Brain最新文献

Focal epilepsy is a difficult disease to treat as two-thirds of patients will not respond to oral antiseizure medications (ASMs) or have severe off-target effects that lead to drug discontinuation. Current non-pharmaceutical treatment methods (resection or ablation) are underutilized due to the associated morbidities, invasive nature, and inaccessibility of seizure foci. Less invasive non-ablative modalities may potentially offer an alternative. Targeting the seizure focus in this way may avoid unassociated critical brain structures to preserve function and alleviate seizure burden. Here we report use of an implantable, miniaturized neural drug delivery system [Microinvasive neural implant infusion platform (MINI)] to administer antiseizure medications (ASMs) directly to the seizure focus in a mouse model of temporal lobe epilepsy. We examined the effect local delivery of phenobarbital (PB) and valproate (VPA) had on focal seizures, as well as adverse effects, and compared this to systemic delivery. We show that local delivery of PB and VPA using our chronic implants significantly reduced focal seizures at all doses given. Furthermore, we show that local delivery of these compounds resulted in no adverse effects to motor function, whereas systemic delivery resulted in significant motor impairment. The results of this study demonstrate the potential of ASM micro dosing to the epileptic focus as a treatment option for people with drug resistant epilepsy. This technology could also be applied to a variety of disease states, enabling a deeper understanding of focal drug delivery in the treatment of neurological disorders.

Functional Neurological Disorder (FND) is continuing to gain increasing recognition globally as a valid and potentially treatable disorder. Iatrogenic harm towards patients with FND is significant however, and has been around for centuries. Despite advances in our understanding around the aetiology, pathophysiology, and treatment of FND, many aspects of such harm continue to persist. Avoidance of iatrogenic harm has been highlighted by clinicians as one of the most important therapeutic considerations in FND, however, the sources and range of potential harms, or indeed ways to mitigate them, have not been previously summarised. Using a combination of clinical and research experience and scoping review methodology, this review aims to describe the main sources of iatrogenic harm towards patients with FND, including harm from misdiagnosis, delayed diagnosis and treatment, direct harm from professional interactions, other stigma-related harms, harm related to diagnostic overshadowing and over-diagnosis of FND. We also describe some potential ways to address and prevent such harms, such as ways to reduce misdiagnosis with a focus on rule in signs, optimising teaching and communication, ensuring parity of FND with other medical conditions, and continued integration of patient and professional organisations.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of motor neurons in the brain and spinal cord. Accumulation of misfolded proteins is central in the pathogenesis of ALS and the glymphatic system is emerging as a potential therapeutic target to reduce proteinopathy. Using diffusion tensor imaging analysis along the perivascular spaces (DTI-ALPS) to assess glymphatic function, we perform a longitudinal analysis of glymphatic function in ALS and compare it to a disorder in the motor neuron disease spectrum, primary lateral sclerosis (PLS). From a cohort of 45 participants from the Calgary site in the CALSNIC study (Canadian ALS Neuroimaging Consortium), including 18 ALS, 5 PLS and 22 control participants, DTI-ALPS was analyzed and correlated to clinical features (age, sex, disease presentation, disease severity and progression rate), and white matter hyperintensity (WMH) burden. This included longitudinal measurements at three time points, 4 months apart. The DTI-ALPS index was reduced in ALS participants compared to PLS and control participants across all three time points. There was no association with clinical factors, however the index tended to decline with advancing age. Our study suggests heterogeneity in glymphatic dysfunction in motor neuron diseases that may be related to the underlying pathogenesis.