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Dilantha B. Ellegala, Christopher Kligora, Scott Vandenberg, Aaron Dumont, and Mark E. Shaffrey

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Jonas M. Sheehan, Mary L. Vance, Jason P. Sheehan, Dilantha B. Ellegala, and Edward R. Laws Jr.

Object. Although transsphenoidal surgery has become the standard of care for Cushing's disease, it is often unsuccessful in normalizing cortisol production. In this study the authors investigate the safety and efficacy of gamma knife radiosurgery (GKRS) for Cushing's disease after failed transsphenoidal surgery.

Methods. The records of all patients who underwent GKRS at the authors' institution after unsuccessful transsphenoidal surgery for Cushing's disease were retrospectively reviewed. Successful treatment was considered a normal or below-normal 24-hour urinary free cortisol (UFC) level. Records were also evaluated for relapse, new-onset endocrine deficiencies, interval change in tumor size, and visual complications.

Forty-three patients underwent 44 gamma knife procedures with follow up ranging from 18 to 113 months (mean 39.1, median 44 months). Normal 24-hour UFC levels were achieved in 27 patients (63%) at an average time from treatment of 12.1 months (range 3–48 months). Three patients had a recurrence of Cushing's disease at 19, 37, and 38 months, respectively, after radiosurgery. New endocrine deficiencies were noted in seven patients (16%). Follow-up magnetic resonance images obtained in 33 patients revealed a decrease in tumor size in 24, no change in nine, and an increase in size in none of the patients. One patient developed a quadrantanopsia 14 months after radiosurgery despite having received a dose of only 0.7 Gy to the optic tract.

Conclusions. Gamma knife radiosurgery appears to be safe and effective for the treatment of Cushing's disease refractory to pituitary surgery. Delayed recurrences and new hormone deficiencies may occur, indicating the necessity for regular long-term follow up.

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Peter Heppner, Dilantha B. Ellegala, Marcel Durieux, John A. Jane Sr., and Jonathan R. Lindner

Object

The aims of this study were to determine whether contrast-enhanced ultrasonography (CEU) could be used for noninvasive evaluation of cerebral perfusion in patients with traumatic brain injury (TBI) and to assess the effect of decompressive surgery on cerebral perfusion as measured by CEU.

Methods

Contrast-enhanced ultrasonography with intravenous administration of a microbubble contrast agent was performed in six patients with TBI undergoing decompressive craniectomy. Contrast-enhanced ultrasonography was performed through a bur hole before craniectomy and through the calvarial defect immediately after craniectomy and on postoperative Days 1 and 2. For the latter two studies, patients were placed in the recumbent position and at a 35° incline to investigate changes in perfusion produced by modulation of intracranial pressure (ICP). Cerebral microvascular blood flow increased by almost threefold immediately after craniectomy, from a mean of 7.5 ± 6.9 (standard deviation [SD]) to 20.9 ± 11.6 (p < 0.05), and further improved on postoperative Day 1 (mean 37.1 ± 13.9 [SD], p < 0.05, compared with postcraniectomy microvascular blood flow) without subsequent change on Day 2. The change in microvascular perfusion correlated inversely with the initial ICP (p < 0.01), indicating less recovery of flow when preoperative ICP was markedly elevated. On postoperative Days 1 and 2, head-of-bed elevation produced an increase in microvascular perfusion on CEU (mean 37 ± 11 compared with 51 ± 20, p < 0.05) and a small decrease in ICP (mean 16 ± 5 mm Hg compared with 12 ± 4 mm Hg, p < 0.05). In patients with parenchymal hematoma, CEU provided spatial information on perfusion abnormalities in the hemorrhagic core and surrounding tissues.

Conclusions

Contrast-enhanced ultrasonography has potential for the intraoperative and bedside assessment of cerebral perfusion in patients with TBI. The technique may be appropriate for evaluating responses to therapies aimed at preventing secondary ischemia and for assessing regional perfusion abnormalities.

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Dilantha B. Ellegala, Stephen J. Monteith, David Haynor, Thomas D. Bird, Robert Goodkin, and Michel Kliot

Object. Charcot-Marie-Tooth (CMT) disease is a collection of related genetic disorders affecting peripheral nerves with an incidence of one in every 2500 individuals. A diagnosis of CMT disease has classically relied on a medical history, examination, and measurement of nerve conduction velocities. Advancements in genetic testing and magnetic resonance (MR) imaging techniques may provide clinicians with a more precise diagnostic armamentarium. The authors investigated MR neurography as a possible method to characterize CMT subtypes.

Methods. The authors performed MR neurography to evaluate sciatic nerves in the mid-thigh area of seven patients with genetically defined subtypes of CMT, one patient with chronic inflammatory demylinating polyneuropathy, and one patient without neuropathy. The authors correlate their findings with normal nerve conduction velocities (NCVs) and present their results as a descriptive case series.

Although MR neurography could not be used to distinguish subtypes of CMT disease on nerve area or fascicle number, it appears to characterize phenotypic features and disease progression noninvasively in patients with some subtypes.

Conclusions. In conjunction with NCV measurements, MR neurography may be useful in the diagnosis of CMT neuropathies and in monitoring disease progression.

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Dilantha B. Ellegala, Tord D. Alden, Daniel E. Couture, Mary L. Vance, Nicholas F. Maartens, and Edward R. Laws Jr.

Object. Older men with clinically nonfunctioning pituitary tumors have been noted to be anemic, to have hypopituitarism, and to have low serum levels of testosterone. The authors hypothesized that men with pituitary adenomas and hypogonadism have a physiologically related decrease in hematocrit.

Methods. A retrospective analysis was conducted of 216 patients older than 50 years of age who harbored pituitary adenomas. In 100 men serum testosterone levels and a complete blood (cell) count (CBC) were obtained before treatment; a CBC was also acquired in a series of women with pituitary adenomas. Using clinical laboratory standards, anemia was defined as a hematocrit less than 40% in men and less than 35% in women.

Thirty-one (46.3%) of 67 men with low serum concentrations of testosterone were anemic. In men with low levels of testosterone, the average hematocrit was 39.9%, compared with 45.6% for men with normal testosterone levels (p < 0.001). Men with macroadenomas were most likely to have both anemia and a low serum concentration of testosterone. Anemia was associated with a low level of testosterone, adjusting for tumor size (odds ratio 19, 95% confidence interval 4.86–77.03). Of patients with anemia, 84% were men and 16% were women (p < 0.001). The prevalence of anemia in women was low and was not correlated with tumor size. Men receiving testosterone replacement therapy had a significantly higher hematocrit value than men with low or normal testosterone levels.

Conclusions. These findings support a direct relationship between serum testosterone levels and hematopoiesis in men, and demonstrate that hematopoiesis is compromised in men who have low concentrations of testosterone due to a pituitary adenoma.

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Björn P. Meij, Maria-Beatriz S. Lopes, Dilantha B. Ellegala, Tord D. Alden, and Edward R. Laws Jr.

Object. Pituitary adenomas are considered benign tumors; however, they may infiltrate surrounding tissues including the dura mater. In this paper the authors analyze the clinical significance of microscopically confirmed dural invasion by comparing a range of variables (age and sex of patients, adenoma type, adenoma size on magnetic resonance [MR] images, remission, residual pituitary disease, recurrence, survival, and disease-free interval after surgery) between patients with noninvasive adenomas and those with invasive ones.

Methods. Between 1992 and 1997 dural specimens were obtained in 354 patients with pituitary adenomas who underwent transsphenoidal surgery performed by the senior author (E.R.L.). Dural specimens were examined using routine histological methods and assessed for invasion by pituitary adenoma tissue.

The dura was invaded by the pituitary adenoma in 161 patients (45.5%), and in 192 patients (54.5%) no evidence of dural invasion was found. Dural invasion was present significantly more frequently in the repeated surgery group (69%, 55 patients) than in the primary transsphenoidal surgery group (41%, 291 patients). The mean age of patients undergoing primary transsphenoidal surgery was significantly older in cases of invasive adenomas (50 years) compared with cases of noninvasive adenomas (43 years), and these age differences also correlated with adenoma size. Women tend to develop clinically evident, smaller adenomas at a younger age than men. Of the patients with pituitary adenomas that were 20 mm or smaller, 117 (76%) of 154 were women, whereas of the patients with adenomas that were larger than 20 mm, 74 (54%) of 137 were men. The frequency of dural invasion increased with increasing size of the pituitary adenoma as measured on MR images. In 291 patients who underwent primary pituitary surgery, the frequency of dural invasion according to adenoma size was 24% (≤ 10 mm), 35% (> 10 to ≤ 20 mm), 55% (> 20 to ≤ 40 mm), and 70% (> 40 mm). In patients who underwent primary transsphenoidal surgery, dural invasion was present in more than 50% of those with nonfunctioning adenomas and in 30 to 35% of patients with endocrinologically active adenomas. The mean diameter of the gonadotrophic adenomas and null-cell adenomas was significantly larger than that of each of the endocrinologically active adenomas.

In 58 (20%) of 291 patients who underwent primary pituitary surgery there was residual pituitary disease postsurgery, and 20% of this subset of patients showed clinical improvement to such an extent that no further management was recommended. After pituitary surgery, residual tumor tissue was demonstrable significantly more frequently in patients with invasive adenomas than in those with noninvasive adenomas.

Recurrences after initial remission (cure) of pituitary disease occurred in 18 (8.8%) of 205 patients between 2 and 79 months after primary pituitary surgery (median 25 months). The recurrence rate was not related to dural invasion in a consistent or significant fashion. Seven patients died between 14 and 79 months after pituitary surgery and all had invasive adenomas identified on gross observation at surgery and on microscopy. The survival rate was slightly but significantly decreased for patients with invasive adenomas (91%) compared with patients with noninvasive adenomas (100%) at 6 years postsurgery.

Conclusions. The principal significance of dural invasion by pituitary adenoma is the persistence of tumor tissue after transsphenoidal surgery (incomplete adenomectomy; 20% in primary pituitary tumor resections). The increase in adenoma size with time and the concurrent development of dural invasion are the major factors that determine an incomplete adenomectomy. When the adenoma remains restricted to the sellar compartment or shows only moderate suprasellar extension, dural invasion may not yet have developed and conditions for complete selective adenomectomy are improved.

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Aaron S. Dumont, Paul T. Boulos, John A. Jane Jr., Dilantha B. Ellegala, Steven A. Newman, and John A. Jane Sr.

Fibrous dysplasia is a benign but slowly progressive disorder of bone in which normal cancellous bone is replaced by immature woven bone and fibrous tissue. Significant deformity and both acute and chronic visual impairment can result. A contemporary understanding of fibrous dysplasia, emphasizing the origins of visual impairment, indications for decompressive surgery, and the techniques for correction of the cosmetic deformity are presented.

In their experience and review of the literature, the authors found the most frequent clinical presentations to be exophthalmos, displacement of the globe, abnormalities of extraocular motility, cosmetic deformity, and visual impairment. Although traditionally the cause of visual impairment has been ascribed to impingement of the optic canal on the optic nerve, the authors' experience is that the most common cause of visual loss is cystic degeneration of the tumor, particularly with those involving the anterior clinoid process. Exophthalmos and optic canal stenosis are less common causes of visual impairment. Indications for surgical intervention include acute and/or serially radiographically documented and relentless visual impairment and significant cosmetic deformity. Individualized management strategies are also discussed.

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Dilantha B. Ellegala, Lauren Simpson, Emanuel Mayegga, Emanuel Nuwas, Hayte Samo, Naftal Naman, Doyle B. Word, and Joyce S. Nicholas

Object

In Tanzania, there are 4 neurosurgeons for a population of 46 million. To address this critical shortage of neurosurgical care, the authors worked with local Tanzanian health care workers, neurosurgeons, the Ministry of Health and Social Welfare, and the Office of the President of Tanzania to develop a train-forward method for sustainable, self-propagating basic and emergency neurosurgery in resource-poor settings. The goal of this study was to assess the safety and effectiveness of this method over a 6-year period.

Methods

The training method utilizes a hands-on bedside teaching technique and was introduced in 2006 at a remote rural hospital in northern Tanzania. Local health care workers were trained to perform basic and emergency neurosurgical procedures independently and then were taught to train others. Outcome information was retrospectively collected from hospital records for the period from 2005 (1 year before method implementation) through 2010. Analysis of de-identified data included descriptive statistics and multivariable assessment of independent predictors of complications following a patient's first neurosurgical procedure.

Results

By 2010, the initial Tanzanian trainee had trained a second Tanzanian health care worker, who in turn had trained a third. The number of neurosurgical procedures performed increased from 18 in 2005 to an average of 92 per year in the last 3 years of the study period. Additionally, the number of neurosurgical cases performed independently by Tanzanian health care providers increased significantly from 44% in 2005 to 86% in 2010 (p < 0.001), with the number of complex cases independently performed also increasing over the same time period from 34% to 83% (p < 0.001). Multivariable analysis of clinical patient outcome information to assess safety indicated that postoperative complications decreased significantly from 2005 through 2010, with patients who had been admitted as training progressed being 29% less likely to have postoperative complications (OR 0.71, 95% CI 0.52–0.96, p = 0.03).

Conclusions

The Madaktari Africa train-forward method is a reasonable and sustainable approach to improving specialized care in a resource-poor setting.

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James K. Liu, Aclan Dogan, Dilantha B. Ellegala, Jonathan Carlson, Gary M. Nesbit, Stanley L. Barnwell, and Johnny B. Delashaw Jr.

Object

Surgical intervention may be required if endovascular embolization is insufficient to completely obliterate intracranial dural arteriovenous fistulas (DAVFs). The authors report their 14-year experience with 23 patients harboring diverse intracranial DAVFs that required surgical intervention.

Methods

Between 1993 and 2007, 23 patients underwent surgery for intracranial DAVFs. The following types of DAVFs were treated: superior petrosal sinus (in 10 patients); parietooccipital (in 3); confluence of sinuses and ethmoidal (in 2 each); and tentorial, falcine, occipital, transverse-sigmoid, superior sagittal, and cavernous sinuses (in 1 patient each). In all cases, the authors' goal was to obliterate the DAVF venous outflow by direct surgical interruption of the leptomeningeal venous drainage. Transarterial embolization was used primarily as an adjunct to decrease flow to the DAVF prior to definitive treatment.

Results

Complete angiographic obliteration of the DAVF was achieved in all cases. There were no complications of venous hypertension, venous infarction, or perioperative death. There were no recurrences and no further clinical events (new hemorrhages or focal neurological deficits) after a mean follow-up of 45 months.

Conclusions

The authors' experience emphasizes the importance of occluding venous outflow to obliterate intracranial DAVFs. Those that drain purely through leptomeningeal veins can be safely obliterated by surgically clipping the arterialized draining vein as it exits the dura. Radical excision of the fistula is not necessary.