BACKGROUND: Spinal tuberculosis is often associated with poor outcomes; host-directed inflammation involving the spine contributes to this disability.
METHODS: A retrospective review of patients with complicated spinal tuberculosis having received tumor necrosis factor-alpha (TNF-α) antagonists at a referral hospital in South Africa. A literature review was performed to identify all published cases of complicated spinal tuberculosis that received a TNF-α antagonist as part of their treatment.
RESULTS: We describe 23 cases, of which 19 were previously reported in the literature. All patients were treated with either thalidomide (n=6) or infliximab (n=16), except for one who received both. All in all, 21 (91%) cases improved neurologically and, at the end of follow-up, 18 could walk.
CONCLUSIONS: There is accumulating experience to confer the efficacy and safety of TNF-α antagonists in treating complicated spinal tuberculosis cases. Evidence from randomized controlled trials is urgently required to substantiate these findings.

Cyclic adenosine monophosphate (cAMP) is a key second messenger that regulates signal transduction pathways pivotal for numerous biological functions. Intracellular cAMP levels are spatiotemporally regulated by their hydrolyzing enzymes called phosphodiesterases (PDEs). It has been shown that increased cAMP levels in the central nervous system (CNS) promote neuroplasticity, neurotransmission, neuronal survival, and myelination while suppressing neuroinflammation. Thus, elevating cAMP levels through PDE inhibition provides a therapeutic approach for multiple CNS disorders, including multiple sclerosis, stroke, spinal cord injury, amyotrophic lateral sclerosis, traumatic brain injury, and Alzheimer\'s disease. In particular, inhibition of the cAMP-specific PDE4 subfamily is widely studied because of its high expression in the CNS. So far, the clinical translation of full PDE4 inhibitors has been hampered because of dose-limiting side effects. Hence, focusing on signaling cascades downstream activated upon PDE4 inhibition presents a promising strategy, offering novel and pharmacologically safe targets for treating CNS disorders. Yet, the underlying downstream signaling pathways activated upon PDE(4) inhibition remain partially elusive. This review provides a comprehensive overview of the existing knowledge regarding downstream mediators of cAMP signaling induced by PDE4 inhibition or cAMP stimulators. Furthermore, we highlight existing gaps and future perspectives that may incentivize additional downstream research concerning PDE(4) inhibition, thereby providing novel therapeutic approaches for CNS disorders.

In the immunocompromised setting, there are distinct radiologic findings of primary central nervous system lymphoma (PCNSL), including necrotic ring-enhancing lesions, increased propensity for intralesional haemorrhage, and multiplicity. In this clinical context, advanced imaging with MR perfusion, spectroscopy, and diffusion-weighted imaging can be used to increase accuracy in the diagnosis of lymphoma over mimics such as high-grade glioma, metastases, or infection. This review summarizes the histology and pathophysiology of PCNSL in immunodeficient hosts, which provide a basis for its imaging appearances, prognosis, and treatment. This discussion is important for the general radiologist as the incidence of immunodeficiency-related PCNSL may be increasing.

Background: type 1 neurofibromatosis (NF1) is the most common neurocutaneous disorder, and it is an inherited condition that causes a tumour predisposition. Central nervous system (CNS) manifestations are a significant cause of morbidity and mortality in NF1. We provide a pictorial review of neuroradiological features of NF1, with emphasis on magnetic resonance imaging (MRI), and we assess the frequency of those features on a cohort of NF1 patients. Methods: we retrospectively evaluated all patients with a diagnosis of NF1 who underwent MRI of the spine and brain in our centre over a period of almost 5 years. A total of 74 patients were enrolled, 28 males and 46 females, with a mean age of 21 ± 12.67 years. The frequency of CNS manifestations encountered in our cohort of NF1 patients was assessed and compared with the data found in other studies published in the literature. Results: many of our findings were in line with the literature, and possible interpretations for those that turned out to be different were suggested in the discussion. Conclusion: imaging plays a central role in the diagnosis and management of NF1, and the knowledge of CNS manifestations could be critical for its early detection and identification, such as for treatment planning and prognostic implications.

Due to the inevitable differences in physiological and/or genetic factors between genders, the possibility that differences in pharmacokinetics between genders may occur when exposed to the same dose of the same drug is subject to reasonable inference and suspicion. Nevertheless, a significant number of medicines still rely on empirical usage and uniform clinical application without consideration of inter-individual diversity factors. In particular, in the pharmacokinetic diversity of medicines related to central nervous system (CNS) activity, consideration of gender factors and access to comparative analysis are very limited. The purpose of this study was to conduct an integrated analysis and review of differences in pharmacokinetics between genders that have not been specifically reported to date for medicines related to CNS effects, which are a group of drugs with relatively significant concerns about systemic side effects. This study was accessible through extensive data collection and analyzes using a web-based scientific literature search engine of pharmacokinetic results of CNS-related drugs performed on humans, taking gender into account. As a result, significant differences in pharmacokinetics between genders were identified for many drugs related to CNS. And most of the pharmacokinetic differences between genders suggested a higher in vivo exposure in females. This study suggests that consideration of gender factors cannot be ignored and will be an important point of interest in the precision medicine application of CNS-related medicines.

UNASSIGNED: To explore the clinical characteristics and treatment outcomes of children with central nervous system (CNS) involvement in eosinophilic granulomatosis with polyangiitis (EGPA).
UNASSIGNED: A child who presented with EGPA complicated by CNS involvement was admitted to our hospital in June 2023. The clinical features were analyzed retrospectively, and relevant literatures were reviewed to provide a comprehensive overview of this condition.
UNASSIGNED: A ten-year-old girl, who had a history of recurrent cough and asthma accompanied by peripheral blood eosinophilia for eight months, was admitted to our hospital. On admission, spotted papules were visible on her hands and feet, bilateral pulmonary rales were audible. The laboratory examination revealed that the proportion of eosinophils (EOS) exceeded 10% of white blood cells, the anti-neutrophil cytoplasmic antibody (MPO-ANCA) was positive, the immunoglobulin G level was 15.80g/L, and the immunoglobulin E level was greater than 2500.00IU/mL. The imaging examination showed multiple patchy and nodular high-density shadows in both lungs as well as sinusitis. Pulmonary function tests indicated moderate ventilation and diffusion dysfunction. Bone marrow cytology demonstrated a significant increase in the proportion of eosinophils. Skin pathology confirmed leukocytoclastic vasculitis. During the hospitalization, the child had a convulsion. The magnetic resonance imaging (MRI) scan of the brain showed multiple abnormal signal shadows in the bilateral cerebral cortex and the electroencephalogram (EEG) showed epileptic waves. Following the administration of methylprednisolone pulse therapy in combination with cyclophosphamide treatment, her cough and asthma resolved, the skin rash disappeared without any further convulsions. We found that only a young EGPA patient with CNS involvement had been previously reported. The previously reported case began with long-term fever, weight loss, and purpuric rash. Both patients responded well to treatment with glucocorticoids and cyclophosphamide, experiencing significant improvement in their clinical symptoms and normalization of their peripheral blood eosinophils.
UNASSIGNED: The diagnosis of EGPA in children can be challenging. When a child is affected by EGPA, it is essential to remain vigilant for signs of CNS involvement. The treatment with glucocorticoids and cyclophosphamide is effective in managing EGPA in children.

In the present study, we conducted a scoping review to provide an overview of the existing literature on the carbocyanine dye DiI, in human neuroanatomical tract tracing. The PubMed, Scopus, and Web of Science databases were systematically searched. We identified 61 studies published during the last three decades. While studies incorporated specimens across human life from the embryonic stage onwards, the majority of studies focused on adult human tissue. Studies that utilized peripheral nervous system (PNS) tissue were a minority, with the majority of studies focusing on the central nervous system (CNS). The most common topic of interest in previous tract tracing investigations was the connectivity of the visual pathway. DiI crystals were more commonly applied. Nevertheless, several studies utilized DiI in a paste or dissolved form. The maximum tracing distance and tracing speed achieved was, respectively, 70 mm and 1 mm/h. We identified studies that focused on optimizing tracing efficacy by varying parameters such as fixation, incubation temperature, dye re-application, or the application of electric fields. Additional studies aimed at broadening the scope of DiI use by assessing the utility of archival tissue and compatibility of tissue clearing in DiI applications. A combination of DiI tracing and immunohistochemistry in double-labeling studies have been shown to provide the means for assessing connectivity of phenotypically defined human CNS and PNS neuronal populations.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a natural focal disease transmitted mainly by tick bites, and the causative agent is SFTS virus (SFTSV). SFTS can rapidly progress to severe disease, with multiple-organ failure (MOF) manifestations such as shock, respiratory failure, disseminated intravascular coagulation (DIC) and death, but cases of SFTS patients with central nervous system (CNS) symptoms onset and marked persistent involuntary shaking of the perioral area and limbs have rarely been reported.
METHODS: A 69-year-old woman with fever and persistent involuntary shaking of the perioral area and limbs was diagnosed with SFTS with CNS symptom onset after metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) and peripheral blood identified SFTSV. The patient developed a cytokine storm and MOF during the course of the disease, and after aggressive antiviral, glucocorticoid, and gamma globulin treatments, her clinical symptoms improved, her laboratory indices returned to normal, and she had a good prognosis.
CONCLUSIONS: This case gives us great insight that when patients with CNS symptoms similar to those of viral encephalitis combined with thrombocytopenia and leukopenia are encountered in the clinic, it is necessary to consider the possibility of SFTS involving the CNS. Testing for SFTSV nucleic acid in CSF and blood (mNGS or polymerase chain reaction (PCR)) should be carried out, especially in critically ill patients, and treatment should be given accordingly.

Central nervous system (CNS) tuberculosis is a post-primary form of tuberculosis. It has high mortality and morbidity rates despite early diagnosis and treatment. CNS tuberculosis can manifest as subacute/chronic meningitis, parenchymal tuberculous lesions, and spinal tuberculosis. Hematogenous spread of tuberculous bacilli to the brain results in the development of so called \"rich foci\" on the pial surface, ependyma, and grey-white matter junction. Rupture of these \"rich foci\" into the subarachnoid space triggers an intense granulomatous inflammatory reaction. Tuberculous meningitis can manifest as leptomeningitis or pachymeningitis. Intracranial parenchymal tuberculous lesions may present as tuberculoma, tuberculous abscess, cerebritis, rhombencephalitis, and encephalopathy, with atypical presentations not uncommon. Complications of CNS tuberculosis encompass hydrocephalus, syrinx formation, vasculitis, infarcts, neuritis, and enduring neurological deficits. Post-contrast 3D fluid-attenuated inversion recovery (FLAIR) and post-contrast T1 spin-echo sequences excel in detecting tuberculous meningitis compared to other conventional magnetic resonance imaging (MRI) sequences. In proton magnetic resonance spectroscopy (PMRS), the presence of a lipid peak at 1.3 ppm is indicative of tuberculous lesions. Magnetization transfer (MT) imaging enhances the detection of tuberculous lesions, as the magnetization transfer ratio (MTR) of tuberculous pathologies, owing to their high lipid content, is lower than that in bacterial or fungal pathologies and higher than that in viral pathologies. This review article delves into the various typical and atypical imaging presentations of CNS tuberculosis in MRI, along with recent advances in imaging techniques.

UNASSIGNED: Primary Sjogren\'s syndrome (pSS) is an autoimmune exocrinopathy in which extraglandular signs of pSS are determinant for the prognosis. Involvement of both peripheral and central nervous system (CNS) are known to be among the sites of high systemic activity in pSS.
UNASSIGNED: We, herein, report a case of a 57-year-old female patient with pSS presenting with typical Guillan-Barré syndrome (GBS), shortly followed by acute headaches accompanied by cortical blindness. Cerebral magnetic resonance imaging (MRI) demonstrated T2 signal abnormalities on the occipital region with narrowing and irregularities of the cerebral arteries, suggestive of CNS vasculitis.Subtle sicca symptoms occurring prior to neurological symptoms by 8 months together with immunological disturbances (anti-SSA, anti-SSB antibodies positivity, type II cryoglobulins positivity, and C4 hypocomplementemia) allowed us to retain the diagnosis of pSS. Recovery of motor symptoms was possible under the combined use of immunoglobulins and corticotherapy during the initial phase. A three-years follow-up confirmed progressive motor recovery and stabilization under 6-months cyclophosphamide cycles relayed by azathioprine therapy.
UNASSIGNED: Neurological complications can be inaugural in lead to urgent investigations and treatment. Peripheral and central neurological manifestations can coexist. The approach should integrate careful clinical assessment, as well as radiological and immunological findings.