COVID-19 Molecular Pathophysiology: Acetylation of Repurposing Drugs.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces immune-mediated type 1 interferon (IFN-1) production, the pathophysiology of which involves sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) tetramerization and the cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. As a result, type I interferonopathies are exacerbated. Aspirin inhibits cGAS-mediated signaling through cGAS acetylation. Acetylation contributes to cGAS activity control and activates IFN-1 production and nuclear factor-κB (NF-κB) signaling via STING. Aspirin and dapsone inhibit the activation of both IFN-1 and NF-κB by targeting cGAS. We define these as anticatalytic mechanisms. It is necessary to alleviate the pathologic course and take the lag time of the odds of achieving viral clearance by day 7 to coordinate innate or adaptive immune cell reactions.

The Optimal Approach for a Superior Hypogastric Plexus Block.

INTRODUCTION: Superior hypogastric plexus block (SHGPB) is technically difficult, and an accurate procedure is required to avoid potential complications. We attempted to determine the reference angles for fluoroscopy-assisted SHGPB and to establish a predictor as a guide to select the optimal approach between the classic posterior approach and transdiscal approach. METHODS: Abdominopelvic computed tomography (CT) scans from 268 patients diagnosed with pelvic malignancies were examined. The oblique and axial angles needed for the fluoroscope were measured both for posterior and transdiscal approaches by simulating the needle trajectory on CT imaging. We developed an SHGPB index defined by the ratio (%) of the interposterior iliac border distance to the L5 body transverse diameter, which represents the relative transverse diameter of the bony pelvis. We evaluated whether it can help select the optimal approach for the SHGPB between the posterior and transdiscal approaches. RESULTS: Males had a significantly smaller angle than females (right oblique angle for posterior approach, males 14 [range 12 to 17] degrees vs. females 19 [range 16 to 23] degrees; P < 0.001). An SHGPB index of < 150 was an independent predictor for failure of the classic posterior approach (odds ratio 31.3, 95% confidence interval 5.1 to 104.7). CONCLUSIONS: The optimal right oblique angle of fluoroscopy for the posterior approach is 13° to 15° in males and 19° to 20° in females. The transdiscal approach may be favored over the posterior approach when the bony pelvis is narrow relative to the target vertebral body, which can be measured by the SHGPB index being < 150.

Effect of Hyaluronidase Addition to Lidocaine for Trigger Point Injection in Myofascial Pain Syndrome.

INTRODUCTION: This randomized, double-blind study compared the efficacy of hyaluronidase co-injection with that of local anesthesia alone on the degree of pain and quality of life in patients with myofascial pain syndrome (MPS). METHODS: Sixty-one adults, aged 25 to 75 years, with MPS affecting both trapezius muscles were randomly assigned to one of the 2 treatment groups: lidocaine (group L: n = 31) or hyaluronidase (group H: n = 30). All patients received Trigger point injection (TPI). Group L received 3.2 mL 0.5% lidocaine alone. Group H received the same solution of lidocaine mixed with hyaluronidase (600 iu/mL). Patients were followed for 14 days (pre- and post-TPI days 0, 1, 4, 7, and 14) with the verbal numerical rating scale (VNRS), and the primary outcome was VNRS on day 7. Also, we evaluated the neck disability index (NDI) and the short form of brief pain inventory (BPI-SF) on pre- and post-TPI day 14. RESULTS: In both groups, VNRS decreased on days 4, 7, and 14 compared to the pre-TPI. However, in group H, VNRS decreased on day 1 also. There were no significant differences of VNRS between the 2 groups during 14 days. NDI and BPI-SF scores also significantly decreased after TPI in both groups. CONCLUSIONS: There were no significant differences between groups in terms of VNRS, NDI, or BPI-SF scores. However, TPI consisting of lidocaine mixed with hyaluronidase worked more effectively than lidocaine alone on post-TPI day 1. Further, hyaluronidase showed a tendency to reduce TPI-related soreness.

Basic implications on three pathways associated with SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interacts between the host and virus and govern induction, resulting in multiorgan impacts. Its pathophysiology involves the followings: 1) the angiotensin-converting enzyme (ACE2) and Toll-like receptor (TLR) pathways: 2) the neuropilin (NRP) pathway: 3) the spike protein pathway. Therefore, it is necessary to block the pathological course with modulating innate lymphoid cells against diverse corona variants in the future.

Pain from intramuscular vaccine injection in adults.

BACKGROUND: Vaccine use has been increasing worldwide, and adult populations are presented with more opportunities to experience pain from vaccine injection. The insertion of a needle through the skin is the most common source of iatrogenic pain, and needle phobia is a major concern in medical practice. However, it is unclear which factors play major roles in the perception of pain from vaccine injection in adults. AIM: To evaluate the influences of patient characteristics on pain perception due to intramuscular vaccine injection in healthy adult volunteers. MATERIAL AND METHODS: The injection of hepatitis B vaccine using a 24 mm, 24-G needle was performed as a uniform stimulus, and the intensity of injection pain was measured immediately after the injection using a 100-mm visual analogue scale (VAS). The influences of patient characteristics on pain intensity were investigated. RESULTS: One hundred sixty volunteers (65 males, 95 females) were enrolled in this study. The average VAS score was 20.8 ± 17.1 (range 0 to 67) in males and 34.4 ± 19.7 (range 2 to 76) in females (P < 0.001). However, there were no correlations between VAS score and age, body mass index or maximal pain score from previous painful experiences. The VAS score was also not affected by the experience of previous vaccine injections, a history of childbirth in females, or religion. CONCLUSIONS: Gender appears to be the only major factor that influences the pain of intramuscular vaccine injection. Therefore, pain-reducing methods will be needed when performing injection procedures, particularly in women.

Dapsone is an anticatalysis for Alzheimer's disease exacerbation.

Brain inflammation generally accelerates neurodegeneration. Alzheimer's disease (AD) triggers an innate immune response by activating a cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway. Our study investigated patients with leprosy and AD. They were treated with dapsone (4,4'-diaminodiphenyl sulfone, DDS) as a neuroinflammasome competitor and cGAS/STING pathway inhibitor. Four groups were defined: Treatment (T) 1: DDS prescribed AD diagnosed, T 2: DDS prescribed AD undiagnosed, T 3 DDS unprescribed AD diagnosed, and T 4: DDS unprescribed AD undiagnosed. Dapsone effects on AD can be clearly distinguished according to dapsone presence or absence. T1:T3 proved that the incidence of AD was significantly reduced by dapsone. T2:T3 proved that the prevalence of AD was significantly high without dapsone. T1:T4 proved that the prevalence decreased when taking dapsone. Our study demonstrates that dapsone can prevent AD exacerbation and may represent a preventive therapeutic option for exacerbated AD.

Early thoracic sympathetic block improves the treatment effect for upper extremity neuropathic pain.

BACKGROUND: The sympathetic nervous system has important roles in mediating many neuropathic pain conditions. A thoracic sympathetic block (TSB) is a useful therapeutic procedure for neuropathic pain in the upper extremities and thorax. However, no studies have examined the factors related to an improved therapeutic effect of TSB. In this study, we evaluated the influence of potential prognostic factors for a better TSB effect and identified clinically important prognostic factors. METHODS: Percutaneous TSB was performed in 51 patients, under fluoroscopic guidance. Data collected for each patient included age, gender, body mass index, diagnosis, pain intensity, and symptom duration. The adjusted odds ratios and 95% confidence intervals for each variable were calculated by logistic regression. RESULTS: TSB was more effective in patients with symptom durations of ≤1 year compared with >1 year (P = 0.006; odds ratio, 8.037; 95% confidence interval, 1.808-35.729). Patient age, gender, body mass index, diagnosis, and intensity of pre-TSB pain were not associated with TSB effectiveness. CONCLUSION: The results showed that an earlier TSB produced a better outcome for patients with chronic pain syndrome. Thus, early TSB should be performed in patients with chronic pain in the upper extremities.

A comparison of the effects of preanesthetic administration of crystalloid versus colloid on intrathecal spread of isobaric spinal anesthetics and cerebrospinal fluid movement.

BACKGROUND: Movement of the cerebrospinal fluid (CSF) is one of the most important factors in determining the intrathecal spread of isobaric spinal anesthetics. Preanesthetic administration of either crystalloid or colloid immediately before spinal anesthesia (preload) may result in different CSF pulsatile movement because of their different physical properties. We examined whether preload of crystalloid versus colloid may have different effects on the intrathecal spread of isobaric spinal anesthetics as a result of their different CSF dynamics regarding its pulsatile movement. METHODS: In a clinical study of isobaric spinal anesthesia, patients were allocated into 1 of 2 groups according to preload with either crystalloid (n = 30) or colloid (n = 30) before spinal anesthesia with 0.5 isobaric tetracaine. The pulsatile movements of CSF at the L2-3 intervertebral space and midportion of the aqueduct of Sylvius were also examined by magnetic resonance images in healthy volunteers (n = 23) at 0, 30, and 60 minutes after administering either crystalloid or colloid. RESULTS: In the clinical study, the time to reach the peak sensory block level was delayed significantly in the crystalloid preload group (27.2 ± 17.8 minutes; P < 0.01) compared with the colloid preload group (13.9 ± 7.0 minutes). The median sensory block levels of the crystalloid preload group at 15 minutes (T10, P < 0.05) and 20 minutes (T9.5, P < 0.05) were significantly lower than those (T8, T7, respectively) of the colloid preload group. In the magnetic resonance imaging study, cranially directed CSF pulsatile movement decreased significantly at the L2-3 intervertebral intrathecal space at 30 minutes after crystalloid administration, but not after colloid administration. The CSF production rate significantly increased at 30 minutes (637 µL/min, P < 0.05) after crystalloid preload compared with the baseline measurement (448 µL/min), and then slightly decreased (609 µL/min) at 60 minutes. In the colloid preload group, the CSF production rate was not statistically significant compared with the baseline measurement (464, 512, and 542 µL/min at baseline, 30, and 60 minutes, respectively). CONCLUSIONS: Compared with a colloid preload, which may be comparable to the no-preload condition, crystalloid preload prolonged the time to reach the peak sensory block level in isobaric spinal anesthesia, which might have been caused by a significant decrease in CSF pulsatile movement. This attenuated CSF pulsatile movement in the crystalloid preload group might have resulted from significant increases of CSF production.

The optimal oblique angle of fluoroscope for thoracic sympathetic ganglion block.

OBJECTIVE: The target in the thoracic sympathetic ganglion block (TSGB) is the anterior edge of the costovertebral articulation along the lateral surface of vertebral bodies T2-4. The present study attempts to determine an optimal safe angle for fluoroscopy in fluoroscope-assisted TSGB through the use of chest CT scan images. Additionally, we seek to determine if differences in these measurements exist in patients with chronic obstructive pulmonary disease (COPD). METHODS: Chest CT scans from 320 patients were included. The range of angle and entry point distance to midline was measured in all subjects. The range of angle was from the minimum angle to thoracic sympathetic ganglion passing over the lateral aspect of body to the maximum angle to the thoracic sympathetic ganglion not puncturing the pleural space. Additionally, these measurements from 50 COPD patients were subsequently compared age-matched individuals without COPD. RESULTS: No significant difference in optimal angle was found for any of the levels between T2 and T4. The optimal angle was significantly different between right and left sides, although no such difference was identified between genders. The older patients had a significantly smaller optimal angle than the younger. Similarly, individuals with COPD had a significantly smaller optimal angle and entry distance. INTERPRETATION: The measurements derived from this study can be used as a reference for TSGB and radiofrequency lesioning to prevent the complications. Specifically, our data indicate that the optimal oblique angle of fluoroscopy is 18°-19° for non-COPD patients and 16°-17° for COPD patients.

Novel Use of Hydromorphone as a Pretreatment Agent: A Double-blind, Randomized, Controlled Study in Adult Korean Surgical Patients.

BACKGROUND: Hydromorphone is a potent µ-opioid selective agonist that has an onset time within 5 minutes and reaches peak effect between 10 and 20 minutes. However, it may show immediate analgesic effect to rocuronium-induced pain because of its peripheral analgesic property and also may attenuate noxious stimuli from tracheal intubation during induction. The opioid receptors are known to be present in peripheral sensory nerve terminals as well as in the dorsal root ganglion and the central terminal of primary afferent nerves. Therefore, we hypothesized that hydromorphone may be considered a potent pretreatment or adjuvant drug during the induction of anesthesia with its peripherally and centrally mediated analgesia. OBJECTIVE: The aim of this study was to compare the effects of pretreatment with hydromorphone in reducing rocuronium-induced withdrawal movements and hemodynamic changes during tracheal intubation with the effects of fentanyl and normal saline. METHODS: In this double-blind, randomized, controlled study, consecutive adult patients aged 20 to 70 years who were scheduled to undergo general anesthesia for elective gastric or colorectal surgery at the Samsung Seoul Hospital (Seoul, Republic of Korea) were randomly assigned to receive 5 mL hydromorphone 0.03 mg/kg or fentanyl 2 µg/kg or normal saline. Thirty seconds after administering the study drug, anesthesia was induced with 2.5% thiopental sodium 5 mg/kg. After loss of consciousness, rocuronium 0.6 mg/kg was injected and immediate withdrawal movements were recorded. Two minutes after rocuronium injection, tracheal intubation was performed and hemodynamic changes were observed. RESULTS: A total of 194 patients were enrolled, with 65 in the hydromorphone group, 67 in the fentanyl group, and 62 in the saline group. The overall incidence of withdrawal movements was significantly lower in the hydromorphone group (2 patients; 3.1%) and the fentanyl group (5 patients; 7.5%) (both, P < 0.001) than in the saline group (36 patients; 58.1%). The mean arterial pressure (MAP) and heart rate (HR) after intubation (median [interquartile range]) in the fentanyl group (101.5 [84-115] mm Hg; 93.5 [82-102] beats per minute [bpm]) and the hydromorphone group (93.0 [83-106] mm Hg; 90.0 [86.3-93.6] bpm) were significantly lower than these measures in the saline group (111.5 [105-123] mm Hg; 103.5 [96-113] bpm) (fentanyl group MAP and HR, P < 0.001; hydromorphone group MAP and HR, P < 0.001). CONCLUSIONS: Pretreatment with hydromorphone and fentanyl may have similar effectiveness in reducing withdrawal movements in response to rocuronium injection pain and inducing immediate general anesthesia.

Specific Treatment Exists for SARS-CoV-2 ARDS.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), seems to be difficult to overcome. A pandemic of such a scale has not been seen since the 1918 influenza pandemic. Although the predominant clinical presentation is respiratory disease, neurological manifestations and sequelae are increasingly being recognized. We observed a case series of rapid recovery of ARDS within 24 h in the preliminary clinical features of COVID-19 ARDS-associated neurological disease. It was also noted that by 15 April, 2021, there was no SARS-CoV-2 ARDS on Sorok Island in South Korea, where lepers had been living together. We compared each of dapsone's effects on humans and considered those of SARS-CoV-2. Dapsone showed different effects in the brain. The Sorokdo National Hospital reported a relationship between dapsone and the neuroinflammasome of Alzheimer's disease (AD) in Sorok Island from January 2005 to June 2020. AD prevalence was low in the leprosy patient group who took dapsone regularly. The preliminary cross-sectional study of the trial group (22 subjects) and the control group (22 subjects) in the Hunt Regional Hospital reported the following results: The chi-square statistic is 5.1836. The p-value is 0.022801. The result is considered significant at p < 0.05. The results from the medical treatment from 21 December to 29 December 2020 were considered. The mortality rates at the ARDS onset stage were 0% with dapsone administered as a standard COVID-19 treatment and 40% without dapsone administered as a standard COVID-19 treatment, respectively. Based on the respiratory failure and sudden high death rate originating from the involvement of the brainstem, especially the pre-Bötzinger complex, dapsone can be used to significantly reduce the incidence of the cases of acute respiratory distress syndrome and other illnesses caused by SARS-CoV-2.

The Neuroinflammasome in Alzheimer's Disease and Cerebral Stroke.

AIM/BACKGROUND: This review investigated a patient with Alzheimer's disease (AD) treated with 4,4'-diaminodiphenyl sulfone (DDS) as a neuroinflammasome competitor. METHODS: We monitored AD's progression through numeric clinical staging (NCS) with a new biomarker. NCS was determined by the presence of AD symptoms and neuropsychiatric (NP) symptoms caused by anti-AD (AAD) drugs (D) as a biomarker. We also monitored the function of DDS for stroke in a no-intake emergency state. RESULTS: By introducing (D), AD's progression was monitored through NCS staging. AAD side effects and neuropsychiatric symptoms were identified. DDS was stopped in patients with stroke with NCS 6 caused by AAD, and it rapidly proceeded to cerebral infarct. CONCLUSIONS: AAD can occasionally exacerbate AD and stroke. DDS can alleviate mild cognitive impairment (MCI), early AD and stroke. We clinically confirmed the role of DDS as a neuroinflammasome competitor after stroke. DDS preserved neuronal survival within 24-55 h in the Seoul Study cohort.

Efficacy of milrinone versus nitroglycerin in controlling pulmonary arterial hypertension induced by intravenous injections of absolute ethanol in anesthetized dogs.

PURPOSE: To compare the attenuating effects of milrinone versus nitroglycerin on pulmonary artery pressure (PAP) increase caused by repeat intravenous bolus injection of absolute ethanol in anesthetized dogs. MATERIALS AND METHODS: Twenty-four dogs were randomly distributed into three groups: a control group (group C), a nitroglycerin group (treated with a continuous infusion of nitroglycerin at 5.0 microg/kg/min; group N), and a milrinone group (treated with a continuous infusion of milrinone at 3.0 microg/kg/min after an initial bolus dose of 100 microg/kg; group M). Absolute ethanol (0.1 mL/kg) was injected at 10-minute intervals via a 5-F angiographic catheter advanced into the proximal portion of the inferior vena cava. Immediately before and after each intravenous injection of absolute ethanol, hemodynamic values were obtained through a pulmonary arterial catheter. RESULTS: Group M showed more stable hemodynamic values of systolic, mean, and diastolic PAP and pulmonary vascular resistance (PVR) compared with groups C and N. In addition, group M showed significantly higher values of cardiac output versus group C at 10 minutes after the 10th bolus of ethanol. After restoration of spontaneous breathing, group M also showed the least hemodynamic changes in systolic, mean, and diastolic PAPs and PVR among the groups. CONCLUSIONS: Although a continuous infusion of nitroglycerin or milrinone effectively prevented cardiovascular deterioration, milrinone was superior to nitroglycerin in managing the acute hemodynamic changes that resulted from repeated intravenous bolus injections of absolute ethanol (0.1 mL/kg) in healthy anesthetized dogs.

Cardiovascular effects and predictability of cardiovascular collapse after repeated intravenous bolus injections of absolute ethanol in anesthetized pigs.

PURPOSE: To evaluate the effects of repeated intravenous bolus injections of absolute ethanol on cardiopulmonary hemodynamic changes and to investigate the predictability of ethanol-induced cardiovascular collapse in anesthetized pigs. MATERIALS AND METHODS: Twenty pigs aged 3-6 months and weighing 28-38 kg were enrolled in the study. Absolute ethanol (0.1 mL/kg of body weight) was repeatedly injected through the inferior vena cava central to the renal vein at 10-minute intervals up to a total volume of 1.0 mL/kg. The subjects were divided into a cardiovascular collapse group and a no-collapse group according to the development or absence of cardiac collapse. RESULTS: Among the 20 pigs, 12 died before the final injection. Hemodynamic parameters measured immediately before the injection of absolute ethanol did not differ between the cardiovascular collapse group and the no-collapse group except that among animals with cardiovascular collapse, the injection immediately before the one causing cardiovascular collapse resulted in significant increases in the following hemodynamic parameters: mean pulmonary arterial pressure (P < .01), pulmonary vascular resistance (P = .04), and right ventricular end-diastolic volume (P = .02). No such increases were observed in the no-collapse group. CONCLUSIONS: Hemodynamic profiles in pigs obtained immediately before intravenous injection of absolute ethanol did not predict the subsequent occurrence of cardiovascular collapse except after the injection immediately preceding the one resulting in cardiovascular collapse. In this animal model, significant increases in select hemodynamic parameters occurred after the injection immediately preceding the one resulting in cardiovascular collapse.

Analgesic effects of ketamine infusion therapy in korean patients with neuropathic pain: A 2-week, open-label, uncontrolled study.

BACKGROUND: The overexcitation of the N-methyl-D-aspartate receptor complex appears to play a critical role in the development of neuropathic pain, and ketamine acts as an antagonist to that receptor. Some publications have reported on the prominent relief of neuropathic pain with intravenous or subcutaneous ketamine infusions or a single-dose intravenous ketamine injection despite adverse effects. OBJECTIVES: The primary objective of this study was to determine the analgesic effect of intravenous ketamine infusion therapy for neuropathic pain refractory to conventional treatments. Secondary objectives included identifying the variables related to the analgesic effect and the pain descriptors susceptible to ketamine infusion. METHODS: This 2-week, open-label, uncontrolled study was conducted in Korean patients with neuropathic pain recruited from the Samsung Seoul Hospital (Seoul, Republic of Korea) outpatient pain management unit. Patients were required to have a pain severity score >5 (visual analog scale [VAS], where 0 = no pain and 10 = worst pain imaginable) over a period of ≥1 month while on standard treatment. The patients were required to have shown no benefit from standard treatment and no pain relief lasting over 1 month. The ketamine infusion therapy was composed of 3 sessions performed consecutively every other day. Midazolam was administered concomitantly to reduce the occurrence of central nervous system-related adverse events (AEs) secondary to ketamine. Each session was as follows: ketamine 0.2 mg/kg and midazolam 0.1 mg/kg were administered intravenously for 5 minutes as a loading dose, followed by a continuous infusion of ketamine 0.5 mg/kg/h and midazolam 0.025 mg/kg/h for 2 hours. AEs were assessed in the following ways: close monitoring of ECG, blood pressure, oxygen saturation, and evaluating the need for treatment of AEs during infu- sion and until discharge by an attending anesthesiologist; an open question about discomfort at the end of each session; spontaneous reports about AEs during each session; and the patients' and caregivers' checklist of AEs occurring at home for 2 weeks after discharge. All the descriptors of pain expressed by the patients in Korean were recorded and translated into appropriate English terminology on the basis of the literature on Korean verbal descriptors of pain. Each of the translated pain descriptors was then classified into 1 of 18 sensory items. RESULTS: The overall VAS score for pain decreased from a baseline mean (SD) of 7.20 (1.77) to 5.46 (2.29) (P < 0.001) 2 weeks after treatment in 103 patients (53 males and 50 females; mean age, 52.56 [17.33] years) who completed the study. Variables such as age, sex, and the duration and diagnosis of pain were not found to be associated with analgesic effect. Seven of the 18 pain descriptors were found to have a significant response to ketamine infusion treatment between baseline and 2 weeks follow-up: burning pain (P = 0.008); dull, aching pain (P < 0.001); overly sensitive to touch (P = 0.002); stabbing pain (P = 0.008); electric pain (P = 0.031); tingling pain (P < 0.001); and squeezing pain (P < 0.001). A total of 52 patients reported AEs: 33 during infusion and 44 during recovery and up to 2 weeks follow up. The most commonly reported AEs were snoring (15 [15%]) during infusion and dizziness (43 [42%]) during recovery. CONCLUSIONS: Ketamine infusion therapy was associated with reduced severity of neuropathic pain and generally well tolerated for up to 2 weeks in these patients with neuropathic pain refractory to standard treatment. Variables such as sex, age, and the diagnosis and duration of pain had no association with the analgesic effect of this treatment. Randomized controlled trials are needed to evaluate the efficacy and tolerability of treatment with ketamine infusion.

Recovery of Dementia Syndrome following Treatment of Brain Inflammation.

AIM/BACKGROUND: This research aims to prevent progression from mild cognitive impairment (MCI) to Alzheimer's disease. A Japanese study of leprosy patients revealed that the incidence of dementia in leprosy patients was lower than that in patients taking dapsone who had never been treated. But a similar study the following year refuted the finding of less dementia in leprosy patients taking dapsone. According to conflicting reports, Mycobacterium leprae was a factor in reducing the incidence of Alzheimer's disease. Thus, we formed a hypothesis that if dapsone is administered to patients without leprosy but with MCI and the prophylactic effect of dementia syndrome is observed over a long period of time, we can determine whether dapsone can prevent the progression of MCI to dementia syndrome. If dementia does not occur after treating inflammation in brain cells while dementia develops after a certain long-term period (usually within 2-3 years), brain cell inflammation can be demonstrated as the cause of dementia. METHODS: This is a prospective cohort research. We report on an elderly patient diagnosed with MCI from February 2008 to January 2019. The patient took dapsone 100 mg once a day from 2010 to 2015 for the treatment of MCI. Since 2016, the production of dapsone has ceased in Korea. In June 2018, the patient was diagnosed with Alzheimer's disease. The patient took Aricept for the treatment of Alzheimer's disease but complained of serious side effects. And dapsone was re-administered to the patient from November 2018. RESULTS: The patient recovered to MCI and improved her daily life owing to the treatment with dapsone. The drug controls the inflammatory response in the brain, irrespective of whether proteins are deposited in neurons. CONCLUSIONS: This finding means that dementia syndrome is an inflammatory disease. This research suggests that diagnostic criteria for Alzheimer's disease should be based on the presence or absence of inflammation in neurons. Because inflammation in neurons can occur in middle age due to various causes, we can treat inflammation in neurons and prevent and treat dementia syndrome, including Alzheimer's disease.

Dermatome variation of lumbosacral nerve roots in patients with transitional lumbosacral vertebrae.

BACKGROUND: The presence of a transitional vertebra can create difficulty in identifying the lumbar level corresponding to an exiting nerve root at the time of a spinal nerve block. We investigated the possibility that the muscle innervation pattern and sensory dermatomes of the lumbar nerve roots are altered when a lumbosacral transitional vertebra is present using electrical stimulation. METHODS: We determined the existence of transitional vertebrae using Castellvi's criteria. Patients having transitional vertebrae with lumbosacral radiculopathy were recruited for the study. Selective nerve root blocks using electrical stimulation were performed. Neurologic symptoms caused by S1 or L5 nerve root compression in the patients with a lumbarized S1 or sacralized L5, respectively, were compared with those caused by either L5 or S1 nerve root compression in patients with a normal configuration. RESULTS: Thirty-two patients had transitional vertebrae, of whom 12 had a lumbarized S1 and 20 had a sacralized L5. The distribution of motor and sensory symptoms caused by the lumbarized S1 (L6) nerve root stimulation was similar to that of the S1 nerve root stimulation in the normal configuration. In 17 patients, the distribution of motor and sensory symptoms caused by the sacralized L4 nerve root stimulation was similar to that of L5 nerve root stimulation in the normal configuration. CONCLUSIONS: Our findings suggest that the function of the lumbosacral nerve roots is altered in patients with a sacralized L5, and that the L4 nerve root serves the usual function of the L5 nerve root.

Intravascular injection in lumbar medial branch block: a prospective evaluation of 1433 injections.

BACKGROUND: The successful outcome and validity of lumbar medial branch block (MBB) are largely dependent on technique accuracy. Intravascular uptake of injectate causes a false-negative response to block and is associated with various possible complications. In the current study, we prospectively evaluated the incidence of, and the factors associated with, intravascular injection during block. In addition, we assessed the efficiencies of generally accepted safety measures, such as preinjection aspiration and intermittent fluoroscopy to avoid intravascular injections. METHODS: We prospectively examined 1433 lumbar MBBs in 456 patients performed by seven physicians. Aspiration test, spot radiography, and contrast injection under real-time fluoroscopic visualization were performed sequentially without repositioning the needle. Incidences of blood flashback and the presence of intravascular contrast spread on spot radiographic images and during real-time fluoroscopy were checked. The factors studied for intravascular injection included physician experience, patient age and sex, needle gauge, and block spinal level. RESULTS: No specific factors were found to affect the incidence of intravascular uptake during block. The overall incidence of intravascular uptake was 6.1% per nerve block (88/1433), and 30 of these were predicted by preinjection aspiration (sensitivity = 34.1%) and 52 by spot radiography (sensitivity = 59.1%). CONCLUSIONS: The aspiration test with or without spot radiography frequently missed the intravascular uptake of contrast during lumbar MBBs. We strongly advocate the use of real-time fluoroscopy during contrast injection to increase diagnostic and therapeutic value and to avoid possible complications.

Lumbar Sympathetic Block with Botulinum Toxin Type A and Type B for the Complex Regional Pain Syndrome.

A lumbar sympathetic ganglion block (LSB) is a therapeutic method for complex regional pain syndrome (CRPS) affecting the lower limbs. Recently, LSB with botulinum toxin type A and B was introduced as a novel method to achieve longer duration of analgesia. In this study, we compared the botulinum toxin type A (BTA) with botulinum toxin type B (BTB) in performing LSB on patients with CRPS. LSB was performed with either BTA or BTB on patients with CRPS in their lower extremities. The length of time taken for patients to return to the pre-LSB pain score and the adverse effect of LSB with BTA/BTB were investigated. The median length of time taken for the patients to return to the pre-LSB pain score was 15 days for the BTA group and 69 days for the BTB group (P = 0.002). Scores on a visual analogue scale decreased in the patients of both groups, and no significant adverse effects were experienced. In conclusion, the administration of either BTA or BTB for LSB is a safe method to prolong the sympathetic blocking effect in patients with CRPS. BTB is more effective than BTA to prolong the sympathetic blocking effect in CRPS patients.

The influence of neck flexion and extension on the distribution of contrast medium in the high thoracic epidural space.

BACKGROUND: For safe and effective thoracic epidural analgesia (TEA), it is important to control the level of TEA and to identify factors that influence its spread. In this study, we observed the distribution of contrast injected into the high thoracic epidural space during neck flexion and extension. METHODS: An epidural catheter was inserted into the epidural space until its tip was located at the T1-2 intervertebral level. Patients were randomly allocated to three groups (extension, flexion, and neutral groups), and were injected with 5 mL of contrast when the neck was extended, flexed, or in the neutral position. Extent of contrast spread was determined by counting the number of vertebral body units (VBUs) through lateral epidurography. RESULTS: Forty-two patients were equally allocated to the three groups. Radiographic spreads in the cephalad direction (median) was 1.0, 5.5, and 1.5 VBUs in the extension, flexion, and neutral groups, and spread was greater in the flexion than in the other two groups (P < 0.001). Median radiographic caudal spread was 10.0, 10.0, and 7.0 VBUs in the extension, flexion, and neutral groups, respectively, which was not significantly different among groups (P = 0.145). CONCLUSIONS: Cranial spread of contrast in the high thoracic epidural space is limited. However, neck flexion increases cranial spread. These results suggest that when TEA is high, the tip of the epidural catheter should be located at the upper part of the level to be blocked and that neck flexion may cause an unwanted cervical block.