Microanatomy Relevant to Intrathecal Drug Delivery.

This chapter describes the microanatomy of the spinal cord that is relevant to intrathecal drug delivery started with covering of the spinal cord that are pierced to enter the intrathecal space. The dural sac is mostly constituted by the outer layer of dura and the inner layer called arachnoid membrane, which regulates diffusion of drugs into the intrathecal space. The pia matter surrounding the spinal cord is a permeable structure allowing the passage of drugs through intercellular spaces. The relationship between nerve roots, CSF, and subarachnoid catheters determines the passage of an intrathecal catheter which can cause damage to nerve roots and spinal cord. Multiple factors may be involved in the mechanisms of drug diffusion across the membranes of the spinal cord, as well as in their dilution with the CSF, which will lead to the final drug distribution and availability at nerve roots and the spinal cord.

Manejo anestésico del síndrome de Brugada para cesárea: cuando menos es más / Anaesthetic management of C-section in Brugada syndrome: When less is more

El síndrome de Brugada (SBr) es una condición infrecuente y de alto riesgo que rara vez se encuentra en la sala de partos. Las pacientes embarazadas con SBr se benefician de las dosis más bajas posibles de fármacos arritmogénicos, como los anestésicos locales. Sobre la base de esta premisa, el siguiente caso expone cómo un abordaje subaracnoideo podría ser una técnica deseable en los procedimientos de cesárea para pacientes con SBr. El manejo del dolor y la ansiedad es prioritario en esta población específica. La planificación periparto, con una cita previa de anestesiología, y la atención multidisciplinaria en las instalaciones de hospitales terciarios son cruciales para evitar complicaciones

Brugada Syndrome (BrS) is a rare and high risk condition, seldom encountered in the delivery room. Pregnant patients with BrS benefit from the lowest possible doses of arrhythmogenic drugs such as local anesthetics. Based on this premise, the following case report exposes how a subarachnoid approach might be a desirable technique in C-section procedures for BrS patients. Pain and anxiety management are priorities in this specific population. Peri-partum planning, with a previous anesthesiology appointment and mutidisciplinary care in tertiary hospital facilities are crucial to avoid complications

Dispersion in porous media in oscillatory flow between flat plates: applications to intrathecal, periarterial and paraarterial solute transport in the central nervous system.

BACKGROUND: As an alternative to advection, solute transport by shear-augmented dispersion within oscillatory cerebrospinal fluid flow was investigated in small channels representing the basement membranes located between cerebral arterial smooth muscle cells, the paraarterial space surrounding the vessel wall and in large channels modeling the spinal subarachnoid space (SSS). METHODS: Geometries were modeled as two-dimensional. Fully developed flows in the channels were modeled by the Darcy-Brinkman momentum equation and dispersion by the passive transport equation. Scaling of the enhancement of axial dispersion relative to molecular diffusion was developed for regimes of flow including quasi-steady, porous and unsteady, and for regimes of dispersion including diffusive and unsteady. RESULTS: Maximum enhancement occurs when the characteristic time for lateral dispersion is matched to the cycle period. The Darcy-Brinkman model represents the porous media as a continuous flow resistance, and also imposes no-slip boundary conditions at the walls of the channel. Consequently, predicted dispersion is always reduced relative to that of a channel without porous media, except when the flow and dispersion are both unsteady. DISCUSSION/CONCLUSIONS: In the basement membranes, flow and dispersion are both quasi-steady and enhancement of dispersion is small even if lateral dispersion is reduced by the porous media to achieve maximum enhancement. In the paraarterial space, maximum enhancement Rmax = 73,200 has the potential to be significant. In the SSS, the dispersion is unsteady and the flow is in the transition zone between porous and unsteady. Enhancement is 5.8 times that of molecular diffusion, and grows to a maximum of 1.6E+6 when lateral dispersion is increased. The maximum enhancement produces rostral transport time in agreement with experiments.

Characterizing the glymphatic influx by utilizing intracisternal infusion of fluorescently conjugated cadaverine.

AIMS: Accumulating evidence supports that cerebrospinal fluid (CSF) in the subarachnoid space (SAS) could reenter the brain parenchyma via the glymphatic influx. The present study was designed to characterize the detailed pathway of subarachnoid CSF influx by using a novel CSF tracer. MAIN METHODS: Fluorescently conjugated cadaverine (A488-ca), for the first time, was employed to investigate CSF movement in the brain. Following intracisternal infusion of CSF tracers, mice brain was sliced and prepared for fluorescence imaging. Some brain sections were immunostained in order to observe tracer distribution and cellular uptake. KEY FINDINGS: A488-ca moved into the brain parenchyma rapidly, and the influx was time and region dependent. A488-ca entered the mice brain more readily and spread more widely than another commonly used CSF tracer-fluorescently conjugated ovalbumin (OA-45). Furthermore, A488-ca could enter the brain parenchyma either along the paravascular space or across the pial surface. Suppression of glymphatic transport by administration with acetazolamide strikingly reduced the influx of A488-ca. More importantly, relative to OA-45 largely remained in the extracellular space, A488-ca exhibited obvious cellular uptake by astrocytes surrounding the blood vessels and neurons in the cerebral cortex. SIGNIFICANCE: Subarachnoid CSF could flow into the brain parenchyma via the glymphatic influx, in which the transcellular pathway was faithfully traced by intracisternal infusion with fluorescently conjugated cadaverine. These observations extend our comprehension on the glymphatic influx pathway.

Parenchymal Pressure Inconsistency in Different Brain Areas After Kaolin Injection into the Subarachnoid Space of Neonatal Rats.

AIM: To describe the relationship between the parenchymal pressure changes and the development of hydrocephalus in kaolininjected neonatal rats according to cerebral regions and time intervals of developing hydrocephalus. MATERIAL AND METHODS: Neonatal rats aged 2 to 3 days were examined in 5 groups as kaolin frontal "K-F", kaolin parietal "KP", saline frontal "SF-F", saline parietal "SF-P" and control "C", based on the injected material and injection sites. All injections were performed into the cortical subarachnoid space of the right frontal and right parietal regions. The fifth group was injection free. On the 3 < sup > rd < /sup > , 7 < sup > th < /sup > , 15 < sup > th < /sup > , 30 < sup > th < /sup > and 60 < sup > th < /sup > days after injection, parenchymal pressures (PP) of 5-7 rats from each group were measured from different regions. RESULTS: We compared the control group with saline-injected and kaolin-injected groups and found statistically significant parenchymal pressure differences based on regional measurements. In the kaolin groups, the mean PP values were obviously higher than the saline-injected group. Within each kaolin-injected group, the pressure values were variable and inconsistent regarding the parenchymal regions. CONCLUSION: Hydrocephalus cannot be totally explained with existent "bulk-flow" or "hydrodynamic" theories. Although our experimental design was planned to develop hydrocephalus according to the bulk flow theory, our results were more compatible with the hydrodynamic theory. The present comments on the occurrence and pathogenesis of hydrocephalus are still open to debate and may require further comprehensive studies.

Mdivi-1 ameliorates early brain injury after subarachnoid hemorrhage via the suppression of inflammation-related blood-brain barrier disruption and endoplasmic reticulum stress-based apoptosis.

Aberrant modulation of mitochondrial dynamic network, which shifts the balance of fusion and fission towards fission, is involved in brain damage of various neurodegenerative diseases including Parkinson's disease, Huntington's disease and Alzheimer's disease. A recent research has shown that the inhibition of mitochondrial fission alleviates early brain injury after experimental subarachnoid hemorrhage, however, the underlying molecular mechanisms have remained to be elucidated. This study was undertaken to characterize the effects of the inhibition of dynamin-related protein-1 (Drp1, a dominator of mitochondrial fission) on blood-brain barrier (BBB) disruption and neuronal apoptosis following SAH and the potential mechanisms. The endovascular perforation model of SAH was performed in adult male Sprague Dawley rats. The results indicated Mdivi-1(a selective Drp1 inhibitor) reversed the morphologic changes of mitochondria and Drp1 translocation, reduced ROS levels, ameliorated the BBB disruption and brain edema remarkably, decreased the expression of MMP-9 and prevented degradation of tight junction proteins-occludin, claudin-5 and ZO-1. Mdivi-1 administration also inhibited the nuclear translocation of nuclear factor-kappa B (NF-κB), leading to decreased expressions of TNF-ɑ, IL-6 and IL-1ß. Moreover, Mdivi-1 treatment attenuated neuronal cell death and improved neurological outcome. To investigate the underlying mechanisms further, we determined that Mdivi-1 reduced p-PERK, p-eIF2α, CHOP, cleaved caspase-3 and Bax expression as well as increased Bcl-2 expression. Rotenone (a selective inhibitor of mitochondrial complexes I) abolished both the anti-BBB disruption and anti-apoptosis effects of Mdivi-1. In conclusion, these data implied that excessive mitochondrial fission might inhibit mitochondrial complex I to become a cause of oxidative stress in SAH, and the inhibition of Drp1 by Mdivi-1 attenuated early brain injury after SAH probably via the suppression of inflammation-related blood-brain barrier disruption and endoplasmic reticulum stress-based apoptosis.

A numerical investigation of intrathecal isobaric drug dispersion within the cervical subarachnoid space.

Intrathecal drug and gene vector delivery is a procedure to release a solute within the cerebrospinal fluid. This procedure is currently used in clinical practice and shows promise for treatment of several central nervous system pathologies. However, intrathecal delivery protocols and systems are not yet optimized. The aim of this study was to investigate the effects of injection parameters on solute distribution within the cervical subarachnoid space using a numerical platform. We developed a numerical model based on a patient-specific three dimensional geometry of the cervical subarachnoid space with idealized dorsal and ventral nerve roots and denticulate ligament anatomy. We considered the drug as massless particles within the flow field and with similar properties as the CSF, and we analyzed the effects of anatomy, catheter position, angle and injection flow rate on solute distribution within the cerebrospinal fluid by performing a series of numerical simulations. Results were compared quantitatively in terms of drug peak concentration, spread, accumulation rate and appearance instant over 15 seconds following the injection. Results indicated that solute distribution within the cervical spine was altered by all parameters investigated within the time range analyzed following the injection. The presence of spinal cord nerve roots and denticulate ligaments increased drug spread by 60% compared to simulations without these anatomical features. Catheter position and angle were both found to alter spread rate up to 86%, and catheter flow rate altered drug peak concentration up to 78%. The presented numerical platform fills a first gap towards the realization of a tool to parametrically assess and optimize intrathecal drug and gene vector delivery protocols and systems. Further investigation is needed to analyze drug spread over a longer clinically relevant time frame.

A modified procedure for lumbar intrathecal catheterization in rats.

OBJECTIVES: Intrathecal catheterization and drug delivery in rats has always been a very important method for neuroscience and pain research. Although the technique has been continually improved since the first report, the experience gained over the years suggested that some defects remained unsolved. On the basis of modification of the standard epidural needle, lumbar needle, and intrathecal tube, we aimed to develop a simple and practical technique for intrathecal catheterization, which was similar to the 'needle-through-needle technique' used in combined spinal-epidural (CSE) anesthesia. METHODS: For comparison, rats received intrathecal catheterization via either laminectomy at L3-4 (control group) or our modified method (modification group). The operation time, success rate, and the incidence of postoperative complication were recorded. Thermal paw withdrawal latency, mechanical paw withdrawal threshold, Rota-rod, and body weight were measured on pre-operative day 1 and postoperative day 1-3, 5, 7, 14, 21, respectively. RESULTS: Compared with control group, our modified method was more practical to grasp and could bring about higher success rate, firmer catheters immobility, less weight loss, and minimal mortality. There was no difference between the two groups in spinal cord injury, hematoma, location of lumbar enlargement, and lateral location of the catheters tip. The procedure itself did not interfere with behavioral tests and motor coordination. CONCLUSION: We suggest that the modified method of intrathecal catheterization is well suitable for long-term behavior and pharmacology research on spinal cord.

Does Ondansetron Modify Sympathectomy Due to Subarachnoid Anesthesia?: Meta-analysis, Meta-regression, and Trial Sequential Analysis.

BACKGROUND: Disagreement among many underpowered studies has led to an equivocal understanding of the efficacy of the 5-HT3 antagonist ondansetron in preventing the consequences of sympathectomy after subarachnoid anesthesia. The authors assessed the efficacy of ondansetron with respect to the overall quality and statistical power of the meta-analyses. METHODS: The authors used a standard and a newer method of meta-analysis, trial sequential analysis (TSA), to estimate adjusted CIs based on how much information has been accrued. They also used random-effects meta-analyses techniques, small trial bias assessment, selection models, sensitivity analyses, and the Grading of Recommendations on Assessment, Development, and Evaluation system. These results from the aforementioned techniques were compared, and importance of consideration of these factors was discussed. RESULTS: Fourteen randomized placebo-controlled trials (1,045 subjects) were identified and analyzed. By using conventional meta-analyses, the authors determined that ondansetron was associated with reduction in the incidence of hypotension (relative risk = 0.62 [95% CI, 0.46 to 0.83], P = 0.001; TSA-adjusted CI, 0.34 to 1.12; I = 60%, P = 0.002) and bradycardia (relative risk = 0.44 [95% CI, 0.26 to 0.73], P = 0.001; TSA-adjusted CI, 0.05 to 3.85; I = 0%, P = 0.84). However, the authors found indications of bias among these trials. TSAs demonstrated that the meta-analysis lacked adequate information size and did not achieve statistical significance when adjusted for sparse data and repetitive testing. The Grading of Recommendations on Assessment, Development, and Evaluation system showed that the results had low to very low quality of evidence. CONCLUSIONS: The analyses fail to confirm evidence that ondansetron reduces the incidence of hypotension and bradycardia after subarachnoid anesthesia due to the risk of bias and information sizes less than the required. As results from meta-analysis are given significant weight, it is important to carefully evaluate the quality of the evidence that is input.

Clinical and Histological Effects of the Intrathecal Administration of a Single Dose of Dexmedetomidine in Rabbits.

BACKGROUND: There is experimental evidence that dexmedetomidine has neuroprotective effects. So, it could be expected that its intrathecal or epidural administration presents no harm. However, whether dexmedetomidine is neurotoxic to the spinal cord remains to be fully elucidated. OBJECTIVE: To evaluate the effect of preservative-free dexmedetomidine administered as a subarachnoid single injection on the spinal cord and meninges of rabbits. STUDY DESIGN: Research article. SETTING: Experimental research laboratory. METHODS: Twenty young adult female rabbits, each weighing between 3200 and 4900 g, and having a spine length between 36 and 40 cm, were divided by lot into 2 groups (G): 0.9% saline in G1 and preservative-free dexmedetomidine in G2 (dose of 10 µg). After intravenous anesthesia with ketamine and xylazine, the subarachnoid space was punctured at S1-S2 under ultrasound guidance, and a random 5 µl.cm-1 of spinal length (0.2 mL) of solution (saline or dexmedetomidine) was injected. The animals remained in captivity for 21 days under medical observation and were sacrificed by decapitation. The lumbosacral spinal cord portion was removed for immunohistochemistry to assess the glial fibrillary acidic protein (GFAP), and histology was assessed using hematoxylin and eosin (HE) stain. RESULTS: None of the animals had impaired motor function or decreased nociception during the period of clinical observation. None of the animals from the control group showed signs of injuries to meninges. In the dexmedetomidine group, however, 9 animals presented with signs of meningeal injury. The main histological changes observed were areas with meningeal thickening and lymphoplasmocitary infiltration in the pia-mater and arachnoid. Further histological examination also revealed adherence areas among the pia and arachnoid. There was no signal of injury in neural tissue in any animal of both groups. LIMITATIONS: Evaluation of the possible analgesic effects of the intrathecal dexmedetomidine was not performed. CONCLUSION: On the basis of the present results, dexmedetomidine administered in the subarachnoid space in a single dose of 10 µg is capable of producing histological changes over the meninges of rabbits.

The blood-brain barrier and nasal drug delivery to the central nervous system.

BACKGROUND: The blood-brain barrier (BBB) is a highly efficient system that separates the central nervous system (CNS) from general circulation and promotes selective transport of molecules that are essential for brain function. However, it also limits the distribution of systemically administered therapeutics to the brain; therefore, there is a restricted number of drugs available for the treatment of brain disorders. Several drug-targeting strategies have been developed to attempt to bypass the BBB, but none has proved sufficiently effective in reaching the brain. METHODS: The objective of this study is to generally review these strategies of drug administration to the CNS. RESULTS: Noninvasive methods of drug delivery, such as chemical and biologic transport systems, do not represent a feasible platform, whereas for most drugs, it is still not possible to achieve therapeutic levels within the brain tissue after intravenous or oral administration, and the use of higher potency or more concentrated doses may cause serious toxic side effects. Direct intrathecal drug delivery through a catheter into the CNS also presents several problems. Intranasal drug delivery is a potential alternative method due to the direct transport into the cerebrospinal fluid (CSF) compartment along the olfactory pathway, but the study's conclusions are controversial. An endoscopic intranasal surgical procedure using established skull base surgery reconstruction techniques based on the use of a nasal mucosa surgical flap as the only obstacle between the nose and the subarachnoid space has appeared as a potential solution to increase the absorption of intranasal drugs to the CNS. CONCLUSION: Despite extensive efforts to develop new techniques to cross the BBB, none has proved sufficiently effective in reaching the brain, whereas minimizing adverse effects and the endoscopic mucosal grafting technique offers new potential promise.

Intrathecal treatment of anti-N-Methyl-D-aspartate receptor encephalitis in children.

Anti-NDMA receptor (NMDAR) encephalitis is an auto-immune condition. There is no uniformly agreed treatment strategy for the disorder in children. We report the use of intrathecal treatment with methotrexate and methylprednisolone in three children (one male, two females, age 10y, 11y, and 14y) with anti-NMDAR encephalitis, who did not respond to steroids, plasmapheresis, or rituximab. There was significant clinical improvement and stabilization of the anti-NMDAR antibody titers in cerebrospinal fluid (CSF) and blood in two patients. In the third patient, although anti-NMDAR antibody titers in CSF decreased, clinical recovery was less satisfactory. Intrathecal treatment with methotrexate and methylprednisolone seems to be a promising alternative treatment for some paediatric cases of resistant anti-NMDAR encephalitis.

Intracisternal injection of palmitoylethanolamide inhibits the peripheral nociceptive evoked responses of dorsal horn wide dynamic range neurons.

Endogenous palmitoylethanolamide (PEA) has a key role in pain modulation. Central or peripheral PEA can reduce nociceptive behavior, but no study has yet reported a descending inhibitory effect on the neuronal nociceptive activity of Aδ- and C-fibers. This study shows that intracisternal PEA inhibits the peripheral nociceptive responses of dorsal horn wide dynamic range cells (i.e., inhibition of Aδ- and C-fibers), an effect blocked by spinal methiothepin. These results suggest that a descending analgesic mechanism mediated by the serotonergic system could be activated by central PEA.

The effects on sensorial block, motor block, and haemodynamics of levobupivacaine at different temperatures applied in the subarachnoid space.

AIM: To evaluate the effects of 0.5% levobupivacaine at 37 °C preheated from room temperature, on sensorial block, motor block, and haemodynamics in patients undergoing transurethral prostate resection (TUR-P). MATERIAL AND METHOD: The patients were randomly allocated to two groups: Group I patients were injected with 3 mL 0.5% levobupivacaine solution which had been kept at room temperature for at least 24 hours and Group II patients were injected with 3 mL 0.5% levobupivacaine solution which had been kept at 37 °C for at least 24 hours. The patients were examined in terms of sensorial block, motor block, haemodynamic profile, and incidence of side effects. RESULTS: No significant difference was found between the groups in terms of demographic data. The time to reach T 10 sensory block and the time of starting motor block were found to be significantly shorter in Group II. The duration of sensory block over T 10 and T 6, the duration of L 1 regression, the duration of the sensory block, and the regression time of the motor blocks from 3 to 2 were found to be longer in Group II. CONCLUSION: The use of 0.5% levobupivacaine spinal anaesthesia heated to 37 °C accelerated the start of sensory and motor block.

Cortical grey matter demyelination can be induced by elevated pro-inflammatory cytokines in the subarachnoid space of MOG-immunized rats.

A substantial proportion of cases with secondary progressive multiple sclerosis have extensive inflammation in the leptomeninges that is associated with increased subpial demyelination, neuronal loss and an exacerbated disease course. However, the mechanisms underlying this extensive subpial pathology are poorly understood. We hypothesize that pro-inflammatory cytokine production within the meninges may be a key to this process. Post-mortem cerebrospinal fluid and dissected cerebral leptomeningeal tissue from patients with multiple sclerosis were used to study the presence of tumour necrosis factor and interferon gamma protein and messenger RNA levels. A novel model of subpial cortical grey matter demyelination was set up in Dark Agouti rats and analysed using quantitative immunohistochemistry. Increased expression of the pro-inflammatory cytokines tumour necrosis factor and interferon gamma was found in the meninges of cases with secondary progressive multiple sclerosis exhibiting tertiary lymphoid-like structures. Injection of tumour necrosis factor and interferon gamma into the subarachnoid space of female Dark Agouti rats pre-immunized with a subclinical dose of myelin oligodendrocyte glycoprotein mimicked the pathology seen in multiple sclerosis, including infiltration of lymphocytes (CD4+ and CD8+ T cells and CD79+ B cells) into the meninges and extensive subpial demyelination. Extensive microglial/macrophage activation was present in a gradient from the pial surface to deeper cortical layers. Demyelination did not occur in control animals immunized with incomplete Freund's adjuvant and injected with cytokines. These results support the hypothesis that pro-inflammatory molecules produced in the meninges play a major role in cortical demyelination in multiple sclerosis, but also emphasize the involvement of an anti-myelin immune response.

The influence of spinal flexion in the lateral decubitus position on the unilaterality of spinal anesthesia.

BACKGROUND: For unilateral spinal block, local anesthetics should affect the spinal nerves of 1 side. With full flexion of the spine, the sunken cauda equina becomes tightened and is suspended in the middle of the subarachnoid space. We performed this study to assess whether spinal flexion facilitates unilateral spinal anesthesia. METHODS: Hyperbaric bupivacaine (8 mg) was administered at the L3-4 interspace through a 25-gauge Quincke needle at a rate of 0.02 mL/s. Patients were randomly allocated to group F (with full spinal flexion) or group N (the hips and back straightened). After maintaining the lateral position for 15 minutes with or without spinal flexion, patients were gently returned to the supine position. Spinal blockade was assessed by loss of pinprick sensation and the modified Bromage motor scale. RESULTS: While the lateral position was maintained, sensory block was noted on the nondependent side in 14 of 16 patients in group N (87.5%) but only in 1 of 16 patients in group F (6.3%) (P < 0.001). The median level of sensory block in group N was L5 on the nondependent side just before turning to the supine position. When patients were returned to the supine position, sensory blockade on the nondependent side was noted in all group N patients (100%) and 15 group F patients (93.7%). The sensory level on the nondependent side between group N and group F were similar after turning supine. CONCLUSIONS: Strict unilateral sensory block was not achieved even after lateral decubitus positioning with spinal flexion, when 8 mg hyperbaric bupivacaine was administered manually at a conventionally slow rate through a beveled spinal needle. However, maintaining flexion of the spinal column during lateral decubitus positioning altered the initial onset of sensory block with respect to laterality.

Injection of ropivacaine into the subarachnoid changes the ultrastructure and proteome of the rat spinal cord.

1. In the present study, we investigated the impact of 1.0% ropivacaine on the ultrastructure and proteome of the rat spinal cord. 2. Rats received three injections (90-min intervals, 0.2 mL/kg) of 0.9% NaCl, 0.5% ropivacaine or 1.0% ropivacaine via an implanted intrathecal catheter. Transmission electron microscopy was performed to exam the ultrastructure of the spinal cord. Two-dimensional electrophoresis followed by mass spectrometry identification were carried out to investigate the proteome. 3. In the rats administered 1.0% ropivacaine, deformed organelles, detached myelinated nerve fiber layer, and incomplete inner and outer shaft membranes were observed in the spinal cord and posterior root shrunken nuclei. Furthermore, in the rat spinal cord 1.0% ropivacaine induced the down-regulation of voltage-dependent anion channel 2 (VDAC2) and mitochondrial pyruvate dehydrogenase subunit alpha (ODPA), the upregulation of myelin basic protein (MBP), the disappearance of myelin transcription factor 1 (MYT1) and the appearance of heat shock protein 25 (HSP25). Little change was observed in the 0.5% ropivacaine or control groups. 4. Our results suggest that 1.0% ropivacaine treatment led to neurotoxicity, as shown by ultrastructural and proteomic changes in the rat spinal cord. Specific proteins were identified that are implicated in 1.0% ropivacaine-induced neurotoxicity.

Percutaneous treatment of subarachnoid-pleural fistula with Onyx.

Subarachnoid-pleural fistula is a well-described complication after anterior surgery for thoracic disc herniation, but is difficult to treat by means of traditional chest and lumbar drains due to interference by positive ventilation pressures that may keep the fistula open and prevent proper closure. Current treatment strategies include surgical repair, which is technically challenging, and noninvasive positive pressure ventilation, which can take several weeks to be effective. In this report, the authors describe a novel treatment for subarachnoid-pleural fistula using percutaneous obliteration with Onyx. Surgery for removal of a T7-8 disc herniation associated with ossification of the posterior longitudinal ligament was performed in a 56-year-old woman via an anterior transthoracic transpleural approach. Ten days after surgery, she presented with diplopia due to a subarachnoid-pleural fistula that was confirmed by CT myelography. Percutaneous injection of Onyx was performed under local anesthesia. Postprocedure CT showed complete obliteration of the fistula with no adverse events. A CT scan obtained 1 month later showed complete resolution of the pleural effusion. Neurological examination at 3 months postsurgery was normal. Clinical and radiological follow-up at 1 year showed complete recovery and no sign of fistula recurrence. Percutaneous treatment for subarachnoid-pleural fistula is an easy, safe, and effective strategy and can therefore be proposed as a first-line option for this challenging complication.

[Usefulness of subarachnoid phenol-glycerin block therapy for enabling cancer patients with refractory anal pain to proceed to home-based care].

In recent years, the number of cancer patients and their families desiring palliative home-based care in Japan has increased. Subarachnoid phenol-glycerin block therapy is offered to relieve refractory anal pain in cancer patients, and to reduce the side effects of systemic administration of opioids, such as drowsiness. The effects of phenol-glycerin, which is a medicine used for neurodegenerative diseases, lasted for 1 week to 3 months. Eight patients with this manipulation showed a significant improvement in their pain level, calculated by the numerical rating scale(NRS). Five of these patients could proceed to homebased care. It is important to establish common guidelines for the management of phenol-glycerin. The participation of pharmacists in the palliative care team will contribute to further growth of home-based care.