healthcare infrastructure is not prepared for the expected huge demands for diagnostics and eventual treatment, especially given the suggested list price and a potentially large population of people with mild cognitive impairment due to AD and mild AD dementia. A lower price point would allow wider access to the treatment and reduce disparities in health equity.
Background: Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) is an autoimmune disease that appears as a fulminant, subacute or chronic course of altered mental status, often accompanied by seizures and myoclonus. This case report demonstrates that SREAT can be present with solitary neuropsychiatric signs long before seizures and myoclonus. Methods: A 42-year-old female presented with abrupt-onset whole-body myoclonic jerks. She had been suffering from depression for 15 years before being diagnosed with hypothyroidism. She was conscious, oriented and alert. At rest, all four limbs had multifocal mild-to-moderate myoclonus, which was significantly aggravated by muscle activation; her Hamilton Depression Rating Scale score was 21. Results: Antithyroglobulin and antithyroid peroxidase autoantibodies were both above 2,000 IU/mL. The thyroid-stimulating hormone level was 5.65 mIU/mL, free triiodothyronine level was 3.36 pg/mL and free thyroxine level was 1.02 ng/dL. Vasculitis profile and the serum test for autoimmune encephalitis panel were negative. Brain neuroimaging was normal. Pulse dose of methylprednisolone followed by oral steroids resulted in significant clinical improvement. Conclusion: SREAT can present with chronic neuropsychiatric symptoms with abrupt exacerbation of seizures and myoclonus. This case study emphasizes the importance of screening individuals with depression and thyroid problems for serum antithyroid antibody levels. In most cases, steroid treatment yields positive results.
The coronavirus disease 2019 (COVID-19) pandemic has caused significant disruptions to almost every healthcare system worldwide. Older adults have been hit disproportionately hard by the pandemic, with most deaths occurring among people aged 75 or older. Dementia researchers have noted the increased dementia-related mortality among older adults and fewer dementia diagnoses during the pandemic. Questions have therefore been raised regarding the effects of the COVID-19 virus on dementia prevalence and mortality. As a groundbreaking dementia treatment is about to hit the market, proper diagnoses of dementia are now more important than ever. There are also concerns that the COVID-19 virus could precipitate dementia and worsen dementia symptoms. This short review examines the current scientific evidence on the impact of COVID-19 on dementia mortality and prevalence, as well as describing the pathophysiological mechanisms by which COVID-19 might cause dementia and worsen dementia symptoms. Lastly, this review speculates on how dementia epidemiology might change during the next years as a result of the pandemic and provide suggestions for clinicians on how to respond to the coming changes.
Radiosurgical methods have made significant advancements in the past 50 years. From the patient’s perspective, the transition from invasive to non-invasive frames has been the most meaningful change. In this review article, we provide an overview of the stepwise evolution of frame technology and discuss the external pressures that prompted modifications.
The concept of wellness has yet to be formally adopted in Parkinson’s disease (PD) management despite its potential to improve quality of life. Currently, PD treatment is usually focused on symptomatic therapies for motor symptom relief using medications or devices. While the focus on non-motor symptoms has increased in the last decade, it remains suboptimal. Future clinical practice should strive to incorporate the more holistic 'dashboard vitals of PD', which include comorbidities/polypharmacy and dental, vision, bone, and gut health and go beyond just motor and non-motor issues. Furthermore, recognizing and addressing the cultural context of the patient and practising healthcare from a place of cultural humility can help decrease barriers to care and build trust. Promoting self-agency through personalized lifestyle interventions, such as healthy diet, exercise, sleep routines, mind–body approaches and social support, can make them more accessible and easier to maintain. Building upon the concept of personalized medicine in PD, wellness programmes can proactively target non-motor issues and mental and psychosocial health by enhancing resilience and supporting social connections. The desired outcome of a wellness approach extends beyond the traditional medical model to improve quality of life in a more enduring manner.
Friedrich’s ataxia (FRDA), a neurodevelopmental and progressive neurodegenerative disease, is the most common inherited form of ataxia. Omaveloxolone was approved by the US Food and Drugs Administration in early 2023, making it the first treatment available to patients with FRDA. This approval was made possible by combining a compelling cellular mechanism and strong clinical evidence provided through the MOXIe study, the multipart clinical trial evaluating the efficacy of omaveloxolone in patients with FRDA. This review discusses the underlying cellular pathology and proposed mechanism of omaveloxolone in FRDA. The MOXIe study is presented in detail, including a discussion of the challenges faced in clinical trials in FRDA, and rare diseases more broadly. Finally, other therapies under investigation are reviewed briefly.
Muscle diseases with prominent limb–joint contractures (LJCs) are a subgroup of rare neuromuscular disorders. Prominent LJCs are not specific to genetic myopathies. Myositis can also induce severe contractures, especially in the late stages. We report the case of a 12-year-old girl with a 3-year history of painful muscular weakness with generalized LJCs. The inflammatory pattern associated with positive anti-PM/ Scl antibodies on muscle biopsy allowed us to initially retain the diagnosis of scleromyositis. After 12 months of corticosteroids and immunosuppressive treatment, there was no clinical improvement, and creatine kinase levels remained high (over 10 times the normal value). A second muscle biopsy showed persistent inflammatory infiltrate with the appearance of dystrophic features. Immunohistochemical analysis showed the absence of class 1 major histocompatibility complex expression on muscle fibres, raising the possibility of the diagnosis of muscular dystrophy. Whole-exome sequencing revealed a missense homozygous novel mutation c.386G>T (p.Arg129Ile) on the calpain 3 gene, finally confirming the diagnosis of autosomal recessive limb–girdle muscular dystrophy recessive type 1 (or calpainopathy). This case report highlights the diagnostic challenges and the importance of a comprehensive evaluation in cases of muscle diseases with prominent LJCs.
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an increasingly recognized disorder, particularly in children. Acute disseminated encephalomyelitis (ADEM) is the most common presentation of paediatric MOGAD. Children with ADEM should always be evaluated for MOGAD, as appropriate and timely treatment may help improve long-term outcomes.
Opioids are commonly prescribed for chronic pain despite potential adverse side effects, risks of misuse and abuse, and limited evidence for improved outcomes. Patients’ perspectives and understanding of pain management may impact treatment approaches and the success of therapies. Yet, few studies have investigated how patients’ beliefs in optimal pain management may influence their care. We prospectively surveyed 200 patients with chronic pain with the aim of assessing patients’ beliefs on the optimal management of their chronic pain. The following significant findings were made: 1) most responders agreed that opioid medication was the best way to control pain (p<0.05), especially those currently taking opioids (p<0.0001); 2) those who received injections for pain disagreed that opioids were the best way to control pain (p<0.0001); 3) most participants were aware of other options to control pain (p<0.05), but patients on opioids were significantly less aware of other options for pain control (p<0.05). This study demonstrated that most patients with chronic pain surveyed in our clinic believed that opioids were the best option for treating their chronic pain, but this finding did not hold true for those who were exposed to other interventions for their pain, such as injections. Pain physicians may encounter resistance when attempting to incorporate non-opioid and or non-pharmacological therapies for chronic pain management. Further research may help determine whether patient education and exposure to such therapies can help combat these challenges.
Nurses specializing in the care of patients with multiple sclerosis (MS) are uniquely positioned to provide personalized care. Patients prescribed cladribine tablets (taken for ≤10 days per year for 2 years), indicated for adults with highly active relapsing MS in the EU and Australia, can benefit from an active partnership with their healthcare professionals, including MS nurses, who can promote an understanding of and the adherence to treatment. In clinical studies, patients treated with cladribine tablets had lower annual relapse rates, greater odds of being relapse free, a longer time to sustained progression of disability and a significant reduction in radiological disease activity compared with patients receiving placebo. Patients should be advised that, although everyone will have a different experience, the safety of cladribine tablets is supported by 16 years of clinical trial and post-approval data. Furthermore, there is no indication of a more serious disease course or more severe outcomes for patients with MS treated with cladribine tablets who acquire coronavirus disease 2019 compared with the general population or other patients with MS. This article presents practical considerations that may help achieve a greater understanding of the potential benefits and drawbacks of MS treatment, build the patient–nurse relationship, encourage shared decision-making and ultimately may improve care.
Social media platforms, such as Twitter, are increasingly used by clinicians, including neurologists. Twitter represents a convenient means to reach out to fellow clinicians, researchers and patients alike. To make maximum use of these platforms, they must be used pragmatically and within the ambit of ethical principles that guide all medical practice. As neurologists, familiarizing ourselves with the technical know-how and potential uses of Twitter empowers us best to use it as a valuable clinical and networking tool. Twitter offers diverse formats for a neurologist, thus enabling the creation and dissemination of specific types of information in the form of tweetorials, journal clubs, conference-based tweeting, tweetchats and the like. In this practical step-by-step guide, we demonstrate how to harness Twitter for myriad academic uses.
Background: Endovascular thrombectomy (EVT) has proven to be successful in acute ischaemic stroke (AIS) with a National Institutes of Health Stroke Scale (NIHSS) score of >8, but remains controversial in AIS with an NIHSS score of <8. This study evaluated computed tomography (CT) perfusion indicators for EVT in large-vessel occlusion (LVO) ischaemic strokes with low NIHSS scores. Methods: We retrospectively reviewed data from 49 patients with AIS, LVO and an NIHSS score of <8 who received medical therapy (n=27), or rescue (n=10) or urgent (n=12) thrombectomy. Therapy decision was made from clinical course and perfusion imaging. The urgent group underwent EVT in <6 hours. The rescue group underwent EVT in >6 hours due to increasing NIHSS scores; this included patients who presented after 6 hours and underwent urgent EVT. Modified Rankin scores were obtained at 3 months to assess outcomes. Results: More patients in the urgent group (91.7%) had a discharge NIHSS improvement (>1) compared with the rescue (50.0%) and medical (51.9%) groups (p=0.02). The urgent group displayed thrombolysis in cerebral infarction (TICI) scores of 2b/3 in 100% of patients, whereas the rescue group displayed TICI scores of 2b/3 in 80% and 1/2a in 20% (p=0.076). The perfusion core (cerebral blood flow [CBF] <30%) was not different between the groups (2.1 cm3, 1.0 cm3 and 9.2 cm3, for urgent, rescue and medical groups, respectively). The perfusion penumbra (time to max [Tmax] >6 s) and mismatch (Tmax minus CBF) were significantly larger for the urgent and rescue groups. Penumbra volume was 80.1 cm3, 107.5 cm3 versus 50.6 cm3 (p=0.011), and mismatch was 78.0 cm3, 106.5 cm3 versus 41.5 cm3 (p=0.002) for urgent and rescue thrombectomy versus medical therapy, respectively. Conclusion: The biggest driver of urgent reperfusion was a larger penumbra seen on CT perfusion, which appeared to show better outcomes in NIHSS scores at discharge without any difference in 3-month outcomes graded by modified Rankin scores. Our data suggest that larger perfusion deficits on CT imaging may serve as a tool for patient selection for EVT in LVO with an NIHSS score of <8 and should be investigated further.
