Ophthalmologic Involvement in Adults with Histiocytic Disorders: Clinical Presentation and Treatment Outcomes.

PURPOSE: To evaluate the clinical presentation, treatment, and outcomes in adult patients with histiocytic disorders with ocular, orbital, optic nerve, or cavernous sinus involvement. DESIGN: Observational, retrospective chart review. PARTICIPANTS: Adult patients (age ≥ 18 years) at Mayo Clinic from January 1, 1996, to July 1, 2021, with histiocytic disorders. Inclusion criteria were (1) histiocytic disorder by biopsy and appropriate clinical phenotype; (2) available medical records; and (3) ocular, orbital, optic nerve, or cavernous sinus involvement. METHODS: Retrospective chart review. MAIN OUTCOME MEASURES: Response to therapy, measured in clinical and radiographic impact. RESULTS: Thirty-two patients were identified: 7 with Langerhans cell histiocytosis (LCH); 15 with Erdheim-Chester disease (ECD); 1 with mixed LCH/ECD phenotype; 8 with Rosai-Dorfman disease (RDD); and 1 with mixed RDD/ECD phenotype. Ophthalmologic involvement was part of the initial presentation in 69% of patients (22/32). Eyelid edema (13/32, 41%) and proptosis (12/32, 38%) were the most frequent presentations. Isolated orbital or cavernous sinus involvement was present in 3 of 7 patients with LCH and 1 of 8 patients with RDD. Optic nerve sheath involvement was present in 2 of 7 LCH patients, 14 of 15 ECD patients, and 1 RDD/ECD patient. Diffuse (> 75%) orbital involvement was seen in 12 of 15 ECD patients and 1 of 7 LCH patients. Ocular involvement was seen in 1 of 15 ECD patients, 6 of 8 RDD patients, and 1 of 1 mixed RDD/ECD patient. The cavernous sinuses were involved in 1 of 7 LCH patients, 5 of 15 ECD patients, and both mixed phenotype patients. Visual acuity was affected in 14 patients (14/24, 58%) with a median logarithm of the minimum angle of resolution visual acuity of 0.1 (range, -0.12 to 3). BRAF V600E mutations were found in 75% (3/4) of LCH patients and 91% (10/11) of ECD patients. Patients received a variety of treatment, and response was variable across disease types. CONCLUSIONS: Orbital involvement was more commonly seen in LCH and ECD, whereas ocular involvement was more common in RDD. Visual acuity may be impacted from ocular involvement or compression of the optic nerve with diffuse orbital involvement.

Neurological Manifestations of Histiocytic Disorders.

PURPOSE OF REVIEW: Histiocytic disorders, including Erdheim-Chester disease (ECD), Langerhans cell histiocytosis (LCH), and Rosai-Dorfman disease (RDD), are rare neoplasms that may present with a spectrum of neurologic involvement. Diagnostic delay is common due to heterogeneity in presentation and challenging pathology. RECENT FINDINGS: Recent advances in the treatment of these diseases targeted towards mutations in the MAP kinase pathway have led to an improved prognosis in these patients with neurologic involvement. It is critical for clinicians to have a high index of suspicion to allow for early targeted treatment and optimize neurologic outcomes. A systematic approach to diagnosis is presented in this article to allow for accurate diagnosis of these rare diseases.

Brainstem and cerebellar involvement in MOG-IgG-associated disorder versus aquaporin-4-IgG and MS.

OBJECTIVE: To determine the frequency and characteristics of brainstem or cerebellar involvement in myelin-oligodendrocyte-glycoprotein-antibody-associated-disorder (MOGAD) versus aquaporin-4-IgG-seropositive-neuromyelitis optica spectrum disorder (AQP4-IgG-NMOSD) and multiple sclerosis (MS). METHODS: In this observational study, we retrospectively identified 185 Mayo Clinic MOGAD patients with: (1) characteristic MOGAD phenotype, (2) MOG-IgG seropositivity by live cell-based assay and (3) MRI lesion(s) of brainstem, cerebellum or both. We compared the symptomatic attacks to AQP4-IgG-NMOSD (n=30) and MS (n=30). RESULTS: Brainstem or cerebellar involvement occurred in 62/185 (34%) MOGAD patients of which 39/62 (63%) were symptomatic. Ataxia (45%) and diplopia (26%) were common manifestations. The median age in years (range) in MOGAD of 24 (2-65) was younger than MS at 36 (16-65; p=0.046) and AQP4-IgG-NMOSD at 45 (6-72; p=0.006). Isolated attacks involving the brainstem, cerebellum or both were less frequent in MOGAD (9/39 (23%)) than MS (22/30 (73%); p<0.001) but not significantly different from AQP4-IgG-NMOSD (14/30 (47%); p=0.07). Diffuse middle cerebellar peduncle MRI-lesions favoured MOGAD (17/37 (46%)) over MS (3/30 (10%); p=0.001) and AQP4-IgG-NMOSD (3/30 (10%); p=0.001). Diffuse medulla, pons or midbrain MRI lesions occasionally occurred in MOGAD and AQP4-IgG-NMOSD but never in MS. Cerebrospinal fluid (CSF) oligoclonal bands were rare in MOGAD (5/30 (17%)) and AQP4-IgG-NMOSD (2/22 (9%); p=0.68) but common in MS (18/22 (82%); p<0.001). Disability at nadir or recovery did not differ between the groups. CONCLUSION: Involvement of the brainstem, cerebellum or both is common in MOGAD but usually occurs as a component of a multifocal central nervous system attack rather than in isolation. We identified clinical, CSF and MRI attributes that can help discriminate MOGAD from AQP4-IgG-NMOSD and MS.

Modification of Firearm Law-Firearm Injury Association by Economic Disadvantage.

INTRODUCTION: Firearm-related injuries in the U.S. have risen 37% since 2015. Understanding how the association between firearm incidents and state-level firearm restrictiveness is modified by community-level distress and economic connectedness (EC) may inform upstream injury prevention efforts. METHODS: A national cross-sectional study of firearm incidents (interpersonal and unintentional firearm events) occurring between 1/2015 and 12/2021 was performed using the Gun Violence Archive. The exposures were community distress (Distressed Communities Index, DCI), EC, and year-state-level firearm restrictiveness. The primary outcome was mean annual urban firearm incidence rate per ZIP Code Tabulation Area. Generalized linear mixed models were fit to evaluate the modification of the firearm law-firearm incident association by DCI and EC. Data analyses took place in 2022. RESULTS: About 266,020 firearm incidents were included. The mean rate was higher with each DCI tertile, with a RR of 3.18 (95% CI: 3.06, 3.30) in high versus low distress communities. Low EC was associated with over 1.8 times greater rate of firearm-related injury. The least restrictive firearm laws were associated with 1.20 times higher risk of firearm incidents (95% CI: 1.12, 1.28). The association between restrictive laws and lower incidence rates was strongest in low and medium distress and high EC communities. CONCLUSIONS: Stricter firearm laws are associated with lower rate of firearm incidents. The magnitude of this association is smallest for communities experiencing the greatest economic disadvantage.

Community-Level Disadvantage of Adults With Firearm- vs Motor Vehicle-Related Injuries.

Importance: Motor vehicle crash (MVC) and firearm injuries are 2 of the top 3 mechanisms of adult injury-related deaths in the US. Objective: To understand the differing associations between community-level disadvantage and firearm vs MVC injuries to inform mechanism-specific prevention strategies and appropriate postdischarge resource allocation. Design, Setting, and Participants: This multicenter cross-sectional study analyzed prospectively collected data from the American College of Surgeons (ACS) Firearm Study. Included patients were treated either for firearm injury between March 1, 2021, and February 28, 2022, or for MVC-related injuries between January 1 and December 31, 2021, at 1 of 128 participating ACS trauma centers. Exposures: Community distress. Main outcome and Measure: Odds of presenting with a firearm as compared with MVC injury based on levels of community distress, as measured by the Distressed Communities Index (DCI) and categorized in quintiles. Results: A total of 62 981 patients were included (mean [SD] age, 42.9 [17.7] years; 42 388 male [67.3%]; 17 737 Black [28.2%], 9052 Hispanic [14.4%], 36 425 White [57.8%]) from 104 trauma centers. By type, there were 53 474 patients treated for MVC injuries and 9507 treated for firearm injuries. Patients with firearm injuries were younger (median [IQR] age, 31.0 [24.0-40.0] years vs 41.0 [29.0-58.0] years); more likely to be male (7892 of 9507 [83.0%] vs 34 496 of 53 474 [64.5%]), identified as Black (5486 of 9507 [57.7%] vs 12 251 of 53 474 [22.9%]), and Medicaid insured or uninsured (6819 of 9507 [71.7%] vs 21 310 of 53 474 [39.9%]); and had a higher DCI score (median [IQR] score, 74.0 [53.2-94.8] vs 58.0 [33.0-83.0]) than MVC injured patients. Among admitted patients, the odds of presenting with a firearm injury compared with MVC injury were 1.50 (95% CI, 1.35-1.66) times higher for patients living in the most distressed vs least distressed ZIP codes. After controlling for age, sex, race, ethnicity, and payer type, the DCI components associated with the highest adjusted odds of presenting with a firearm injury were a high housing vacancy rate (OR, 1.11; 95% CI, 1.04-1.19) and high poverty rate (OR, 1.17; 95% CI, 1.10-1.24). Among patients sustaining firearm injuries patients, 4333 (54.3%) received no referrals for postdischarge rehabilitation, home health, or psychosocial services. Conclusions and Relevance: In this cross-sectional study of adults with firearm- and motor vehicle-related injuries, we found that patients from highly distressed communities had higher odds of presenting to a trauma center with a firearm injury as opposed to an MVC injury. With two-thirds of firearm injury survivors treated at trauma centers being discharged without psychosocial services, community-level measures of disadvantage may be useful for allocating postdischarge care resources to patients with the greatest need.

Association between sociodemographic factors and cholesterol-lowering medication use in U.S. adults post-myocardial infarction.

INTRODUCTION: Cholesterol-lowering medications offer effective secondary prevention after myocardial infarction (MI). Our objective was to evaluate the association between sociodemographic factors and cholesterol-lowering medication use in high-risk adults. METHODS: We conducted an analysis using weighted data from 31,408 participants in the 2017 and 2019 Behavioral Risk Factor Surveillance Systems cross-sectional surveys, who had a self-reported history of MI and high blood cholesterol. The sociodemographic factors evaluated were sex, age, race and ethnicity, annual household income, education level, relationship status, and reported healthcare coverage. We estimated the weighted prevalence of medication use, and weighted prevalence differences (with 95% confidence intervals) across categories, adjusting for sex, age group, healthcare coverage, smoking status, hypertension, and diabetes. RESULTS AND DISCUSSION: Overall, 83% of survey participants with a self-reported history of both MI and high blood cholesterol reported currently using a cholesterol-lowering medication. The prevalence of use was only 61% in those without self-reported healthcare coverage, compared to 85% of those with healthcare coverage (adjusted prevalence difference of -20%; 95% CI: -25% to -14%). Use of cholesterol-lowering medication was relatively low in younger adults and higher in older adults, leveling off after age 65 years. The proportion of Native Hawaiian or Pacific Islanders who were using a cholesterol-lowering medication was relatively low, but otherwise there was little variation by race and ethnicity. Household income, education level, and relationship status were weakly or not associated with medication use. CONCLUSIONS: Knowledge of characteristics of persons who are relatively less likely to be adherent with cholesterol-lowering medications for secondary prevention may be useful to policymakers and healthcare providers involved in the long-term treatment of MI patients. Policy makers might consider a reduced cost prescription coverage for persons without current healthcare coverage who have sustained an MI to reduce future cardiovascular morbidity and mortality.

Firearm Injuries treated at Trauma Centers in the United States.

BACKGROUND: While firearm injuries and deaths continue to be a major public health problem, the number of non-fatal firearm injuries and the characteristics of patients is not well known. The American College of Surgeons (ACS) Committee on Trauma leveraged an existing data system to collect additional data on fatal and non-fatal firearm injuries presenting to trauma centers. This report provides an overview of this initiative and highlights the challenges associated with capturing actionable data on firearm-injured patients. METHODS: 128 trauma centers that are part of the ACS Trauma Quality Improvement Program (TQIP) collected data on individuals of any age arriving alive between March 1, 2021 and February 28, 2022 with a firearm injury. In addition to the standard data collected for TQIP, abstractors also extracted additional data specific to this study. We linked data from the Distressed Community Index (DCI) to patient records using zip code of residence. RESULTS: A total of 17,395 patients were included, with mean (SD) age of 30.2 (13.5) years, 82.5% were male and the majority were Black and non-Hispanic. The mean proportion of variables with missing data varied among trauma centers, with a mean of 20.7% missing data. Injuries occurred most commonly in homes (31.2%) or on the street (26.6%); 70.4% of injuries were due to assaults. Nearly one-third of patients were discharged from the ED, 25.9% were admitted directly to the operating room, 10.9% to the ICU; 5.9% died in the ED and 10.3% died overall during their course of care. Nearly two-thirds of patients lived in the two highest distressed categories of communities; only 7.5% lived in the least distressed quintile. CONCLUSIONS: Utilizing trauma center data can be a valuable tool to improve our knowledge of firearm injuries if clinical practices and documentation of patient risks and circumstances are standardized. LEVEL OF EVIDENCE: III Level, epidemiological.

Firearm injuries in Missouri.

Firearm deaths continue to be a major public health problem, but the number of non-fatal firearm injuries and the characteristics of patients and injuries is not well known. The American College of Surgeons Committee on Trauma, with support from the National Collaborative on Gun Violence Research, leveraged an existing data system to capture lethal and non-lethal injuries, including patients treated and discharged from the emergency department and collect additional data on firearm injuries that present to trauma centers. In 2020, Missouri had the 4th highest firearm mortality rate in the country at 23.75/100,000 population compared to 13.58/100,000 for the US overall. We examined the characteristics of patients from Missouri with firearm injuries in this cross-sectional study. Of the overall 17,395 patients, 1,336 (7.7%) were treated at one of the 11 participating trauma centers in Missouri during the 12-month study period. Patients were mostly male and much more likely to be Black and uninsured than residents in the state as a whole. Nearly three-fourths of the injuries were due to assaults, and overall 7.7% died. Few patients received post-discharge services.

Characteristics of Progressive Multifocal Leukoencephalopathy Associated With Sarcoidosis Without Therapeutic Immune Suppression.

Importance: Progressive multifocal leukoencephalopathy can occur in the context of systemic sarcoidosis (S-PML) in the absence of therapeutic immune suppression and can initially be mistaken for neurosarcoidosis or other complications of sarcoidosis. Earlier recognition of S-PML could lead to more effective treatment of the disease. Objective: To describe characteristics of patients with S-PML. Design, Setting, and Participants: For this case series, records from 8 academic medical centers in the United States were reviewed from 2004 to 2022. A systematic review of literature from 1955 to 2022 yielded data for additional patients. Included were patients with S-PML who were not receiving therapeutic immune suppression. The median follow-up time for patients who survived the acute range of illness was 19 months (range, 2-99). Data were analyzed in February 2023. Exposures: Sarcoidosis without active therapeutic immune suppression. Main Outcomes and Measures: Clinical, laboratory, and radiographic features of patients with S-PML. Results: Twenty-one patients with S-PML not receiving therapeutic immune suppression were included in this study, and data for 37 patients were collected from literature review. The median age of the 21 study patients was 56 years (range, 33-72), 4 patients (19%) were female, and 17 (81%) were male. The median age of the literature review patients was 49 years (range, 21-74); 12 of 34 patients (33%) with reported sex were female, and 22 (67%) were male. Nine of 21 study patients (43%) and 18 of 31 literature review patients (58%) had simultaneous presentation of systemic sarcoidosis and PML. Six of 14 study patients (43%) and 11 of 19 literature review patients (58%) had a CD4+ T-cell count greater than 200/µL. In 2 study patients, a systemic flare of sarcoidosis closely preceded S-PML development. Ten of 17 study patients (59%) and 21 of 35 literature review patients (60%) died during the acute phase of illness. No meaningful predictive differences were found between patients who survived S-PML and those who did not. Conclusions and Relevance: In this case series, patients with sarcoidosis developed PML in the absence of therapeutic immune suppression, and peripheral blood proxies of immune function were often only mildly abnormal. Systemic sarcoidosis flares may rarely herald the onset of S-PML. Clinicians should consider PML in any patient with sarcoidosis and new white matter lesions on brain magnetic resonance imaging.

Tumefactive Demyelination in MOG Ab-Associated Disease, Multiple Sclerosis, and AQP-4-IgG-Positive Neuromyelitis Optica Spectrum Disorder.

BACKGROUND AND OBJECTIVES: Studies on tumefactive brain lesions in myelin oligodendrocyte glycoprotein-immunoglobulin G (IgG)-associated disease (MOGAD) are lacking. We sought to characterize the frequency clinical, laboratory, and MRI features of these lesions in MOGAD and compare them with those in multiple sclerosis (MS) and aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD). METHODS: We retrospectively searched 194 patients with MOGAD and 359 patients with AQP4+NMOSD with clinical/MRI details available from the Mayo Clinic databases and included those with ≥1 tumefactive brain lesion (maximum transverse diameter ≥2 cm) on MRI. Patients with tumefactive MS were identified using the Mayo Clinic medical record linkage system. Binary multivariable stepwise logistic regression identified independent predictors of MOGAD diagnosis; Cox proportional regression models were used to assess the risk of relapsing disease and gait aid in patients with tumefactive MOGAD vs those with nontumefactive MOGAD. RESULTS: We included 108 patients with tumefactive demyelination (MOGAD = 43; AQP4+NMOSD = 16; and MS = 49). Tumefactive lesions were more frequent among those with MOGAD (43/194 [22%]) than among those with AQP4+NMOSD (16/359 [5%], p < 0.001). Risk of relapse and need for gait aid were similar in tumefactive and nontumefactive MOGAD. Clinical features more frequent in MOGAD than in MS included headache (18/43 [42%] vs 10/49 [20%]; p = 0.03) and somnolence (12/43 [28%] vs 2/49 [4%]; p = 0.003), the latter also more frequent than in AQP4+NMOSD (0/16 [0%]; p = 0.02). The presence of peripheral T2-hypointense rim, T1-hypointensity, diffusion restriction (particularly an arc pattern), ring enhancement, and Baló-like or cystic appearance favored MS over MOGAD (p ≤ 0.001). MRI features were broadly similar in MOGAD and AQP4+NMOSD, except for more frequent diffusion restriction in AQP4+NMOSD (10/15 [67%]) than in MOGAD (11/42 [26%], p = 0.005). CSF analysis revealed less frequent positive oligoclonal bands in MOGAD (2/37 [5%]) than in MS (30/43 [70%], p < 0.001) and higher median white cell count in MOGAD than in MS (33 vs 6 cells/µL, p < 0.001). At baseline, independent predictors of MOGAD diagnosis were the presence of somnolence/headache, absence of T2-hypointense rim, lack of T1-hypointensity, and no diffusion restriction (Nagelkerke R 2 = 0.67). Tumefactive lesion resolution was more common in MOGAD than in MS or AQP4+NMOSD and improved model performance. DISCUSSION: Tumefactive lesions are frequent in MOGAD but not associated with a worse prognosis. The clinical, MRI, and CSF attributes of tumefactive MOGAD differ from those of tumefactive MS and are more similar to those of tumefactive AQP4+NMOSD with the exception of lesion resolution, which favors MOGAD.

Autoimmune encephalopathies presenting as dementia of subacute onset and rapid progression.

The terms autoimmune dementia and autoimmune encephalopathy may be used interchangeably; autoimmune dementia is used here to emphasize its consideration in young-onset dementia, dementia with a subacute onset, and rapidly progressive dementia. Given their potential for reversibility, it is important to distinguish the rare autoimmune dementias from the much more common neurodegenerative dementias. The presence of certain clinical features [e.g. facio-brachial dystonic seizures that accompany anti-leucine-rich-glioma-inactivated-1 (LGI1) encephalitis that can mimic myoclonus] can be a major clue to the diagnosis. When possible, objective assessment of cognition with bedside testing or neuropsychological testing is useful to determine the degree of abnormality and serve as a baseline from which immunotherapy response can be judged. Magnetic resonance imaging (MRI) head and cerebrospinal fluid (CSF) analysis are useful to assess for inflammation that can support an autoimmune etiology. Assessing for neural autoantibody diagnostic biomarkers in serum and CSF in those with suggestive features can help confirm the diagnosis and guide cancer search in paraneoplastic autoimmune dementia. However, broad screening for neural antibodies in elderly patients with an insidious dementia is not recommended. Moreover, there are pitfalls to antibody testing that should be recognized and the high frequency of some antibodies in the general population limit their diagnostic utility [e.g., anti-thyroid peroxidase (TPO) antibodies]. Once the diagnosis is confirmed, both acute and maintenance immunotherapy can be utilized and treatment choice varies depending on the accompanying neural antibody present and the presence or absence of cancer. The target of the neural antibody biomarker may help predict treatment response and prognosis, with antibodies to cell-surface or synaptic antigens more responsive to immunotherapy and yielding a better overall prognosis than those with antibodies to intracellular targets. Neurologists should be aware that autoimmune dementias and encephalopathies are increasingly recognized in novel settings, including post herpes virus encephalitis and following immune-checkpoint inhibitor use.

Emerging Nondopaminergic Medications for Parkinson's Disease: Focusing on A2A Receptor Antagonists and GLP1 Receptor Agonists.

Parkinson's disease (PD) is a severe neurodegenerative disease characterized by classic motor features associated with the loss of dopaminergic neurons and appearance of Lewy bodies in the substantia nigra. Due to the complexity of PD, a definitive diagnosis in the early stages and effective management of symptoms in later stages are difficult to achieve in clinical practice. Previous research has shown that colocalization of A2A receptors (A2AR) and dopamine D2 receptors (D2R) may induce an antagonistic interaction between adenosine and dopamine. Clinical trials have found that the A2AR antagonist istradefylline decreases dyskinesia in PD and could be used as an adjuvant to levodopa treatment. Meanwhile, the incretin hormone glucagon-like peptide 1 (GLP1) mainly facilitates glucose homeostasis and insulin signaling. Preclinical experiments and clinical trials of GLP1 receptor (GLP1R) agonists show that they may be effective in alleviating neuroinflammation and sustaining cellular functions in the central nervous system of patients with PD. In this review, we summarize up-to-date findings on the usefulness of A2AR antagonists and GLP1R agonists in PD management. We explain the molecular mechanisms of these medications and their interactions with other neurotransmitter receptors. Furthermore, we discuss the efficacy and limitations of A2AR antagonists and GLP1R agonists in clinical practice.

Variability of cerebrospinal fluid findings by attack phenotype in myelin oligodendrocyte glycoprotein-IgG-associated disorder.

BACKGROUND: The variability in cerebrospinal fluid (CSF) findings of myelin oligodendrocyte glycoprotein-IgG-associated disorder (MOGAD) is not fully elucidated. OBJECTIVE AND METHODS: We retrospectively analyzed 203 attack-associated CSFs from Mayo Clinic patients (2000-2019) with MOGAD. RESULTS: White-blood-cell (>5/mm3) elevation was less with clinically isolated optic neuritis (23%), compared to myelitis, brain/brainstem attacks, or combinations thereof (>70%), p<0.0001. CSF pleocytosis in optic neuritis was more common in patients with coexisting asymptomatic brain and/or spine MRI T2-lesions (53%) than in those without (16%), p=0.005. Abnormal CSF oligoclonal bands ranged from 1% (optic neuritis) to 18% (brain/brainstem attacks). CSF pleocytosis was less common after immunotherapy. CONCLUSIONS: CSF findings in MOGAD vary by attack phenotype and preceding treatment.

Sensational MicroRNAs: Neurosensory Roles of the MicroRNA-183 Family.

MicroRNAs (miRNAs, miRs) are short noncoding RNAs that act to repress expression of proteins from target mRNA transcripts. miRNAs influence many cellular processes including stemness, proliferation, differentiation, maintenance, and survival, and miRNA mutations or misexpression are associated with a variety of disease states. The miR-183 family gene cluster including miR-183, miR-96, and miR-182 is highly conserved among vertebrate and invertebrate organisms, and the miRNAs are coordinately expressed with marked specificity in sensory neurons and sensory epithelial cells. The crucial functions of these miRNAs in normal cellular processes are not yet fully understood, but expectedly dependent upon the transcriptomes of specific cell types at different developmental stages or in various maintenance circumstances. This article provides an overview of evidence supporting roles for miR-183 family members in normal biology of the nervous system, including mechanoreception for auditory and vestibular function, electroreception, chemoreception, photoreception, circadian rhythms, sensory ganglia and pain, and memory formation.

A randomized, double-blinded trial of subarachnoid bupivacaine and fentanyl, with or without clonidine, for combined spinal/epidural analgesia during labor.

UNLABELLED: Subarachnoid clonidine may increase the duration of spinal opioid and local anesthetic analgesia during labor, but it may also increase hypotension and sedation, and the therapeutic range is unclear. We studied 110 term parturients of mixed parity having combined spinal/epidural analgesia during labor in this randomized, double-blinded trial. All received subarachnoid fentanyl 20 micro g and bupivacaine 2.5 mg, plus either saline or clonidine (15, 30, or 45 micro g). Of 101 per-protocol parturients (n = 25, 24, 26, and 26 in Groups C0, C15, C30, and C45, respectively), 22 delivered before the cessation of spinal analgesia. Group demographics and pain scores from Time 0 to 120 min were similar. There was no significant difference among groups in the duration of spinal analgesia (P = 0.09) or in the duration of clonidine groups combined compared with control (median, 120 min [interquartile range, 96-139 min] versus 98 min [80-120 min]; P = 0.07). Systolic blood pressure was significantly lower in all clonidine groups between 40 and 90 min (P = 0.001). Hypotension (P = 0.05) and the requirement for ephedrine (P = 0.02) were dose dependent, but groups had a similar incidence of hypotension. The addition of clonidine 15-45 micro g to subarachnoid fentanyl and bupivacaine reduced blood pressure and did not significantly increase the duration of spinal analgesia. IMPLICATIONS: The addition of 15-45 micro g of clonidine to subarachnoid fentanyl plus bupivacaine did not significantly increase the duration of spinal analgesia but did decrease maternal blood pressure. The results of this study do not support the use of subarachnoid clonidine to prolong the action of spinal labor analgesia when fentanyl plus bupivacaine are administered.

Postcesarean analgesia with spinal morphine, clonidine, or their combination.

UNLABELLED: In this randomized, double-blind trial in 240 women, we investigated the analgesic efficacy and duration of subarachnoid fentanyl 15 microg with morphine, clonidine, or both morphine and clonidine for cesarean delivery. A dose-finding analysis showed similar postoperative efficacy and side effects for groups receiving morphine 100 microg with clonidine 60, 90, or 150 microg. Data from these groups were combined (MC60-150, n = 113) and compared with groups receiving morphine 100 microg (n = 39), clonidine 150 microg (n = 39), or morphine 100 microg plus clonidine 30 microg (n = 41). The four groups differed in the time to patient-controlled morphine use and cumulative morphine consumption (P < 0.0001 and P < 0.001, respectively), with the longest duration and smallest dose in MC60-150. Pain scores were significantly different among groups. Onset of sensory block, ephedrine requirement and incidence of hypotension, patient satisfaction, and recovery were similar. Groups receiving clonidine had greater sedation, those receiving morphine had more severe pruritus, and group MC60-150 showed a trend to more vomiting intraoperatively. Compared with morphine 100 microg or clonidine 150 microg alone, the combination of subarachnoid morphine 100 microg and at least 60 microg of clonidine was found to increase the duration of postcesarean analgesia, reduce opioid requirement, and increase intraoperative sedation. IMPLICATIONS: A multimodal approach to postcesarean analgesia, using subarachnoid bupivacaine, fentanyl, morphine 100 microg, and clonidine 60 microg, improves pain relief compared with morphine 100 microg or clonidine 150 microg alone, but increases intraoperative sedation and may increase perioperative vomiting.