Joshua R. Dusick

Acute secondary adrenal insufficiency after traumatic brain injury: A prospective study

Objective:To determine the prevalence, time course, clinical characteristics, and effect of adrenal insufficiency (AI) after traumatic brain injury (TBI). Design:Prospective intensive care unit–based cohort study. Setting:Three level 1 trauma centers. Patients:A total of 80 patients with moderate or severe TBI (Glasgow Coma Scale score, 3–13) and 41 trauma patients without TBI (Injury Severity Score, >15) enrolled between June 2002 and November 2003. Measurements:Serum cortisol and adrenocorticotropic hormone levels were drawn twice daily for up to 9 days postinjury; AI was defined as two consecutive cortisols of ≤15 &mgr;g/dL (25th percentile for extracranial trauma patients) or one cortisol of <5 &mgr;g/dL. Principal outcome measures included: injury characteristics, hemodynamic data, usage of vasopressors, metabolic suppressive agents (high-dose pentobarbital and propofol), etomidate, and AI status. Main Results:AI occurred in 42 TBI patients (53%). Adrenocorticotropic hormone levels were lower at the time of AI (median, 18.9 vs. 36.1 pg/mL; p = .0001). Compared with patients without AI, those with AI were younger (p = .01), had higher injury severity (p = .02), had a higher frequency of early ischemic insults (hypotension, hypoxia, severe anemia) (p = .02), and were more likely to have received etomidate (p = .049). Over the acute postinjury period, patients with AI had lower trough mean arterial pressure (p = .001) and greater vasopressor use (p = .047). Mean arterial pressure was lower in the 8 hrs preceding a low (≤15 &mgr;g/dL) cortisol level (p = .003). There was an inverse relationship between cortisol levels and vasopressor use (p = .0005) and between cortisol levels within 24 hrs of injury and etomidate use (p = .002). Use of high-dose propofol and pentobarbital was strongly associated with lower cortisol levels (p < .0001). Conclusions:Approximately 50% of patients with moderate or severe TBI have at least transient AI. Younger age, greater injury severity, early ischemic insults, and the use of etomidate and metabolic suppressive agents are associated with AI. Because lower cortisol levels were associated with lower blood pressure and higher vasopressor use, consideration should be given to monitoring cortisol levels in intubated TBI patients, particularly those receiving high-dose pentobarbital or propofol. A randomized trial of stress-dose hydrocortisone in TBI patients with AI is underway.

Endonasal versus supraorbital keyhole removal of craniopharyngiomas and tuberculum sellae meningiomas.

OBJECTIVE Endonasal and supraorbital “eyebrow” craniotomies are increasingly being used to remove craniopharyngiomas and tuberculum sellae meningiomas. Herein, we assess the relative advantages, disadvantages, and selection criteria of these 2 keyhole approaches. METHODS All consecutive patients who had endonasal or supraorbital removal of a craniopharyngioma or tuberculum sellae meningioma were analyzed. RESULTS Of 43 patients, 22 had a craniopharyngioma (18 endonasal, 4 supraorbital), and 21 had a meningioma (12 endonasal, 7 supraorbital, 2 both routes); 33% had prior surgery. Craniopharyngiomas were primarily retrochiasmal in location in 78% of endonasal cases versus 25% of supraorbital cases (P = 0.08). Meningiomas were larger when approached by the supraorbital route versus the endonasal route (33 ± 10 versus 25 ± 8 mm, respectively; P = 0.008). Endoscopy was used in 84% of endonasal approaches and in 31% of supraorbital approaches (P = 0.001). Of patients having first-time surgery for a craniopharyngioma (n = 14) or meningioma (n = 15), total/near total removal was achieved in 83% and 80% of patients by the endonasal route and in 50% and 80% of patients by the supraorbital route, respectively. Vision improved in 87% and 70% of patients who had surgery by an endonasal versus supraorbital route, respectively (P = 0.3). Visual deterioration occurred in 2 patients with meningiomas, 1 by endonasal (7%), and 1 by supraorbital (11%) removal. The endonasal approach was associated with a higher rate of postoperative cerebrospinal fluid leaks (16 versus 0%; P = 0.3), 4 of 5 of which occurred in patients with meningioma. CONCLUSION The endonasal route is preferred for removal of most retrochiasmal craniopharyngiomas, whereas the supraorbital route is recommended for meningiomas larger than 30 to 35 mm or with growth beyond the supraclinoid carotid arteries. For smaller midline tumors, either approach can be used, depending on surgeon experience and tumor anatomy. Compared with traditional craniotomies, the major limitation of both approaches is a narrow surgical corridor. The endonasal approach has the added challenges of restricted lateral suprasellar access, a greater need for endoscopy, and a more demanding cranial base repair.

PITUITARY HORMONAL LOSS AND RECOVERY AFTER TRANSSPHENOIDAL ADENOMA REMOVAL

OBJECTIVETranssphenoidal adenomectomy carries the possibility of new pituitary failure and recovery. Herein, we present rates and determinants of postoperative hormonal status. METHODSAll consecutive patients who underwent endonasal transsphenoidal adenoma removal over an 8-year period were analyzed. Those with previous sellar radiotherapy were excluded. Pre- and postoperative hormonal status (at least 3 mo after surgery) were determined and correlated with clinical parameters using a multivariate statistical model. RESULTSOf 444 patients (median age 45 years, 75% macroadenoma, 19% with multiple operations), 9 had preoperative panhypopituitarism. Of the remaining 435 patients, new hypopituitarism occurred in 5.5% of patients (anterior loss in 5%; permanent diabetes insipidus in 2.1%; including 2 patients who had total hypophysectomy). Of 346 patients with preoperative hormonal dysfunction, 170 (49%) had improved function. “Stalk compression” hyperprolactinemia resolved in 73% of 133 patients; recovery of at least 1 other anterior axis (excluding isolated hypogonadism associated with “stalk compression” hyperprolactinemia) occurred in 24% of 209 patients. Multivariate analysis showed that new hypopituitarism was most strongly associated with larger tumor diameter (P = 0.04). Of 223 patients with an endocrine-inactive adenoma, new hypopituitarism was seen in 0, 7.2, and 13.6% of patients with tumor diameters of <20, 20 to 29, and ≥30 mm, respectively (P = 0.005). Multivariate analysis revealed that resolution of hypopituitarism was related to younger age (39 versus 52 years, P < 0.0001), absence of an intraoperative cerebrospinal fluid leak and, in patients with an endocrine-inactive adenoma, absence of systemic hypertension (24% versus 6%, P = 0.009). CONCLUSIONAfter transsphenoidal adenomectomy, new unplanned hypopituitarism occurs in approximately 5% of patients, whereas improved hormonal function occurs in 50% of patients. The likelihood of new hormonal loss or recovery appears to depend on several factors. New hypopituitarism occurs most commonly in patients with tumors larger than 20 mm in size, whereas hormonal recovery is most likely to occur in younger, nonhypertensive patients and those without an intraoperative cerebrospinal fluid leak.

Increased pentose phosphate pathway flux after clinical traumatic brain injury : a [1,2.13C2]glucose labeling study in humans

Patients with traumatic brain injury (TBI) routinely exhibit cerebral glucose uptake in excess of that expected by the low levels of oxygen consumption and lactate production. This brings into question the metabolic fate of glucose. Prior studies have shown increased flux through the pentose phosphate cycle (PPC) during cellular stress. This study assessed the PPC after TBI in humans. [1,2-13C2]glucose was infused for 60 mins in six consented, severe-TBI patients (GCS < 9) and six control subjects. Arterial and jugular bulb blood sampled during infusion was analyzed for 13C-labeled isotopomers of lactate by gas chromatography/mass spectroscopy. The product of lactate concentration and fractional abundance of isotopomers was used to determine blood concentration of each isotopomer. The difference of jugular and arterial concentrations determined cerebral contribution. The formula PPC = (m1/m2)/(3 + (m1/m2)) was used to calculate PPC flux relative to glycolysis. There was enrichment of [1,2-13C2]glucose in arterial-venous blood (enrichment averaged 16.6% in TBI subjects and 28.2% in controls) and incorporation of 13C-label into lactate, showing metabolism of labeled substrate. The PPC was increased in TBI patients relative to controls (19.6 versus 6.9%, respectively; P = 0.002) and was excellent for distinguishing the groups (AUC = 0.944, P < 0.0001). No correlations were found between PPC and other clinical parameters, although PPC was highest in patients studied within 48 h of injury (averaging 33% versus 13% in others; P = 0.0006). This elevation in the PPC in the acute period after severe TBI likely represents a shunting of substrate into alternative biochemical pathways that may be critical for preventing secondary injury and initiating recovery.

The role of the endoscope in the transsphenoidal management of cystic lesions of the sellar region

Cystic mass lesions within the sella turcica are common, and they include cystic pituitary adenomas, craniopharyngiomas, Rathke’s cleft cysts, arachnoid cysts, and other entities. Until recently, such lesions were typically removed by a microsurgical transsphenoidal route. Given the increased use of the endoscope in transsphenoidal surgery, we evaluated the potential benefits of this tool in the treatment of such lesions. Between January 1997 and March 2005, 76 consecutive patients with sellar–suprasellar cystic lesions treated in three Neurosurgical Divisions underwent transsphenoidal removal in which the endoscope was used at least during the sellar step of the procedure (endoscope-assisted or fully endoscopic). The series consisted of 26 pituitary macroadenomas, 20 Rathke’s cleft cysts, 18 craniopharyngiomas, 10 arachnoid cysts, one craniopharyngioma associated with an adrenocorticotropic hormone-secreting adenoma, and one chordoid glioma. Rigid 4-mm endoscopes (0°, 30°, and/or 45°) were used, and the advantages and limits of the endoscope during the sellar step of the procedure were recorded. Endoscopic exploration after lesion evacuation was generally easier and of greatest efficacy when the residual cystic cavity was larger as opposed to smaller. The use of angled endoscopes was optimal in larger residual cavities. Early descent of the suprasellar cistern, bleeding inside the residual cyst cavity, and a small sella were the most common causes preventing thorough exploration of the residual cavity after its evacuation. In no cases did the endoscope cause injury during the sellar cavity exploration. Endoscopic exploration of the sellar cavity during transsphenoidal surgery offers both general and specific advantages in the treatment of a variety of different cystic sellar lesions. Its routine use during transsphenoidal surgery for such lesions is recommended to achieve maximal and safe tumor removal.

Chapter 1: pathophysiology of hypopituitarism in the setting of brain injury

The complex pathophysiology of traumatic brain injury (TBI) involves not only the primary mechanical event but also secondary insults such as hypotension, hypoxia, raised intracranial pressure and changes in cerebral blood flow and metabolism. It is increasingly evident that these initial insults as well as transient events and treatments during the early injury phase can impact hypothalamic-pituitary function both acutely and chronically after injury. In turn, untreated pituitary hormonal dysfunction itself can further hinder recovery from brain injury. Secondary adrenal insufficiency, although typically reversible, occurs in up to 50% of intubated TBI victims and is associated with lower systemic blood pressure. Chronic anterior hypopituitarism, although reversible in some patients, persists in 25–40% of moderate and severe TBI survivors and likely contributes to long-term neurobehavioral and quality of life impairment. While the rates and risk factors of acute and chronic pituitary dysfunction have been documented for moderate and severe TBI victims in numerous recent studies, the pathophysiology remains ill-defined. Herein we discuss the hypotheses and available data concerning hypothalamic-pituitary vulnerability in the setting of head injury. Four possible pathophysiological mechanisms are considered: (1) the primary brain injury event, (2) secondary brain insults, (3) the stress of critical illness and (4) medication effects. Although each of these factors appears to be important in determining which hormonal axes are affected, the severity of dysfunction, their time course and possible reversibility, this process remains incompletely understood.

Clinical and Angiographic Outcomes From Indirect Revascularization Surgery for Moyamoya Disease in Adults and Children: A Review of 63 Procedures

BACKGROUND:Several forms of indirect cerebral revascularization have been proposed to promote neovascularity to the ischemic brain. OBJECTIVE:To present clinical and angiographic outcomes of indirect revascularization by encephaloduroarteriosynangiosis and burr holes for the treatment of Moyamoya disease in adults and children. METHODS:Data from 63 hemispheres treated in 42 patients (average age, 30 years; 33 adults; 30 female patients; median follow-up, 14 months) were reviewed. In hemispheres with preoperative and postoperative (6- to 12-month) angiograms available, superficial temporal artery (STA) and middle meningeal artery (MMA) diameters were measured. Preoperative and postoperative corrected arterial sizes were compared. RESULTS:Seven patients (17%) had transient ischemic attacks that resolved within 1 month of surgery. No patients suffered moyamoya-related hemorrhage after treatment. Two patients developed additional symptoms many years after surgery. In 18 hemispheres with preoperative and postoperative angiograms, there was an average postoperative increase in STA and MMA diameters of 51% (P = .003) and 49% (P = .002), respectively. Both children and adults displayed revascularization. Two patients did not demonstrate increased vessel size. STA blush and new branches and MMA blush and new branches were identified in 12, 14, 14, and 16 hemispheres, respectively. Angiographic blush was identified in 59% of frontal and 19% of parietal burr holes (P = .03). Surgical complications included 2 subdural hemorrhages requiring evacuation and 2 new ischemic deficits (1 transient). CONCLUSION:Indirect revascularization by encephaloduroarteriosynangiosis and burr holes for moyamoya results in long-term resolution of ischemic and hemorrhagic manifestations in 95% of adults and children. The MMA appears to contribute significantly to the revascularization on follow-up angiograms with increased size and neovascularity comparable to that of the STA. Angiographically, parietal burr holes do not contribute as significantly as frontal burr holes.

Suboptimal sphenoid and sellar exposure: a consistent finding in patients treated with repeat transsphenoidal surgery for residual endocrine-inactive macroadenomas.

OBJECTIVE:In a series of patients with residual endocrine-inactive macroadenomas who underwent repeat surgery, we assess possible reasons for prior subtotal removal, reoperative success, complication rates, and patient impressions. METHODS:All patients were identified who had a prior subtotal removal of an endocrine-inactive macroadenoma and were reoperated on for residual sellar tumor via an endonasal approach. RESULTS:Over 6 years, of 188 consecutive patients with endocrine-inactive adenomas, 30 (16%) had repeat surgery (age, 15–77 yr; median interval between surgeries, 25 mo; median follow-up, 20 mo). Maximal tumor diameter averaged 2.4 ± 0.9 cm. At reoperation, a suboptimal bony exposure was seen in all 30 patients: at the sphenoid keel, the sella, or both in 97, 93, and 90% of patients, respectively. Cavernous sinus invasion was seen in 16 (53%) patients and a fibrous/rubbery consistency in 12 (40%). Gross total tumor removal was achieved in 17 (57%) patients, including 12 of 14 (86%) with noninvasive tumors and 5 of 16 (31%) with invasive tumors, (P < 0.01). All six fibrous/rubbery but noninvasive tumors were totally removed. Of 16 patients with preoperative visual loss, 15 (94%) improved. Complications included one each of cerebrospinal fluid leak, delayed sinusitis, and new hypothyroidism. In 17 patients with prior sublabial surgery who completed questionnaires, the second (endonasal) surgery was associated with an easier recovery, less pain, and better nasal airflow in 82, 88, and 93%, respectively (P < 0.0001). CONCLUSION:In patients with residual sellar endocrine-inactive adenomas, a suboptimal opening at the sphenoid keel or sella at the first surgery and a high proportion of fibrous/rubbery tumors likely contributed to prior subtotal removal of otherwise accessible tumor. With a wider exposure, most noninvasive tumors can be totally removed, whereas invasive tumors can be effectively debulked. An endonasal reoperation is well tolerated with a low complication rate.

Acute gonadotroph and somatotroph hormonal suppression after traumatic brain injury.

Hormonal dysfunction is a known consequence of moderate and severe traumatic brain injury (TBI). In this study we determined the incidence, time course, and clinical correlates of acute post-TBI gonadotroph and somatotroph dysfunction. Patients had daily measurement of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, estradiol, growth hormone, and insulin-like growth factor-1 (IGF-1) for up to 10 days post-injury. Values below the fifth percentile of a healthy cohort were considered abnormal, as were non-measurable growth hormone (GH) values. Outcome measures were frequency and time course of hormonal suppression, injury characteristics, and Glasgow Outcome Scale (GOS) score. The cohort consisted of 101 patients (82% males; mean age 35 years; Glasgow Coma Scale [GCS] score <or=8 in 87%). In men, 100% had at least one low testosterone value, and 93% of all values were low; in premenopausal women, 43% had at least one low estradiol value, and 39% of all values were low. Non-measurable GH levels occurred in 38% of patients, while low IGF-1 levels were observed in 77% of patients, but tended to normalize within 10 days. Multivariate analysis revealed associations of younger age with low FSH and low IGF-1, acute anemia with low IGF-1, and older age and higher body mass index (BMI) with low GH. Hormonal suppression was not predictive of GOS score. These results indicate that within 10 days of complicated mild, moderate, and severe TBI, testosterone suppression occurs in all men and estrogen suppression occurs in over 40% of women. Transient somatotroph suppression occurs in over 75% of patients. Although this acute neuroendocrine dysfunction may not be TBI-specific, low gonadal steroids, IGF-1, and GH may be important given their putative neuroprotective functions.

Endonasal microscopic removal of clival chordomas

INTRODUCTION Clival chordomas have traditionally been removed using a variety of anterior and lateral skull base approaches. Herein, we evaluate the outcomes of patients who underwent an extended endonasal transsphenoidal removal of a clival chordoma. METHOD All consecutive patients with a clival chordoma treated using an endonasal microscope approach were identified. In 8 cases, frameless surgical navigation was used, and in 4 cases, endoscopic assistance was used. Patients treated with prior radiotherapy were excluded. RESULT Over 5 years, 18 procedures were performed on 14 patients (7 females; mean age, 47 years). Patients were followed from 3 to 58 months (median, 20 months). Mean tumor diameter was 32 +/- 17 mm; 7 (50%) patients had intradural extension. Postoperative MRIs after the initial operation showed gross total, near-total (>90%), and subtotal resection in 43%, 43%, and 14% of patients, respectively. Use of the endoscope was associated with gross total or near-total tumor removal in 4 of 4 cases. Tumor regrowth occurred in 2 (14%) cases 10 and 12 months after the initial surgery and before radiotherapy. Two patients had multiple operations, in one as a planned staged operation, and in the other, 3 additional debulkings were performed despite an initial gross total removal. Nine patients, all with CS invasion, had subsequent stereotactic radiation. Of 10 patients with cranial neuropathy, 80% improved or resolved including 75% and 67% of sixth and fifth CN palsies, respectively. Complications included one each of adrenal insufficiency and chemical meningitis. There were no CSF leaks or new neurological deficits. CONCLUSION In this small series with relatively short follow-up, endonasal microscopic removal of clival chordomas proved safe and elfective with gross total or near-total removal in 86% of patients and improvement of cranial neuropathy in 80% of patients. Endoscopy for aiding tumor removal and assessing completeness of resection, as well as surgical navigation, are recommended for all cases.