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I. Jonathan Pomeraniec, Alexander Ksendzovsky, Ahmed J. Awad, Francis Fezeu and John A. Jane Jr.

OBJECT

The natural and surgical history of Chiari malformation Type I (CM-I) in pediatric patients is currently not well described. In this study the authors discuss the clinical and radiological presentation and outcomes in a large cohort of pediatric CM-I patients treated with either conservative or surgical management.

METHODS

The authors retrospectively reviewed 95 cases involving pediatric patients with CM-I who presented between 2004 and 2013. The patients ranged in age from 9 months to 18 years (mean 8 years) at presentation. The cohort was evenly split between the sexes. Twenty-five patients underwent posterior fossa decompression (PFD) with either dural splitting or duraplasty. Seventy patients were managed without surgery. Patients were followed radiologically (mean 44.8 months, range 1.2–196.6 months) and clinically (mean 66.3 months, range 1.2–106.5 months).

RESULTS

Seventy patients were treated conservatively and followed with serial outpatient neurological and radiological examinations, whereas 25 patients were treated with PFD. Of these 25 surgical patients, 11 were treated with duraplasty (complete dural opening) and 14 were treated with a dura-splitting technique (incomplete dural opening). Surgical intervention was associated with better clinical resolution of symptoms and radiological resolution of tonsillar ectopia and syringomyelia (p = 0.0392). Over the course of follow-up, 20 (41.7%) of 48 nonsurgical patients who were symptomatic at presentation experienced improvement in symptoms and 18 (75%) of 24 symptomatic surgical patients showed clinical improvement (p = 0.0117). There was no statistically significant difference in resolution of symptoms between duraplasty and dura-splitting techniques (p = 0.3572) or between patients who underwent tonsillectomy and tonsillopexy (p = 0.1667). Neither of the 2 patients in the conservative group with syrinx at presentation showed radiological evidence of resolution of the syrinx, whereas 14 (87.5%) of 16 patients treated with surgery showed improvement or complete resolution of syringomyelia (p = 0.0392). In the nonsurgical cohort, 3 patients (4.3%) developed new or increased syrinx.

CONCLUSIONS

The overwhelming majority of CM-I patients (92.9%) managed conservatively do not experience clinical or radiological progression, and a sizeable minority (41.7%) of those who present with symptoms improve. However, appropriately selected symptomatic patients (sleep apnea and dysphagia) and those presenting with syringomyelia should be considered surgical candidates because of the high rates of clinical (75%) and radiological improvement (87.5%).

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I. Jonathan Pomeraniec, Alexander Ksendzovsky, Scott Ellis, Sarah E. Roberts and John A. Jane Jr.

OBJECTIVE

Intraventricular hemorrhage (IVH) is a common complication of premature neonates with small birth weight, which often leads to hydrocephalus and treatment with ventriculoperitoneal (VP) shunting procedures. Trapped fourth ventricle (TFV) can be a devastating consequence of the subsequent occlusion of the cerebral aqueduct and foramina of Luschka and Magendie.

METHODS

The authors retrospectively reviewed 8 consecutive cases involving pediatric patients with TFV following VP shunting for IVH due to prematurity between 2003 and 2012. The patients ranged in gestational age from 23.0 to 32.0 weeks, with an average age at first shunting procedure of 6.1 weeks (range 3.1–12.7 weeks). Three patients were managed with surgery. Patients received long-term radiographic (mean 7.1 years; range 3.4–12.2 years) and clinical (mean 7.8 years; range 4.6–12.2 years) follow-up.

RESULTS

The frequency of TFV following VP shunting for neonatal posthemorrhagic hydrocephalus was found to be 15.4%. Three (37.5%) patients presented with symptoms of posterior fossa compression and were treated surgically. All of these patients showed signs of radiographic improvement with stable or improved clinical examinations during postoperative follow-up. Of the 5 patients treated conservatively, 80% experienced stable ventricular size and 1 patient experienced a slight increase (3 mm) on imaging. All of the nonsurgical patients showed stable to improved clinical examinations over the follow-up period.

CONCLUSIONS

The frequency of TFV among premature IVH patients is relatively high. Most patients with TFV are asymptomatic at presentation and can be managed without surgery. Symptomatic patients may be treated surgically for decompression of the fourth ventricle.

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I. Jonathan Pomeraniec, Aaron E. Bond, M. Beatriz Lopes and John A. Jane Sr.

OBJECT

Normal pressure hydrocephalus (NPH) remains most often a clinical diagnosis and has been widely considered responsive to the placement of a cerebrospinal fluid (CSF) shunt. The high incidence of patients with Alzheimer’s disease (AD) with NPH symptoms leads to poorer outcomes than would be expected in patients with NPH alone. This article reviews a series of patients operated on for presumed NPH in whom preoperative high-volume lumbar puncture (HVLP) and intraoperative cortical brain biopsies were performed. The data derived from these procedures were then used to understand the incidence of AD in patients presenting with NPH symptoms and to analyze the efficacy of HVLP in patients with NPH and patients with concurrent AD (NPH+AD). A review of the outcomes of shunt surgery is provided.

METHODS

The cases of all patients who underwent placement of a CSF shunt for NPH from 1998 to 2013 at the University of Virginia by the senior author were retrospectively reviewed. Patients who underwent HVLP and patients who underwent cortical brain biopsies were stratified based on the biopsy results into an NPH-only group and an NPH+AD group. The HVLP results and outcomes were then compared in these 2 groups.

RESULTS

From 1998 to 2013, 142 patients underwent shunt operations because of a preoperative clinical diagnosis of NPH. Of the patients with a shunt who had a diagnosis of NPH, 105 (74%) received HVLPs. Of 142 shunt-treated patients with NPH, 27 (19%) were determined to have concomitant Alzheimer’s pathology based on histopathological findings at the time of shunting. Patients who underwent repeat biopsies had an initial positive outcome. After they clinically deteriorated, they underwent repeat biopsies during shunt interrogation, and 13% of the repeat biopsies demonstrated Alzheimer’s pathology. Improvements in gait and cognition did not reach significance between the NPH and NPH+AD groups. In total, 105 patients underwent HVLP before shunt placement. In the NPH cohort, 44.6% of patients experienced improvement in symptoms with HVLP and went on to experience resolution or improvement. In the NPH+AD cohort, this proportion was lower (18.2%), and the majority of patients who experienced symptomatic relief with HVLP actually went on to experience either no change or worsening of symptoms (p = 0.0136).

CONCLUSIONS

A high prevalence of AD histopathological findings (19%) occurred in patients treated with shunts for NPH based on cortical brain biopsies performed during placement of CSF shunts. HVLP results alone were not predictive of clinical outcome. However, cortical brain biopsy results and the presence of Alzheimer’s pathology had a strong correlation with success after CSF shunting. Thirteen percent of patients who initially had a normal cortical brain biopsy result had evidence of AD pathology on repeat biopsy, demonstrating the progressive nature of the disease.

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I. Jonathan Pomeraniec, Robert F. Dallapiazza, Zhiyuan Xu, John A. Jane Jr. and Jason P. Sheehan

OBJECT

Gamma Knife radiosurgery (GKRS) is frequently employed to treat residual or recurrent nonfunctioning pituitary macroadenomas. There is no consensus as to whether GKRS should be used early after surgery or if radiosurgery should be withheld until there is evidence of radiographic progression of tumor.

METHODS

This is a retrospective review of patients with nonfunctioning pituitary macroadenomas who underwent transsphenoidal surgery followed by GKRS between 1996 and 2013 at the University of Virginia Health System. Patients were stratified based on the interval between resection and radiosurgery. Operative results and imaging and clinical outcomes were compared across groups following early (≤ 6 months) or late (> 6 months) radiosurgery.

RESULTS

Sixty-four patients met the study criteria and were grouped based on early (n = 32) or late (n = 32) GKRS following transsphenoidal resection. There was a greater risk of tumor progression after GKRS in the late radiosurgical group (p = 0.027) over a median radiographic follow-up period of 68.5 months. Furthermore, there was a significantly higher occurrence of post-GKRS endocrinopathy in the late radiosurgical cohort (p = 0.041). Seventeen percent of patients without endocrinopathy in the early cohort developed new endocrinopathies during the follow-up period versus 64% in the late cohort (p = 0.036). This difference was primarily due to a significantly higher rate of tumor growth during the observation period of the late treatment cohort (p = 0.014). Of these patients with completely new endocrinopathies, radiation-associated pituitary insufficiency developed in 1 of 2 patients in the early group and in 3 of 7 (42.9%) patients in the late group.

CONCLUSIONS

Early treatment with GKRS appears to decrease the rate of radiographic and symptomatic progression of subtotally resected nonfunctioning pituitary macroadenomas compared with late GKRS treatment after a period of expectant management. Delaying radiosurgery may place the patient at increased risk for adenoma progression and endocrinopathy.

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Adeel Ilyas, Ching-Jen Chen, Dale Ding, Panagiotis Mastorakos, Davis G. Taylor, I. Jonathan Pomeraniec, Cheng-Chia Lee and Jason Sheehan

OBJECTIVE

Cyst formation can occasionally occur after stereotactic radiosurgery (SRS) for brain arteriovenous malformations (AVMs). Given the limited data regarding post-SRS cyst formation in patients with AVM, the time course, natural history, and management of this delayed complication are poorly defined. The aim of this systematic review was to determine the incidence, time course, and optimal management of cyst formation after SRS for AVMs.

METHODS

A literature review was performed using PubMed to identify studies reporting cyst formation in AVM patients treated with SRS. Baseline and outcomes data, including the incidence and management of post-SRS cysts, were extracted from each study that reported follow-up duration. The mean time to cyst formation was calculated from the subset of studies that reported individual patient data.

RESULTS

Based on pooled data from 22 studies comprising the incidence analysis, the overall rate of post-SRS cyst formation was 3.0% (78/2619 patients). Among the 26 post-SRS cyst patients with available AVM obliteration data, nidal obliteration was achieved in 20 (76.9%). Of the 64 cyst patients with available symptomatology and management data, 21 (32.8%) were symptomatic; 21 cysts (32.8%) were treated with surgical intervention, whereas the remaining 43 (67.2%) were managed conservatively. Based on a subset of 19 studies reporting individual time-to-cyst-formation data from 63 patients, the mean latency period to post-SRS cyst formation was 78 months (6.5 years).

CONCLUSIONS

Cyst formation is an uncommon complication after SRS for AVMs, with a relatively long latency period. The majority of post-SRS cysts are asymptomatic and can be managed conservatively, although enlarging or symptomatic cysts may require surgical intervention. Long-term follow-up of AVM patients is crucial to the appropriate diagnosis and management of post-SRS cysts.

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I. Jonathan Pomeraniec, Dale Ding, Robert M. Starke, Kenneth C. Liu, E. Kelly Mrachek, M. Beatriz Lopes and Jason P. Sheehan

OBJECTIVE

Stereotactic radiosurgery (SRS) is a commonly employed treatment modality for brain arteriovenous malformations (AVMs). However, due to the low frequency of delayed cyst formation after AVM SRS, as well as the prolonged time interval between treatment and its occurrence, the characteristics of post-SRS cyst formation are not well defined. Therefore, the aims of this retrospective cohort study are to determine the rate of cyst formation after SRS for AVMs, identify predictive factors, and evaluate the clinical sequelae of post-SRS cysts.

METHODS

The authors analyzed an SRS database for AVM patients who underwent SRS at the University of Virginia and identified those who developed post-SRS cysts. Statistical analyses were performed to determine predictors of post-SRS cyst formation and the effect of cyst formation on new or worsening seizures after SRS.

RESULTS

The study cohort comprised 1159 AVM patients treated with SRS; cyst formation occurred in 17 patients (post-SRS cyst rate of 1.5%). Compared with patients who did not develop post-SRS cysts, those with cyst formation were treated with a greater number of radiosurgical isocenters (mean 3.8 vs 2.8, p = 0.047), had a longer follow-up (mean 132 vs 71 months, p < 0.001), were more likely to develop radiological radiation-induced changes (RIC) (64.7% vs 36.1%, p = 0.021), and had a longer duration of RIC (57 vs 21 months, p < 0.001). A higher number of isocenters (p = 0.014), radiological RIC (p = 0.002), and longer follow-up (p = 0.034) were found to be independent predictors of post-SRS cyst formation in the multivariate analysis. There was a trend toward a significant association between cyst formation and new or worsening seizures in univariate analysis (p = 0.054).

CONCLUSIONS

Patients with greater nidal complexity appear to be more prone to post-SRS cyst formation. The findings of this study emphasize the importance of long-term follow-up for patients who have undergone AVM SRS, even after nidal obliteration is achieved. Post-SRS cysts may be epileptogenic, although seizure outcomes after AVM SRS are multifactorial.

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I. Jonathan Pomeraniec, Davis G. Taylor, Or Cohen-Inbar, Zhiyuan Xu, Mary Lee Vance and Jason P. Sheehan

OBJECTIVE

Gamma Knife radiosurgery (GKRS) provides a safe and effective management option for patients with all types of pituitary adenomas. The long-term adverse effects of targeted radiation to the hypothalamic-pituitary axis in relationship to radiation dose remain unclear. In this retrospective review, the authors investigated the role of differential radiation doses in predicting long-term clinical outcomes and pituitary function after GKRS for pituitary adenomas.

METHODS

A cohort of 236 patients with pituitary tumors (41.5% nonfunctioning, 58.5% functioning adenomas) was treated with GKRS between 1998 and 2015. Point dosimetric measurements, with no minimum volume, to 14 consistent points along the hypothalamus bilaterally, pituitary stalk, and normal pituitary were made. Statistical analyses were performed to determine the impact of doses to critical structures on clinical, radiological, and endocrine outcomes.

RESULTS

With a median follow-up duration of 42.9 months, 18.6% of patients developed new loss of pituitary function. The median time to endocrinopathy was 21 months (range 2–157 months). The median dose was 2.1 Gy to the hypothalamus, 9.1 Gy to the pituitary stalk, and 15.3 Gy to the normal pituitary. Increasing age (p = 0.015, HR 0.98) and ratio of maximum dose to the pituitary stalk over the normal pituitary gland (p = 0.013, HR 0.22) were independent predictors of new or worsening hypopituitarism in the multivariate analysis. Sex, margin dose, treatment volume, nonfunctioning adenoma status, or ratio between doses to the pituitary stalk and hypothalamus were not significant predictors.

CONCLUSIONS

GKRS offers a low rate of delayed pituitary insufficiency for pituitary adenomas. Doses to the hypothalamus are low and generally do not portend endocrine deficits. Patients who are treated with a high dose to the pituitary stalk relative to the normal gland are at higher risk of post-GKRS endocrinopathy. Point dosimetry to specific neuroanatomical structures revealed that a ratio of stalk-to-gland radiation dose of 0.8 or more significantly increased the risk of endocrinopathy following GKRS. Improvement in the gradient index toward the stalk and normal gland may help preserve endocrine function.

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Thomas J. Buell, Daniel M. S. Raper, I. Jonathan Pomeraniec, Dale Ding, Ching-Jen Chen, Davis G. Taylor and Kenneth C. Liu

Stenosis of the transverse sinus (TS) and sigmoid sinus (SS), with a trans-stenosis pressure gradient, has been implicated in the pathophysiology of idiopathic intracranial hypertension (IIH). MRI has shown improvement in TS and SS stenosis after high-volume lumbar puncture (HVLP) in a subset of patients with IIH. The authors present the first report of an IIH patient with immediate post-HVLP TS and SS trans-stenosis pressure gradient reduction and an attendant increase in TS and SS cross-sectional area confirmed using intravascular ultrasonography (IVUS). Recurrence of the patient’s TS-SS stenosis coincided with elevated HVLP opening pressure, and venous sinus stent placement resulted in clinical improvement. This report suggests that TS and SS stenosis may be a downstream effect of elevated intracranial pressure in IIH, rather than its principal etiological mechanism. However, the authors hypothesize that endovascular stenting may obliterate a positive feedback loop involving trans-stenosis pressure gradients, and still benefit appropriately selected patients.

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Colin J. Przybylowski, Robert F. Dallapiazza, Brian J. Williams, I. Jonathan Pomeraniec, Zhiyuan Xu, Spencer C. Payne, Edward R. Laws and John A. Jane Jr.

OBJECTIVE

The object of this study was to compare the outcomes of primary and revision transsphenoidal resection (TSR) of nonfunctioning pituitary macroadenomas (NFPMAs) using endoscopic methods.

METHODS

The authors retrospectively reviewed the records of 287 consecutive patients who had undergone endoscopic endonasal TSR for NFPMAs at their institution in the period from 2005 to 2011. Fifty patients who had undergone revision TSR were retrospectively matched for age, sex, and duration of follow-up to 46 patients who had undergone primary TSR. Medical and surgical complications were documented, and Kaplan-Meier analysis was performed to assess rates of radiological progression-free survival (PFS).

RESULTS

The median follow-up periods were 45 and 46 months for the primary and revision TSR groups, respectively. There were no significant differences between the primary and revision groups in rates of new neurological deficit (0 in each), vascular injury (2% vs 0), postoperative CSF leak (6% vs 2%), transient diabetes insipidus (DI; 15% vs 12%), chronic DI (2% vs 2%), chronic sinusitis (4% vs 6%), meningitis (2% vs 2%), epistaxis (7% vs 0), or suprasellar hematoma formation (0 vs 2%). However, patients who underwent primary TSR had significantly higher rates of syndrome of inappropriate antidiuretic hormone (SIADH; 17% vs 4%, p = 0.04). Patients who underwent primary operations also had significantly higher rates of gross-total resection (GTR; 63% vs 28%, p < 0.01) and significantly lower rates of adjuvant radiotherapy (13% vs 42%, p < 0.01). Radiological PFS rates were similar at 2 years (98% vs 96%) and 5 years (87% vs 80%, p = 0.668, log-rank test).

CONCLUSIONS

Patients who underwent primary TSR of NFPMAs experienced higher rates of SIADH than those who underwent revision TSR. Patients who underwent revision TSR were less likely to have GTR of their tumor, although they still had a PFS rate similar to that in patients who underwent primary TSR. This finding may be attributable to an increased rate of adjuvant radiation treatment to subtotally resected tumors in the revision TSR group.