There are no practice guidelines for the treatment of moyamoya disease in pregnant women. The need for such guidelines, however, is evidenced by the numerous case reports, case series, and systematic reviews in the literature highlighting an at-risk period for female moyamoya patients of childbearing age. Here the authors review and interpret the existing literature as it applies to their index patient and expand the literature in support of treating select patients during pregnancy. The authors describe what is to their knowledge the first case reported in the literature of a patient successfully treated with indirect surgical revascularization during the first trimester, who went on to deliver a healthy term baby without complications.
Katie P. Fehnel, Craig D. McClain, and Edward R. Smith
Edward R. Smith, Craig D. McClain, Matthew Heeney, and R. Michael Scott
Many children with sickle cell anemia (SCA) also have clinical and radiographic findings of an arteriopathy suggestive of moyamoya syndrome. These patients may continue to experience strokes despite optimal medical management. The authors wished to define features of moyamoya syndrome associated with SCA and determine the results of surgical revascularization in these patients at early and late follow-up.
The authors reviewed the clinical and radiographic records of all patients with moyamoya syndrome and SCA who underwent cerebral revascularization surgery using a standardized surgical procedure—pial synangiosis—from 1985 to 2008.
Twelve patients had SCA and moyamoya syndrome. Six patients were female and 6 were male. The average patient age at surgery was 11.3 years (range 3–22 years). All patients presented with ischemic symptoms, 11 (92%) with previous transient ischemic attacks, and 10 (83%) with completed strokes. Eleven patients (92%) had radiographic evidence of previous stroke at presentation. None presented with hemorrhage. Surgical treatment included pial synangiosis in all patients. Complications included 1 perioperative stroke, 1 wound infection, and 1 perioperative pneumonia. The average length of hospital stay was 5.7 days (including a 24-hour preoperative admission for hydration) and average blood loss was 92.5 ml/hemisphere (in a total of 19 hemispheres). Clinical and radiographic follow-up with an average of 49 months (range 9–144 months) demonstrated no worsening in neurological status in any patient. No clinical or radiographic evidence of new infarcts was observed in any patient at late follow-up, despite disease progression in 13 (68%) of 19 hemispheres.
The clinical and radiographic features of moyamoya syndrome associated with SCA appear comparable to primary moyamoya disease. Successful treatment of these patients requires multidisciplinary care involving hematologists, anesthesiologists, and neurosurgeons. Operative treatment of moyamoya syndrome using pial synangiosis appears to be safe and confers long-lasting protection against further stroke in this population, and provides an alternative for failure of optimal medical therapy in patients. This study underscores the potential merit of screening patients with SCA for moyamoya syndrome.
A. Byron Young, Linda G. Ott, David Beard, Robert J. Dempsey, Phillip A. Tibbs, and Craig J. McClain
✓ The acute response to injury and infection is manifested by increased synthesis of acute-phase proteins by the liver, an increased white blood cell count, fever, a negative nitrogen balance, and altered serum mineral levels (zinc, iron, and copper). This response is thought to be partially mediated by cytokines such as interleukin-1, but has not been well studied in head-injured patients. In this study, 25 patients were studied for evidence of the acute-phase response extending from hospital admission up to 21 days postinjury. The patients were divided into two groups to determine if severity of injury influenced the response. Group 1 consisted of nine patients with admission peak 24-hour Glasgow Coma Scale (GCS) scores of 4 or less; Group 2 consisted of 16 patients with admission peak 24-hour GCS scores of 8 or greater. All patients demonstrated some evidence of the acute-phase response. Serum alpha-1 acid glycoprotein, ceruloplasmin, and C-reactive protein levels were elevated on admission and throughout the study. Serum albumin and zinc levels were depressed on admission; zinc levels gradually normalized by Day 21 in both groups, but hypoalbuminemia was observed throughout the study period. Serum copper levels were normal on admission but increased to above normal in both groups by Day 11 postinjury. Urinary urea nitrogen excretion was elevated in both groups and peaked on Day 7 for Group 1 and Day 11 for Group 2 patients. The patients with admission GCS scores equal to or less than 4 had overall higher temperatures than were seen in those with GCS scores greater than or equal to 8 (p = 0.009). All patients but one had an elevated white blood cell count on admission. It is concluded that braininjured patients with admission GCS scores of 3 to 4 and 8 to 14 demonstrate an acute-phase response which lasts for at least 3 weeks postinjury. It is speculated that this response is at least partially mediated by increased intraventricular interleukin-1 activity.
Craig J. McClain, Bernhard Hennig, Linda G. Ott, Simeon Goldblum, and A. Byron Young
✓ Severely head-injured patients are hypermetabolic/hypercatabolic and exhibit many aspects of the postinjury acute-phase response. These patients have hypoalbuminemia, hypozincemia, hypoferremia, hypercupria, fever, and increased synthesis of acute-phase proteins such as ceruloplasmin and higher C-reactive protein levels. It has been suggested that increased interleukin-1 (IL-1) in the ventricular fluid may be responsible, at least in part, for these metabolic abnormalities. In the present study, serum albumin levels were evaluated throughout an 18-day study period in 62 head-injured patients receiving aggressive nutritional support. Hypoalbuminemia (mean ± standard error of the mean 3.10 ± 0.2 gm/dl; normal value 3.5 to 5 gm/dl) was observed upon hospital admission; these albumin levels continued to decrease until 2 weeks postinjury, despite aggressive nutritional support. This hypoalbuminemia may be mediated via altered endothelial permeability properties due to endothelial cell dysfunction caused by cytokines such as IL-1. Transendothelial movement of albumin was assayed using a pulmonary artery endothelial cell culture system. Both a crude macrophage supernatant derived from a murine P388D cell line having IL-1 activity (mIL-1) and human recombinant IL-1 (rIL-1) were tested. The amount of albumin transferred was time- and concentration-dependent, with maximal transfer at 24 hours and 20 U of mIL-1 per 0.5 ml of culture medium. Endothelial permeability changes observed after incubation with mIL-1 were confirmed using rIL-1. Compared to control cultures, 20 U of rIL-1 and 20 U of mIL-1 increased albumin transfer across endothelial monolayers 205% and 459%, respectively. These findings suggest that the mechanism of hypoalbuminemia seen after severe head trauma can be explained in part by IL-1-induced endothelial cell injury, resulting in enhanced endothelial permeability to albumin.
Madeline B. Karsten, Steven J. Staffa, Craig D. McClain, Jennifer Amon, and Scellig S. D. Stone
Selective dorsal rhizotomy (SDR) requires significant postoperative pain management, traditionally relying heavily on systemic opioids. Concern for short- and long-term effects of these agents has generated interest in reducing systemic opioid administration without sacrificing analgesia. Epidural analgesia has been applied in pediatric patients undergoing SDR; however, whether this reduces systemic opioid use has not been established. In this retrospective cohort study, the authors compared postoperative opioid use and clinical measures between patients treated with SDR who received postoperative epidural analgesia and those who received systemic analgesia only.
All patients who underwent SDR at Boston Children’s Hospital between June 2013 and November 2019 were reviewed. Treatment used the same surgical technique. Postoperative systemic opioid dosage (in morphine milligram equivalents per kilogram [MME/kg]), pain scores, need for respiratory support, vomiting, bowel movements, and length of hospital and ICU stay were compared between patients who received postoperative epidural analgesia and those who did not, by using the Wilcoxon rank-sum test or Fisher’s exact test.
A total of 35 patients were identified, including 18 females (51.4%), with a median age at surgery of 6.1 years. Thirteen patients received postoperative epidural and systemic analgesia and 22 patients received systemic analgesia only. Groups were otherwise similar, with treatment selection based solely on surgeon routine. Patients who received epidural analgesia required less systemic morphine milligram equivalents/kg on postoperative days (PODs) 0–4 (p ≤ 0.042). Patients who did not receive epidural analgesia were more likely to require respiratory support on POD 1 (45% vs 8%; p = 0.027). Reported pain scores did not differ between groups, although patients receiving epidural analgesia trended toward less severe pain on PODs 1 and 2. Groups did not differ with respect to postoperative vomiting or time to first bowel movement, although epidural analgesia use was associated with a longer hospital stay (median 7 vs 5 days; p < 0.001).
Patients who received postoperative epidural analgesia required less systemic opioid use and had at least equivalent reported pain scores on PODs 1–4, and they required less respiratory support on POD 1, although they remained in the hospital longer when compared to patients who received systemic analgesia only. A larger prospective study is needed to confirm whether epidural analgesia lowers systemic opioid use in children, contributes to a safer postoperative hospital stay, and results in better pain control following SDR.
Craig D. McClain, Sulpicio G. Soriano, Liliana C. Goumnerova, Peter M. Black, and Mark A. Rockoff
✓The authors report unanticipated intraoperative intracranial hemorrhaging in two pediatric neurosurgical patients. Both children were undergoing elective craniotomies with the aid of intraoperative magnetic resonance (iMR) imaging. In both cases, the ability of iMR imaging to aid in diagnosis allowed prompt and definitive treatment of potentially life-threatening complications. These cases illustrate the ability of iMR imaging to aid in differentiating unexpected and/or unexplained intraoperative events in pediatric neurosurgery.
Linda Ott, Byron Young, Reneé Phillips, Craig McClain, Linas Adams, Robert Dempsey, Phillip Tibbs, and U. Yun Ryo
✓ Most patients with moderate to severe head injury initially do not tolerate enteral feedings postinjury. This intolerance is more prolonged than that found in patients suffering other types of trauma. The authors prospectively evaluated 12 patients with moderate to severe head injury (Glasgow Coma Scale score between 4 and 10) throughout their hospitalization for liquid gastric emptying as a possible mechanism for intolerance to enteral feeding. During Week 1, the majority of patients displayed a delay in gastric emptying. Patients also displayed an abnormal biphasic response (gastric emptying faster than normal during the early stage but prolonged later). By Week 2, many patients still had delayed and abnormal biphasic responses to gastric emptying. By Week 3, an improvement was observed with the majority of patients exhibiting rapid gastric emptying, but delays and abnormal biphasic responses were still seen. Patients who initially had rapid or normal gastric emptying tolerated full-strength full-rate feedings significantly earlier compared with those who experienced delayed gastric emptying (8.5 ± 0.5 days vs. 13.7 ± 3.2 days, p < 0.001). All patients tolerated full-strength full-rate feedings by Day 16 postinjury (range 7 to 16 days) except the two patients who displayed delayed gastric emptying for prolonged periods of time (mean 25 days).
This is the first study to longitudinally evaluate gastric emptying following head injury. The authors suggest that patients with moderate to severe head injury often experience alterations in gastric emptying which may affect their ability to tolerate enteral feedings.
Jane A. Norton, Linda G. Ott, Craig McClain, Linas Adams, Robert J. Dempsey, Dennis Haack, Phillip A. Tibbs, and A. Byron Young
✓ Calorie and protein supplementation improves nutritional status. This support may improve outcome and decrease morbidity and mortality in acutely brain-injured patients. Investigators have observed a poor tolerance to enteral feedings after brain injury and have noted that this persists for approximately 14 days postinjury. This delay has been attributed to increased gastric residuals, prolonged paralytic ileus, abdominal distention, aspiration pneumonitis, and diarrhea.
In the present investigation, 23 brain-injured patients with an admission 24-hour peak Glasgow Coma Scale (GCS) score between 4 and 10 were studied for 18 days from hospital admission. The mean duration from injury to initiation of full-strength, full-rate enteral feeding was 11.5 days. Seven of the 23 patients tolerated enteral feedings within the first 7 days following hospital admission (mean 4.3 days), four patients tolerated feedings between 7 and 10 days postadmission (mean 9 days), and 12 patients did not tolerate feedings until after 10 days postinjury (mean 15.9 days). There was a marginally significant relationship between low GCS scores on admission and length of days to enteral feeding tolerance (p = 0.07). A significant inverse relationship was observed between daily peak intracranial pressure (ICP) and time to tolerance of feedings (p = 0.02). There was no significant relationship between feeding tolerance and days to return of bowel sounds (p = 0.12). Serum albumin levels decreased during the investigation (mean ± standard error to the mean: 3.2 ± 0.12 gm/dl on Day 1; 2.7 ± 0.23 gm/dl on Day 16; normal = 3.5 to 5.0 gm/dl), whereas the percentage of patients tolerating feedings increased over the course of the study. The authors conclude that patients with acute severe brain injury do not adequately tolerate feedings via the enteral route in the early postinjury period. Tolerance of enteral feeding is inversely related to increased ICP and severity of brain injury. It is suggested that parenteral nutritional support is required following brain injury until enteral nutrition can be tolerated.
Jimmi Hatton, Robert P. Rapp, Kenneth A. Kudsk, Rex O. Brown, Mark S. Luer, Julie G. Bukar, Sharon A. Chen, Craig J. McClain, Neil Gesundheit, Robert J. Dempsey, and Byron Young
✓ The purpose of this study was to determine the effect of insulin-like growth factor-I (IGF-I) on the catabolic state and clinical outcome of head-injured patients. Thirty-three patients between the ages of 18 and 59 years with isolated traumatic head injury and Glasgow Coma Scale (GCS) scores of 4 to 10 were randomized to one of two groups. All patients received standard neurosurgical intensive care plus aggressive nutritional support; the patients in the treatment group also received intravenous therapy with continuous IGF-I (0.01 mg/kg/hour).
During the 14-day dosing period, the control patients lost weight, whereas treated patients gained weight despite a significantly higher measured energy expenditure and lower caloric intake (p = 0.02). Daily glucose concentrations and nitrogen outputs were greater in control patients (p = 0.03) throughout the study period. During Week 1, only treated patients achieved positive nitrogen balance. Fifteen of 17 treated and 13 of 16 control patients survived the 1st week. No deaths occurred in patients whose serum IGF-I concentrations were higher than 350 ng/ml. Dichotomized Glasgow Outcome Scale scores for patients with baseline GCS scores of 5 to 7 improved from poor to good for eight of 12 treated patients but for only three of 11 control patients (p = 0.06). Eight of 11 treated patients with serum IGF-I concentrations that were at least 350 ng/ml achieved moderate-to-good outcome scores at 6 months, compared to only one of five patients with lower concentrations (p < 0.05). These findings indicate that pharmacological concentrations of IGF-I may improve clinical outcome and nitrogen utilization in patients with moderate-to-severe head injury.