Cost-Effectiveness Analysis of the Application of a Porcine-Derived Fibrin Sealant for the Treatment of Cerebrospinal Fluid Leak in China.

PURPOSE: This study aimed to evaluate the cost-effectiveness of a porcine-derived fibrin sealant (PFS) for treating cerebrospinal fluid (CSF) leaks in cranial surgery compared with sutures alone from the perspective of public hospital management in China. METHODS: A decision tree model of cranial surgery patients with intraoperative CSF leak was constructed in R 3.6.3. The cost-effectiveness of using PFS with dural sutures was compared versus using sutures alone. Efficacy and safety data were obtained from a randomized controlled, single-blinded clinical trial that enrolled 200 patients (NCT03110783). Effectiveness was measured as the success rate of CSF leak treatment and the rate of postoperative complication. Hospital procurement costs were used to provide cost measurements from the hospital administrator's perspective. FINDINGS: The PFS strategy had a higher success rate of CSF leak treatment (97.81% vs 49.21%) and a lower complication rate (9.49% vs 14.29%), based on results from the clinical trial. Using PFS also resulted in cost savings amounting to $374.97 in additional intraoperative CSF leak repairs ($18.07 vs $393.04) and $66.68 in postoperative complication treatment ($131.90 vs $198.58). Both one-way sensitivity analysis and probabilistic sensitivity analysis confirmed that the model results were stable against input variations. IMPLICATIONS: The decision tree analysis revealed that using PFS in conjunction with sutures was associated with improved clinical performance and lower overall costs. PFS in combination with sutures is the dominant strategy for treating CSF leak from the perspective of hospital decision-makers.

Cerebrospinal fluid dynamics modulation by diet and cytokines in rats.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a neurological disorder characterised by raised cerebrospinal fluid (CSF) pressure in the absence of any intracranial pathology. IIH mainly affects women with obesity between the ages of 15 and 45. Two possible mechanisms that could explain the increased CSF pressure in IIH are excessive CSF production by the choroid plexus (CP) epithelium or impaired CSF drainage from the brain. However, the molecular mechanisms controlling these mechanisms in IIH remain to be determined. METHODS: In vivo ventriculo-cisternal perfusion (VCP) and variable rate infusion (VRI) techniques were used to assess changes in rates of CSF secretion and resistance to CSF drainage in female and male Wistar rats fed either a control (C) or high-fat (HF) diet (under anaesthesia with 20 µl/100 g medetomidine, 50 µl/100 g ketamine i.p). In addition, CSF secretion and drainage were assessed in female rats following treatment with inflammatory mediators known to be elevated in the CSF of IIH patients: C-C motif chemokine ligand 2 (CCL2), interleukin (IL)-17 (IL-17), IL-6, IL-1ß, tumour necrosis factor-α (TNF-α), as well as glucocorticoid hydrocortisone (HC). RESULTS: Female rats fed the HF diet had greater CSF secretion compared to those on control diet (3.18 ± 0.12 µl/min HF, 1.49 ± 0.15 µl/min control). Increased CSF secretion was seen in both groups following HC treatment (by 132% in controls and 114% in HF) but only in control rats following TNF-α treatment (137% increase). The resistance to CSF drainage was not different between control and HF fed female rats (6.13 ± 0.44 mmH2O min/µl controls, and 7.09 ± 0.26 mmH2O min/µl HF). and when treated with CCL2, both groups displayed an increase in resistance to CSF drainage of 141% (controls) and 139% (HF) indicating lower levels of CSF drainage. CONCLUSIONS: Weight loss and therapies targeting HC, TNF-α and CCL2, whether separately or in combination, may be beneficial to modulate rates of CSF secretion and/or resistance to CSF drainage pathways, both factors likely contributing to the raised intracranial pressure (ICP) observed in female IIH patients with obesity.

The effectiveness of epidural blood patch in patients with cerebral palsy treated with intrathecal baclofen implantation.

BACKGROUND: Cerebrospinal fluid leak and postdural puncture spinal headache following intrathecal baclofen therapy are known complications. Although primary treatments are conservative, epidural blood patch is an alternative in patients with persistent and severe symptoms. AIM: The purpose of this article is to review the effectiveness of epidural blood patch for the treatment of spinal headache and cerebrospinal fluid leak associated with intrathecal baclofen treatment in children with cerebral palsy. METHODS: Our database was reviewed for epidural blood patch in 341 pediatric patients with cerebral palsy who underwent primary intrathecal baclofen treatment from 2004 to 2018 at one institution. The number of patches, time frame of treatment, and effectiveness of the epidural blood patch were collected. All patients treated with epidural blood patch were evaluated for primary and secondary intrathecal baclofen-related procedures, and subsequent treatment of intrathecal baclofen associated with cerebrospinal fluid leak and spinal headache. RESULTS: Twenty-nine epidural blood patch procedures were performed on 26 patients who had received intrathecal baclofen procedures. Of these 26 patients, four had a secondary epidural blood patch. The incidence of spinal headache/cerebrospinal fluid leak was 31% (107/341), and 81/107 (76%) patients with spinal headache/cerebrospinal fluid leak responded to conservative treatments. Success rate for initial epidural blood patch was 79.3% (23/29). The second epidural blood patch was performed in four patients after failure of initial epidural blood patch. Second epidural blood patch success rate was 75% (3/4). CONCLUSION: Spinal headache and cerebrospinal fluid leak are known complications after intrathecal baclofen treatment in children with cerebral palsy. When conservative treatments are unsuccessful, epidural blood patch can be used with confidence for these patients. In patients with ongoing symptoms, it is possible to obtain success by repeating the epidural blood patch to continue intrathecal baclofen treatment and avoid aggressive surgery.

Preoperative management of spontaneous cerebrospinal fluid rhinorrhea with acetazolamide.

BACKGROUND: Spontaneous cerebrospinal fluid (CSF) rhinorrhea has been associated with elevated intracranial pressure (ICP). As such, ICP reducing measures are commonly employed to optimize repair. Although postoperative acetazolamide use has been described, no data currently exists on the potential for preoperative use. METHODS: A retrospective review was performed including patients treated for anterior spontaneous CSF leaks by a single surgeon over a 6-year period during which acetazolamide therapy (250 mg twice daily) was employed before considering surgical repair. The primary endpoint was whether the patient went on to require surgical repair. RESULTS: A total of 16 patients were identified who were pretreated with acetazolamide. Leak sites were noted as cribriform (5/16), sphenoid (8/16), ethmoid (1/16), multiple (1/16), and indeterminate (1/16). Five patients had resolution of their rhinorrhea without surgery (31.3%). Mean follow-up for these nonsurgical patients was 470 days (range, 64 to 857 days). There were no differences in the patients' age or site of leak between surgical and nonsurgical patients (p = 0.65, p = 0.52, respectively). Nonsurgical patients had a lower body mass index (BMI) than surgical patients (p = 0.04). CONCLUSION: This is the first study to report the use of acetazolamide therapy as a primary treatment option for spontaneous CSF rhinorrhea. This therapy enabled surgery to be avoided in 31.3% of patients. This would indicate that in the absence of other contraindications for delaying repair, a trial of acetazolamide therapy could be considered as an initial option in the management of isolated spontaneous CSF rhinorrhea.

Clinical Significance of Long-Term Follow-Up of Children with Posttraumatic Skull Base Fracture.

OBJECTIVE: To assess the incidence of cerebrospinal fluid (CSF) leak and meningitis, and the need for prophylactic antibiotics, antipneumococcal vaccination, and surgical interventions, in children with a skull base fracture. METHODS: We reviewed the records of children with a skull base fracture who were admitted to our tertiary care center between 2009 and 2014. RESULTS: A total of 196 children (153 males), age 1 month to 18 years (mean age, 6 ± 4 years), were hospitalized with skull base fracture. Causes of injury were falls (n = 143), motor vehicle accidents (n = 34), and other (n = 19). Fracture locations were the middle skull base in 112 patients, frontal base in 62, and occipital base in 13. Fifty-four children (28%) had a CSF leak. In 34 of these children (63%), spontaneous resolution occurred within 3 days. Three children underwent surgery on admission owing to a CSF leak from an open wound, 3 underwent CSF diversion by spinal drainage, and 4 (2%) required surgery to repair a dural tear after failure of continuous spinal drainage and acetazolamide treatment. Twenty-eight children (14%) received prophylactic antibiotic therapy, usually due to other injuries, and 11 received pneumococcal vaccination. Two children developed meningitis, and 3 children died. Long-term follow up in 124 children revealed 12 children with delayed hearing loss and 3 with delayed facial paralysis. CONCLUSIONS: This is the largest pediatric series of skull base fractures reporting rates of morbidity and long-term outcomes published to date. The rate of meningitis following skull base fracture in children is low, supporting a policy of not administering prophylactic antibiotics or pneumococcal vaccine. Long-term follow up is important to identify delayed complications.

The Effect of l-Arginine on Dural Healing After Experimentally Induced Dural Defect in a Rat Model.

BACKGROUND: Incomplete repair of the dura mater may result in numerous complications such as cerebrospinal fluid leakage and meningitis. For this reason, accurate repair of the dura mater is essential. In this study, the effect of systemic and local supplementation of l-arginine on dural healing was evaluated. METHODS: Thirty male Wistar rats were used and divided into control, local, and systemic l-arginine groups, with 10 rats in each. In each group, a 5-mm experimental incision was made at the lumbar segment of the dura mater and cerebrospinal fluid leakage was induced. Each group was divided into 2 subgroups and at the end of the first and sixth weeks, the rats were killed and the damaged segments of the dura were separated, histologically evaluated and the dural healing indicators including cell types, granulation tissue formation, collagen deposit, and vascularization were compared between groups. RESULTS: The systematic supplementation of l-arginine showed a significant effect in dural healing compared with the control group. After the first week, granulation formation increased considerably (P < 0.031), and after 6 weeks, collagen deposition and neovascularization were significantly different compared with the control group (P < 0.030; P < 0.009). In comparison between different groups at the end of the first and sixth weeks, maximum changes in healing indicators were observed in the systemic group and the least variations were related to the control group. CONCLUSIONS: The systemic supplementation of l-arginine may accelerate dural healing by increasing the level of granulation tissue formation, collagen deposition, and vascularization.

Randomized clinical trial of acetazolamide administration and/or prone positioning in mitigating wound complications following untethering surgeries.

OBJECTIVE No evidence-based guideline has been approved for the postoperative management of pediatric patients with tethered cord syndrome (TCS). The purpose of this randomized clinical trial was to evaluate the effectiveness of prone positioning and acetazolamide administration on complication rates following spinal cord untethering surgeries. METHODS From October 2012 to February 2015, patients with a primary diagnosis of TCS who were admitted to the Children's Medical Center Hospital of Iran were randomly allocated to 1 of 4 intervention modality groups postoperatively: 1) Group A, acetazolamide administration for 10 days; 2) Group B, prone positioning for 10 days; 3) Group C, acetazolamide administration and prone positioning for 10 days; and 4) Group D, no intervention. CSF leakage, CSF collection, wound dehiscence, operative site infection, and secondary surgical wound repair were considered failure. RESULTS A total of 161 patients were enrolled in this study (Group A, n = 39 [24.2%]; Group B, n = 41 [25.5%]; Group C, n = 39 [24.2%]; and Group D, n = 42 [26.1%]). The overall failure rate was 12.42% (20 patients). Complication rates through pooled analyses were as follows: CSF leakage (n = 9, 5.6%), CSF collection (n = 12, 7.5%), wound dehiscence (n = 2, 1.2%), and infection of operation site (n = 3, 1.9%). Two patients (1.2%) required surgical secondary wound repair due to complications. CSF leakage and collection rates were significantly lower in patients who underwent prone positioning (p = 0.042 and 0.036, respectively). The administration of acetazolamide, either isolated or in combination with prone positioning, not only could not significantly lower the complication rates, but also added the burden of side effects. CONCLUSIONS The current study demonstrates the possible role of prone positioning in mitigating the complication rates subsequent to untethering surgeries. Clinical trial registration no.: NCT01867268 ( clinicaltrials.gov ).

[Acetazolamide in the resolution of cerebrospinal fluid cutaneous fistula after peridural analgesia: case report]. / Acetazolamida en el manejo de la fístula de líquido cefalorraquídeo posterior a analgesia peridural: reporte de caso.

BACKGROUND: Cerebrospinal fluid cutaneous fistula following spinal anesthesia is a serious and rare complication which mandates prompt diagnosis, although the treatment modalities are not well codified. CLINICAL CASE: Female aged 50 with a stage IIB cervical carcinoma; a peridural catheter was passed at lumbar level; three days after surgery, refers severe headache and to corroborate leakage cerebrospinal fluid through the puncture. The prescription was antibiotics and acetazolamide 250mg every 8hours for five days with favorable evolution. CONCLUSION: In this case, management with acetazolamide and suture of the fistula inhibits cerebrospinal fluid leakage without blood patch.

Local vascularized flap reconstruction of the skull base­clinical outcomes and analysis.

OBJECTIVE: The purpose of this study was to describe the effectiveness of local vascularized flaps for the repair of various skull base defects. METHODS: We analyzed a cohort of 138 patients undergoing skull base surgery in a retrospective review of all head and neck surgical oncology cases done at a major tertiary care center between 2005 and 2008. RESULTS: Eighteen patients met our inclusion criteria, requiring local vascularized flap or free graft reconstruction. The mean age of our patients was 39.7 years, with an equal distribution of men and women. The mean follow-up was 16.4 months. Neoplastic causes accounted for the majority of skull base lesions (11/18 cases), followed by traumatic lesions (5/18 cases). Other causes of lesions in our study included encephalocele (1 case), and infection (1 case). The most common location for skull base defects in our study was the anterior skull base (14/18 cases). Other locations included the infratemporal fossa (1 case). The mean size of defect repaired was 4.46 cm, and the mean area was 12.85 cm(2). Repair with local vascularized tissue flaps resulted in a success rate of 87.5%. Moreover, our meningitis and cerebrospinal fluid leak rate was only 11.1% after repair. CONCLUSION: Local vascularized flap utilization in open reconstruction of the skull base has an excellent success rate, with no second donor site morbidity. The success is comparable to free tissue transplant reconstruction and should be in the armamentarium of every neurosurgeon and skull base surgeon. Appropriate incision planning and preoperative evaluation and selection is essential for the success of this type of reconstructive technique.

[Headache can be caused by spontaneous intracranial hypotension].

Spontaneous intracranial hypotension (SIH) is an uncommon condition associated with postural headache, nausea and dizziness. It is believed to be secondary to a dural tear with resultant cerebrospinal fluid (CSF) leak. This is a case report of a pregnant woman (gestational age 31 weeks) who contacted an obstetric department because of severe headache. Pre-eclamp-sia was suspected, but not found. An MRI showed a CSF leak at C1-C2 level and intracranial signs of SIH. The woman was treated with an autologous blood patch and recovered quickly. Focus on subjective symptoms and MRI findings seem to be important in the diagnostic procedure of SIH.