JIP3 links lysosome transport to regulation of multiple components of the axonal cytoskeleton

Lysosome axonal transport is important for the clearance of cargoes sequestered by the endocytic and autophagic pathways. Building on observations that mutations in the JIP3 (MAPK8IP3) gene result in lysosome-filled axonal swellings, we analyzed the impact of JIP3 depletion on the cytoskeleton of human neurons. Dynamic focal lysosome accumulations were accompanied by disruption of the axonal periodic scaffold (spectrin, F-actin and myosin II) throughout each affected axon. Additionally, axonal microtubule organization was locally disrupted at each lysosome-filled swelling. This local axonal microtubule disorganization was accompanied by accumulations of both F-actin and myosin II. These results indicate that transport of axonal lysosomes is functionally interconnected with mechanisms that control the organization and maintenance of the axonal cytoskeleton. They have potential relevance to human neurological disease arising from JIP3 mutations as well as for neurodegenerative diseases associated with the focal accumulations of lysosomes within axonal swellings such as Alzheimer’s disease.

CONCEPTUAL UNDERSTANDING OF TRANSVERSE MYELITIS IN AYURVEDA: A CRITICAL REVIEW

Transverse myelitis (TM) is a rare neurological disease of spinal cord inflammation. Onslaught inflammation damage the myelin is leading to nervous system scaring. Consequently, the patient presents devastating neurological effects. It can afflict people of any age, gender or race. Symptoms per usual evolve over hours or days and then deteriorate over days to weeks. Symptoms include pain, sensory problems, weakness in the legs and arms, and bladder and bowel problems. Most people partially recover within three months; others may be permanently disabled. There is no cure for TM thus far, but neurological deficit can be minimised. From the purview of Ayurveda, TM can be categorised under the spectrum of Vata disorder. Recent research report the successful treatment of TM. However, each explains the pathology differently. This review will discuss the concepts of TM apropos to Mishravarana (combined occlusion) and its management. We suggest that symptoms and pathology of TM simulate closely with Avaranajanya Vatavyadi (disease of Vata due to occlusion). Mishravarana (combined occlusion) illustrates the complexity of the disease process involved.

Leukoencephalopathy with brain calcifications and cysts (Labrune syndrome) case report: diagnosis and management of a rare neurological disease

Background Leukoencephalopathy with brain calcifications and cysts (LCC; also known as Labrune syndrome) is a rare genetic microangiopathy caused by biallelic mutations in SNORD118. The mechanisms by which loss-of-function mutations in SNORD118 lead to the phenotype of leukoencephalopathy, calcifications and intracranial cysts is unknown. Case presentation We present the histopathology of a 36-year-old woman with ataxia and neuroimaging findings of diffuse white matter abnormalities, cerebral calcifications, and parenchymal cysts, in whom the diagnosis of LCC was confirmed with genetic testing. Biopsy of frontal white matter revealed microangiopathy with small vessel occlusion and sclerosis associated with axonal loss within the white matter. Conclusions These findings support that the white matter changes seen in LCC arise as a consequence of ischemia rather than demyelination.

Total, hemi, or dual-mobility arthroplasty for the treatment of femoral neck fractures in patients with neurological disease

Aims The aim of this study was to investigate the potentially increased risk of dislocation in patients with neurological disease who sustain a femoral neck fracture, as it is unclear whether they should undergo total hip arthroplasty (THA) or hemiarthroplasty (HA). A secondary aim was to investgate whether dual-mobility components confer a reduced risk of dislocation in these patients. Methods We undertook a longitudinal cohort study linking the Swedish Hip Arthroplasty Register with the National Patient Register, including patients with a neurological disease presenting with a femoral neck fracture and treated with HA, a conventional THA (cTHA) with femoral head size of ≤ 32 mm, or a dual-mobility component THA (DMC-THA) between 2005 and 2014. The dislocation rate at one- and three-year revision, reoperation, and mortality rates were recorded. Cox multivariate regression models were fitted to calculate adjusted hazard ratios (HRs). Results A total of 9,638 patients with a neurological disease who also underwent unilateral arthroplasty for a femoral neck fracture were included in the study. The one-year dislocation rate was 3.7% after HA, 8.8% after cTHA < 32 mm), 5.9% after cTHA (= 32 mm), and 2.7% after DMC-THA. A higher risk of dislocation was associated with cTHA (< 32 mm) compared with HA (HR 1.90 (95% confidence interval (CI) 1.26 to 2.86); p = 0.002). There was no difference in the risk of dislocation with DMC-THA (HR 0.68 (95% CI 0.26 to 1.84); p = 0.451) or cTHA (= 32 mm) (HR 1.54 (95% CI 0.94 to 2.51); p = 0.083). There were no differences in the rate of reoperation and revision-free survival between the different types of prosthesis and sizes of femoral head. Conclusion Patients with a neurological disease who sustain a femoral neck fracture have similar rates of dislocation after undergoing HA or DMC-THA. Most patients with a neurological disease are not eligible for THA and should thus undergo HA, whereas those eligible for THA could benefit from a DMC-THA. Cite this article: Bone Joint J 2022;104-B(1):134–141.

Melatonin and Epilepsy

Epilepsy is a chronic neurological disease with recurrent seizures. Its incidence, the social and psychological aspects of epilepsy-associated stigmatization in society, the medical risk of severe seizures, and the challenges in treatment confirm its medical and social significance. The pathogenesis of the diseases is associated with abnormal activity of a population of neurons due to various mechanisms, the most frequent being oxidative stress, glutamate excitotoxicity, and mitochondrial dysfunction. In the last 3-4 decades, the possible connection between epilepsy and melatonin &ndash; a neurohormone secreted by the pineal gland &ndash; has been sought and studied. Various physiological functions of melatonin in humans have been proven &ndash; regulation of circadian rhythms (diurnal, seasonal), sleep and wakefulness, participation in the processes of thermoregulation, tumour growth and aging, sexual activity and reproductive functions. It also has immunomodulatory, cytoprotective and antioxidant activity. The results from the studies with experimental models with animals conducted so far in search of a correlation between melatonin and epileptogenesis are mainly in support of the hypothesis of its anticonvulsant effect. The studies with humans are diverse in design, with a smaller number of participants, and the results are not always in explicit support of this hypothesis. The correlation between melatonin concentration and the course of the disease in patients with epilepsy has been discussed. The possibility of adding melatonin to anti-epileptic therapy has also been studied recently.

Alimentary Infections by Tick-Borne Encephalitis Virus

Tick-borne encephalitis virus (TBEV) causes serious the neurological disease, tick-borne encephalitis (TBE). TBEV can be transmitted to humans by ticks as well as by the alimentary route, which is mediated through the consumption of raw milk products from infected ruminants such as sheep, goats, and cows. The alimentary route of TBEV was recognized in the early 1950s and many important experimental studies were performed shortly thereafter. Nowadays, alimentary TBEV infections are recognized as a relevant factor contributing to the overall increase in TBE incidences in Europe. This review aims to summarize the history and current extent of alimentary TBEV infections across Europe, to analyze experimental data on virus secretion in milk, and to review possible alimentary infection preventive measures.