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Ramin A. Morshed, Seunggu J. Han, Darryl Lau and Mitchel S. Berger

Surgery guided by 5-aminolevulinic acid (ALA) fluorescence has become a valuable adjunct in the resection of malignant intracranial gliomas. Furthermore, the fluorescence intensity of biopsied areas of a resection cavity correlates with histological identification of tumor cells. However, in the case of lesions deep within a resection cavity, light penetration may be suboptimal, resulting in less excitation of 5-ALA metabolites, leading to decreased fluorescence emission. To address this obstacle, the authors report on the use of a 400-nm wavelength fiber-optic lighted suction instrument that can be used both during resection of a tumor and to provide direct light to deeper areas of a resection cavity. In the presented case, this wavelength-specific lighted suction instrument improved the fluorescence intensity of patches of malignant tissue within the resection cavity. This technique may further improve the utility of 5-ALA in identifying tumor-infiltrated tissue for deep-seated lesions. Additionally, this tool may have implications for scoring systems that correlate 5-ALA fluorescence intensity with histological identification of malignant cells.

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Ramin A. Morshed, Darryl Lau, Peter P. Sun and Lauren R. Ostling

Choroid plexus papillomas (CPPs) are typically benign tumors that can occur in any age group but are more commonly found in pediatric patients. Although these tumors are benign, there are several reports in adult patients of distant metastases present either at the time of diagnosis or occurring months to years after initial resection. Here, the authors report the case of a 14-year-old boy who presented with symptoms of elevated intracranial pressure due to obstructive hydrocephalus that was caused by a large fourth ventricular mass. Preoperative imaging included a full MRI of the spine, which revealed an intradural lesion that encased the distal sacral nerve roots at the tip of the thecal sac and was concerning for a drop metastasis. The patient underwent gross-total resection of both the fourth ventricular and sacral tumors with histology of both lesions consistent with benign CPP (WHO Grade I). In addition, the authors review prior reports of both pediatric and adult patients in whom benign CPPs have metastasized with either benign or atypical pathology found at a distant site. Taking into account this unusual case and reports in the literature, patients with even benign CPPs may warrant initial and routine follow-up imaging of the total neural axis in search of the rare, but possible, occurrence of drop metastasis.

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Ramin A. Morshed, Jacob S. Young, Seunggu J. Han, Shawn L. Hervey-Jumper and Mitchel S. Berger

OBJECTIVE

Many surgical approaches have been described for lesions within the mesial temporal lobe (MTL), but there are limited reports on the transcortical approach for the resection of tumors within this region. Here, the authors describe the technical considerations and functional outcomes in patients undergoing transcortical resection of gliomas of the MTL.

METHODS

Patients with a glioma (WHO grades I–IV) located within the MTL who had undergone the transcortical approach in the period between 1998 and 2016 were identified through the University of California, San Francisco (UCSF) tumor registry and were classified according to tumor location: preuncus, uncus, hippocampus/parahippocampus, and various combinations of the former groups. Patient and tumor characteristics and outcomes were determined from operative, radiology, pathology, and other clinical reports that were available through the UCSF electronic medical record.

RESULTS

Fifty patients with low- or high-grade glioma were identified. The mean patient age was 46.8 years, and the mean follow-up was 3 years. Seizures were the presenting symptom in 82% of cases. Schramm types A, C, and D represented 34%, 28%, and 38% of the tumors, and the majority of lesions were located at least in part within the hippocampus/parahippocampus. For preuncus and preuncus/uncus tumors, a transcortical approach through the temporal pole allowed for resection. For most tumors of the uncus and those extending into the hippocampus/parahippocampus, a corticectomy was performed within the middle and/or inferior temporal gyri to approach the lesion. To locate the safest corridor for the corticectomy, language mapping was performed in 96.9% of the left-sided tumor cases, and subcortical motor mapping was performed in 52% of all cases. The mean volumetric extent of resection of low- and high-grade tumors was 89.5% and 96.0%, respectively, and did not differ by tumor location or Schramm type. By 3 months’ follow-up, 12 patients (24%) had residual deficits, most of which were visual field deficits. Three patients with left-sided tumors (9.4% of dominant-cortex lesions) experienced word-finding difficulty at 3 months after resection, but 2 of these patients demonstrated complete resolution of symptoms by 1 year.

CONCLUSIONS

Mesial temporal lobe gliomas, including larger Schramm type C and D tumors, can be safely and aggressively resected via a transcortical equatorial approach when used in conjunction with cortical and subcortical mapping.

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Michael M. Safaee, Ramin A. Morshed, Jordan Spatz, Sujatha Sankaran, Mitchel S. Berger and Manish K. Aghi

OBJECTIVE

Interfacility neurosurgical transfers to tertiary care centers are driven by a number of variables, including lack of on-site coverage, limited available technology, insurance factors, and patient preference. The authors sought to assess the timing and necessity of surgery and compared transfers to their institution from emergency departments (ED) and inpatient units at other hospitals.

METHODS

Adult neurosurgical patients who were transferred to a single tertiary care center were analyzed over 12 months. Patients with traumatic injuries or those referred from skilled nursing facilities or rehabilitation centers were excluded.

RESULTS

A total of 504 transferred patients were included, with mean age 55 years (range 19–92 years); 53% of patients were women. Points of origin were ED in 54% cases and inpatient hospital unit in 46%, with a mean distance traveled for most patients of 119 miles. Broad diagnosis categories included brain tumors (n = 142, 28%), vascular lesions, including spontaneous and hypertensive intracerebral hemorrhage (n = 143, 28%), spinal lesions (n = 126, 25%), hydrocephalus (n = 45, 9%), wound complications (n = 29, 6%), and others (n = 19, 4%). Patients transferred from inpatient units had higher rates of surgical intervention (75% vs 57%, p < 0.001), whereas patients transferred from the ED had higher rates of urgent surgery (20% vs 8%, p < 0.001) and shorter mean time to surgery (3 vs 5 days, p < 0.001). Misdiagnosis rates were higher among ED referrals (11% vs 4%, p = 0.008). Across the same timeframe, patients undergoing elective admission (n = 1986) or admission from the authors’ own ED (n = 248) had significantly shorter lengths of stay (p < 0.001) and ICU days (p < 0.001) than transferred patients, as well as a significantly lower total cost ($44,412, $46,163, and $72,175, respectively; p < 0.001).

CONCLUSIONS

The authors present their 12-month experience from a single tertiary care center without Level I trauma designation. In this cohort, 65% of patients required surgery, but the rates were higher among inpatient referrals, and misdiagnosis rates were higher among ED transfers. These data suggest that admitting nonemergency patients to local hospitals may improve diagnostic accuracy of patients requiring urgent care, more precisely identify patients in need of transfer, and reduce costs. Referring facilities may lack necessary resources or expertise, and the Emergency Medical Treatment and Active Labor Act (EMTALA) obligates tertiary care centers to accept these patients under those circumstances. Telemedicine and integration of electronic medical records may help guide referring hospitals to pursue additional workup, which may eliminate the need for unnecessary transfer and provide additional cost savings.

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Ramin A. Morshed, Jacob S. Young, Seunggu J. Han, Shawn L. Hervey-Jumper and Mitchel S. Berger

OBJECTIVE

Greater extent of resection (EOR) improves overall survival and progression-free survival for patients with low- and high-grade glioma. While resection for newly diagnosed insular gliomas can be performed with minimal morbidity, perioperative morbidity is not clearly defined for patients undergoing a repeat resection for recurrent insular gliomas. In this study the authors report on tumor characteristics, tumor EOR, and functional outcomes in patients undergoing reoperation for recurrent insular glioma.

METHODS

Adult patients with insular gliomas (WHO grades II–IV) who underwent index resection followed by reoperation were identified through the University of California San Francisco Brain Tumor Center. Treatment history and functional outcomes were collected retrospectively from the electronic medical record. Pre- and postoperative tumor volumes were quantified using software with region-of-interest analysis based on FLAIR and T1-weighted postgadolinium sequences from pre- and postoperative MRI.

RESULTS

Forty-four patients (63.6% male, 36.4% female) undergoing 49 reoperations for recurrent insular tumors were identified with a median follow-up of 741 days. Left- and right-sided tumors comprised 52.3% and 47.7% of the cohort, respectively. WHO grade II, III, and IV gliomas comprised 46.9%, 28.6%, and 24.5% of the cohort, respectively. Ninety-five percent (95.9%) of cases involved language and/or motor mapping. Median EOR of the insular component of grade II, III, and IV tumors were 82.1%, 75.0%, and 94.6%, respectively. EOR during reoperation was not impacted by Berger-Sanai insular zone or tumor side. At the time of reoperation, 44.9% of tumors demonstrated malignant transformation to a higher WHO grade. Ninety-day postoperative assessment confirmed that 91.5% of patients had no new postoperative deficit attributable to surgery. Of those with new deficits, 3 (6.4%) had a visual field cut and 1 (2.1%) had hemiparesis (strength grade 1–2/5). The presence of a new postoperative deficit did not vary with EOR.

CONCLUSIONS

Recurrent insular gliomas, regardless of insular zone and pathology, may be reoperated on with an overall acceptable degree of resection and safety despite their anatomical and functional complexities. The use of intraoperative mapping utilizing asleep or awake methods may reduce morbidity to acceptable rates despite prior surgery.

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Seunggu J. Han, Ramin A. Morshed, Irene Troncon, Kesshi M. Jordan, Roland G. Henry, Shawn L. Hervey-Jumper and Mitchel S. Berger

OBJECTIVE

Herein, the authors report their experience with intraoperative stimulation mapping to locate the descending subcortical motor pathways in patients undergoing surgery for hemispheric gliomas within or adjacent to the rolandic cortex, with particular description of the morbidity and functional outcomes associated with this technique.

METHODS

This is a retrospective analysis of patients who, in the period between 1997 and 2016, had undergone resection of hemispheric perirolandic gliomas within or adjacent to descending motor pathways. Data regarding intraoperative stimulation mapping and patient postoperative neurological status were collected.

RESULTS

Of 702 patients, stimulation mapping identified the descending motor pathways in 300 cases (43%). A new or worsened motor deficit was seen postoperatively in 210 cases (30%). Among these 210 cases, there was improvement in motor function to baseline levels by 3 months postoperatively in 161 cases (77%), whereas the deficit remained in 49 cases (23%). The majority (65%) of long-term deficits (persisting beyond 3 months) were mild or moderate (antigravity strength or better). On multivariate analysis, patients in whom the subcortical motor pathways had been identified with stimulation mapping during surgery were more likely to develop an additional and/or worsened motor deficit postoperatively than were those in whom the subcortical pathways had not been found (45% vs 19%, respectively, p < 0.001). This difference remained when considering the likelihood of a long-term deficit (i.e., persisting > 3 months; 12% vs 3.2%, p < 0.001). A higher tumor grade and the presence of a preoperative motor deficit were also associated with higher rates of motor deficits persisting long-term. A region of restricted diffusion adjacent to the resection cavity was seen in 20 patients with long-term deficits (41%) and was more common in cases in which the motor pathways were not identified (69%). Long-term deficits that occur in settings in which the subcortical motor pathways are not identified seem in large part due to ischemic injury to descending tracts.

CONCLUSIONS

Stimulation mapping allows surgeons to identify the descending motor pathways during resection of tumors in perirolandic regions and to attain an acceptable rate of morbidity in these high-risk cases.

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Andrew J. Gogos, Jacob S. Young, Matheus P. Pereira, Ramin A. Morshed, Matthew B. Potts, Shawn L. Hervey-Jumper and Mitchel S. Berger

OBJECTIVE

Although most patients with low-grade glioma (LGG) present after a seizure, a small proportion is diagnosed after neuroimaging is performed for a sign or symptom unrelated to the tumor. While these tumors invariably grow, some surgeons argue for a watchful waiting approach. Here, the authors report on their experience in the surgical treatment of patients with incidental LGG (iLGG) and describe the neurological outcomes, survival, and complications.

METHODS

Relevant cases were identified from a prospective registry of patients undergoing glioma resection at the University of California, San Francisco, between 1997 and 2019. Cases were considered iLGG when the lesion was noted on imaging performed for a reason unrelated to the tumor. Demographic, clinical, pathological, and imaging data were extracted from the electronic medical record. Tumor volumes, growth, and extent of resection were calculated from pre- and postoperative volumetric FLAIR sequences.

RESULTS

One hundred thirteen of 657 (17.2%) first-time resections for LGG were for incidental lesions. The most common reasons for the discovery of an iLGG were headaches (without mass effect, 34.5%) or trauma (16.8%). Incidental tumors were no different from symptomatic lesions in terms of laterality or location, but they were significantly smaller (22.5 vs 57.5 cm3, p < 0.0001). There was no difference in diagnosis between patients with iLGG and those with symptomatic LGG (sLGG), incorporating both molecular and pathological data. The median preoperative observation time for iLGG was 3.1 months (range 1 month–12 years), and there was a median growth rate of 3.9 cm3/year. Complete resection of the FLAIR abnormality was achieved in 57% of patients with incidental lesions but only 23.8% of symptomatic lesions (p < 0.001), and the residual volumes were smaller for iLGGs (2.9 vs 13.5 cm3, p < 0.0001). Overall survival was significantly longer for patients with incidental tumors (median survival not reached for patients with iLGG vs 14.6 years for those with sLGG, p < 0.0001). There was a 4.4% rate of neurological deficits at 6 months.

CONCLUSIONS

The authors present the largest cohort of iLGGs. Patient age, tumor location, and molecular genetics were not different between iLGGs and sLGGs. Incidental tumors were smaller, a greater extent of resection could be achieved, and overall survival was improved compared to those for patients with sLGG. Operative morbidity and rates of neurological deficit were acceptably low; thus, the authors advocate upfront surgical intervention aimed at maximal safe resection for these incidentally discovered lesions.

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Stephen T. Magill, Ramin A. Morshed, Calixto-Hope G. Lucas, Manish K. Aghi, Philip V. Theodosopoulos, Mitchel S. Berger, Oreste de Divitiis, Domenico Solari, Paolo Cappabianca, Luigi M. Cavallo and Michael W. McDermott

OBJECTIVE

Tuberculum sellae meningiomas (TSMs) are surgically challenging tumors that can severely impair vision. Debate exists regarding whether the transcranial (TC) or endoscopic transsphenoidal (TS) approach is best for resecting these tumors, and there are few large series comparing these approaches.

METHODS

A retrospective chart review was performed at 2 academic centers comparing TC and TS approaches with respect to vision, extent of resection, recurrence, and complications. The authors report surgical outcomes and propose a simple preoperative tumor grading scale that scores tumor size (1–2), optic canal invasion (0–2), and arterial encasement (0–2). The authors performed univariate, multivariate, and recursive partitioning analysis (RPA) to evaluate outcomes.

RESULTS

The TSMs were resected in 139 patients. The median follow-up was 29 months. Ninety-five (68%) cases were resected via a TC and 44 (32%) via a TS approach. Tumors treated via a TC approach had a higher tumor (p = 0.0007), artery (p < 0.0001), and total score (p = 0.0012) on the grading scale. Preoperative visual deficits were present in 87% of patients. Vision improved in 47%, stayed the same in 35%, declined in 10%, and was not recorded in 8%. The extent of resection was 65% gross-total resection, 23% near-total resection (95%–99% resection), and 12% subtotal resection (< 95%). A lower tumor score was significantly associated with better or stable vision postoperatively (p = 0.0052). The RPA confirmed low tumor score as the key predictor of postoperative visual improvement or stability. Multivariate analysis and RPA demonstrate that lower canal score (p < 0.0001) and TC approach (p = 0.0019) are associated with gross-total resection. Complications occurred in 20 (14%) patients, including CSF leak (5%) and infection (4%). There was no difference in overall complication rates between TC and TS approaches; however, the TS approach had more CSF leaks (OR 5.96, 95% CI 1.10–32.04). The observed recurrence rate was 10%, and there was no difference between the TC and TS approaches.

CONCLUSIONS

Tuberculum sellae meningiomas can be resected using either a TC or TS approach, with low morbidity and good visual outcomes in appropriately selected patients. The simple proposed grading scale provides a standard preoperative method to evaluate TSMs and can serve as a starting point for selection of the surgical approach. Higher scores were associated with worsened visual outcomes and subtotal resection, regardless of approach. The authors plan a multicenter review of this grading scale to further evaluate its utility.

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Andrew J. Gogos, Jacob S. Young, Ramin A. Morshed, Lauro N. Avalos, Roger S. Noss, Javier E. Villanueva-Meyer, Shawn L. Hervey-Jumper and Mitchel S. Berger

OBJECTIVE

Maximal safe resection of gliomas near motor pathways is facilitated by intraoperative mapping. The authors and other groups have described the use of bipolar or monopolar direct stimulation to identify functional tissue, as well as transcranial or transcortical motor evoked potentials (MEPs) to monitor motor pathways. Here, the authors describe their initial experience using all 3 modalities to identify, monitor, and preserve cortical and subcortical motor systems during glioma surgery.

METHODS

Intraoperative mapping data were extracted from a prospective registry of glioma resections near motor pathways. Additional demographic, clinical, pathological, and imaging data were extracted from the electronic medical record. All patients with new or worsened postoperative motor deficits were followed for at least 6 months.

RESULTS

Between January 2018 and August 2019, 59 operations were performed in 58 patients. Overall, patients in 6 cases (10.2%) had new or worse immediate postoperative deficits. Patients with temporary deficits all had at least Medical Research Council grade 4/5 power. Only 2 patients (3.4%) had permanently worsened deficits after 6 months, both of which were associated with diffusion restriction consistent with ischemia within the corticospinal tract. One patient’s deficit improved to 4/5 and the other to 4/5 proximally and 3/5 distally in the lower limb, allowing ambulation following rehabilitation. Subcortical motor pathways were identified in 51 cases (86.4%) with monopolar high-frequency stimulation, but only in 6 patients using bipolar stimulation. Transcranial or cortical MEPs were diminished in only 6 cases, 3 of which had new or worsened deficits, with 1 permanent deficit. Insula location (p = 0.001) and reduction in MEPs (p = 0.01) were the only univariate predictors of new or worsened postoperative deficits. Insula location was the only predictor of permanent deficits (p = 0.046). The median extent of resection was 98.0%.

CONCLUSIONS

Asleep triple motor mapping is safe and resulted in a low rate of deficits without compromising the extent of resection.

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Anthony T. Lee, Claire Faltermeier, Ramin A. Morshed, Jacob S. Young, Sofia Kakaizada, Claudia Valdivia, Anne M. Findlay, Phiroz E. Tarapore, Srikantan S. Nagarajan, Shawn L. Hervey-Jumper and Mitchel S. Berger

OBJECTIVE

Gliomas are intrinsic brain tumors with the hallmark of diffuse white matter infiltration, resulting in short- and long-range network dysfunction. Preoperative magnetoencephalography (MEG) can assist in maximizing the extent of resection while minimizing morbidity. While MEG has been validated in motor mapping, its role in speech mapping remains less well studied. The authors assessed how the resection of intraoperative electrical stimulation (IES)–negative, high functional connectivity (HFC) network sites, as identified by MEG, impacts language performance.

METHODS

Resting-state, whole-brain MEG recordings were obtained from 26 patients who underwent perioperative language evaluation and glioma resection that was guided by awake language and IES mapping. The functional connectivity of an individual voxel was determined by the imaginary coherence between the index voxel and the rest of the brain, referenced to its contralesional pair. The percentage of resected HFC voxels was correlated with postoperative language outcomes in tasks of increasing complexity: text reading, 4-syllable repetition, picture naming, syntax (SYN), and auditory stimulus naming (AN).

RESULTS

Overall, 70% of patients (14/20) in whom any HFC tissue was resected developed an early postoperative language deficit (mean 2.3 days, range 1–8 days), compared to 33% of patients (2/6) in whom no HFC tissue was resected (p = 0.16). When bifurcated by the amount of HFC tissue that was resected, 100% of patients (3/3) with an HFC resection > 25% displayed deficits in AN, compared to 30% of patients (6/20) with an HFC resection < 25% (p = 0.04). Furthermore, there was a linear correlation between the severity of AN and SYN decline with percentage of HFC sites resected (p = 0.02 and p = 0.04, respectively). By 2.2 months postoperatively (range 1–6 months), the correlation between HFC resection and both AN and SYN decline had resolved (p = 0.94 and p = 1.00, respectively) in all patients (9/9) except two who experienced early postoperative tumor progression or stroke involving inferior frontooccipital fasciculus.

CONCLUSIONS

Imaginary coherence measures of functional connectivity using MEG are able to identify HFC network sites within and around low- and high-grade gliomas. Removal of IES-negative HFC sites results in early transient postoperative decline in AN and SYN, which resolved by 3 months in all patients without stroke or early tumor progression. Measures of functional connectivity may therefore be a useful means of counseling patients about postoperative risk and assist with preoperative surgical planning.