Neurological heterotopic ossification:novel mechanisms,prognostic biomarkers and prophylactic therapies

Neurological heterotopic ossification(NHO)is a debilitating condition where bone forms in soft tissue,such as muscle surrounding the hip and knee,following an injury to the brain or spinal cord.This abnormal formation of bone can result in nerve impingement,pain,contractures and impaired movement.Patients are often diagnosed with NHO after the bone tissue has completely mineralised,leaving invasive surgical resection the only remaining treatment option.Surgical resection of NHO creates potential for added complications,particularly in patients with concomitant injury to the central nervous system(CNS).Although recent work has begun to shed light on the physiological mechanisms involved in NHO,there remains a significant knowledge gap related to the prognostic biomarkers and prophylactic treatments which are necessary to prevent NHO and optimise patient outcomes.This article reviews the current understanding pertaining to NHO epidemiology,pathobiology,biomarkers and treatment options.In particular,we focus on how concomitant CNS injury may drive ectopic bone formation and discuss considerations for treating polytrauma patients with NHO.We conclude that understanding of the pathogenesis of NHO is rapidly advancing,and as such,there is the strong potential for future research to unearth methods capable of identifying patients likely to develop NHO,and targeted treatments to prevent its manifestation.

Impaired glymphatic function in the early stages of disease in a TDP-43 mouse model of amyotrophic lateral sclerosis

Background: Multiple lines of evidence suggest possible impairment of the glymphatic system in amyotrophic lateral sclerosis (ALS). To investigate this, we used in vivo magnetic resonance imaging (MRI) to assess glymphatic func-tion early in the course of disease in a transgenic mouse with doxycycline (Dox)-controlled expression of cytoplasmic human TDP-43 (hTDP-43ΔNLS), mimicking the key pathology implicated in ALS. Methods: Adult TDP-43 transgenic and littermate monogenic control mice underwent longitudinal multimodal MRI one and three weeks after the cessation of Dox feed, together with weekly rotarod assessments of motor per-formance. Glymphatic function was assessed using dynamic contrast-enhanced MRI to track the clearance of an MR contrast agent injected into the cisterna magna. Results: Compared to their littermate controls, TDP-43 mice exhibited progressive neurodegeneration including that within the primary motor cortex, primary somatosensory cortex and corticospinal tract, significant weight loss includ-ing gastrocnemius atrophy, and shortened telomere length. Furthermore, in the presence of this ALS-like phenotype, these mice have significantly disrupted glymphatic function. Conclusions: Although the relationship between glymphatic clearance and ALS disease progression remains to be elucidated, these changes occurred very early in the disease course. This provides initial evidence to suggest that the glymphatic system might be a potential therapeutic target in the treatment of ALS.

Practical considerations of dietary therapies for epilepsy in adults

Despite the increasing number of anti-seizure medications becoming available,the proportion of patients with drug-resistant epilepsy remains unchanged.Dietary therapy for epilepsy is well-established practice in paediatric care,but relatively underutilised in adults.Recently,international recommendations have been published to guide the treatment of adults receiving dietary therapy for epilepsy.This review focuses on the specific aspects of care unique to the management of adults receiving dietary therapy for epilepsy,including patient selection,diet composition,initiation,monitoring and cessation of dietary treatment.We emphasise the need for a multidisciplinary team approach with appropriately trained neurologists and dietitians to provide holistic care while the patients are receiving dietary therapy.Future research should focus on the optimal diet composition and meeting the psychosocial needs of adults with epilepsy to maximise efficacy and adherence to dietary treatment.