Treatment outcome of metastasis to the pituitary gland: a case series of 21 patients with pathological diagnosis.

OBJECTIVE: The aim of this study was to report the treatment course of histologically confirmed metastases to the pituitary gland (pituitary metastasis). METHODS: The Mayo data explorer was used to find patients with pituitary metastasis. Twenty-one patients were identified between the years 2001 and 2021, and their data were retrospectively collected. RESULTS: The most common primary cancer origin was lung in men (45%) and breast in women (33%). The median age was 66 years (IQR 56-68 years). Patients presented with headache (67% [14/21]), vision problems (86% [18/21]), anterior hypopituitarism (71% [15/21]), and arginine vasopressin deficiency (38% [8/21]). Pituitary metastases were found before the diagnosis of the primary cancer in 5 patients (24%). The mean ± SD tumor size was 2.0 ± 0.7 cm, and 90% (19/21) presented as a solitary pituitary mass with no other intracranial metastatic lesions. Common radiological features were pituitary stalk thickening (90% [19/21]), cavernous sinus involvement (71% [15/21]), and constriction at the diaphragma sellae (52% [11/21]). Transsphenoidal surgery was performed in 20 patients, and subtotal resection was most frequently attained (76% [16/21]). Fourteen patients (67%) had adjuvant radiation therapy, and 15 patients (71%) were treated with systemic therapy. The median time from surgery to the initiation of radiation therapy was 16 days (IQR 11-21 days), and that from surgery to the initiation of systemic therapy was 5.0 months (IQR 1.5-14 months). During management, headaches improved in 57% (8/14) and vision problems improved in 61% (11/18) of cases; new hypopituitarism occurred in 5 patients. Six patients developed recurrence, and the median progression-free survival was 24 months (95% CI 5.4-43 months). After recurrence, 1 patient with adenoid cystic carcinoma was treated with rescue radiotherapy twice, and 4 patients responded well to systemic therapy. The median overall survival (OS) was 25 months (95% CI 7.1-43 months). The mean OS was better in patients with neuroendocrine lung tumor (261 months) and papillary thyroid carcinoma (80 months) and worse in patients with small cell lung cancer (4 months) and unknown origin (5 months). CONCLUSIONS: Surgery with or without adjuvant radiotherapy is effective for mass reduction, rapid symptomatic improvement of vision and headaches, and definitive diagnosis. Even after local tumor control failure, some patients still benefit from radiation and/or systemic therapy.

Surgical management of sacral schwannomas: a 21-year mayo clinic experience and comparative literature analysis.

INTRODUCTION: Sacral and presacral schwannomas are rare, accounting for a minority of spinal schwannomas. We present our institution's experience surgically treating spinal schwannomas and compare it to the literature. METHODS: Data were collected for 27 patients treated surgically for sacral or presacral schwannoma between 1997 and 2018 at all Mayo Clinic locations and 93 patients in the literature. Kaplan-Meier disease-free survival analysis was conducted. Unpaired two-sample t tests and Fisher's exact tests assessed statistical significance between groups. RESULTS: Our patients and those in the literature experienced a similar age at diagnosis (49.9 y/o. vs 43.4 y/o., respectively). Most of our patients (59.3%) reported full recovery from symptoms, while a minority reported partial recovery (33.3%) and no recovery (11.1%). A smaller percentage in the literature experienced full recovery (31.9%) and partial recovery (29.8%) but also no recovery (1.1%). Our patients experienced fewer complications (14.8% versus 25.5%). Disease-free survival curves for all patients showed no significant variation in progression by extent of resection of schwannoma (log-rank P = 0.26). No lesion progression was associated with full or partial symptom improvement (p = 0.044), and female patients were more likely to undergo resection via a posterior approach (p = 0.042). CONCLUSION: Outcomes of patients with sacral or presacral schwannomas vary based on patient demographics, tumor characteristics, symptoms, and surgical treatment. Among the range of symptoms experienced by these patients, the most common is pain. Prognosis improves and overall survival is high when the surgical approach towards sacral schwannomas is prepared and executed appropriately.

Surgical outcomes of medically failed prolactinomas: a systematic review and meta-analysis.

PURPOSE: In Prolactinomas, surgery or radiation are reserved for DA failure due to tumor resistance, intolerance to medication-induced side-effects, or patient preference. This systematic review and meta-analysis summarizes the currently available literature regarding the effectiveness of surgery to treat prolactinomas in patients who have failed DA therapy. METHOD: A literature search was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for studies that reported outcomes of medically resistant and intolerant prolactinoma treated surgically. RESULTS: 10 articles (Total N = 816, Surgery N = 657) met the inclusion criteria. 38% of patients who underwent surgery following DA failure achieved remission without need for further treatment (p < 0.001, I2 = 67.09%) with a median follow-up of 49.2 +/- 40 months. 62% achieved remission with multimodal treatment (p < 0.001, I2 = 93.28%) with a median follow-up of 53 +/- 39.8 months. 16% of cases demonstrated recurrence after early remission (p = 0.02, I2 = 62.91%) with recurrence occurring on average at 27 +/- 9 months. Overall, 46% of patients required reinstitution of postoperative DA therapy at last follow up (p < 0.001, I2 = 82.57%). Subgroup analysis of macroprolactinoma and microprolactinoma has demonstrated that there is no statistical significance in achieving long-term remission with surgery stand-alone in macroprolactinoma group (p = 0.49) although 43% of patients were able to achieve remission with multimodal therapy at last follow-up in the same group (p < 0.001, I2 = 86.34%). CONCLUSIONS: This systematic review and meta-analysis revealed 38% of operated patients achieved remission, while 62% achieved remission when additional modes of therapy were implemented. Therefore, although surgery has not been initial therapeutic choice for prolactinoma, it plays a significant role in medically failed prolactinoma care.

Clinical, biological, radiological, and pathological comparison of sparsely and densely granulated somatotroph adenomas: a single center experience from a cohort of 131 patients with acromegaly.

PURPOSE: Growth hormone-producing pituitary adenomas are divided into two clinically relevant histologic subtypes, densely (DG-A) and sparsely (SG-A) granulated. Histologic subtype was evaluated in a large cohort of patients with acromegaly, separating DG-A and SG-A, and correlated with clinicopathological characteristics. METHODS: Patients with acromegaly undergoing surgery as initial therapy between 1995 and 2015 were identified. Histologic subtype was determined by keratin expression pattern with CAM5.2 and correlated with clinical and imaging parameters, somatostatin receptor subtype 2 (SST2) expression, post-surgical remission rate, and application of a prognostic scoring system incorporating proliferation and invasiveness. RESULTS: One hundred thirty-one patients were included. Tumors were classified as DG-A (75, 57.3%), SG-A (29, 22.1%), intermediate (I-A) (9, 6.9%), and unclassified (18, 13.7%) when CAM5.2 was negative. DG-A and I-A were combined for analysis (DG/I-A) and compared to SG-A. Age, gender, proliferation, and post-surgical remission did not differ. SG-A were larger [2 vs. 1.5 cm (median), p = 0.03], more frequently invasive [65.5% vs. 32.9%, p = 0.004], associated with higher MRI T2-weighted signal ratio [1.01 vs. 0.82 (median), p = 0.01], showed lower SST2 expression (p < 0.0001), and scored higher in the prognostic classification (p = 0.004). Surgical remission occurred in 41.7% DG/I-A and 41.4% SG-A (p = 1.0). On multivariate analysis, absence of invasion (p = 0.009) and lower pre-operative IGF-1 index (p = 0.0002) were associated with post-surgical remission. CONCLUSION: CAM5.2 allowed distinction between DG/I-A and SG-A in most but not all cases. Histologic subtype did not predict surgical outcome. Absence of invasion and lower pre-operative IGF-1 index were the only significant predictors of post-surgical remission in this cohort.

SURGICAL OUTCOMES OF PROLACTINOMAS IN RECENT ERA: RESULTS OF A HETEROGENOUS GROUP.

OBJECTIVE: Prolactinomas are primarily treated with medical therapy. Given the efficacy of dopamine agonists (DAs), surgery has remained a second-line treatment option. Despite medical therapy, some tumors display resistance and/or patients maybe intolerant of DA and require alternative treatment options. We examined the indications, efficacy, and safety of pituitary surgery for the treatment of prolactinomas. METHODS: We performed a retrospective analysis of all patients who had surgery for a prolactinoma at our institution from January 1993 to October 2014. RESULTS: Seventy-eight patients (46 females, mean age 32 years) with a median follow-up of 12 months were analyzed. Macroprolactinomas accounted for 65% (51/78) of tumors. The most common indication for surgery in microprolactinomas was medication intolerance (37%, 10/27) and medication failure (33%, 17/51) in macroprolactinomas. DA therapy had been tried in 76% (59/78) patients prior to surgery. Following surgery, long-term remission was seen in 72% (18/25) of micro-adenomas and 20% (10/49) of macro-adenomas (32% [10/32] in those without cavernous sinus invasion). Despite persistent disease in those with macro-adenomas (34% [13/38]) were able to remain off medication. Early surgical failure was more common in males (P = .004) and those with large (P≤.001) or atypical (P = .003) adenomas. CONCLUSION: Surgery can result in prolonged remission in 72% of microprolactinomas. Despite lower remission rates among macroprolactinomas, a third of patients with persistent disease did not require medical therapy. Therefore, surgery remains an alternative effective treatment option, particularly for those who are intolerant or resistant to medical therapy. ABBREVIATIONS: ACTH = adrenocorticotropic hormone CI = confidence interval CSF = cerebrospinal fluid DA = dopamine agonist IQR = interquartile range MIB-1 = methylation inhibiting binding protein-1 VF = visual field.

Total lumbar facetectomy without fusion: short and long term follow-up in a single surgeon series.

BACKGROUND: Total lumbar facetectomy may be advantageous for exposure or to completely free a constricted nerve root. OBJECTIVE: We retrospectively reviewed a single surgeon series without fusion for short and long term outcomes regarding radicular pain relief, subsequent relevant surgeries, and any identifiable instability. METHODS: All operations in which a single, total lumbar facetectomy was performed were reviewed. A total of 222 patients were identified with a minimal follow-up of 3 months; 187 (84.2%) were available for long term follow-up ≥1 year by continued accessible health care records, correspondence, or mailed questionnaire. RESULTS: Short term success (3-month follow-up) for radicular pain relief in 222 patients found the following results: 176 patients (79.3%) had no pain or minimal pain, and 16 patients (7.2%) were improved, and thus resulting in 192 (86.5%) with no pain, or improved radicular pain. 30 patients (13.5%) were postoperative failures at 3 months. Long term follow-up ≥1 year was available for 187 patients (84.2%); (range 1-17 years; mean 7 years); found the following results: 23/30 (76.6%) short term surgical failures remained failures in long term follow-up with (7 patients) or without (16 patients) further surgery of any kind; 13/16 improved patients at long term follow-up remained improved (6), were pain free (6), or worse (1); 19/151 no or minimal pain patients at long term follow-up recurred or worsened by 1 year or longer, 12/19 pursued a second surgery with (9) or without (4) fusion and many improved. A total of 13 patients had a subsequent fusion operation (6.95%). DISCUSSION: Most patients do well in the short term for radicular pain relief. Most patients continue to do well in long term follow-up. Surgically induced clinical instability is uncommon in this highly selected series.

Intracranial Pressure Monitoring in Acute Liver Failure: Institutional Case Series.

Acute liver failure (ALF) has been associated with cerebral edema and elevated intracranial pressure (ICP), which may be managed utilizing an ICP monitor. The most feared complication of placement is catastrophic intracranial hemorrhage in the setting of severe coagulopathy. Previous studies reported hemorrhage rates between 3.8-22 % among various devices, with epidural catheters having lower hemorrhage rates and precision relative to subdural bolts and intraparenchymal catheters. We sought to identify institutional hemorrhagic rates of ICP monitoring in ALF and its associated factors in a modern series guided by protocol implantation. Patient records treated for ALF with ICP monitoring at Mayo Clinic in Rochester, MN from 1995 to 2014 were reviewed. Protocalized since 1995, epidural (EP) ICP monitors were first used followed by intraparenchymal (IP) for stage III-IV hepatic encephalopathy. The following variables and outcomes were collected: patient demographics, ICPs and treatment methods, laboratory data, imaging studies, number of days for ICP monitoring, radiographic and symptomatic hemorrhage rates, orthotopic liver transplantation rates, and death. A total of 20 ICP monitors were placed for ALF, 7 EP, and 13 IP. International normalized ratio (INR) at placement of an EP monitor was 2.4 (1.7-3.2) with maximum of 2.7 (2.0-3.6) over the following 2.3 (1-3) days. Mean EP ICP at placement was 36.3 (11-55) and maximum of 43.1 (20-70) mm Hg. INR at placement of an IP monitor was 1.3 (<0.8-3.0) with maximum value of 2.9 (1.6-5.4) over the following 4.2 (2-6) days. Mean IP ICP at placement was 9.9 (2-19) and maximum was 39.8 (11-100) mm Hg. There was one asymptomatic hemorrhage in the EP group (14.3 % hemorrhage rate) and two hemorrhages in the IP group (hemorrhage rate was 15.4 %), both of which were fatal. Overall mortality rate in the EP group was 71.4 % (5/7) with two patients receiving transplantation, and one death in the transplant group. Overall mortality in the IP group was 38.5 % (5/13) with nine liver transplantations; three of the transplanted patients died, including one of the fatal hemorrhages due to monitor placement. Intracranial hypertension is common in patients with ALF with severe hepatic encephalopathy. Monitored patients in both groups experienced elevations of ICP in the setting of intermittent coagulopathy. Severity of coagulopathy did not influence hemorrhage rate. Yet, hemorrhages related to IP monitoring can be catastrophic and may add to the overall mortality.

A Novel Preoperative Score to Predict Long-Term Biochemical Remission in Patients with Growth-Hormone Secreting Pituitary Adenomas.

OBJECTIVE: Transsphenoidal surgery (TSS) is considered the treatment of choice in most patients with growth hormone (GH)-secreting pituitary adenomas. Several preoperative factors have been studied to predict postsurgical remission. Our objective was to design a score that could be used in the preoperative setting to identify patients that will achieve long-term biochemical remission after TSS. METHODS: A retrospective analysis of consecutive patients with GH-secreting pituitary adenomas that underwent TSS in our institution from 2000 to 2015 who fulfilled prespecified criteria were included. Logistic regression methods were used to evaluate independent preoperative variables predicting long-term remission. Beta coefficients were used to create a scoring system for clinical practice. RESULTS: Sixty-eight patients were included, with a mean follow-up time of 87 months. Twenty (29%) patients had tumors with a Knosp grade ≥ 3A. Gross-total resection was achieved in 43 (63%) patients. Thirty-three (48%) patients had long-term biochemical remission after TSS. In a multivariate analysis, the following variables were statistically significantly associated with long-term biochemical remission: age, adenoma size (diameter), Knosp grade, GH level, and insulin growth-factor 1index 1 at diagnosis. A score of <3 out of 8 total points was identified as a cutoff associated with long-term remission, with a sensitivity of 91.4% and specificity of 72.7% (AUC 0.867, OR 28.44, 95% CI 6.94-116.47, P = < 0.001). CONCLUSIONS: A novel, simple, easy-to-use scoring system was created to identify patients with the highest chances of long-term biochemical remission following TSS. This scale should be prospectively validated in a multicenter study before widespread adoption.

Surgical management of malignant melanotic nerve sheath tumors: an institutional experience and systematic review of the literature.

OBJECTIVE: Malignant melanotic nerve sheath tumors are rare tumors characterized by neoplastic melanin-producing Schwann cells. In this study, the authors report their institution's experience in treating spinal and peripheral malignant melanotic nerve sheath tumors and compare their results with the literature. METHODS: Data were collected from 8 patients who underwent surgical treatment for malignant melanotic nerve sheath tumors between 1996 and 2023 at Mayo Clinic and 63 patients from the literature. Time-to-event analyses were performed for the combined group of 71 cases to evaluate the risk of recurrence, metastasis, and death based on tumor location and type of treatment received. Unpaired 2-sample t-tests and Fisher's exact tests were used to determine statistical significance between groups. RESULTS: Between 1996 and 2023, 8 patients with malignant melanotic nerve sheath tumors underwent surgery at the authors' institution, while 63 patients were identified in the literature. The authors' patients and those in the literature had the same mean age at diagnosis (43 years). At the authors' institution, 5 patients (63%) experienced metastasis, 6 patients (75%) experienced long-term recurrence, and 5 patients (62.5%) died. In the literature, most patients (60.3%) were males, with a peak incidence between the 4th and 5th decades of life. Nineteen patients (31.1%) were diagnosed with Carney complex. Nerve root tumors accounted for most presentations (n = 39, 61.9%). Moreover, 24 patients (38.1%) had intradural lesions, with 54.2% (n = 13) being intramedullary and 45.8% (n = 11) extramedullary. Most patients underwent gross-total resection (GTR) (n = 41, 66.1%), followed by subtotal resection (STR) (n = 12, 19.4%), STR with radiation therapy (9.7%), and GTR with radiation therapy (4.8%). Sixteen patients (27.6%) experienced metastasis, 23 (39.7%) experienced recurrence, and 13 (22%) died. Kaplan-Meier analyses showed no significant differences among treatment approaches in terms of recurrence-free, metastasis-free, and overall survival (p > 0.05). Similar results were obtained when looking at the differences with respect to intradural versus nerve root location of the tumor (p > 0.05). CONCLUSIONS: Malignant melanotic nerve sheath tumors are rare tumors with a high potential for malignancy. They carry a dismal prognosis, with a pooled local recurrence rate of 42%, distant metastasis rate of 27%, and mortality rate of 26%. The findings from this study suggest a trend favoring the use of GTR alone or STR with radiation therapy over STR alone. Mortality was similar regardless, which highlights the need for the development of effective treatment options to improve survival in patients with melanotic schwannomas.

Angiographic cross-filling between inferior petrosal sinuses and alteration of adrenocorticotropic hormone sampling results for tumor localization in Cushing disease.

OBJECTIVE: Inferior petrosal sinus (IPS) sampling (IPSS) is a diagnostic procedure used to guide diagnostic localization of imaging-negative adrenocorticotropic hormone (ACTH)-secreting pituitary microadenomas. However, the efficacy of IPSS has been suboptimal at accurately lateralizing the adenoma, reducing surgical cure rates and leading to unintended pituitary dysfunction due to the added exploration. One rationale for the occasional imprecision is the existence of additional petrosal sinus collateral channels that connect the IPS bilaterally, which may lead to false localization results during sampling. The aim of this study was to explore a potential connection between normal anatomical variation in the angioarchitecture of the IPSs and the ACTH results obtained in subsequent IPSS tests. METHODS: A retrospective review was performed on all cases between 1998 and 2013 involving patients at a single institution who underwent IPSS for radiographically equivocal pituitary microadenomas. Cases were reviewed for tumor laterality noted on either operative or pathology reports, as well as the presence of angiographic evidence of cross-filling between the sinuses. In addition, ACTH levels from the right and left IPSs were documented at baseline and at 2, 5, and 10 minutes after corticotropin-releasing hormone (CRH) administration. A ratio of the change in ACTH levels measured at the time of maximal response (10 minutes) versus the levels measured at the initial response (2 minutes) was computed for each patient and compared between patients by their angiographic cross-filling status. RESULTS: There were 41 patients with a histopathologically confirmed right- or left-sided ACTH-secreting pituitary microadenoma who underwent preoperative IPSS. Among these patients, 28 (68%) showed angiographic evidence of cross-filling between the IPSs, and 13 showed no cross-filling. On average, ACTH levels increased by a factor of 3.91 ± 0.77 in the contralateral IPS in patients with angiographic cross-filling, compared with a factor increase of only 1.80 ± 0.27 in patients without cross-filling (p = 0.014). In comparison, ACTH levels increased by a factor of 2.01 ± 0.57 in the ipsilateral IPS in patients with cross-filling, and by 8.78 ± 7.30 in those without cross-filling (p = 0.373). CONCLUSIONS: The presence of angiographic cross-filling, suggestive of a greater degree of vascular channel networking between the right and left IPS, is a significant factor influencing the measured rates of change of ACTH in IPSS and may impact the specificity of this test to accurately determine microadenoma laterality in the preoperative setting.

Correlation of older age with better progression-free survival despite less aggressive resection in nonfunctioning pituitary adenomas.

OBJECTIVE: Nonfunctioning pituitary adenomas (NFPAs) present at a wide range of ages; it is possible that variable outcomes are based on patient age at presentation. This study aimed to explore long-term outcomes of patients with NFPAs following endonasal transsphenoidal surgery (ETS), considering age stratification. METHODS: This retrospective study included 228 patients with NFPAs who underwent ETS, with a median follow-up period of 63 months. The outcomes included progression-free survival (PFS) rates and neurological and endocrinological outcomes. Age-stratified Kaplan-Meier and Cox proportional hazards analyses were performed. Patients were classified into four age groups: ≤ 49, 50-59, 60-69, and ≥ 70 years. RESULTS: Age-stratified analysis showed a significant correlation between age and PFS in NFPAs (5-year PFS rates: 63.0% in those ≤ 49 years, 76.7% in those 50-59 years, 85.0% in those 60-69 years, and 88.1% in those ≥ 70 years; p = 0.001, log-rank test). Bivariate (HR 1.03, 95% CI 1.01-1.05; p = 0.001) and multivariable (HR 1.03, 95% CI 1.02-1.05; p = 0.001) analyses demonstrated that older age was significantly associated with longer PFS. Multivariable analysis also demonstrated that smaller maximum tumor diameter (HR 0.77, 95% CI 0.60-0.99; p = 0.036) and gross-total resection (HR 8.55, 95% CI 3.90-18.75; p = 0.001) were significantly associated with longer PFS. Multivariable logistic regression analysis demonstrated that only younger age was associated with postoperative improvement of male hypogonadism (HR 0.91, 95% CI 0.84-0.99; p = 0.019). Other postoperative neurological and endocrinological outcomes were not significantly associated with age. CONCLUSIONS: Older patients with NFPAs treated with ETS demonstrated a longer PFS. Of endocrinological outcomes studied, only male hypogonadism improvement was associated with younger patient age.

The clinical presentation of PIT1 positive pituitary neuroendocrine tumor immunonegative for growth hormone, prolactin, and thyroid stimulating hormone with analysis of clinical and immunostaining dissociation.

BACKGROUND: PIT1 is a pituitary transcription factor that is associated with either growth hormone (GH), prolactin (PRL), or thyroid-stimulating hormone (TSH) production. However, PIT1-positive pituitary neuroendocrine tumors (PitNETs) are occasionally immunonegative for GH, PRL, and TSH. This paper describes the clinical presentation of PIT1 positive however immunonegative PitNETs. METHODS: We conducted a retrospective analysis, identifying 228 PIT1-positive PitNET patients between 2017 and 2022. Out of these, ten (4%) tested negative for GH, PRL, and TSH. Functioning PitNETs were defined as those causing hormonal excess symptoms or hormonal overproduction. RESULTS: As for 10 patients immunonegative for all three hormones however PIT1-positive, the mean ( ± standard deviation) age was 46 ± 13 years with 70% women. Six patients exhibited signs of excess GH or PRL, and three had visual problems. Additionally, one patient had secondary hypothyroidism and adrenal insufficiency resulting from the mass effect. All tumors were macroadenoma, with a median volume of 2.1 cm3 (range, 0.8-17.5 cm3). Gross total resection was attained in six patients by trans-sphenoidal surgery. Postoperatively, eight patients experienced clinical improvement: three in vision, two in amenorrhea, two in headache, and one in acromegaly symptoms. Biochemical improvement was observed in six patients, with all experiencing remission in hormonal excess and one showing improvement in secondary hypothyroidism. Stereotactic radiosurgery was performed in three patients. CONCLUSIONS: Patients with functioning PitNETs may exhibit PIT1 staining without GH, PRL, or TSH staining. Hormonally active tumors exist in this patient population; therefore, close endocrine follow-up is necessary despite the lack of staining for GH, PRL, and TSH.

Sellar meningiomas: an endocrinologic perspective.

To review the clinical manifestations and outcomes of those with sellar meningiomas treated surgically at Mayo Clinic between 1975 and 2003. This is a retrospective chart and pathology review of 17 patients with a diagnosis of purely or largely intrasellar meningiomas treated surgically at our institution. Data in regards to presentation, endocrine hormonal status, surgical approach, pathology findings, outcome and adjunctive treatment were abstracted from the medical records. The majority of patients present with visual disturbances. All 17 tumors were WHO grade I. Surgical cure was achieved in 53 % after initial surgery. Postsurgical hypopituitarism occurred with high frequency. A substantial proportion of patients required subsequent surgical intervention or adjunctive treatment with external beam radiation. Sellar meningiomas are technically challenging and carry a high risk for visual disturbance and pituitary hormonal abnormalities. Many patients experience persistent disease requiring further intervention. These patients require long-term follow-up for evaluation of recurrence or development of new pituitary hormonal insufficiencies.

Unrecognized notochordal lesions as a likely cause of idiopathic clival cerebrospinal fluid leaks.

OBJECTIVE: To examine an association between idiopathic transclival cerebrospinal fluid (CSF) leak and notochordal lesions. METHODS: This study consisted of the illustrations of institutional patients who underwent surgery for transclival CSF leak between January 1, 2009 and April 25, 2020 and comprehensive review of the existing literature conducted on April 25, 2020. The cases were classified based on the presumed etiologies that were originally proposed in the articles ("idiopathic" vs. "secondary"). The baseline characteristics were compared between the groups, and the surgical outcomes were summarized. RESULTS: In 3 institutional cases, ecchordosis physaliphora (EP) was confirmed at the fistula either pathologically (1) or radiologically (2). Among 42 literature cases, 28 were recognized as idiopathic, while 14 were secondary cases with histologically (n = 12) or radiologically (n = 2) confirmed notochordal lesion at the fistula. Thus, any notochordal lesions were histologically confirmed in 13 among a total of 45 cases (28.9%). Fourteen of the idiopathic cases had undescribed radiographic signs suggestive of small ecchordosis physaliphora at the fistula. Both idiopathic and secondary cases demonstrated resemblance in their ages (mean, 51.4 and 56.6 years; p = 0.102), female predominance (male, 36% vs. 25%; P = 0.521), no association with obesity (7% vs. 18%; P = 0.350) or increased intracranial pressure (7% vs. 6%; P = 1.000). All the fistulas were in the midline or paramidline clivus within several millimeters below the dorsum sellae. All the patients were treated surgically with a multilayer closure, resulting in a success rate of 93% with one surgery. CONCLUSION: Our analyses suggest the association of transclival CSF leak and notochord lesions. A prospective study is needed for definitive conclusion.

A False Pituitary Tumor.

A false pituitary tumor describes pituitary enlargement due to intracranial hypotension. Reported previously primarily in the neurological literature, we present this case referred to endocrinology for evaluation of a pituitary mass. A 24-year-old male was referred to endocrinology for evaluation of pituitary enlargement without a hypo-enhancing lesion on magnetic resonance imaging (MRI). The main symptom reported was headache that was worse in the standing position and in the afternoon. He had no symptoms or signs of pituitary mass-effect, or hormone excess or deficiencies. Past medical history was relevant for a history of nerve schwannoma status post resection with subsequent spinal fusion. Biochemical evaluation of pituitary hormones was normal. Upon review of his pituitary MRI, other abnormalities seen were suggestive of intracranial hypotension. Based on his history and imaging findings, he was diagnosed with intracranial hypotension causing a "false pituitary tumor" rather than pituitary enlargement or abnormality. Further evaluation revealed multiple spinal leaks that were patched. His symptoms subsided within a few days of repair. Endocrinologists should be aware of the possible misdiagnosis of a pituitary mass due to intracranial hypotension.

Contemporary Treatment Outcome of Metastases to the Pituitary Gland.

OBJECTIVE: Metastasis to the pituitary gland is uncommon. With life expectancy after cancer diagnosis improving, we sought to understand the effects of treating pituitary metastasis in the modern era of advanced cancer treatment. METHODS: Patients who had been diagnosed with, and treated for, pituitary metastasis from 2000 to 2021 were retrospectively analyzed. RESULTS: A total of 48 patients were identified, of whom 23 (48%) were women. The most common primary cancer was the lung (n = 23; 48%), followed by the breast (n = 9; 19%). Of the 48 patients, 29 (60%) had had hypopituitarism and 12 (25%), visual field deficits. Twenty-seven patients (56%) had had solitary pituitary metastasis, with no evidence of other intracranial metastatic lesions. Of the 48 patients, 14 (29%) had undergone surgery and 20 (42%) had undergone standalone radiation therapy (preceded by biopsy for 3). After surgery and/or radiation therapy, the visual field deficits had improved in 6 patients, hypopituitarism had improved in 4 patients, and hypopituitarism had occurred in 3 patients. The median overall survival (OS) was 12 months (interquartile range, 3.0-28 months). Multivariate analysis showed nonsolitary pituitary metastasis (hazard ratio, 2.8; 95% confidence interval, 1.5-5.5; P = 0.0021) and no surgery or radiation therapy (hazard ratio, 2.08; 95% confidence interval, 1.04-4.15; P = 0.038) were associated with OS. For those with solitary pituitary metastasis, the patients who had undergone surgery and/or radiation therapy had had better 1-year OS than patients who had not received either (P = 0.03). In contrast, for patients with nonsolitary pituitary metastasis, those who had undergone standalone radiation therapy had had better 1-year OS than the patients who had not received either (P = 0.03). CONCLUSIONS: In the selected population, metastasis-directed therapy was associated with improved OS. Either correct patient selection for additional therapy or surgery and/or radiation therapy directly benefited patients' OS.

Clinical and imaging outcomes of 100 patients with cerebrospinal fluid-venous fistulas treated by transvenous embolization.

BACKGROUND: Cerebrospinal fluid-venous fistulas (CSFVF) are a common cause of spontaneous intracranial hypotension (SIH). Transvenous embolization has emerged as a reliable treatment option. We review the clinical presentation, imaging, and clinical outcomes of 100 consecutive CSFVF patients who underwent embolization over 2 years. METHODS: Baseline clinical characteristics, imaging findings (including Bern SIH score), technical outcomes, and long-term imaging and clinical outcomes were collected. All patients had at least 3 months of clinical follow-up and had baseline MRI. 99/100 patients underwent follow-up imaging at ≥3 months post-treatment. RESULTS: 100 patients were included. Mean imaging and clinical follow-up duration was 8.3±7.7 months and 15.0±6.8 months, respectively. The mean duration of symptoms before embolization was 40.9±52 months. Mean baseline Bern SIH score was 5.9±3.3. The most common baseline symptoms were headache (96 patients), tinnitus (55 patients), and cognitive dysfunction (44 patients). Technical success rate was 100%. Mean post-treatment Bern SIH score was 0.9±1.6 (P<0.0001). Following treatment, 95% of patients reported significant improvement or resolution in symptoms (58 patients reporting resolution and 37 reporting improvement). 5 patients reported no improvement. There were no major procedural or periprocedural complications. 10 patients had minor procedural complications that did not result in any change in management (Onyx emboli, venous perforation). 19 patients had rebound intracranial hypertension requiring acetazolamide therapy. 7 patients had recurrent fistula at the initially treated level. CONCLUSIONS: Transvenous embolization of CSFVF in SIH patients is safe and effective with a 95% treatment response, significant improvement in imaging outcomes, and a very low rate of complications.

Clinical and Imaging Outcomes of Surgically Repaired Cerebrospinal Fluid-Venous Fistulas Identified by Lateral Decubitus Digital Subtraction Myelography.

OBJECTIVE: To describe clinical and radiographic outcomes of surgical repair of cerebrospinal fluid-venous fistula (CVF), an increasingly recognized cause of spontaneous intracranial hypotension that is poorly responsive to epidural blood patch (EBP). METHODS: Retrospective review identified adult patients who had lateral decubitus digital subtraction myelography indicative of cerebrospinal fluid leak at Mayo Clinic between November 2018 and February 2020, with clearly localized CVF, followed by surgical treatment. Patients without available imaging before or after surgery were excluded. History of EBP and clinical response to EBP were evaluated along with surgical outcomes. RESULTS: Of 25 patients with CVF who met protocol criteria and were included in the data analysis, 22 (88%) received EBP, but clinical benefit lasting ≥4 weeks occurred in only 2 of 22 (9%). Headache was the most prominent preoperative feature among patients (24/25; 96%). Following surgery, 18 of 24 (75%) patients had complete headache improvement, 4 (17%) had partial improvement, and 2 (8%) had no improvement. Ten of 25 (40%) patients reported cognitive disturbance at baseline; at follow-up, 5 of 10 (50%) had complete improvement, 3 (30%) had partial improvement, and 2 (20%) had no improvement. On postoperative brain magnetic resonance imaging, 6 of 25 (24%) patients had complete resolution of findings by Bern score criteria, 18 (72%) showed partial improvement, and 1 (4%) patient showed no improvement. Adverse events were minor and included surgical site pain and paresthesias. CONCLUSIONS: Surgical repair of CVF resulted in improvements in headache and other symptoms, with few side effects.

Clinical and imaging outcomes of cerebrospinal fluid-venous fistula embolization.

BACKGROUND: We report outcomes of spontaneous intracranial hypotension (SIH) patients who underwent transvenous embolization of cerebrospinal fluid-venous fistulas (CSFVFs) confirmed on digital subtraction myelography (DSM) performed at our institution. METHODS: This is a retrospective evaluation of a prospectively collected database of SIH patients who underwent transvenous embolization of CSFVFs. Only patients who had fistulas confirmed on DSM performed at our institution were included. All patients had a baseline MRI and an MRI performed at least 90 days post-embolization, as well as clinical evaluation using the six item Headache Impact Test (HIT-6) and the Patient Global Impression of Change (PGIC) scales. Paired t-test was used to report changes in Bern MRI scores and HIT-6 scores at follow-up. RESULTS: 40 patients were included (29 female, 11 male). Mean age was 57.4±10.3 years. Mean Bern score improved from 5.7±3.0 at baseline to 1.3±2.0 at follow-up (p<0.0001). Mean HIT-6 score at baseline was 67.2±11.1 and at follow-up was 41.5±10.1 (p<0.0001). Median PGIC was 1, with 36 patients (90.0%) reporting at least minimal improvement and 32 patients (82.5%) reporting much or very much improvement. Complications included persistent local site pain in 12 patients (30%), suspected rebound intracranial hypertension requiring medical intervention in 7 patients (17.5%), and asymptomatic tiny Onyx emboli to the lungs in 3 patients (7.5%). CONCLUSIONS: Transvenous embolization of CSFVFs using Onyx is safe and effective, resulting in significant improvement in headache and overall clinical outcomes in nearly 90% of patients, and substantial improvements in brain MRI abnormalities.

Streamlining the External Ventricular Drain and Intracranial Pressure Monitor Procedural Setup: A Quality Improvement Initiative.

OBJECTIVE: External ventricular drain (EVD) and intracranial pressure (ICP) monitor placements are among the most common critical care procedures for severe brain injury. Quality improvement initiatives have streamlined similar processes. The aim of the project was to decrease the time to collect supplies for EVD or ICP monitor placement by 25% by April 1, 2021. METHODS: The project followed the define-measure-analyze-improve-control 6 sigma framework. Several quality gaps were identified: equipment stored separately, delays in replacing faulty items, and wasted resources. The team defined the process using the suppliers-inputs-processes-outputs-customers + requirements method, measured time to collect supplies, and analyzed data with an Ishikawa/fishbone diagram. The improve phase included a kaizen burst to generate solutions and an impact/effort grid to evaluate options. The team concluded that the optimal plan was to stock a mobile EVD cart and an ICP monitor pole with disposable go-bags. RESULTS: The average time for nurses to collect EVD placement supplies decreased from 411 to 63 seconds (7-1 minute), and the average time for nurses to collect ICP monitor placement supplies decreased from 418 to 53 seconds (7-<1 minute). Residents decreased the time to obtain EVD placement supplies from 330 to 56 seconds (6-<1 minute) and ICP monitor supplies from 489 to 77 seconds (8-1 minute). Feedback was overwhelmingly positive and focused on improved process efficiency and reduced waste. CONCLUSIONS: The time reduction and enthusiasm are likely associated with the simplicity and comprehensiveness of the intervention design. Including key stakeholders in decision-making and succinct communications reduced resistance to change.