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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.

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.

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.

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 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.

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&lt;0.05), especially those currently taking opioids (p&lt;0.0001); 2) those who received injections for pain disagreed that opioids were the best way to control pain (p&lt;0.0001); 3) most participants were aware of other options to control pain (p&lt;0.05), but patients on opioids were significantly less aware of other options for pain control (p&lt;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.