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Benjamin T. Himes, Thomas J. Wilson, Andres A. Maldonado, Naveen S. Murthy and Robert J. Spinner

The authors present a case of delayed peroneal neuropathy following a lateral gastrocnemius rotational flap reconstruction. The patient presented 1.5 years after surgery with a new partial foot drop, which progressed over 3 years. At operation, a fascial band on the deep side of the gastrocnemius flap was compressing the common peroneal nerve proximal to the fibular head, correlating with preoperative imaging. Release of this fascial band and selective muscle resection led to immediate improvement in symptoms postoperatively.

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Benjamin T. Himes, Michael W. Ruff, Jaimie J. Van Gompel, Sean S. Park, Evanthia Galanis, Timothy J. Kaufmann and Joon H. Uhm

The authors present the case of a man with a papillary craniopharyngioma, first diagnosed at 47 years of age, who experienced multiple recurrences. Review of the pathologic specimen from his first resection demonstrated the BRAF V600E mutation. With his most recent recurrence following previous surgery and radiotherapy, at 52 years of age, the decision was made to initiate treatment with the BRAF V600E inhibitor dabrafenib. Imaging following initiation of dabrafenib demonstrated reduction in tumor size. He remained on dabrafenib therapy for approximately 1 year and continued to demonstrate a good clinical result. At that time the decision was made to discontinue dabrafenib therapy and follow up with serial imaging. After more than 1 year of follow-up since stopping dabrafenib, the patient has continued to do well with no radiographic evidence of tumor progression and continues to be monitored with frequent interval imaging.

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Benjamin T. Himes, Adip G. Bhargav, Desmond A. Brown, Timothy J. Kaufmann, Irina Bancos and Jamie J. Van Gompel

OBJECTIVE

Cushing’s disease arises from functioning adrenocorticotropic hormone (ACTH)–secreting pituitary adenomas. These tumors can be very small and evade detection by MRI. Empty sella syndrome is a phenomenon by which an arachnoid outpouching of CSF into the sella leads to compression of the pituitary, likely due to intracranial hypertension (a common issue in Cushing’s disease), further leading to difficulty in visualizing the pituitary gland that may contribute to difficulty in finding a tumor on MRI, so-called MRI-negative Cushing’s disease. The authors sought to examine the association between empty sella syndrome and MRI-negative Cushing’s disease.

METHODS

A single-institution database of Cushing’s disease cases from 2000 to 2017 was reviewed, and 197 cases were included in the analysis. One hundred eighty patients had a tissue diagnosis of Cushing’s disease and 17 had remission with surgery, but no definitive tissue diagnosis was obtained. Macroadenomas (tumors > 1 cm) were excluded. The degree of empty sella syndrome was graded on the degree of CSF visualized in the sella on midline sagittal T1-weighted MRI.

RESULTS

Of the 197 cases identified, 40 (20%) presented with MRI-negative disease, and empty sella syndrome was present in 49 cases (25%). MRI-negative disease was found in 18 (37%) of 49 empty sella cases versus 22 (15%) of 148 cases without empty sella syndrome present. Empty sella syndrome was significantly associated with MRI-negative disease (OR 3.32, 95% CI 1.61–6.74, p = 0.0018). Decreased thickness of the pituitary gland was also associated with MRI-negative disease (mean thickness 5.6 vs 6.8 mm, p = 0.0002).

CONCLUSIONS

Empty sella syndrome is associated with an increased rate of MRI-negative Cushing’s disease. Pituitary compression causing a relative reduction in the volume of the pituitary for imaging is a plausible cause for not detecting the tumor mass with MRI.

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Benjamin T. Himes, Michael W. Ruff, Jaimie J. Van Gompel, Sean S. Park, Evanthia Galanis, Timothy J. Kaufmann and Joon H. Uhm

The authors present the case of a man with a papillary craniopharyngioma, first diagnosed at 47 years of age, who experienced multiple recurrences. Review of the pathologic specimen from his first resection demonstrated the BRAF V600E mutation. With his most recent recurrence following previous surgery and radiotherapy, at 52 years of age, the decision was made to initiate treatment with the BRAF V600E inhibitor dabrafenib. Imaging following initiation of dabrafenib demonstrated reduction in tumor size. He remained on dabrafenib therapy for approximately 1 year and continued to demonstrate a good clinical result. At that time the decision was made to discontinue dabrafenib therapy and follow up with serial imaging. After more than 1 year of follow-up since stopping dabrafenib, the patient has continued to do well with no radiographic evidence of tumor progression and continues to be monitored with frequent interval imaging.

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Benjamin T. Himes, Grant W. Mallory, Arnoley S. Abcejo, Jeffrey Pasternak, John L. D. Atkinson, Fredric B. Meyer, W. Richard Marsh, Michael J. Link, Michelle J. Clarke, William Perkins and Jamie J. Van Gompel

OBJECTIVE

Historically, performing neurosurgery with the patient in the sitting position offered advantages such as improved visualization and gravity-assisted retraction. However, this position fell out of favor at many centers due to the perceived risk of venous air embolism (VAE) and other position-related complications. Some neurosurgical centers continue to perform sitting-position cases in select patients, often using modern monitoring techniques that may improve procedural safety. Therefore, this paper reports the risks associated with neurosurgical procedures performed in the sitting position in a modern series.

METHODS

The authors reviewed the anesthesia records for instances of clinically significant VAE and other complications for all neurosurgical procedures performed in the sitting position between January 1, 2000, and October 8, 2013. In addition, a prospectively maintained morbidity and mortality log of these procedures was reviewed for instances of subdural or intracerebral hemorrhage, tension pneumocephalus, and quadriplegia. Both overall and specific complication rates were calculated in relation to the specific type of procedure.

RESULTS

In a series of 1792 procedures, the overall complication rate related to the sitting position was 1.45%, which included clinically significant VAE, tension pneumocephalus, and subdural hemorrhage. The rate of any detected VAE was 4.7%, but the rate of VAE requiring clinical intervention was 1.06%. The risk of clinically significant VAE was highest in patients undergoing suboccipital craniotomy/craniectomy with a rate of 2.7% and an odds ratio (OR) of 2.8 relative to deep brain stimulator cases (95% confidence interval [CI] 1.2–70, p = 0.04). Sitting cervical spine cases had a comparatively lower complication rate of 0.7% and an OR of 0.28 as compared with all cranial procedures (95% CI 0.12–0.67, p < 0.01). Sitting cervical cases were further subdivided into extradural and intradural procedures. The rate of complications in intradural cases was significantly higher (OR 7.3, 95% CI 1.4–39, p = 0.02) than for extradural cases. The risk of VAE in intradural spine procedures did not differ significantly from sitting suboccipital craniotomy/craniectomy cases (OR 0.69, 95% CI 0.09–5.4, p = 0.7). Two cases (0.1%) had to be aborted intraoperatively due to complications. There were no instances of intraoperative deaths, although there was a single death within 30 days of surgery.

CONCLUSIONS

In this large, modern series of cases performed in the sitting position, the complication rate was low. Suboccipital craniotomy/craniectomy was associated with the highest risk of complications. When appropriately used with modern anesthesia techniques, the sitting position provides a safe means of surgical access.

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Benjamin T. Himes, Arnoley S. Abcejo, Panagiotis Kerezoudis, Adip G. Bhargav, Katherine Trelstad-Andrist, Patrick R. Maloney, John L. D. Atkinson, Fredric B. Meyer, W. Richard Marsh and Mohamad Bydon

OBJECTIVE

The sitting or semisitting position in neurosurgery allows for several technical advantages, including improved visualization of the surgical field. However, it has also been associated with an increased risk of venous air embolisms and positioning-related complications that limit its commonplace adoption. The authors report a large, single-center series of cervical spine procedures performed with patients in the sitting or prone position in order to assess the perceived risk of intraoperative and postoperative complications associated with the sitting position.

METHODS

Noninstrumented, single-level posterior cervical spine procedures performed with patients in the sitting/semisitting or prone position from 2000 to 2016 at a single institution were reviewed. Institutional abstraction tools (DataMart and Chart Plus) were used to collect data from the medical records. The two positions were compared with regard to preoperative factors, intraoperative variables, and postoperative outcomes. Multivariable logistic regression models were fitted for 30-day readmission, 30-day return to the operating room, and complication rates.

RESULTS

A total of 750 patients (sitting, n = 480; prone, n = 270) were analyzed. The median age was 53 years for those who underwent surgery in the prone position and 50 years for those who underwent surgery in the sitting position (IQRs 45–62 years and 43–60 years, respectively), and 35% of the patients were female. Sitting cases were associated with significantly longer anesthetic times (221 minutes [range 199–252 minutes] vs 205 minutes [range 179–254 minutes]) and operative times (126 minutes [range 101–163 minutes] vs 149 minutes [120–181 minutes]). Cardiorespiratory events in the postanesthesia care unit (PACU) were comparable between the two groups, with the exception of episodes of apnea (2.6% vs 0.6%, p = 0.041) and hypoventilation (4.4% vs 0.8%, p < 0.003), which were more frequent in the prone-position cohort. On multivariable analysis, the effect of the sitting versus the prone position was not significant for 30-day readmission (OR 0.77, 95% CI 0.34–1.71, p = 0.52) or reoperation (OR 0.71, 95% CI 0.31–1.60, p = 0.40). The sitting position was associated with lower odds of developing any complication (OR 0.31, 95% CI 0.16–0.62, p < 0.001).

CONCLUSIONS

Based on the intraoperative and postoperative complications chosen in this study, the sitting position confers a similar safety profile to the prone position. This can be explained by a more anatomic positioning accounting for reduced temporary neurological deficits and reduced PACU-associated hypoventilation noted in this series. Nevertheless, the findings may also reflect institutional familiarity, experience, and mastery of this position type, and outcomes may not reflect practices in general.

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Ross C. Puffer, Luz M. Cumba Garcia, Benjamin T. Himes, Mi-Yeon Jung, Frederic B. Meyer, David O. Okonkwo and Ian F. Parney

OBJECTIVE

The objective of this study was to isolate extracellular vesicles (EVs) from plasma in a cohort of patients with traumatic brain injury (TBI) and analyze their contents for novel biomarkers that could prove useful for rapid diagnosis and classification of brain injury during initial evaluation.

METHODS

Plasma EVs were isolated by serial ultracentrifugation from patients with TBI (n = 15) and healthy controls (n = 5). Samples were obtained from the TRACK-TBI biorepository (2010–present). Size and concentration were determined by nanoparticle tracking. Glial fibrillary acidic protein (GFAP) concentration was determined in EV protein. EV RNA was isolated and deep sequencing of short noncoding RNA was performed.

RESULTS

Plasma EVs are physically similar but contained approximately 10 times more GFAP in TBI patients with altered consciousness than patients and controls with normal consciousness. Eleven highly differentially expressed microRNAs (miRNAs) were identified between these groups. Genes targeted by these miRNAs are highly associated with biologically relevant cellular pathways, including organismal injury, cellular development, and organismal development. Multiple additional coding and noncoding RNA species with potential biomarker utility were identified.

CONCLUSIONS

Isolating plasma EVs in patients with TBI is feasible. Increased GFAP concentration—a validated plasma TBI marker—in EVs from TBI patients with altered consciousness, along with differential expression of multiple miRNAs targeting TBI-relevant pathways, suggests that EVs may be a useful source of TBI biomarkers. Additional evaluation in larger patient cohorts is indicated.

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Salomon Cohen-Cohen, Desmond A. Brown, Benjamin T. Himes, Lydia P. Wheeler, Michael W. Ruff, Brittny T. Major, Naykky M. Singh Ospina, John L. D. Atkinson, Fredric B. Meyer, Irina Bancos, William F. Young Jr. and Jamie J. Van Gompel

OBJECTIVE

Multiple endocrine neoplasia type 1 (MEN1) is a rare, autosomal-dominant tumor disorder characterized by the development of pituitary tumors and other endocrine neoplasms. Diagnosis is made clinically based on the development of 2 or more canonical lesions (parathyroid gland, anterior pituitary, and enteropancreatic tumors) or in family members of a patient with a clinical diagnosis of MEN1 and the occurrence of one of the MEN1-associated tumors. The goal of this study was to characterize pituitary tumors arising in the setting of MEN1 at a single institution. The probability of tumor progression and the likelihood of surgical intervention in patients with asymptomatic nonfunctional pituitary adenomas were also analyzed.

METHODS

A retrospective review of a prospectively maintained institutional database was performed for patients with MEN1 diagnosed from 1970 to 2017. Data included patient demographics, tumor characteristics, treatment strategies, and outcomes.

RESULTS

A review of the database identified 268 patients diagnosed with MEN1, of whom 158 (59%) were female. Among the 268 patients, 139 (51.8%) had pituitary adenomas. There was a higher prevalence in women than in men (65% vs 35%, p < 0.005). Functional adenomas (57%) were more common. Prolactin-secreting adenomas were the most common functional tumors. Macroadenomas were seen in 27% of patients and were more likely to be symptomatic and locally aggressive (p < 0.001). Forty-nine patients (35%) underwent transsphenoidal resection at some point during their disease course. In 52 patients who were initially observed with MEN1 asymptomatic nonfunctional adenomas, only 5 (10%) progressed to need surgery. In MEN1 patients, an initial parathyroid lesion is most likely followed in order by pituitary, pancreatic, adrenal, and, finally, rare carcinoid tumors.

CONCLUSIONS

Asymptomatic nonfunctional pituitary adenomas in patients with MEN1 may be followed safely with MRI. In this series, parathyroid tumors developed at the lowest median age of all cardinal tumors, and development of additional cardinal MEN1 lesions followed a predictable pattern. This pattern of disease progression could have significant implications for disease surveillance in clinical practice and may help to target clinical resources to the lesions most likely to develop next. This may aid with early detection and treatment and warrants further study.