Non-eloquent Areas Research Articles

5-aminolevulinic acid and neuronavigation in high-grade glioma surgery: results of a combined approach

In high-grade glioma surgery, several techniques are used to achieve the maximum cytoreductive treatment preserving neurological functions. However, the effectiveness of all the methods used alone is reduced by specific limitations of each. We assessed the reliability of a multimodal strategy based on 5-aminolevulinic acid (5-ALA) and neuronavigation. We prospectively studied 18 patients with suspected, non eloquent-area malignant gliomas amenable for complete resection. Conventional illumination was used until the excision appeared complete. The cavity was then systematically inspected in violet-blue light to identify any residual tumour. Multiple biopsies of both fluorescent and non-fluorescent tissue were performed in all cases. Each specimen was labelled according to the sampling location (inside or outside the boundary set by the neuronavigator). The samples were analysed by a neuropathologist blinded to the intraoperative classification. We reviewed the results of both methods, either singly or in combination. Individual analysis showed higher 5-ALA reliability compared to neuronavigation. However, several false-negative fluorescent specimens were detected. With the combined use of fluorescence and neuroimaging, only 1 sample (negative for both 5-ALA and navigation) was tumoral tissue. In our experience, the combined approach showed the best sensitivity and it is recommended in cases of lesions involving non-eloquent areas.

Aspiration Versus Excision: A Single Center Experience of Forty-Seven Patients With Brain Abscess Over 10 Years

The efficacies of two different surgical approaches, aspiration and excision, were investigated for the management of large solitary encapsulated pyogenic brain abscess located in superficial non-eloquent areas, and the impact on length of hospital stay, duration of postoperative antibiotic use, improvement in neurological status, and morbidity and mortality were compared. This retrospective study at Sher-i-Kashmir Institute of Medical Sciences included 47 patients with pyogenic brain abscess from a total of 114 patients evaluated in the Department of Neurosurgery over a period of 10 years from October 2001 to October 2011. Comparisons were made between aspiration and excision in terms of duration of antibiotic use, length of hospital stay, and overall treatment cost. Aspiration was performed in 29 patients (61.7%), of whom 7 patients needed second aspiration, and 18 patients underwent excision (38.3%) of the abscess capsule. The mean duration of antibiotic use in the excision group was significantly shorter at 2.7 weeks (standard deviation [SD]±1.1) compared to the aspiration group at 3.8 weeks (SD±1.3) (p=0.006). Similarly, mean length of hospital stay was significantly shorter in the excision group at 18.1 days (SD±7.7) compared to the aspiration group at 24.9 days (SD±6.6) (p=0.002). In addition, significantly earlier improvement in neurological function (p=0.025) and significantly lower rate of re-surgery (p=0.0238) were found in the excision group compared to the aspiration group. Excision is better than aspiration as far as duration of antibiotic use, length of hospital stay, and overall cost of treatment is concerned, with no significant difference in morbidity and mortality.

Early prognostic factors related to progression and malignant transformation of low-grade gliomas

Objective Low-grade gliomas (LGGs) are infiltrative tumors characterized by slow growth. However, during early period, LGGs can progress and transform into a malignant pathology. We analyzed the prognostic factors for progression and malignant transformation in LGGs. Materials and methods From 2000 to 2009, we operated on 86 patients: 42 oligodendrogliomas, 12 oligoastrocytomas, and 32 astrocytomas. The male:female ratio was 47:39, and the median age was 41 (±17.4) years. The mean follow-up period was 4.25 (±2.8) years. We analyzed the prognostic factors for progression-free survival (PFS), overall survival (OS), and malignant transformation, considering age, sex, KPS, clinical presentation, tumor location, radiologic pattern, extent of removal, pathologic subtype, and adjuvant treatment. Results In univariate analysis, non-eloquent location, gross total removal, and oligodendroglial pathology statistically correlated with improved PFS and OS. In multivariate analysis, gross total removal correlated with longer PFS ( p = 0.043), and gemistocytic astrocytoma had a poor PFS ( p = 0.004). Younger age and non-eloquent area showed an improved OS ( p = 0.002 and 0.041), and astrocytic pathology showed a poor OS ( p = 0.01). Malignant transformation was pathologically diagnosed in 13 out of 86 patients (15%). Gemistocytic astrocytoma correlated independently with malignant transformation ( p = 0.022). Conclusion In LGGs, extent of removal associated with tumor progression. The pathology of astrocytoma, especially gemistocytic astrocytoma, was an independent prognostic factor for recurrence and malignant transformation.

Editorial: Low-grade gliomas

At first glance the study reported in this issue of the Journal of Neurosurgery by Yordanova et al.,7 “Awake surgery for WHO grade II gliomas within ‘noneloquent’ areas in the left dominant hemisphere: Toward a ‘supratotal’ resection,” may not seem to be a novel observation with significant implications for patient care. However, a closer look at the take-home message could very well change the way in which we, as surgeons, approach lowgrade gliomas in so-called “noneloquent” locations. The authors reviewed, in a retrospective fashion, 17 low-grade gliomas (LGGs) in 15 patients who underwent a resection of the tumor beyond the margins as defined on anatomical MR images. This group of patients who underwent “supracomplete” resection was compared to a similar group of patients who underwent a complete tumor removal, based on volumetric extent of resection. While the number of patients was indeed small and the follow-up not as long as I would like to have seen, the results were quite dramatic. The number of relapses seen during the postoperative period were nonsignificantly greater in the control group (41%) than in the supracomplete resection group (26%), yet, the incidence of anaplastic transformation was significantly greater in the control group. In fact, there were no cases of anaplastic transformation in the supracomplete resection group. Previous work from our own group, and that of others,1,6 has demonstrated that extent of resection significantly impacts the occurrence of anaplastic transformation. In addition to age of the patient and tumor size, this feature is a critical determinant of eventual biological behavior of LGGs. This makes a good deal of sense when one considers the studies demonstrating tumor cell infiltration beyond the anatomical imaging boundaries of LGGs, especially, within 1 to 2 centimeters of the FLAIR MR imaging margin. This makes a strong argument for obtaining physiological imaging studies—such as diffusion weighted imaging, MR spectroscopy, perfusion—to better define the true volume of the lesion beyond the anatomical confines of the mass3–5 and designing a surgical strategy to resect both components (the tumor and the perilesional infiltrated margin). That said, the other major consideration, which, at the same time may be a limitation, is the functional nature of the region to be removed. Herein lies the beauty of this study: utilize awake functional mapping in noneloquent areas to resect the tumor plus the surrounding infiltrated margin—in other words, to perform “supracomplete” resection. This ensures that the resection is not limited by the “suspicion” of functional tissue, and the removal of additional infiltrated tissue does not result in significant permanent deficits.2 Our goal as glioma surgeons is to maximize extent of tumor resection while minimizing morbidity. The results, published throughout the past many years, are convincing to the point of being indisputable. With regard to LGGs, our goal should be to make this a chronic disease and delay anaplastic transformation for as long as possible. Although we have shown this to be possible with a complete radiographic resection, the authors of this study may have found a more effective strategy to achieve this lofty goal. In essence, they are definitely on to something.

Awake surgery for WHO Grade II gliomas within “noneloquent” areas in the left dominant hemisphere: toward a “supratotal” resection

It has been demonstrated that an extensive resection (total or subtotal) may significantly increase the overall survival in patients with WHO Grade II gliomas (low-grade gliomas [LGGs]). Yet, recent data have shown that conventional MR imaging underestimates the spatial extent of LGG, since tumor cells were found up to 20 mm around MR imaging abnormalities. Thus, it was hypothesized that an extended resection with a margin beyond MR imaging-defined abnormalities-a "supratotal" resection-might improve the outcome of LGG. However, because of the frequent location of LGG within "eloquent" brain areas, it is often difficult to achieve such a supratotal resection. This could nevertheless be possible when LGGs involve "noneloquent" areas, even in the left dominant hemisphere. The authors report on their use of awake electrical mapping to tailor the resection according to functional boundaries, that is, to pursue the resection beyond MR imaging-defined abnormalities, until corticosubcortical eloquent structures are encountered. Their aim was to apply this reliable surgical technique to LGGs located not within eloquent areas but distant from eloquent areas, to take a margin around the LGG visible on MR imaging while preserving brain function. Fifteen right-handed patients with a total of 17 tumors underwent resection of WHO Grade II gliomas involving nonfunctional areas within the left dominant hemisphere. In all patients, seizures were the initial manifestation of the tumors. Awake surgery with intraoperative electrostimulation was performed in all cases. The resection was continued until the surgeon reached cortical and subcortical areas crucial for brain function, especially language, as defined by the intrasurgical electrical mapping. The extent of resection was evaluated on postoperative FLAIR-weighted MR images. Despite transient neurological worsening in 60% of cases, all patients recovered and returned to a normal life. Seizure control was obtained in all patients with a decrease of antiepileptic drug therapy. Postoperative MR imaging showed that total resection was achieved in all 17 tumors and supratotal resection in 15. The average volume of the postoperative cavity (36.8 cm(3)) was significantly larger than the mean preoperative tumor volume (26.6 cm(3)) (p = 0.009). Neuropathological examination confirmed the diagnosis of WHO Grade II glioma in all cases. The mean duration of postoperative follow-up was 35.7 months (range 6-135 months). Only 4 of 15 patients experienced recurrence (without anaplastic transformation); the average time to recurrence in these cases was 38 months; radiotherapy was performed 6 years after the relapse in 1 case; no other patients received any adjuvant treatment. This series was compared with a control group of 29 patients who had "only" complete resection: anaplastic transformation was observed in 7 cases in the control group but not in any case in the series of patients who underwent supracomplete resection (p = 0.037). Furthermore, adjuvant treatment was administered in 10 patients in the control group compared with 1 patient who underwent supracomplete resection (p = 0.043). These findings support the usefulness of awake surgery with intraoperative functional (language) mapping with the attempt to perform supratotal resection of LGGs involving noneloquent areas in the left hemisphere. Indeed, the extent of resection was significantly increased in all cases but 2, with no additional permanent deficit and with control of seizures in all patients. The goal of supracomplete resection is currently to delay the anaplastic transformation, even if it does not (yet) enable a cure.

Uneven interhemispheric connections between left and right primary sensori‐motor areas

To clarify the characteristics of interhemispheric connections, we investigated cortico-cortical evoked potentials (CCEP) in human. Fourteen patients with temporal lobe epilepsy who underwent invasive EEG monitoring with bilaterally implanted subdural electrodes were studied. Electric pulse stimuli were given in a bipolar fashion at two adjacent electrodes on and around the motor area (MA) or sensory area (SA), and CCEP responses were recorded by averaging electrocorticograms from the contralateral hemisphere. Seventy-two pairs of electrodes were stimulated, and 468 recordings were analyzed. Fifty-one of 468 recordings demonstrated CCEP responses. Of 51 responses, 16 consisted of an initial positive triphasic wave (Type 1), 27 had an initial negative biphasic wave (Type 2), and 8 showed an initial positive biphasic wave (type 3). The mean latencies of the earliest peaks were 13.1, 28.9, and 29.4 ms in Types 1, 2, and 3 responses, respectively. The responses were more frequently evoked by stimulating facial MA (f-MA) and nonfacial MA (nf-MA) than by stimulating SA or noneloquent area. In both f-MA and nf-MA stimulation, the responses were more frequently recorded at the contralateral f-MA than at the contralateral nf-MA or other areas. SA stimulation never evoked CCEP responses at the contralateral MA or SA. The amplitudes were maximal when f-MA was stimulated and responses recorded at the contralateral f-MA. These findings suggest that the interhemispheric connections are uneven. Both f-MA and nf-MA send dense interhemispheric connections to the contralateral f-MA. SA may have no or only rare direct connection with the contralateral MA or SA.

Neurological complications and symptom resolution following Gamma Knife surgery for brain metastases 2 cm or smaller in relation to eloquent cortices

Object Reports on resection of tumors in or near eloquent cortices have noted neurological complications in up to 30% of patients. This paper contains an analysis of symptom resolution and neurological morbidity following 20-Gy Gamma Knife surgery (GKS) for supratentorial brain metastases ≤ 2 cm in greatest diameter. Methods The authors performed a retrospective analysis of 98 consecutively treated adults (33 men and 65 women with a median age of 61.4 years at the time of GKS) with Karnofsky Performance Scale score ≥ 60, who underwent GKS for supratentorial brain metastases ≤ 2 cm in diameter. Lesion location was classified as noneloquent (Grade I), near eloquent (Grade II), or eloquent (Grade III), in accordance with the grading system developed by the group at M. D. Anderson Cancer Center. Following treatment, the patients underwent MR imaging and clinical examinations at 6 weeks and every 3 months thereafter. Results Ninety-eight patients underwent 20-Gy GKS for 131 metastases at initial presentation and 31 patients underwent salvage 20-Gy GKS for 76 new lesions, for a total of 207 lesions (mean lesion volume 0.44 cm3). Lesions were classified as follows: Grade I, 96 (46.4%); Grade II, 51 (24.6%); and Grade III, 60 (29%). Fifteen patients (2 with Grade II and 13 with Grade III lesions) presented with deficits referable to their lesions, yielding pre-GKS deficit rates of 7.2% per lesion and 15.3% per patient. The pre-GKS deficits improved or resolved in 10 patients (66.7%) at a median time of 2.8 months and remained stable in 3 patients (20%). Two patients (13.3%) experienced worsened neurological deficits. One patient who was neurologically intact prior to treatment developed a new hemiparesis (1 of 83 patients [1.2%]). The rates of permanent neurological deterioration following GKS for Grades I, II, and III lesions were 0% (0 of 96 tumors), 2% (1 of 51), and 3.3% (2 of 60), respectively. The pre-GKS neurological deficits and larger lesions were the most significant risk factors for post-GKS neurological deterioration. Conclusions Gamma Knife surgery performed using a 20-Gy dose provides amelioration of neurological deficits from brain metastases that are ≤ 2 cm in diameter and located in or near eloquent cortices in nearly two-thirds of patients with a low incidence of morbidity. Consistent with the surgical literature, higher rates of neurological complications were observed as proximity to eloquent regions and lesion size increased. There was no neurological deterioration in patients harboring metastases in noneloquent areas.

Functional mapping–guided resection of low-grade gliomas in eloquent areas of the brain: improvement of long-term survival

Low-grade gliomas (LGGs) frequently infiltrate highly functional or "eloquent" brain areas. Given the lack of long-term survival data, the prognostic significance of eloquent brain tumor location and the role of functional mapping during resective surgery in presumed eloquent brain regions are unknown. We performed a retrospective analysis of 281 cases involving adults who underwent resection of a supratentorial LGG at a brain tumor referral center. Preoperative MR images were evaluated blindly for involvement of eloquent brain areas, including the sensorimotor and language cortices, and specific subcortical structures. For high-risk tumors located in presumed eloquent brain areas, long-term survival estimates were evaluated for patients who underwent intraoperative functional mapping with electrocortical stimulation and for those who did not. One hundred and seventy-four patients (62%) had high-risk LGGs that were located in presumed eloquent areas. Adjusting for other known prognostic factors, patients with tumors in areas presumed to be eloquent had worse overall and progression-free survival (OS, hazard ratio [HR] 6.1, 95% CI 2.6-14.1; PFS, HR 1.9, 95% CI 1.2-2.9; Cox proportional hazards). Confirmation of tumor overlapping functional areas during intraoperative mapping was strongly associated with shorter survival (OS, HR 9.6, 95% CI 3.6-25.9). In contrast, when mapping revealed that tumor spared true eloquent areas, patients had significantly longer survival, nearly comparable to patients with tumors that clearly involved only noneloquent areas, as demonstrated by preoperative imaging (OS, HR 2.9, 95% CI 1.0-8.5). Presumed eloquent location of LGGs is an important but modifiable risk factor predicting disease progression and death. Delineation of true functional and nonfunctional areas by intraoperative mapping in high-risk patients to maximize tumor resection can dramatically improve long-term survival.

Reduced local recurrence of a single brain metastasis through microscopic total resection

The goal of this study was to evaluate the therapeutic impact of the resection of metastatic brain tumor cells infiltrating adjacent brain parenchyma. Between July 2001 and February 2007, 94 patients (67 males and 27 females, with a mean age of 55.0 +/-12.0 years) underwent resection of a single brain metastasis, followed by systemic chemotherapy with or without radiotherapy. In 43 patients with tumors located in noneloquent areas, the authors performed microscopic total resections (MTRs) that included tumor cells infiltrating adjacent brain parenchyma, and they pathologically confirmed during surgery that the resection margins were free of tumor cells (MTR group). In 51 patients with lesions in eloquent locations, gross-total resections (GTRs) were performed without the removal of neighboring brain parenchyma (GTR group). The 2 groups were then compared for local recurrence and survival. The MTR group had better local control of the tumor than did the GTR group; 10 (23.3%) of 43 patients in the MTR group and 22 (43.1%) of 51 patients in the GTR group had a local recurrence (p = 0.04). The median time to tumor progression in the MTR group could not be calculated using the Kaplan-Meier method, whereas it was 11.4 months in the GTR group. The 1- and 2-year respective local recurrence rates were 29.1 and 29.1% in the MTR group and 58.6 and 63.2% in the GTR group (p = 0.01). Multivariate analysis showed that the MTR procedure was associated with a decreased risk of local recurrence (p = 0.003). A Cox regression analysis revealed that the hazard ratio for a local recurrence in the MTR group versus the GTR group was 3.14 (95% CI 1.47-6.72, p = 0.003). There was no significant difference in the local recurrence rate between the MTR group without radiotherapy (10 [30.3%] of 33) and the GTR group with postoperative radiotherapy (5 [26.3%] of 19). The results in this study suggest that MTRs including tumor cells infiltrating adjacent brain parenchyma for a single brain metastasis provide better local tumor control.

Traitement chirurgical des cavernomes corticaux et sous-corticaux. Principes généraux et série personnelle de 20 cas opérés entre 2000 et 2006

The surgical treatment of cortical or subcortical hemispheric cavernomas is founded on a series of questions: Is the cavernoma located in an eloquent or non-eloquent area? Is the cavernoma tangent to the cortex and visible immediately after the dura opening or deep seated in the hemisphere? Does the cavernoma lie in the depth of a sulcus and identifiable on the pretrans-sulcal approach MRI? Will perilesional tissue have to be removed to cure the epilepsy? What is the appropriate technology for each particular case: preoperative functional MRI, angiography, preoperative stereotactic guidance, peroperative ultrasonography, neuronavigation, peroperative neurophysiology and cortical stimulation, preoperative MRI? Based on a personal series of 20 cases operated on between 2000 and 2006, we describe our personal experience.

Supratentorial cerebral cavernous malformations: clinical, surgical, and genetic involvement

Although there is general agreement on the methods of treatment for symptomatic supratentorial cerebral cavernous malformations (CMs) located in noneloquent areas, some controversy exists regarding the management of cerebral CMs that are asymptomatic and/or located in eloquent or deep areas. Moreover, recent advances in genetic findings could influence both standard clinical management and the follow-up strategy in affected individuals. Thus, the objective of this study was to develop, based on the authors' experience and a literature review, a management algorithm to deal with supratentorial cerebral CMs. The authors retrospectively reviewed the clinical data related to 118 patients who underwent surgery for symptomatic supratentorial cerebral CMs at their institution. Twenty-eight of 118 patients harbored multiple lesions, and nine of these 28 patients had a clinically positive familial history. Genetic investigations were performed in 89 patients (75%). Surgery for supratentorial cerebral CMs in noneloquent locations is safe and curative. In cerebral CMs located in deep and eloquent areas and with symptoms including progressive neurological deficits, evidence of hemorrhage, and uncontrolled seizures, surgical treatment according to an integrated plan based on frameless stereotactic guidance and functional magnetic resonance imaging is recommended and results in acceptably low morbidity. The data support the need for long-term imaging follow up in all patients, careful preoperative vascular studies to detect associated venous anomalies, and the importance of genetic mutational analysis. The DNA screening protocol will change the care of family members of patients with familial forms of cerebral CMs, because affected asymptomatic family members may benefit by early detection of lesions. At the same time, the exclusion of family members who are not carriers of the mutation as members of the population at risk reduces the economic and psychological burden of clinical and instrumental monitoring.

Focal cortical dysplasia: pathophysiological approach

Clinical and experimental studies on focal cortical dysplasia (FCD) were carried out. For the experimental study, an experimental FCD model of rats was developed. Twenty Wistar rats at 0-2 days after birth were used for the study. Kainic acid (KA) solution was injected stereotaxically into medial and lateral sites of the sensori-motor cortex. Bipolar electrodes were inserted in five rats. Their behavior and electroencephalogram (EEG) were recorded using a digital-video-EEG monitoring system. After observation periods of 1, 2, and 6 months, rats were perfused for pathological study. FCD was observed adjacent to the site of KA injection in all rats more than 1 month after the injection. EEG recording demonstrated focal spike discharges in and around the site of injection. However, clinical seizure was not observed. Pathological studies showed decrease in GABA-A receptors and increase in GABA-B receptors not only in the lesion but also in perilesional areas. Fifteen surgical cases of FCD with intractable epilepsy were subjected to the clinical study. Neuro-imaging studies including high-resolution magnetic resonance imaging and single-photon emission computed tomography were performed. Conventional EEG studies demonstrated focal EEG abnormalities with epileptic phenomena. At surgery, intraoperative electrocorticography (ECoG) was performed to localize epileptic foci under neuroleptoanalgesia. Thirteen patients showed epileptiform discharges on preresection ECoG. All foci in non-eloquent areas were resected. Pathological studies including immunohistochemical staining were performed, and the characteristics of the FCD in relation to EEG findings were analyzed. Patients in whom total lesionectomy with complete focus resection was performed had favorable postoperative courses. Nine patients (64.3%) have been seizure-free with reduced medication, and significant improvement was achieved in two patients (14.3%). Electrophysiological examination revealed epileptogenecity not only in the lesions but also in perilesional areas. The immunohistochemical studies showed a decrease in GABA-A receptors and an increase in GABA-B receptors in both the lesions and perilesional areas, but N-methyl-D: -aspartate receptors were almost negative in both areas. Glutamate R1 was decreased in both areas, but glutamate R2 was increased in both areas. These findings support the results of a electrophysiological study. In conclusion, not only the epileptic property of experimental focal cortical dysplasia but also perilesional epileptogenesis was demonstrated. These findings supported the results of surgery for patients with focal cortical dysplasia. In cases of FCD, total removal of the lesion and resection of the perilesional epileptic focus are needed for a good outcome.

Clinical Application of Experimental Cortical Dysplasia in Rats

This report details clinical and experimental studies of focal cortical dysplasia. The first part deals with 14 surgical cases of children with intractable epilepsy. At surgery, intraoperative electrocorticography was performed to localize the epileptic foci under neuroleptanalgesia. Thirteen patients showed epileptiform discharges on this preresection electrocorticography. All foci in noneloquent areas were resected. Patients who had undergone total lesionectomy with complete focus resection showed the most favorable postoperative results. However, the positive correlation between the intraoperative electrocorticographic findings and the pathologic classification of cortical dysplasia was not found in the present study. Nine patients have been seizure free with reduced medication and two patients have achieved worthwhile improvement. We conclude that intraoperative electrocorticography can improve the surgical outcome for intractable epilepsy by localizing epileptic foci for resection. The second part describes a kainic acid-induced experimental model of focal cortical dysplasia, which demonstrated not only the epileptic properties of the dysplasia but also the perilesional epileptogenicity. The findings supported the surgical results for the patients with focal cortical dysplasia.

Brain Metastases in Soft Tissue Sarcomas: Case Report and Literature Review

Background and purpose: Brain metastasis is a relatively uncommon event in the natural history of soft tissue sarcomas. The increasing use of chemotherapy may have caused a reduction in local relapses as well as distant failures leading to an improvement in survival, thereby allowing metachronous seeding of the brain, a sanctuary site. The purpose of this report is to increase awareness amongst clinicians regarding such a possibility. Patients and methods: A review of the departmental sarcoma database following the presentation of this index case in the clinic. Results and discussion: An adolescent male who had previously been treated with surgery and radiotherapy for a spindle cell sarcoma of the left thigh developed a space-occupying lesion in the brain within 6 months of treatment of the primary tumor. He subsequently underwent resection of the presumed solitary brain metastasis followed by whole brain radiotherapy. On radiation he was detected to have pulmonary metastases too, for which he was offered palliative chemotherapy. The patient died of brain metastasis within 4 months. A review of the departmental sarcoma database, restricted to soft tissue sarcomas purely, maintained prospectively from 2000 till date, could not identify any other such case. Conclusion: Brain metastases from soft tissue sarcomas are rare. Patients with neurological symptoms, however, should be appropriately investigated. Surgical resection of brain metastasis could be considered for solitary brain metastasis in non-eloquent areas. Palliative radiotherapy is appropriate for patients with multiple brain metastases or co-existing extra-cranial disease.

Clinical Application of Experimental Cortical Dysplasia in Rats

This report details clinical and experimental studies of focal cortical dysplasia. The first part deals with 14 surgical cases of children with intractable epilepsy. At surgery, intraoperative electrocorticography was performed to localize the epileptic foci under neuroleptanalgesia. Thirteen patients showed epileptiform discharges on this preresection electrocorticography. All foci in noneloquent areas were resected. Patients who had undergone total lesionectomy with complete focus resection showed the most favorable postoperative results. However, the positive correlation between the intraoperative electrocorticographic findings and the pathologic classification of cortical dysplasia was not found in the present study. Nine patients have been seizure free with reduced medication and two patients have achieved worthwhile improvement. We conclude that intraoperative electrocorticography can improve the surgical outcome for intractable epilepsy by localizing epileptic foci for resection. The second part describes a kainic acid—induced experimental model of focal cortical dysplasia, which demonstrated not only the epileptic properties of the dysplasia but also the perilesional epileptogenicity. The findings supported the surgical results for the patients with focal cortical dysplasia. ( J Child Neurol 2005;20:351—356).

Prognostic factors in patients who survived more than 10 years after undergoing surgery for metastatic brain tumors: Report of 5 cases and review of the literature

BACKGROUND Although the overall prognosis of patients with metastatic brain tumors is dismal, a small number survive longer than 10 years after craniotomy. We report 5 patients who survived for more than 10 years after undergoing treatment for metastatic brain tumor. METHODS The 5 patients who survived for more than 10 years after undergoing craniotomy were among 56 consecutively treated patients with solitary metastatic brain tumors. We retrospectively examined their clinical course, treatment, and variables associated with their longer survival and compared these 5 patients with other reported cases of metastatic brain tumor. RESULTS The histologic tumor types and the sites of origin of the primary tumor varied: two were from lung cancer and one each was from colon cancer, renal cell, and cervical carcinoma of the uterus. Common features among the long-term survivors were: systemic disease was absent, the metastatic tumor was located in the non-eloquent area of the non-dominant hemisphere, they were in good neurologic condition before surgery, there was a long interval between the diagnosis and treatment of the primary lesion and the diagnosis of the brain metastasis, and the patients received postoperative irradiation/chemotherapy. CONCLUSION Aggressive surgical treatment may be justified in young patients with a solitary metastatic brain tumor, as long as they are free of active systemic metastases.

Asymptomatic versus symptomatic infarcts from vasospasm in patients with subarachnoid hemorrhage: serial magnetic resonance imaging.

By use of serial magnetic resonance imaging (MRI), we prospectively investigated the incidence of and the risk factors associated with infarction caused by vasospasm with or without a delayed ischemic neurological deficit (DIND) in patients with subarachnoid hemorrhage (SAH). In 125 patients who underwent surgery for early aneurysms, postoperative MRI scans were obtained at four time points. We defined an infarct from vasospasm as a new lesion not present on the initial MRI within 3 days after SAH and therefore not attributable to primary brain damage or surgical complications. Overall, symptoms of infarction (i.e., DIND) occurred in 38% of patients (48 of 125); DIND with a new infarct on MRI was evident in 34% (43 patients), whereas 4% (5 patients) showed no new lesion but had a DIND. However, 29 patients (23%) showed a new infarct but no DIND on MRI studies (asymptomatic infarction). Asymptomatic ischemic lesions due to vasospasm tended to involve noneloquent brain areas in the territory of intraparenchymal perforators. Multivariate analysis identified variables associated with symptomatic infarction to be of poor SAH grade, advanced age of the patient, angiographic findings of vasospasm, multiple cortical infarcts on MRI studies consistent with vasospasm, and chronic hydrocephalus. Analysis of the data confirmed the occurrence of asymptomatic infarcts due to vasospasm. These infarcts often developed in noneloquent areas representing perforator territory. MRI investigation of vasospastic lesions referable to intraparenchymal vessels such as perforators complements the study of extraparenchymal major vessel vasospasm in patients with SAH by computed tomographic angiography.

Treatment outcome of single or hypofractionated single-isocentric stereotactic irradiation (STI) using a linear accelerator for intracranial arteriovenous malformation

Background and purpose: We investigated the use of hypofractionated stereotactic radiotherapy (HFSR) to reduce adverse radiation effects in comparison to single-fraction stereotactic radiosurgery (SRS) for intracranial arteriovenous malformations (AVMs).Materials and methods: This study includes 53 intracranial AVMs treated between 1991–1998. HFSR was selected for 26 AVMs with a maximum diameter ≥2.5 cm or at eloquent area. Twenty-seven patients were treated with SRS (18 AVMs <2.5 cm at non-eloquent area, nine patients who were unfit for prolonged ring-wearing). The most frequent minimum dose (Dmin) was 20 Gy for SRS and 28 Gy for HFSR in four fractions. The mean follow-up duration was 34.6 months for SRS and 35.4 months for HFSR.Results: As a whole, the 3 and 5-year actuarial obliteration rates were 64 and 92%. Age <20 years old (P=0.02) and a maximum diameter <2 cm were favorable factors (P=0.05). A difference in the distribution of patients was observed in size (≥2.5 cm or not) (P<0.001) and location (eloquent or not) (P<0.001) between SRS and HFSR due to the treatment selection. However, no significant differences were observed in the actuarial rates of obliteration and transient increased signals with T2-weighted MR images between SRS and HFSR. Radiation necrosis occurred in two patients treated with SRS and in none with HFSR. Intracranial hemorrhage after treatment happened in two treated with SRS and three with HFSR.Conclusions: HFSR appears to be at least as effective as SRS in achieving complete obliteration of intracranial AVM, although its definitive role remains to be investigated.

Neurosurgical outcomes in a modern series of 400 craniotomies for treatment of parenchymal tumors.

The goals were to critically review all complications resulting within 30 days after craniotomies performed for excision of intra-axial brain tumors relative to factors likely to affect complication rates and to assess the value of these data in predicting the risk of surgical morbidity, particularly for surgery in eloquent brain regions. Neurosurgical outcomes were studied for 327 patients who underwent 400 craniotomies for removal of intra-axial parenchymal brain neoplasms in a 21-month period. Tumors removed included gliomas (206 tumors) and metastases (194 tumors) located both supratentorially (358 tumors) and infratentorially (42 tumors). The major complication incidence was 13%, and the operative mortality rate was 1.7%. The overall morbidity rate was 32%, but more types of complications were considered than in previous studies. The major neurological morbidity rate was 8.5%. Based on pre- versus postoperative (at 4 wk) Karnofsky Performance Scale scores, 9% of patients deteriorated neurologically, 32% improved, and 58% showed no change. The median postoperative hospital stay was 5 days. Tumors were defined as Grade I, II, or III based on their location relative to brain function, and this tumor functional grade was the most important variable affecting the incidence of any neurological deficit. Patients with tumors in eloquent (Grade III) or near-eloquent (Grade II) brain areas incurred more neurological deficits than did patients with tumors in noneloquent areas (Grade I). Neither repeat surgery for recurrent disease nor extent of surgical resection affected outcome significantly. Although most tumors in this study, including those in eloquent regions, were removed by gross total resection, this did not lead to more major neurological deficits. Regional complications (at the surgical sites) and systemic complications (medical) were more prevalent among older patients (age >60 yr) with lower preoperative Karnofsky Performance Scale scores (< or = 50) and posterior fossa masses. We showed how our data can be used to predict the total risk of surgical morbidity for a given patient, to facilitate patient counseling and surgical decision-making. The finding that gross total resections could be performed in eloquent brain regions with an acceptable level of neurological impairment suggested that the mere presence of a tumor in eloquent brain does not automatically contraindicate surgery. Our results have practical risk-predictive value, and they should aid in the construction of subsequent outcome studies, because we have identified the key areas to monitor.

Treatment of unruptured arteriovenous malformations in the brain

Clinical features and treatment results of 33 patients with unruptured arteriovenous malformations (AVMs) were evaluated. Nine AVMs were located in the frontal lobe, 8 in the motor cortex, 5 in the parietal lobe, 6 in the temporal lobe, 2 in the occipital lobe and 3 in other parts of the brain. Nine patients were treated with microsurgery and 24 with radiosurgery. Total extirpation of the AVM was performed in all 9 microsurgery patients. One patient with an AVM in the motor cortex experienced upper extremity weakness postoperatively. Eleven of 24 patients treated with radiosurgery had follow-up imaging studies. Obliteration was obtained in 8 patients and decreased size in 3. Complications included 1 patient with a hemiparesis and 1 with an AVM rupture prior to obliteration. The remaining 13 patients did not experience any complications over a mean period of 21.2 months. Microsurgery appears to be the best treatment for unruptured AVMs in non-eloquent areas. Radiosurgery is a safe, effective treatment for unruptured AVMs in eloquent areas, although a bleeding risk remains during the latency period prior to obliteration.