Neuroprotection and Recovery in Multiple Sclerosis

Multiple sclerosis is a complex and heterogeneous immune-mediated disease that results in the progressive accumulation of mental and physical symptoms. Currently approved disease-modifying drugs (DMDs) are immunomodulatory or immunosuppressive, but these drugs have little effect on disease progression. In addition to studies that have directly targeted inflammation and immune responses, a large number of studies, most of them experimental, have investigated neuroprotective therapies and remyelination strategies. However, to date, attempts to provide neuroprotection have failed not just in multiple sclerosis but in neurological disorders in general; this situation has emphasized the need to revise the old paradigm of a “magic bullet” with a single mechanism of action. Remyelination strategies involve either promoting endogenous remyelination or replacing lost myelinating cells through exogenous sources. However, several puzzle pieces regarding the physiology of remyelination remain unknown, including feasible treatment monitoring methods, the selection of patients, and the optimal time of treatment initiation. This chapter will describe the direct and indirect neuroprotective effects of DMDs, as suggested by basic research studies and confirmed by clinical studies in some cases. Current knowledge of potential neuroprotective therapies and remyelination strategies is also reviewed

Rehabilitation and clinical evolution aspects in a case of Osteoid Osteoma

Abstract: Introduction. Osteoid osteoma represents about 3% of all primary bone tumors and 11% of all benign bone tumors. Data from the literature suggest that a neuromuscular rehabilitation program after osteoid osteoma surgery is very beneficial and improves the general quality of life. Material and methods. A 30-year-old male patient with intermittent right shoulder pain radiating to the right hand, and recurrent myalgias in the past year presented to our neuro-logical department. The neurological examination highlighted limitation of the abduction of the right upper limb. The paraclinical investigations included plain radiography of the right upper limb and electroneurography, which were normal, and native cervical MRI which revealed discrete C5 disc overflow, without visible signs of compression. The patient presented limited initial response to NSAIDs, so his treatment was changed to corticoster-oid therapy. Further, the patient was guided to undergo a rheumatological examination where a musculoskeletal ultrasound was performed, showing no any specific modifica-tion. Additionally, we indicated a native right shoulder MRI, which revealed a signal mod-ification of the proximal humeral diaphysis. We further indicated an MRI scan with con-trast of the upper right limb, which revealed a nidus at the top one-third of the humerus. Additionally, a CT scan with contrast of the same region displayed images that were high-ly suggestive of osteoma. The patient was referred to the orthopedics department, where a complete resection of the tumor was performed, and the pathology report confirmed the fi-nal diagnosis of osteoid osteoma. Conclusions. Recovery after osteoid osteoma surgery is more beneficial if the neuromuscu-lar rehabilitation program, that has an important role in increasing muscle strength, is combined with orthopedic devices and pain medication

Cerebrolysin and repetitive transcranial magnetic stimulation (rTMS) in patients with traumatic brain injury: a three-arm randomized trial

IntroductionTraumatic brain injury (TBI) is a major public health problem affecting millions worldwide. Despite significant advances in medical care, there are limited effective interventions for improving cognitive and functional outcomes in TBI patients.MethodsThis randomized controlled trial investigated the safety and efficacy of combining repetitive transcranial magnetic stimulation (rTMS) and Cerebrolysin in improving cognitive and functional outcomes in TBI patients. Ninety-three patients with TBI were randomized to receive either Cerebrolysin and rTMS (CRB + rTMS), Cerebrolysin and sham stimulation (CRB + SHM), or placebo and sham stimulation (PLC + SHM). The primary outcome measures were the composite cognitive outcome scores at 3 and 6 months after TBI. Safety and tolerability were also assessed.ResultsThe study results demonstrated that the combined intervention of rTMS and Cerebrolysin was safe and well-tolerated by patients with TBI. Although no statistically significant differences were observed in the primary outcome measures, the descriptive trends in the study support existing literature on the efficacy and safety of rTMS and Cerebrolysin.DiscussionThe findings of this study suggest that rTMS and Cerebrolysin may be effective interventions for improving cognitive and functional outcomes in TBI patients. However, limitations of the study, such as the small sample size and exclusion of specific patient populations, should be considered when interpreting the results. This study provides preliminary evidence for the safety and potential efficacy of combining rTMS and Cerebrolysin in improving cognitive and functional outcomes in TBI patients. The study highlights the importance of multidisciplinary approaches in TBI rehabilitation and the potential for combining neuropsychological measurements and interventions to optimize patient outcomes.ConclusionFurther research is needed to establish these findings’ generalizability and identify the optimal dosages and treatment protocols for rTMS and Cerebrolysin

Плейотропный нейропротективный и метаболический эффекты актовегина

В обзоре рассматриваются механизмы действия актовегина в контексте изучения его эффектов на доклиническом уровне и новой концепции фармакологического лечения неврологических расстройств. Актовегин, получаемый при ультрафильтрации крови телят, состоит из более чем 200 биологических субстанций. Препарат используется при широком спектре заболеваний, включая нарушения периферического и мозгового кровообращения, ожоги, плохое заживление ран, радиационные поражения и диабетическую полинейропатию. Актовегин состоит из молекул малого размера, которые находятся в организме в нормальных физиологических условиях, и поэтому исследования их фармакокинетики и фармакодинамики для определения активной субстанции препарата затруднены. Результаты преклинических исследований показали, что актовегин улучшает метаболический баланс путем повышения усвоения глюкозы и потребление кислорода в условиях ишемии. Актовегин также повышает устойчивость к гамма-радиации и стимулирует ранозаживление. В более поздних работах было установлено, что антиоксидантный и антиапоптотический механизмы действия лежат в основе нейропротективных свойств актовегина, подтвержденных в экспериментах на первичных нейронах гиппокампа крыс и стрептозотоцининдуцированной модели диабетической полинейропатии у крыс. Последние данные свидетельствуют о положительном влиянии актовегина на фактор NF-κB, но при этом многие молекулярные и клеточные механизмы его действия остаются неизвестными. В первую очередь это касается влияния актовегина на нейропластичность, нейрогенез и трофическую функцию нервной системы, и данный аспект требует дальнейших исследований. Тем не менее становится очевидным, что мультифакториальная и многокомпонентная природа актовегина определяет его плейотропный нейропротективный механизм действия и клиническую эффективность

Severe sensory ganglionopathy as a manifestation of mixed connective tissue disease

Sensory ganglionopathies (SG) are a rare but distinct clinical subgroup of peripheral neuropathies characterized by damage to dorsal root ganglia. Typical manifestations include early gait and limb ataxia, widespread diminished or absent deep tendon reflexes accompanied by Romberg sign and pseudoathetoid movements.The diagnosis of SG is valuable since it may prompt towards early recognition of an underlying malignancy or autoimmune disorder. We report the case of a female diagnosed with mixed connective tissue disease (MCTD) along with severe SG. To our knowledge, such disease association has not been reported yet. The pathophysiology in cases linked to MCTD is unclear and asks for further studies. Moreover, the important degree of disability associated with this condition highlights the need for effective therapies’ development

Variants of Amyotrophic lateral sclerosis and rehabilitation: an overview

Amyotrophic lateral sclerosis (ALS) represents a progressive neurodegenerative disease that affects motor neurons in the brain and spinal cord leading to the impairment of volun-tary muscle control and eventually death. It accounts for about 80%-90% of all motor neu-ron diseases, and is characterized by a marked variability in terms of clinical forms, gene-tics, survival rate and diagnostic particularities. A diagnosis of ALS or one of the variants comes with a great burden for the patient and patient’s family because of the high morbidi-ty and mortality rate of this disorder. As a consequence, it is mandatory to optimize the ac-curacy of the diagnostic process of ALS spectrum for providing the best clinical manage-ment and quality of life for patients and avoiding diagnostic mistakes. Our review focuses on the general and particular aspects of ALS and its variants in an effort to improve the process of diagnosis, therapy and exclusion of mimics of this group of diseases and to pro-vide the latest findings in this field

WITHDRAWN: Clinical Neurorestorative Therapeutic Guidelines for Spinal Cord Injury (IANR/CANR Version 2019)

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Advances and perspectives for Central Nervous System drug delivery: the interface between nanotechnology and neuroscience

EditorialAdvances and perspectives for Central Nervous System drug delivery: the interface between nanotechnology and neuroscience A report from the World Health Organization (WHO) recently highlighted that Central Nervous System (CNS) disorders (brain injuries, neuroinfections, multiple sclerosis, epilepsy, stroke, Alzheimer and Parkinson disease) are affecting more than one billion people worldwide (WHO, 2006). The majority of these diseases are almost untreatable or featured by poor prognosis, since only 2% of the overall drugs are able to enter the brain as the blood-brain barrier (BBB) restricts the diffusion of substances from blood to the brain (Pardridge, 2002). In recent years, the use of nanotechnology has been considered a valuable strategy in order to achieve the drug delivery to the brain (Pardridge, 2003; Kabanov, 2004; Gabathuler, 2010). Nanomedicine-based approach has deserved considerable results as some medicinal products have reached the phases I and II and some imaging nano-devices obtained the marketing authorization (Tosi et al., 2008). Thus, the research in this field of science has been featured by an increasing number of experimental strategies, in order to maximize and optimize the therapeutic protocols. This issue of Journal of Nanoneuroscience could be divided into two main chapter: one is dealing with the different kinds of approaches for BBB crossing and CNS targeting as nanomedicine-based strategies, nasal route for BBB crossing and gene delivery by carbon nanotubes. The other theme could be summarized as potential treatments and imaging of brain diseases, as glioma treatment by means of nanotech-based delivery of taxanes, quantum dots for imaging and gold nanoparticles with antioxidative effec