Journal of Central Nervous System Disease最新文献

BACKGROUND: Awake craniotomy has emerged as an advanced surgical technique, characterized by keeping the patient awake during brain surgery. In South America, awake craniotomies have grained traction in neurosurgical practices across various medical centres and hospitals, with notable practitioners contributing to its growth and refinement in the region. PURPOSE: This study aims to explore the integration and impact of awake craniotomies in South American neurosurgical practices. The focus is on understanding the benefits, challenges, and potential transformative effects of the procedure in the region. RESEARCH DESIGN: A comprehensive narrative review and analysis through a thorough examination of the existing literature. RESULTS: The findings indicate that awake craniotomies in South America offer substantial benefits, including cost savings thorugh reduced hospitalization time, quicker recovery and decreased morbidity. Enhanced safety, effective pain management and reduced anaesthesia also contribute to this. CONCLUSION: Whilst the adaptation of awake craniotomies in South America holds great promise in transforming neurosurgical care in the region, significant challenges hinder its widespread adoption. Inadequate infrastructure, limited access to equipment, financial instability, and shortages in trained healthcare providers represent challenges that need to be addressed.

Hypothalamic hamartomas (HHs) are congenital developmental malformations located in the hypothalamus. They are associated with a characteristic clinical manifestation known as gelastic seizures (GS). However, the traditional understanding of HHs has been limited, resulting in insufficient treatment options and high recurrence rates of seizures after surgery. This is consistent with the network hypothesis of focal epilepsy that the epileptogenic zone is not only limited to HH but may also involve the distant cerebral cortex external to the HH mass. The epilepsy network theory, on the other hand, provides a new perspective. In this study, we aim to explore HH-related epilepsy as a network disease, challenging the conventional notion of being a focal lesional disease. We analyze various aspects of HHs, including genes and signaling pathways, local circuits, the whole-brain level, phenotypical expression in terms of seizure semiology, and comorbidities. By examining HHs through the lens of network theory, we can enhance our understanding of the condition and potentially identify novel approaches for more effective management and treatment of epilepsy associated with HHs.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune neuroinflammatory disorder with a prevalence of 1-5/100,000 globally, characterized by attacks of the central nervous system including but not limited to optic neuritis, transverse myelitis and brainstem lesions, including area postrema lesions. These autoimmune attacks can lead to irreversible damage if left untreated, therefore strategies have been developed to prevent relapses. Initial off-label treatments have achieved variable levels of success in relapse prevention, but improved relapse prevention and quality of life remain a goal in the field. A better understanding of the underlying pathophysiology of NMOSD over the last 10 years has led to newer, more specific approaches in treatment, culminating in the first FDA approved treatments in the disease. In this review, we will discuss the seminal trials of PREVENT or Eculizumab in the treatment of aquaporin-4 (AQP4)-IgG positive NMOSD, N-Momentum or Inebilizumab in the study of NMOSD (both AQP4-IgG positive and negative) and SAkura Sky and SAkuraStar which studied satralizumab in AQP4-IgG seropositive and seronegative NMOSD patients. We will also discuss the extension trials of each of these medications and what lead to their approval in AQP4-IgG seropositive NMOSD patients. We will then examine treatments in the pipeline for adult and pediatric NMOSD patients and conclude with discussions on treatment considerations in pregnant patients and how to approach treatment of NMOSD patients during COVID.

Background: In spite of the observed immunomodulatory properties of different sex hormones on Multiple Sclerosis (MS) in different investigations, to date, there has been no study to systematically review the documents to add more powerful data to the field.

Objectives: Therefore, in this paper we aim to systematically review clinical and randomized controlled trials (RCT) assessing the effect of sex hormone therapies on individuals with MS.

Design: A comprehensive search of electronic databases including PubMed, EMBASE, and Scopus was conducted. Clinical trials and RCTs that assessed the impact of sex hormones on individuals with MS were selected and included in the systematic review.

Data sources and methods: In the final phase of the search strategy, 9 papers reached the criteria for entering in the systematic review. Two independent reviewers extracted the relevant data from each article according to the standardized data extraction form. Two reviewers also assessed the quality of each study independently using PEDro scale.

Results: We categorized three different classifications of outcomes including clinical, MRI, and immune system findings and put each measured outcome in the category which matched best.

Conclusion: In conclusion, the existed investigations on the effect of sex hormones on inflammatory and neurodegenerative components of MS are promising particularly in relapsing-remitting MS (RRMS).

Recent decades have witnessed significant progress in understanding mechanisms driving neurodegeneration and disease progression in multiple sclerosis (MS), but with a focus on the cerebrum. In contrast, there have been limited studies of cerebellar disease, despite the common occurrence of cerebellar symptoms in this disorder. These rare studies, however, highlight the early cerebellar involvement in disease development and an association between the early occurrence of cerebellar lesions and risk of worse prognosis. In parallel developments, it has become evident that far from being a region specialized in movement control, the cerebellum plays a crucial role in cognitive function, via circuitry connecting the cerebellum to association areas of the cerebrum. This complexity, coupled with challenges in imaging of the cerebellum have been major obstacles in the appreciation of the spatio-temporal evolution of cerebellar damage in MS and correlation with disability and progression. MS studies based on animal models have relied on an induced neuroinflammatory disease known as experimental autoimmune encephalomyelitis (EAE), in rodents and non-human primates (NHP). EAE has played a critical role in elucidating mechanisms underpinning tissue damage and been validated for the generation of proof-of-concept for cerebellar pathological processes relevant to MS. Additionally, rodent and NHP studies have formed the cornerstone of current knowledge of functional anatomy and cognitive processes. Here, we propose that improved insight into consequences of cerebellar damage in MS at the functional, cellular and molecular levels would be gained by more extensive characterization of EAE cerebellar pathology combined with the power of experimental paradigms in the field of cognition. Such combinatorial approaches would lead to improved potential for the development of MS sensitive markers and evaluation of candidate therapeutics.

Migraine is a complex and heterogenous disorder whose disease mechanisms remain disputed. This narrative review summarizes functional MRI (fMRI) and diffusion tensor imaging (DTI) findings and interprets their association with migraine symptoms and subtype to support and expand our current understanding of migraine pathophysiology. Our PubMed search evaluated and included fMRI and DTI studies involving comparisons between migraineurs vs healthy controls, migraineurs with vs without aura, and episodic vs chronic migraineurs. Migraineurs demonstrate changes in functional connectivity (FC) and regional activation in numerous pain-related networks depending on migraine phase, presence of aura, and chronicity. Changes to diffusion indices are observed in major cortical white matter tracts extending to the brainstem and cerebellum, more prominent in chronic migraine and associated with FC changes. Reported changes in FC and regional activation likely relate to pain processing and sensory hypersensitivities. Diffuse white matter microstructural changes in dysfunctional cortical pain and sensory pathways complement these functional differences. Interpretations of reported fMRI and DTI measure trends have not achieved a clear consensus due to inconsistencies in the migraine neuroimaging literature. Future fMRI and DTI studies should establish and implement a uniform methodology that reproduces existing results and directly compares migraineurs with different subtypes. Combined fMRI and DTI imaging may provide better pathophysiological explanations for nonspecific FC and white matter microstructural differences.

Atypical teratoid rhabdoid tumors (ATRTs) are rare embryonal tumors comprising 1-2% of all pediatric CNS neoplasms. Spinal ATRTs are even more uncommon, accounting for 2% of all reported ATRT cases. Despite their rarity, ATRTs affect young children disproportionately and are characterized by a high malignant potential due to a heterogeneous cellular composition and inactivating mutations in the SMARCB1 (90%) and SMARCA4 (10%) genes. A 15-month-old female presented with a 2-week history of decreased lower extremity movement and new-onset need for assistance with ambulation. MRI lumbar spine revealed a contrast-enhancing intradural mass at the L3-L4 level with iso-intensity on T1 and T2 sequences. The patient subsequently underwent subtotal tumor resection (∼80%) given concerns for maintaining neurological function. Final pathology was consistent with spinal ATRT, and she later underwent adjuvant chemoradiation therapy per ACNS0333 protocol. She has since remained in remission with age-appropriate developmental milestones over the past 2 years. ATRTs should be considered in the differential diagnosis of intradural spinal lesions, especially in the pediatric patient population. Clinical course, presentation, and diagnosis is often delayed due to the rarity of these tumors, but contrasted craniospinal MRI is key for diagnosis and histopathology with IHC staining showing loss of INI is confirmatory. While gross total resection is the goal, maximal safe tumor resection should be prioritized in order to preserve neurological function. Adjuvant chemoradiation following gross total/subtotal resection has been shown to significantly improve overall survival.

Antiseizure medications (ASMs) are the mainstay of symptomatic epilepsy treatment. The primary goal of pharmacotherapy with ASMs in epilepsy is to achieve complete seizure remission while minimizing therapy-related adverse events. Over the years, more ASMs have been introduced, with approximately 30 now in everyday use. With such a wide variety, much guidance is needed in choosing ASMs for initial therapy, subsequent replacement monotherapy, or adjunctive therapy. The specific ASMs are typically tailored by the patient's related factors, including epilepsy syndrome, age, sex, comorbidities, and ASM characteristics, including the spectrum of efficacy, pharmacokinetic properties, safety, and tolerability. Weighing these key clinical variables requires experience and expertise that may be limited. Furthermore, with this approach, patients may endure multiple trials of ineffective treatments before the most appropriate ASM is found. A more reliable way to predict response to different ASMs is needed so that the most effective and tolerated ASM can be selected. Soon, alternative approaches, such as deep machine learning (ML), could aid the individualized selection of the first and subsequent ASMs. The recognition of epilepsy as a network disorder and the integration of personalized epilepsy networks in future ML platforms can also facilitate the prediction of ASM response. Augmenting the conventional approach with artificial intelligence (AI) opens the door to personalized pharmacotherapy in epilepsy. However, more work is needed before these models are ready for primetime clinical practice.

A 56-year-old Caucasian man was diagnosed with definite neurosarcoidosis after he presented with progressive bilateral lower extremity weakness and dysesthesia. He was started on a combination immunosuppressant regimen of dexamethasone, methotrexate and infliximab. Two months into treatment with immunosuppressants, he developed devastating disseminated aspergillosis which clinically stabilized with aggressive antifungal treatment however had a protracted radiological course despite prolonged anti-fungal treatment for over two years. Interestingly, he remained in remission from neurosarcoidosis off immunosuppression during the same period. This case emphasizes need for vigilance for fungal infections in patients treated with combination immunosuppressive therapy particularly TNF-α inhibitors such as infliximab.