Comparison Between Ventricular and Spinal Infusion Tests in Suspected Normal Pressure Hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) is an often-overlooked or misdiagnosed brain disorder characterized by overt ventriculomegaly and associated with gait disturbances, cognitive impairment, and urinary incontinence. If correctly diagnosed, it is considered the only form of dementia treatable with surgery, namely through a ventriculoperitoneal or ventriculoatrial shunt with programmable valves.Among the 856 spinal and ventricular infusion tests performed from 2001 to 2017 at our institution, we analyzed 106 cases selected for suspected normotensive hydrocephalus. In all cases, Intracranial Elastance Index (IEI) and outflow resistance (Rout) values were calculated: 52 of these patients underwent Spinal Katzman Test (SKT), and the remaining 54 underwent an intraventricular infusion test (IVKT). Of the 40 patients in the SKT group with pathological elastance (71%), 17 also had a Rout >12 mmHg and 23 a Rout <12 mmHg. Of the 50 patients in the IVKT group with pathological elastance (92%), 38 also had a Rout >12 mmHg and 12 a Rout <12 mmHg.IVKT and SKT to date represent two useful tools in the diagnosis of normal pressure hydrocephalus. Despite being more invasive, IVKT, including both the intracranial elastance index (IEI) and Rout analysis, could be considered more reliable than SKT and therefore could be reserved for the most controversial cases.

Evaluation of Therapies for Peripheral and Neuraxial Opioid-induced Pruritus based on Molecular and Cellular Discoveries.

Opioids are a mainstay of treatment for pain worldwide. Pruritus, a common side effect of opioids, is a patient dissatisfier that limits their use in many clinical settings. Both parenteral and neuraxial administration of opioids frequently evoke pruritus. The ability of opioids to suppress pain while causing itch continues to perplex clinicians and researchers alike. Several mechanisms have been proposed to explain how opioids can give rise to pruritus, but specific knowledge gaps perpetuate debate. This review summarizes the clinical burden of opioid-induced pruritus and emphasizes recent discoveries of peripheral and central mechanisms for opioid-induced pruritus, particularly with respect to scientific and conceptual advances in spinal cord circuitry and mast cell biology. The mechanisms and effectiveness of existing medications used for clinical management of pruritus will be evaluated, and we will highlight the emerging preclinical utility of selective κ-opioid receptor agonists, such as nalfurafine, for the management of opioid-induced pruritus.

Treatment and Management of Loin Pain Hematuria Syndrome.

PURPOSE OF REVIEW: Loin pain hematuria syndrome (LPHS) is rare and seldom diagnosed, yet it has a particularly significant impact on those affected. This is a review of the latest and seminal evidence of the pathophysiology and diagnosis of LPHS and presents the typical clinical presentation and treatment options available. RECENT FINDINGS: LPHS is typically found in young women with characteristic symptoms, including severe recurrent flank pain and gross or microscopic hematuria. The majority of patients will experience crippling pain for many years without effective therapy, often requiring frequent use of narcotic medication. However, the lack of conclusive pathophysiology, in conjunction with the rarity of LPHS, has prohibited the development and trial of definitive treatment options. Nevertheless, in order to combat this rare but severe disease, management strategies have continued to evolve, ranging from conservative measures to invasive procedures. This review presents an overview of the current hypotheses on the pathophysiology of LPHS in addition to summarizing the management strategies that have been utilized. Only 30% of LPHS patients will experience spontaneous resolution, whereas the majority will continue to face chronic, crippling pain. Several methods of treatment, including invasive and non-invasive, may provide an improved outcome to these patients. Treatment should be individually tailored and multi-disciplinary in nature. Further research is required to further elucidate the pathophysiology and develop new, specific, treatment options.

Comparison of Programmed Intermittent Epidural Boluses With Continuous Epidural Infusion for the Maintenance of Labor Analgesia: A Randomized, Controlled, Double-Blind Study.

BACKGROUND: Programmed intermittent epidural boluses may improve the spread of local anesthetics compared to continuous epidural infusion, improving labor analgesia and obstetric outcomes. However, there are limited data from studies using commercially available pumps capable of coadministering programmed intermittent epidural boluses or continuous epidural infusion with patient-controlled epidural analgesia. Therefore, we performed this prospective, randomized, double-blind study to compare the impact of programmed intermittent epidural boluses versus continuous epidural infusion on labor analgesia and maternal/neonatal outcomes. We hypothesized that programmed intermittent epidural boluses will result in lower patient-controlled epidural analgesia consumption compared to that with continuous epidural infusion. METHODS: Following standardized initiation of epidural labor analgesia, women were randomized to receive 0.1% ropivacaine with 2 µg/mL fentanyl as 6-mL programmed intermittent epidural boluses every 45 minutes or continuous epidural infusion at 8 mL/h in a double-blind fashion with similar patient-controlled epidural analgesia settings in both groups. The primary outcome was patient-controlled epidural analgesia consumption per hour. Secondary outcomes included a need for physician interventions, patterns of patient-controlled epidural analgesia use, motor blockade, number of patients who developed hypotension, pain scores, duration of second stage of labor, mode of delivery, and maternal satisfaction. RESULTS: We included 120 patients (61 in programmed intermittent epidural boluses group and 59 in continuous epidural infusion group) in the analysis. The median (interquartile range) patient-controlled epidural analgesia volume consumed per hour was not significantly different between the groups: 4.5 mL/h (3.0-8.6 mL/h) for the continuous epidural infusion group and 4.0 mL/h (2.2-7.1 mL/h) for the programmed intermittent epidural boluses group (P = .17). The Hodges-Lehmann location shift estimate of the difference (95% CI) from the continuous epidural infusion to the programmed intermittent epidural boluses group is 0.9 mL/h (-0.4 to 2.2 mL/h). There were also no significant differences between the groups in any of the secondary outcomes except for higher median (interquartile range) patient-controlled epidural analgesia attempts per given ratio per hour in the programmed intermittent epidural bolus group (0.17 [0.10-0.30] vs 0.12 [0.08-0.18]; P = .03) and more motor block in the continuous epidural infusion group (those with Bromage score <5, 27.5% vs 50.0%; P = .03). CONCLUSIONS: Under the conditions of our study, we did not find improved outcomes with programmed intermittent epidural boluses compared to continuous epidural infusion except for less motor block with programmed intermittent epidural boluses. Future studies should assess whether smaller but clinically important differences exist and evaluate different parameters of programmed intermittent epidural boluses to optimize analgesia and outcomes with this mode of analgesia.

The Rate of Infectious Complications After Intrathecal Drug Delivery System Implant for Cancer-Related Pain Is Low Despite Frequent Concurrent Anticancer Treatment or Leukopenia.

BACKGROUND: The efficacy of intrathecal drug delivery (IDD) for cancer-related pain is well established. Cancer therapies are often associated with immunosuppression and increased risk of infection, and the rate of infection after intrathecal drug delivery system (IDDS) implant in cancer patients has been reported as 2.4%-6.3%. Our objective is to report on the rate of surgical site infections (SSI) in patients implanted with IDDS for cancer-related pain and to provide a data-driven discussion on the relationship between antineoplastic treatment, leukopenia, and other clinical or demographic characteristics and SSI. METHODS: Following local institutional review board approval, we conducted a retrospective chart review of IDDS implants from May 2014 through December 2018. Data collected included demographic data, health status, prophylactic antibiotic administration, surgery duration, presence of leukopenia (white blood cell [WBC] count of <4.0 K/µL) or moderate neutropenia (absolute neutrophil count [ANC] of <1000/µL) within the 30 days before IDDS implant, and details of antineoplastic treatment or systemic corticosteroid use in the perioperative period. This information was assessed in relation to SSI incidence up to 6 months following implant. RESULTS: Two hundred seventeen IDDS implants were identified. A majority of patients (79.3%) received ≥1 form of antineoplastic therapy within 30 days before or after implant, and 42.4% received multiple forms of antineoplastic therapy. Therapies included chemotherapy in 46.5%, immunotherapy in 28.6%, systemic steroids in 32.3%, and radiation therapy in 28.1%. One-quarter of patients (25.8%) were leukopenic within 30 days before implant, with 3.2% having moderate neutropenia. There were 2 infectious complications representing an infection rate of 0.9% (95% CI, 0.1%-3.3%), with limited shared characteristics between those experiencing SSI. CONCLUSIONS: SSI risk after IDDS placement for cancer pain is low, despite frequent concurrent antineoplastic therapy and leukopenia in the perioperative period. Concomitant cancer therapies should not be a barrier to the implementation of IDD for cancer pain.

Efficacy of continuous epidural infusion with epidural electric stimulation compared to that of conventional continuous epidural infusion for acute herpes zoster management: a retrospective study.

BACKGROUND: Continuous epidural infusions are commonly used in clinical settings to reduce the likelihood of transition to postherpetic neuralgia via pain control. The purpose of this study was to compare the efficacy of conventional continuous epidural infusion to that of continuous epidural infusion in which the catheter is guided by electric stimulation to areas with neurological damage for the treatment of zoster-related pain and prevention of postherpetic neuralgia. METHODS: We analyzed the medical records of 114 patients in this study. The patients were divided into two groups: contrast (conventional continuous epidural infusion) and stimulation (continuous epidural infusion with epidural electric stimulation). In the contrast group, the position of the epidural catheter was confirmed using contrast medium alone, whereas in the stimulation group, the site of herpes zoster infection was identified through electric stimulation using a guidewire in the catheter. Clinical efficacy was assessed using a numerical rating scale (pain score) up to 6 months after the procedures. We compared the percentage of patients who showed complete remission (pain score less than 2 and no further medication) in each group. We also investigated whether the patients required additional interventional treatment due to insufficient pain control during the 6-month follow-up period after each procedure. RESULTS: After adjusting for confounding variables, the pain score was significantly lower in the stimulation group than in the contrast group for 6 months after the procedure. After adjustment, the odds of complete remission were 1.9-times higher in the stimulation group than in the contrast group (95% confidence interval [CI]: 0.81-4.44, P = 0.14). Patients in the contrast group were significantly more likely to require other interventions within 6 months of the procedure than patients in the stimulation group (odds ratio: 3.62, 95% CI: 1.17-11.19, P = 0.03). CONCLUSION: Epidural drug administration to specific spinal segments using electric stimulation catheters may be more helpful than conventional continuous epidural infusion for improving pain and preventing postherpetic neuralgia in the acute phase of herpes zoster.

Spinal glial cell line-derived neurotrophic factor infusion reverses reduction of Kv4.1-mediated A-type potassium currents of injured myelinated primary afferent neurons in a neuropathic pain model.

High frequency spontaneous activity in injured primary afferents has been proposed as a pathological mechanism of neuropathic pain following nerve injury. Although spinal infusion of glial cell line-derived neurotrophic factor reduces the activity of injured myelinated A-fiber neurons after fifth lumbar (L5) spinal nerve ligation in rats, the implicated molecular mechanism remains undetermined. The fast-inactivating transient A-type potassium current (IA) is an important determinant of neuronal excitability, and five voltage-gated potassium channel (Kv) alpha-subunits, Kv1.4, Kv3.4, Kv4.1, Kv4.2, and Kv4.3, display IA in heterologous expression systems. Here, we examined the effect of spinal glial cell line-derived neurotrophic factor infusion on IA and the expression of these five Kv mRNAs in injured A-fiber neurons using the in vitro patch clamp technique and in situ hybridization histochemistry. Glial cell line-derived neurotrophic factor infusion reversed axotomy-induced reduction of the rheobase, elongation of first spike duration, and depolarization of the resting membrane potential. L5 spinal nerve ligation significantly reduced the current density of IA and glial cell line-derived neurotrophic factor treatment reversed the reduction. Among the examined Kv mRNAs, only the change in Kv4.1-expression was parallel with the change in IA after spinal nerve ligation and glial cell line-derived neurotrophic factor treatment. These findings suggest that glial cell line-derived neurotrophic factor should reduce the hyperexcitability of injured A-fiber primary afferents by IA recurrence. Among the five IA-related Kv channels, Kv4.1 should be a key channel, which account for this IA recurrence.

Mast Cell Degranulation and Fibroblast Activation in the Morphine-induced Spinal Mass: Role of Mas-related G Protein-coupled Receptor Signaling.

BACKGROUND: As the meningeally derived, fibroblast-rich, mass-produced by intrathecal morphine infusion is not produced by all opiates, but reduced by mast cell stabilizers, the authors hypothesized a role for meningeal mast cell/fibroblast activation. Using the guinea pig, the authors asked: (1) Are intrathecal morphine masses blocked by opiate antagonism?; (2) Do opioid agonists not producing mast cell degranulation or fibroblast activation produce masses?; and (3) Do masses covary with Mas-related G protein-coupled receptor signaling thought to mediate mast cell degranulation? METHODS: In adult male guinea pigs (N = 66), lumbar intrathecal catheters connected to osmotic minipumps (14 days; 0.5 µl/h) were placed to deliver saline or equianalgesic concentrations of morphine sulfate (33 nmol/h), 2',6'-dimethyl tyrosine-(Tyr-D-Arg-Phe-Lys-NH2) (abbreviated as DMT-DALDA; 10 pmol/h; µ agonist) or PZM21 (27 nmol/h; biased µ agonist). A second pump delivered subcutaneous naltrexone (25 µg/h) in some animals. After 14 to 16 days, animals were anesthetized and perfusion-fixed. Drug effects on degranulation of human cultured mast cells, mouse embryonic fibroblast activation/migration/collagen formation, and Mas-related G protein-coupled receptor activation (PRESTO-Tango assays) were determined. RESULTS: Intrathecal infusion of morphine, DMT-DALDA or PZM21, but not saline, comparably increased thermal thresholds for 7 days. Spinal masses proximal to catheter tip, composed of fibroblast/collagen type I (median: interquartile range, 0 to 4 scale), were produced by morphine (2.3: 2.0 to 3.5) and morphine plus naltrexone (2.5: 1.4 to 3.1), but not vehicle (1.2: 1.1 to 1.5), DMT-DALDA (1.0: 0.6 to 1.3), or PZM21 (0.5: 0.4 to 0.8). Morphine in a naloxone-insensitive fashion, but not PZM21 or DMT-DALDA, resulted in mast cell degranulation and fibroblast proliferation/collagen formation. Morphine-induced fibroblast proliferation, as mast cell degranulation, is blocked by cromolyn. Mas-related G protein-coupled receptor activation was produced by morphine and TAN67 (∂-opioid agonist), but not by PZM21, TRV130 (mu biased ligand), or DMT-DALDA. CONCLUSIONS: Opiates that activate Mas-related G protein-coupled receptor will degranulate mast cells, activate fibroblasts, and result in intrathecal mass formation. Results suggest a mechanistically rational path forward to safer intrathecal opioid therapeutics.

Do Epidural Catheter Size and Flow Rate Affect Bolus Injection Pressure in Different Programmed Intermittent Epidural Bolus Regimens? An In Vitro Study.

BACKGROUND: The optimal programmed intermittent epidural bolus regimen for labor analgesia remains unknown. Some studies indicate that better drug spread in the epidural space results from greater injection pressure; however, there is a lack of data regarding the maximum pressure generated by epidural bolus injection using different catheters and flow rates. METHODS: We evaluated the flow and pressure characteristics of 11 commonly used epidural catheters combined with 3 different infusion pumps that deliver epidural infusions according to the programmed intermittent epidural bolus regimen. Pressure changes were measured over time at flow rates of 100, 250, and 400 mL·hour and with a bolus volume of 10 mL. To account for repeated measures, linear mixed models were used. Features were selected with a backward stepwise procedure continued until only statistically significant variables were left in the model. RESULTS: We performed 660 measurements. The mean maximal pressure generated during bolus injection ranged from 86 to 863 mm Hg for different flow rates and catheter designs. The interaction between flow rate and catheter gauge resulted in 1.31, 1.65, and 2.00 mm Hg of pressure increase for 18G, 19G, and 20G catheters, respectively, per 1 mL·hour of increased flow rate (P< .001). Analyses including wire-reinforced catheters revealed a 1.16, 1.76, and 2.36 mm Hg pressure increase for 18G, 19G, and 20G catheters, respectively, per 1 mL·hour of increased flow rate (P< .001). In some cases, it triggered the occlusion pump alarm. CONCLUSIONS: Significant differences were observed in the in vitro maximum pressure value among the various catheter and flow rate combinations with a higher pressure value for wire-reinforced catheters used in the study. The optimal flow rate and epidural catheter combination may allow for delivery of the bolus with high flow rate without triggering the occlusion alarm.

Intrathecal Baclofen Trial Before Device Implantation: 12-Year Experience With Continuous Administration.

OBJECTIVE: To report our experience using continuous intrathecal baclofen (ITB) administration prior to a possible ITB device implantation. DESIGN: Retrospective open label study. Mean duration of follow-up 64 months. SETTING: Primary-care and referral center, ambulatory and hospitalized care. PARTICIPANTS: Patients (N=116) undergoing continuous ITB trials between 2006 and 2017. INTERVENTIONS: Continuous application of baclofen via a temporary intrathecal catheter connected to an external pump. MAIN OUTCOME MEASURES: Assessment of the modified Ashworth Scale and range of movement prior versus end of ITB trial. According to the Barthel Index, definition of high-level patients (60-100 scoring points) and low-level patients (0-55 scoring points). Calculation of the Rivermead Mobility Index in high-level patients prior versus end of ITB trial. Evaluation of occurring adverse events. RESULTS: A total of 119 ITB trials were performed in 116 patients (78 men, mean age 41±16), 113 patients completed the trials (31 of 113 high level, 82 of 113 low level). The median modified Ashworth scale improved from 4 (interquartile range [IQR] 3-4) to 2 (IQR 1-2; P≤.001), the range of movement from 2 (IQR 1-3) to 3 (IQR 3-3; P≤.001). The Rivermead Mobility Index increased from 9 (IQR 6-12) to 10 (IQR 7-12.5; P=.004) in high-level patients. Eighty-eight out of 113 patients (78%) were appropriate candidates for ITB device surgery, 75 of 88 (85%) proceeded to an implantation. A total of 69 adverse events occurred in 57 of 119 trials (48%), 37 of 69 (54%) were drug related, 32 of 69 (46%) were procedure related, and 42 of 69 (61%) were minor. The ITB device was implanted in 69 of 75 patients (92%) at last follow-up. CONCLUSIONS: Continuous administration of ITB is an effective and useful alternative to ITB bolus application during ITB screening period. Half of the patients experienced adverse events; the majority were minor events.

Effect of Intrathecal Baclofen on Pain and Quality of Life in Poststroke Spasticity.

Background and Purpose- Intrathecal baclofen (ITB) is an effective treatment for managing patients with severe poststroke spasticity, who can experience continued pain and decline in their quality of life (QoL). SISTERS (Spasticity In Stroke-Randomized Study) was a randomized, controlled, open-label, multicenter, phase 4 study to evaluate ITB therapy versus conventional medical management (CMM) with oral antispastic medications for treatment of poststroke spasticity. Methods- Poststroke patients with spasticity in ≥2 extremities and an Ashworth Scale score of ≥3 in ≥2 affected lower extremity muscle groups were randomized (1:1) to ITB (N=31) or CMM (N=29). Both treatment arms received physiotherapy throughout. The primary outcome was the change in average Ashworth Scale score in the lower extremities of the affected side from baseline to month 6. Here, we report results for secondary outcomes: pain via the Numeric Pain Rating Scale, health-related QoL by the EuroQol-5 dimensional 3 level utility score and health status visual analog scale score, stroke-specific QoL, and patient satisfaction. Analyses were performed on an intention-to-treat basis. Results- We observed significant treatment effects in favor of ITB over CMM for changes from baseline to month 6 in Numeric Pain Rating Scale scores for actual pain (ITB versus CMM: mean, -1.17 [SD, 3.17] versus 0.00 [3.29]; median, -1.00 versus 0.00; P=0.0380) and least pain (mean, -1.61 [2.29] versus 0.24 [3.07]; median, -1.00 versus 0.00; P=0.0136), and EuroQol-5 dimensional 3 level utility scores (mean, +0.09 [0.26] versus +0.01 [0.16]; median, +0.07 versus 0.00; P=0.0197). Between-group differences were not statistically significant for EuroQol-5 dimensional 3 level visual analog scale, stroke-specific QoL summary, or Numeric Pain Rating Scale worst pain scores, although ITB patients showed greater numeric improvements from baseline during follow-up. More ITB patients than CMM patients (73% versus 48%) were satisfied with the spasticity reduction at month 6. Conclusions- These data support that ITB therapy is associated with improvements in pain and QoL in poststroke patients. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01032239.

Readmission and complications within 30 days after intrathecal baclofen pump placement.

AIM: To describe 30-day outcomes after intrathecal baclofen (ITB) pump placement in children and identify risk factors for readmission, reoperation, and perioperative complication using the National Surgical Quality Improvement Program-Pediatric (NSQIP-P) database. METHOD: Patients aged 0 to 18 years who underwent ITB pump placement (2012-2014) comprised the study cohort defined in the database. Multivariate regression analysis was performed using preoperative and perioperative data from the American College of Surgeons' NSQIP-P database. Outcomes of interest within 30 days of surgery were (1) unplanned reoperation; (2) unplanned readmission; and (3) composite postoperative event, including complication, reoperation, and/or readmission. RESULTS: We identified 423 surgeries; 246 (58.2%) patients were male, 177 (41.8%) patients were female. Median age was 12 years and 11 months. Median operative time was 70 minutes (interquartile range 56-97min). Mean length of stay was 3.8 days. The patient population had a high number of medical comorbidities. The overall readmission rate was 7.3%; mean postoperative admission date was 14.1 days after surgery. Of readmitted patients, 64.5% underwent reoperation. The most common indication for reoperation was surgical site infection. Female sex was associated with decreased risk of readmission (odds ratio [OR] 0.25, 95% confidence interval [CI] 0.09-0.65; p=0.01); American Society of Anesthesiologists Classification of greater than or equal to 3 was associated with decreased risk of unplanned return to surgery (OR 0.26, 95% CI 0.11-0.66; p=0.04); length of stay greater than or equal to 3 days at index surgery was associated with increased risk of composite 30-day perioperative event (OR 2.33, 95% CI 1.29-4.20; p=0.01). INTERPRETATION: Our data provide national perspectives on 30-day perioperative outcomes for ITB pump placement in children. Results illustrate NSQIP-P database collection methodology and highlight opportunities for quality improvement in clinical practice. WHAT THIS PAPER ADDS: Seven percent of patients who underwent intrathecal baclofen pump placement required readmission within 30 days. The most common indication for reoperation was surgical site infection.

Analysis of a Minimally Invasive Intracranial Pressure Signals During Infusion at the Subarachnoid Spinal Space of Pigs.

OBJECTIVE: We developed a new minimally invasive method for intracranial pressure monitoring (ICPMI). The objective of this project is to verify the similarities between the ICPMI and the invasive method (ICPInv), for different components of the intracranial pressure signal-namely, the mean value (trend) as well as its pulsatile component. MATERIALS AND METHODS: A 9 kg anesthetized pig was used for simultaneous ICP monitoring with both methods. ICP was increased by performing ten infusions of 6 ml 0.9% saline into the spinal subarachnoid space, using a catheter implanted in the lumbar region. For correlation analysis, the signals were decomposed into two components-trend and pulsatile signals. Pearson correlation coefficient was calculated between ICPInv and ICPMI. RESULTS: During the infusions, the correlation between the pulsatile components of the signals was above 0.5 for most of the time. The signal trends showed a good agreement (correlation above 0.5) for most of the time during infusions. CONCLUSIONS: The ICPMI signal trends showed a good linear agreement with the signal obtained invasively. Based on the waveform analysis of the pulsatile component of ICP, our results indicate the possibility of using the minimally invasive method for assessing the neuroclinical state of the patient.

Is There a Link Between ICP-Derived Infusion Test Parameters and Outcome After Shunting in Normal Pressure Hydrocephalus?

OBJECTIVE: The term "hydrocephalus" encompasses a range of disorders characterised by clinical symptoms, abnormal brain imaging and derangement of cerebrospinal fluid (CSF) dynamics. The ability to elucidate which patients would benefit from CSF diversion (a shunt or third ventriculostomy) is often unclear. Similar difficulties are encountered in shunted patients to predict the scope for improvement by shunt re-adjustment or revision. MATERIALS AND METHODS: We compared retrospective pre-shunting infusion test results performed in 310 adult patients diagnosed with normal pressure hydrocephalus (NPH) and their improvement after shunting. RESULTS: Resistance to CSF outflow correlated significantly with improvement (p < 0.05). Other markers known from the literature, such as amplitude in CSF pulse pressure, the slope of the amplitude-pressure regression line, or elasticity did not show any correlation with outcome. CONCLUSION: Outcome following shunting in adult NPH is associated with resistance to CSF outflow; however, the latter cannot be taken as an absolute predictor of shunt response.

Critical Closing Pressure During a Controlled Increase in Intracranial Pressure.

OBJECTIVES: The objectives were to compare three methods of estimating critical closing pressure (CrCP) in a scenario of a controlled increase in intracranial pressure (ICP) induced during an infusion test in patients with suspected normal pressure hydrocephalus (NPH). METHODS: We retrospectively analyzed data from 37 NPH patients who underwent infusion tests. Computer recordings of directly measured intracranial pressure (ICP), arterial blood pressure (ABP) and transcranial Doppler cerebral blood flow velocity (CBFV) were used. The CrCP was calculated using three methods: first harmonics ratio of the pulse waveforms of ABP and CBFV (CrCPA) and two methods based on a model of cerebrovascular impedance, as a function of cerebral perfusion pressure (CrCPinv), and as a function of ABP (CrCPninv). RESULTS: There is good agreement among the three methods of CrCP calculation, with correlation coefficients being greater than 0.8 (p < 0.0001). For the CrCPA method, negative values were found for about 20% of all results. Negative values of CrCP were not observed in estimators based on cerebrovascular impedance. During the controlled rise of ICP, all three estimators of CrCP increased significantly (p < 0.05). The strongest correlation between ICP and CrCP was found for CrCPinv (median R = 0.41). CONCLUSION: Invasive CrCP is most sensitive to variations in ICP and can be used as an indicator of the status of the cerebrovascular system during infusion tests.

Spinal anaesthesia with chloroprocaine 1% versus total intravenous anaesthesia for outpatient knee arthroscopy: A randomised controlled trial.

BACKGROUND: Both general and spinal anaesthesia with short-acting local anaesthetics are suitable and reliable for knee arthroscopy as an ambulatory procedure. Chloroprocaine (CP) 1% seems to be the ideal spinal local anaesthetic for this indication. OBJECTIVE: The aim of this study was to compare spinal anaesthesia using CP 1% with general for outpatient knee arthroscopy with regard to procedure times, occurrence of pain, patient satisfaction and recovery, and also costs. DESIGN: A randomised controlled single-centre trial. SETTING: University Medical Centre Mannheim, Department of Anaesthesiology and Surgical Intensive Care Medicine, Mannheim, Germany. April 2014 to August 2015. PATIENTS: A total of 50 patients (women/men, 18 to 80 years old, ASA I to III) undergoing outpatient knee arthroscopy were included. A contra-indication to an allocated anaesthetic technique or an allergy to medication required in the protocol led to exclusion. INTERVENTIONS: Either general anaesthesia with sufentanil, propofol and a laryngeal mask for airway-management or spinal with 40-mg CP 1% were used. We noted procedure times, patient satisfaction/recovery and conducted a 7-day follow-up. MAIN OUTOMES: Primary outcome was duration of stay in the day-surgery centre. Secondary outcomes were first occurrence of pain, patient satisfaction, quality of recovery and adverse effects. In addition, we analysed treatment costs. RESULTS: Spinal had faster recovery than general anaesthesia with patients reaching discharge criteria significantly earlier [117 min (66 to 167) versus 142 min (82 to 228), P = 0.0047]. Pain occurred significantly earlier in the general anaesthesia group (P = 0.0072). Costs were less with spinal anaesthesia (cost ratio spinal: general 0.57). Patients felt significantly more uncomfortable after general anaesthesia (P = 0.0096). CONCLUSION: Spinal anaesthesia with 40-mg CP 1% leads to a significantly earlier discharge and is cheaper compared with general. TRIAL REGISTRATION: German Clinical Trials Register, www.drks.de, identifier: DRKS00005989.

Removal of Intrathecal Catheters Used in Drug Delivery Systems.

INTRODUCTION: Implanted intrathecal drug delivery systems (IDDS) are increasingly used in the treatment of spasticity and in patients with refractory pain. Literature discussing complications associated with intrathecal pump placement is widely available. However, reports of complications following the removal of chronically placed catheters are scarce. We reviewed our series of patients who had surgery to remove the intrathecal catheter. METHODS: Retrospective review was performed for all patients who underwent surgery to remove a catheter linked to an IDDS between 2010 and 2016. Patients older than 18 years were included in final analysis. Demographic (including age at removal, sex, BMI, and comorbidities) and etiologic characteristics (indications of IDDS implant and explant, interval between implant and explant, and concomitant surgery) were analyzed. Simple logistic regression was performed to seek any potential predictor of complications. RESULTS: Fifty-nine patients underwent removal of their intrathecal catheter after variable periods (mean interval of 189 months). On eight occasions, patients developed complications after catheter removal (mean interval between implant and explant was 76 months for these cases). Retained catheter was the cause of complications in half of these occasions. Persistent cerebrospinal fluid leak was the next most common complication, with requirement of an external ventricular drain and lumbar drain to facilitate wound healing on two separate occasions. CONCLUSION: Removal of an intrathecal catheter from IDDS systems may cause complications that in some cases require additional surgery.

Evidence of cognitive flexibility deficits and impaired emotion regulation in childhood survivors of acute lymphoblastic leukaemia: Findings from task switching study.

The objective of the current study was to compare cognitive flexibility and emotion regulation between childhood survivors of Acute Lymphoblastic Leukaemia (ALL) and healthy control subjects. Twenty-five childhood survivors of ALL treated with intrathecal chemotherapy between 2013 to 2016 from Shaukat Khanum Memorial Cancer Hospital, Children Hospital and Jinnah Hospital Lahore and twenty-five healthy demographically matched children (control group) participated in the study. Participants performed task switching experiment as a measure of cognitive flexibility and emotion regulation questionnaire for children and adolescents. In contrast to healthy control group, ALL survivors showed impaired cognitive flexibility and emotion regulation. Results have implications for cognitive rehabilitation to improve functions of frontal-cerebellar system in childhood survivors of ALL.

Unique Intradural Inflammatory Mass Containing Precipitated Morphine: Confirmatory Analysis by LESA-MS and MALDI-MS.

Opioids are often used for analgesia via continuous intrathecal delivery by implantable devices. A higher concentration and daily dose of opioid have been postulated as risk factors for intrathecal granuloma formation. We present a 42-year-old female patient with chronic abdominal pain from refractory pancreatitis, with an intrathecal drug delivery device implanted 21 years prior, delivering continuous intrathecal morphine. After many years without concerning physical signs or complaints, with gradual increases in daily morphine dose, she presented with rapidly progressive neurologic deficits, including lower extremity, bladder, and bowel symptoms. These symptoms were determined to be secondary to mass effect and local inflammation related to an intrathecal catheter tip granuloma, detected on magnetic resonance imaging of the spine. The mass was urgently resected. On histopathologic examination, this granuloma was found to be unique, in that in addition to the expected inflammatory components, it appeared to contain precipitated nonpolarizable crystals. These were identified as precipitated morphine using liquid extraction surface analysis-tandem mass spectrometry (LESA-MS/MS) and matrix-assisted laser desorption ionization-Fourier transform ion cyclotron resonance-mass spectrometry imaging (MALDI-FTICR-MSI). In addition to the unique finding of precipitated morphine crystals, the long-term follow-up of both morphine concentration and daily dose increases provides insight into the formation of intrathecal granulomas.