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This study aims to collect and analyze adverse event (AE) reports related to Nusinersen from the FAERS database. The study employed a combination of signal quantification techniques, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS), to enhance the accuracy of signal detection and reduce the risk of false positives or negatives. Between the first quarter of 2017 and the third quarter of 2023, the FAERS database collected a total of 11,485,105 drug AE reports, of which 5772 were related to Nusinersen. Through signal mining analysis, 218 preferred term (PT) signals involving 27 system organ classes (SOCs) were identified. The study discovered AEs related to metabolism and nutrition disorders, psychiatric disorders, and cardiac disorders SOCs, which were not mentioned in the product information. Additionally, complications directly related to the intrathecal administration of Nusinersen, such as increased CSF pressure, positive CSF red blood cell count, and AEs related to the method of drug use, such as neuromuscular scoliosis and cerebrospinal fluid reservoir placement, were highlighted. Notably, AEs related to renal function abnormalities, such as abnormal Urine protein/creatinine ratio and protein urine presence, showed higher frequency and signal strength. The findings of this study emphasize the importance of comprehensive safety monitoring in the clinical application of Nusinersen. These results are significant for guiding future clinical practices, improving disease management strategies, and developing safer treatment protocols.

BACKGROUND: Spinal muscular atrophy (SMA) is a progressive neurodegenerative disorder that can be treated with intrathecal nusinersen, an antisense oligonucleotide. In addition to efficacy, safety is a determining factor in the success of any therapy. Here, we aim to assess the safety of nusinersen therapy in paediatric patients with SMA.
METHODS: Laboratory data of paediatric patients with SMA who received nusinersen between October 2019 and May 2022 were retrospectively analysed.
RESULTS: During the observation period, 46 infants and children aged 2.9 months to 13.6 years received a total of 213 nusinersen doses without safety concerns. Inflammatory markers were stable throughout the study. International normalized ratio was increased by 0.09 per injection. Urea levels were increased by 0.108 mmol/L, and cystatin C decreased by 0.029 mg/L per injection. There were no significant changes in platelet count, activated partial thrombin time, creatinine levels or liver enzyme levels during treatment. The cerebrospinal fluid (CSF) leukocyte count remained stable, and total protein increased by 24.038 mg/L per injection.
CONCLUSIONS: Our data showed that nusinersen therapy is generally safe in children with SMA. Laboratory monitoring did not identify any persistent or significantly abnormal findings. CSF protein should be monitored to gain more insights.

BACKGROUND: Lumbar puncture is challenging for patients with scoliosis. Previous ultrasound-assisted techniques for lumbar puncture used the angle of the probe as the needle trajectory; however, reproducing the angle is difficult and increases the number of needle manipulations. In response, we developed a technique that eliminated both the craniocaudal and lateromedial angulation of the needle trajectory to overall improve this technique. We assessed the feasibility and safety of this method in patients with scoliosis and identify factors related to difficult lumbar puncture.
METHODS: Patients with spinal muscular atrophy and scoliosis who were referred to the anesthesia department for intrathecal nusinersen administrations were included. With a novel approach that utilized patient position and geometry, lumbar puncture was performed under ultrasound guidance. Success rates, performance times and adverse events were recorded. Clinical-demographic and spinal radiographic data pertaining to difficult procedures were analyzed.
RESULTS: Success was achieved in all 260 (100%) lumbar punctures for 44 patients, with first pass and first attempt success rates of 70% (183/260) and 87% (226/260), respectively. Adverse events were infrequent and benign. Higher BMI, greater skin dural sac depth and smaller interlaminar size might be associated with greater difficulty in lumbar puncture.
CONCLUSIONS: The novel ultrasound-assisted horizontal and perpendicular interlaminar needle trajectory approach is an effective and safe method for lumbar puncture in patients with spinal deformities. This method can be reliably performed at the bedside and avoids other more typical and complex imaging such as computed tomography guided procedure.

To evaluate the effectiveness and safety of a cancer pain information platform combined with semi-implantable intrathecal drug delivery systems among the patients with refractory cancer pain under a \"home analgesia\" model. This was a retrospective study. A total of 49 patients underwent semi-implantable intrathecal drug delivery systems with patient-controlled analgesia in conjunction with the establishment of a cancer pain information platform. Numeric rating scales (NRS), Bruggrmann comfort scale (BCS), high-quality sleep duration, and opioid-related adverse effects were recorded at various time points and analyzed: the day on admission (T0), the day of discharge (T1), 30 days post-discharge (T2), 60 days post-discharge (T3), 90 days post-discharge (T4), 120 days post-discharge (T5), 150 days post-discharge (T6), 180 days post-discharge (T7), and the day before death (T8). Compared with T0, NRS significantly decreased and BCS significantly increased at T1 to T8 time points (P < .05). However, NRS and BCS did not show differences at T1 to T8 time points (P > .05). The duration of high-quality sleep was significantly extended, and the incidence of opioid-related adverse effects was significantly reduced. Postoperative complications included 1 case of cerebrospinal fluid leakage, 3 cases of infection at the butterfly needle insertion site, 6 cases of hospital readmission for equipment malfunction, and no cases of respiratory depression. Eleven patients continued standardized antitreatment after IDDS surgery. The mean survival time for all patients was 135.51 ± 102.69 days, and the survival rate at T7 was 30.61%. The cancer pain information platform combined with semi-implantable IDDS is beneficial for the pain management of refractory cancer patients under the \"home analgesia\" model, improving their quality of life.

BACKGROUND: Dexamethasone palmitate (DEP), a prodrug of dexamethasone (DEX), is a synthetic corticosteroid medication distinguished by the inclusion of a fatty acid component known as palmitate. This study introduces DEP as a novel therapeutic option for spinal epidural injection, aiming to provide safer and longer-lasting pain relief as an alternative to for patients with spinal stenosis.
METHODS: 40 rats were randomly divided into four groups: those receiving epidural administration of normal saline (NS), and DEP in the lumbar spinal stenosis (LSS) model, and non-model rats receiving epidural NS administration. Paw withdrawal thresholds to mechanical stimulation and motor function (neurogenic intermittent claudication) were observed for up to 21 days. Hematology and blood chemistry analyses were performed 1 week after drug therapy. Tissue samples were collected for steroid pathology examination to evaluate adhesion degree, perineural area inflammation, and chromatolysis in the dorsal root ganglion (DRG), and adrenal gland.
RESULTS: The DEX and DEP groups demonstrated significant recovery from mechanical allodynia and motor dysfunction after 2 weeks of drug therapy (p<0.001). However, by the third week, the effect of DEX started to diminish while the effect of DEP persisted. Furthermore, the DEP group exhibited reduced fibrosis and less chromatolysis than the NS group. No steroid overdose or toxin was observed in any group.
CONCLUSIONS: The epidural administration of DEP demonstrated therapeutic efficacy in reducing allodynia and hyperalgesia resulting from chronic DRG compression, thus offering prolonged pain relief. These findings underscore the potential of DEP as a promising treatment alternative for pain associated with LSS, serving as a viable substitute for .

OBJECTIVE: Central nervous system (CNS) infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) present a major health and economic burden worldwide. This multicentre prospective study aimed to assess the feasibility and usefulness of CSF therapeutic drug monitoring (TDM) after intrathecal/intraventricular administration of polymyxin B in patients with CNS infections.
METHODS: Forty-two patients treated with intrathecal/intraventricular administration of polymyxin B against CR-GNB-induced CNS infections were enrolled. CSF trough level (Cmin) was collected beginning on Day 2 post-polymyxin B initiation and thereafter. The primary outcomes were clinical cure and 28-day all-cause mortality.
RESULTS: All patients started with intrathecal/intraventricular administration of polymyxin B at a dose of 5 g/day, corresponding to a median CSF Cmin of 2.93 mg/L (range, 0.21-25.74 mg/L). Clinical cure was 71.4%, and the median CSF Cmin of this group was higher than that of clinical failure group [3.31 (IQR, 1.73-5.62) mg/L versus 2.25 (IQR, 1.09-4.12) mg/L; P = 0.011]. In addition, with MICs ≤ 0.5 mg/L, maintaining polymyxin B CSF Cmin above 2.0 mg/L showed a higher clinical cure rate (P = 0.041). The 28-day all-cause mortality rate was 31.0% and had no association with CSF Cmin.
CONCLUSIONS: After intrathecal/intraventricular administration of polymyxin B, CSF concentrations fluctuated considerably inter- and intra-individual. Polymyxin B CSF Cmin above 2.0 mg/L was associated with clinical cure when MICs were ≤ 0.5 mg/L, and the feasibility of TDM warrants additional clinical studies.

BACKGROUND: The treatment regimen for tuberculous meningitis (TBM) remains unclear and requires optimization. There are some reports on successful adjunct intrathecal dexamethasone and isoniazid (IDI) treatment strategies for TBM, however, there is equivocal evidence on their efficacy and safety.
METHODS: A comprehensive search of English and Chinese databases was conducted from inception to February 2024. A meta-analysis was performed on randomized controlled trials (RCTs) estimating the effects of adjunct IDI on conventional anti-TB (C anti-TB) treatments or C anti-TB alone. Efficacy, adverse reaction rate, cerebrospinal fluid (CSF) leukocytes, and CSF protein were used as primary outcome indicators. CSF glucose, CSF chlorides, CSF pressure, recovery time for laboratory indicators and recovery time for clinical symptoms were used as secondary outcome indicators.
RESULTS: A total of 17 studies involving 1360 (IDI group vs. C anti-TB group: 392 vs. 372; higher-dose IDI group vs. lower-dose IDI group: 319 vs. 277) patients were included in our analysis. Efficacy was significantly higher (RR 1.3, 95% CI 1.2-1.4, P < 0.001) and adverse reaction rate was significantly lower in the IDI groups (RR 0.59, 95% CI 0.37-0.92, P = 0.021). Furthermore, CSF leukocytes (WMD - 29.33, 95% CI [- 40.64 to-18.02], P < 0.001) and CSF protein (WMD - 0.79, 95%CI [-0.96 to-0.61], P < 0.001) were significantly lower in the IDI groups. Recovery time indicators were all shorter in the IDI groups, fever (SMD - 2.45, 95% CI [-3.55 to-1.35], P < 0.001), coma (SMD-3.75, 95% CI [-4.33 to-3.17], P < 0.001), and headache (SMD  - 3.06, 95% CI [- 4.05 to-2.07], P < 0.001), respectively. Higher-dose IDI was more effective than lower-dose IDI (RR 1.23, 95% CI 1.14-1.33, P < 0.001), with no significant difference in adverse reaction rate between the two (RR 0.82, 95%CI 0.43-1.56, P = 0.544).
CONCLUSIONS: Adjunct IDI with C anti-TB can enhance therapeutic outcomes and reduce adverse reaction rate in adult TBM patients, with higher-dose IDI showing superior efficacy. These findings highlight the potential of IDI as an adjunctive therapy in TBM management. However, more high-quality RCTs from more regions should be conducted to support our results.
BACKGROUND: Retrospectively registered in PROSPERO  https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023388860 .

BACKGROUND: Gastrodin (GAS), a main bioactive component of the herbal plant, Gastrodia elata Blume, has shown to have beneficial effects on neuroinflammatory diseases such as Alzheimer\'s disease in animal studies and migraine in clinical studies. Inflammasome is a multimeric protein complex having a core of pattern recognition receptor and has been implicated in the development of neuroinflammatory diseases. Gastrodin has shown to modulate the activation of nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome. This study investigated the effects of GAS on the intensity of mechanical allodynia and associated changes in NLRP3 inflammasome expression at the spinal level using L5/6 spinal nerve ligation model (SNL) in rats.
METHODS: Intrathecal (IT) catheter implantation and SNL were used for drug administration and pain model in male Sprague-Dawley rats. The effect of gastrodin or MCC950 (NLRP3 inflammasome inhibitor) on mechanical allodynia was measured by von Frey test. Changes in NLRP3 inflammasome components and interleukin-1β (IL-1β) and cellular expression were examined in the spinal cord and dorsal root ganglion.
RESULTS: The expression of NLRP3 inflammasome components was found mostly in the neurons in the spinal cord and dorsal root ganglion. The protein and mRNA levels of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, and IL-1β were upregulated in SNL animals compared to Sham animals. IT administration of GAS significantly attenuated the expression of NLRP3 inflammasome and the intensity of SNL-induced mechanical allodynia. NLRP3 inflammasome inhibitor, MCC950, also attenuated the intensity of allodynia, but the effect is less strong and shorter than that of GAS.
CONCLUSIONS: Expression of NLRP3 inflammasome and IL-1β is greatly increased and mostly found in the neurons at the spinal level in SNL model, and IT gastrodin exerts a significant anti-allodynic effect in SNL model partly through suppressing the expression of NLRP3 inflammasome.

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