Apparent diffusion coefficient of piriform cortex and seizure outcome in mesial temporal lobe epilepsy after MR-guided laser interstitial thermal therapy: a single-institution experience.

OBJECTIVE: Piriform cortex (PC) is one of the critical structures in the epileptogenesis of mesial temporal lobe epilepsy (mTLE), but its role is poorly understood. The authors examined the utility of apparent diffusion coefficient (ADC; an MR-based marker of tissue pathology) of the PC as a predictor of seizure outcome in patients with mTLE undergoing MR-guided laser interstitial thermal therapy (MRgLITT). METHODS: A total of 33 patients diagnosed with mTLE who underwent MRgLITT at the authors' institution were included in the study. The 6-month postoperative seizure outcomes were classified using the International League Against Epilepsy (ILAE) system as good (complete seizure freedom, ILAE class I) and poor (seizure present, ILAE classes II-VI). The PC and ablation volumes were manually segmented from both the preoperative and intraoperative MRI sequences, respectively. The mean ADC intensities of 1) preablation PC; 2) total ablation volume; 3) ablated portion of PC; and 4) postablation residual PC were calculated and compared between good and poor outcome groups. Additionally, the preoperative PC volumes and proportion of PC volume ablated were examined and compared between the subjects in the two outcome groups. RESULTS: The mean age at surgery was 36.5 ± 3.0 years, and the mean follow-up duration was 1.9 ± 0.2 years. Thirteen patients (39.4%) had a good outcome. The proportion of PC ablated was significantly associated with seizure outcome (10.16 vs 3.30, p < 0.05). After accounting for the variability in diffusion tensor imaging acquisition parameters, patients with good outcome had a significantly higher mean ADC of the preablation PC (0.3770 vs -0.0108, p < 0.05) and the postoperative residual PC (0.4197 vs 0.0309, p < 0.05) regions compared to those with poor outcomes. No significant differences in ADC of the ablated portion of PC were observed (0.2758 vs -0.4628, p = 0.12) after performing multivariate analysis. CONCLUSIONS: A higher proportion of PC ablated was associated with complete seizure freedom. Preoperative and postoperative residual ADC measures of PC were significantly higher in the good seizure outcome group in patients with mTLE who underwent MRgLITT, suggesting that ADC analysis can assist with postablation outcome prediction and patient stratification.

Piriform Cortex Ablation Volume Is Associated With Seizure Outcome in Mesial Temporal Lobe Epilepsy.

BACKGROUND: Growing evidence suggests that piriform cortex resection during anterior temporal lobectomy is important for achieving good seizure outcome in mesial temporal lobe epilepsy (mTLE). However, the relationship between seizure outcome and piriform cortex ablation during MR-guided laser interstitial thermal therapy (MRgLITT) remains unclear. OBJECTIVE: To determine whether ablation of piriform cortex was associated with seizure outcome in patients with mTLE undergoing MRgLITT. METHODS: We performed preablation and postablation volumetric analyses of hippocampus, amygdala, piriform cortex, and ablation volumes in patients with mTLE who underwent MRgLITT at our institution from 2014 to 2019. RESULTS: Thirty nine patients with mTLE were analyzed. In univariate logistic regression, percent piriform cortex ablation was associated with International League Against Epilepsy (ILAE) class 1 at 6 months (odds ratio [OR] 1.051, 95% CI [1.001-1.117], P = .045), whereas ablation volume, percent amygdala ablation, and percent hippocampus ablation were not ( P > .05). At 1 year, ablation volume was associated with ILAE class 1 (OR 1.608, 95% CI [1.071-2.571], P = .021) while percent piriform cortex ablation became a trend (OR 1.050, 95% CI [0.994-1.109], P = .054), and both percent hippocampus ablation and percent amygdala ablation were not significantly associated with ILAE class 1 ( P > .05). In multivariable logistic regression, only percent piriform cortex ablation was a significant predictor of seizure freedom at 6 months (OR 1.085, 95% CI [1.012-1.193], P = .019) and at 1 year (OR 1.074, 95% CI [1.003-1.178], P = .041). CONCLUSION: Piriform cortex ablation volume is associated with seizure outcome in patients with mTLE undergoing MRgLITT. The piriform cortex should be considered a high yield ablation target to achieve good seizure outcome.

Phase- targeted stimulation modulates phase-amplitude coupling in the motor cortex of the human brain.

BACKGROUND: Phase-amplitude coupling (PAC) in which the amplitude of a faster field potential oscillation is coupled to the phase of a slower rhythm, is one of the most well-studied interactions between oscillations at different frequency bands. In a healthy brain, PAC accompanies cognitive functions such as learning and memory, and changes in PAC have been associated with neurological diseases including Parkinson's disease (PD), schizophrenia, obsessive-compulsive disorder, Alzheimer's disease, and epilepsy. OBJECTIVE: /Hypothesis: In PD, normalization of PAC in the motor cortex has been reported in the context of effective treatments such as dopamine replacement therapy and deep brain stimulation (DBS), but the possibility of normalizing PAC through intervention at the cortex has not been shown in humans. Phase-targeted stimulation (PDS) has a strong potential to modulate PAC levels and potentially normalize it. METHODS: We applied stimulation pulses triggered by specific phases of the beta oscillations, the low frequency oscillations that define phase of gamma amplitude in beta-gamma PAC, to the motor cortex of seven PD patients at rest during DBS lead placement surgery We measured the effect on PAC modulation in the motor cortex relative to stimulation-free periods. RESULTS: We describe a system for phase-targeted stimulation locked to specific phases of a continuously updated slow local field potential oscillation (in this case, beta band oscillations) prediction. Stimulation locked to the phase of the peak of beta oscillations increased beta-gamma coupling both during and after stimulation in the motor cortex, and the opposite phase (trough) stimulation reduced the magnitude of coupling after stimulation. CONCLUSION: These results demonstrate the capacity of cortical phase-targeted stimulation to modulate PAC without evoking motor activation, which could allow applications in the treatment of neurological disorders associated with abnormal PAC, such as PD.

Opioid use and spinal cord stimulation therapy: The long game.

Spinal cord stimulation (SCS) has been considered as an alternative therapy to reduce opioid requirements in certain chronic pain disorders. However, information on long-term opioid consumption patterns and their impact on SCS device explantation is lacking. We conducted a retrospective study of 45 patients to characterize long-term patterns of opioid usage after SCS implantation. Daily morphine equivalent dosage (MED) increased, decreased, and remained the same in 40%, 40%, and 20% of patients at 1-year follow-up, respectively. Twelve (27%) underwent explantation due to treatment failure at a median of 18 months after implantation. Pre-operative opioid status (naïve vs. active use) was not associated with explantation (18% vs. 29%, p = 0.699) and neither was the daily MED change status (i.e. increased, decreased, unchanged) at 1-year (p = 0.499, 1.000, 0.735, respectively). Following explantation, reduction in the daily MED was seen in 92% of patients with dosages falling below pre-operative baseline in nine. Among the opioid naïve patients, 55% were on opioids at last follow-up (average 32.4 ± 14.6 months). Our results indicate that daily opioid consumption does not decrease in most patients 1-year after SCS implantation. Furthermore, post-operative evaluation beyond 1-year is necessary to assess the efficacy and durability of SCS therapy as well as its impact on opioid requirement. Lastly, rigorous patient selection and pre-operative risk assessment for misuse and dependence are paramount to improving outcome after SCS implantation.

Total Fasting and Dehydration in the Operating Room: How Can Surgeons Survive and Thrive?

OBJECTIVES: Hydration and nutrition are critical to achieving optimal performance. This study aimed to assess the impact of limited oral intake in the operating room environment on surgical resident health, well-being, and performance. DESIGN: Electronic survey was sent to 94 surgical trainees at our institution in 2020. Chi-square analyses were performed to assess for differences in survey responses by sex. SETTING: A single tertiary-care institution. PARTICIPANTS: Surveys were sent to surgical residents and fellows in general surgery, neurosurgery, and orthopedic surgery. Seventy-nine (80%) of the 94 residents and fellows responded. RESULTS: Of the 79 responses, most trainees (79%) experienced dehydration within 6 hours of operating. Forty-four (56%) reported no fluid intake for greater than 6 hours on average, and 39 (49%) reported that they frequently had difficulty rehydrating in between cases. Most of the respondents (70%) frequently experienced symptoms of dehydration, including orthostasis, headache, and constipation. Fifty-six (71%) believed that dehydration frequently affected their performance. Compared to men, women were more likely to feel dehydrated within 4 hours of operating (58% vs. 25%, p = 0.005). Women were also more likely to have difficulty rehydrating in between cases (75% vs. 38%, p = 0.0026), experience symptoms of dehydration (92% vs. 60%, p = 0.0049), and report that dehydration affects surgical performance (88% vs. 64%, p = 0.0318). CONCLUSIONS: Prolonged fasting and dehydration are common issues that may negatively impact performance and wellbeing of surgical trainees. Also, dehydration may affect men and women differently.

Traumatic sacral dermoid cyst rupture with intracranial subarachnoid seeding of lipid particles: illustrative case.

BACKGROUND: Intracranial deposits of fat droplets are an unusual presentation of a spinal dermoid cyst after spontaneous rupture and are even more uncommon after trauma. Here, the authors present a case with this rare clinical presentation, along with a systematic review of the literature to guide decision making in these patients. OBSERVATIONS: A 54-year-old woman with Lynch syndrome presented with severe headache and sacrococcygeal pain after a traumatic fall. Computed tomography of the head revealed multifocal intraventricular and intracisternal fat deposits, which were confirmed by magnetic resonance imaging (MRI) of the neuroaxis; in addition, a ruptured multiloculated cyst was identified within the sacral canal with proteinaceous/hemorrhagic debris, most consistent with a sacral dermoid cyst with rupture into the cerebrospinal fluid (CSF) space. An unruptured sacral cyst was later noted on numerous previous MRI scans. In our systematic review, we identified 20 similar cases, most of which favored surgical treatment. LESSONS: Rupture of an intraspinal dermoid cyst must be considered when intracranial fat deposits are found in the context of cauda equina syndrome, meningism, or hydrocephalus. Complete tumor removal with close postoperative follow-up is recommended to decrease the risk of complications. CSF diversion must be prioritized if life-threatening hydrocephalus is present.

Non-staged bilateral Globus Pallidus Internus deep brain stimulation lead revision using intraoperative MRI: a case report and literature review.

BACKGROUND: Deep brain stimulation (DBS) lead revision due to suboptimal therapy is common but there is no standardised protocol. We describe a novel technique using iMRI to perform concurrent new Globus Pallidus Internus (GPi) DBS lead implantation and old lead removal in a dystonia patient.Case-description: A 60-year-old woman with medication and neurotoxin-refractory isolated cervical dystonia underwent awake bilateral GPi DBS surgery with MER-guided lead implantation. She initially had a favourable response but later reported suboptimal benefit despite reprogramming. MRI demonstrated suboptimal lead placement and MRI-guided revision surgery under general anesthesia was planned. The goal was to place new leads superior and medial to the existing leads. Using a 1.5 T iMRI and the ClearPoint® NeuroNavigation system, new leads were placed through the existing burr holes, into the new targets with radial errors < 0.08mm bilaterally without crossing the old leads. The old leads were then removed and the new leads connected to the existing pulse generator. The patient tolerated the procedure well and had improved side-effect profile at all contacts at 1-month follow-up. CONCLUSIONS: Non-staged iMRI-guided DBS revision surgery under general anesthesia is technically feasible and is an alternative strategy to a staged iMRI-guided revision surgery or an awake MER-guided revision surgery in select patients.

Olfactory Testing in Temporal Lobe Epilepsy: a Systematic Review.

PURPOSE OF REVIEW: Olfactory testing is a potentially safe, cost-effective, bedside evaluation tool for diagnosis, monitoring, and risk assessment for surgery in temporal lobe epilepsy (TLE) patients, but testing methods and relevant olfactory domains are not standardized. We conducted a systematic review to evaluate olfactory tests in TLE and summarize the results of the literature. RECENT FINDINGS: Olfactory tests varied significantly in odorant administration tools and devices, target odorants, evaluation timing, and grading scales. The Smell Threshold Test and University of Pennsylvania Smell Identification Test were the most validated single-domain tests for odor detection and odor identification, respectively. For multi-domain tests, Odor Memory/Discrimination Test and the Sniffin' Sticks test were the most validated. Results of olfactory tests in TLE are presented by domain. Rigorous validation, standardization, and comparative analysis of existing olfactory tests by domain is urgently needed to establish the utility and efficacy of olfactory testing in TLE.

Spinal cord stimulation and psychotropic medication use: Missing piece to the puzzle?

Psychotropic medications have modulatory effects on spinal cord stimulator (SCS) therapy and may play an important role in determining treatment success in chronic pain management. However, it remains unknown how SCS affects psychotropic use and whether the medications affect outcome. We performed a retrospective study to determine the prevalence of psychotropic medication (i.e. anxiolytic, antidepressant, and anticonvulsant) use among new SCS patients immediately before implantation and characterized the dosage changes at 1-year. We also sought to understand whether pre-operative medication status affects outcome, defined as device explantation due to treatment failure. In an analysis of 45 patients, 31%, 51% and 71% were actively taking anxiolytics, antidepressants, and anticonvulsants, respectively, before surgery. In the majority of cases, daily dosages remained the same for all three classes of medication at 1-year. Patients who were on two or more classes of medications pre-operatively had significantly lower explantation rate compared to those with one or none (12% vs. 43%, p = 0.041) and had 5.25 times less likelihood of explanation in the future (OR 5.25, 95%CI 1.18-23.2, p = 0.029). Our study suggest that peri-operative multimodality medical treatment may enhance the therapeutic efficacy and durability of SCS in carefully selected chronic pain patients.

Odor identification predicts postoperative seizure control following magnetic resonance-guided laser interstitial thermal therapy.

OBJECTIVE: Olfactory dysfunction has been well documented in individuals with temporal lobe epilepsy, but its use in presurgical planning has yet to be examined. We assessed the role of preoperative odor identification in mesial onset seizure localization utilizing stereoelectroencephalography (S-EEG) and magnetic resonance-guided laser interstitial thermal therapy (MRgLiTT) outcome. METHODS: We identified 30 patients who had typical seizures captured during S-EEG monitoring or MRgLiTT of mesial temporal structures (n = 17 S-EEG, n = 13 MRgLiTT); seizure onset zone was classified as unilateral mesial seizure onset, or multifocal with unilateral mesial onset and nonmesial onset. Odor identification ability was assessed using the Sniffin' Sticks Odor Identification Test (SSOIT). Patients also completed measures of confrontation naming and auditory-verbal learning/memory using the Boston Naming Test and Hopkins Verbal Learning Test-Revised, respectively. RESULTS: Overall, patients with intractable focal epilepsy exhibited poor olfactory performance (median [M] = 10.4, interquartile range [IQR] = 9.4-11.8). Of 19 patients who underwent MRgLiTT, 10 patients (52.6%) were seizure-free at last follow-up (M = 13 months, IQR =10-18). Patients who were seizure-free after MRgLiTT (n = 10) had poorer odor identification scores (M = 9, IQR = 7-13) compared to patients with seizure reoccurrence (M = 13, IQR = 12.5-15). Odor identification score was inversely associated with seizure freedom, with odds ratio = 0.60 (95% confidence interval [CI] = 0.38-0.95, P = .03). Receiver operating characteristic analysis revealed that an SSOIT score of 12 was the ideal cutoff for predicting favorable seizure outcome (area under the curve = 0.84, 95% CI = 0.64-1.0). Sensitivity was 88.9% and specificity was 78.9%, with a likelihood ratio of 2.9 of seizure failure in patients who had an odor identification score ≥ 12. SIGNIFICANCE: Interictal olfactory dysfunction is commonly seen in patients with intractable focal epilepsy. Odor identification is a novel, noninvasive presurgical biomarker to distinguish who may or may not benefit from MRgLiTT of mesial temporal structures.

Laser interstitial thermal therapy after failed anterior temporal lobectomy and amygdalohippocampectomy can improve seizure outcome.

Anterior temporal lobectomy and amygdalohippocampectomy (ATL) is the gold standard surgical treatment for drug resistant mesial temporal lobe epilepsy (mTLE). Nevertheless, seizure recurrence after ATL is not uncommon. Insufficient resection of the mesial temporal structures remains one of the most common reasons for ATL failure. Extending the resection leads to improved seizure outcome in a majority of patients. However, repeat craniotomy can be higher risk for the patient and also can be technically challenging due to scarring and altered anatomy. Laser interstitial thermal therapy (LITT) is a novel minimally invasive alternative to ATL, and it has been shown to be safe and effective. However, it is unclear if LITT has a role in managing post-ATL mTLE patients with recurrent seizures and residual epileptogenic structures. LITT is an attractive option for post-ATL patients with residual mesial structures because the surgery is minimally invasive, and it allows precise targeting and real time confirmation of tissue ablation under MRI guidance. We present a case of an mTLE patient with recurrent seizures after ATL who achieved long-term seizure-freedom after successfully undergoing LITT to ablate the residual hippocampus. This approach, if demonstrated to be safe, effective and durable, can benefit select post-ATL mTLE patients.

Epidural spinal involvement of Erdheim-Chester disease causing myelopathy.

We present a 25-year-old woman with Erdheim-Chester disease (ECD) presenting with progressive myelopathy from multiple compressive spinal epidural lesions who required cervicothoracic decompression and fusion, and summarize the literature on epidural spinal involvement of ECD. ECD is a rare non-Langerhans histiocytosis affecting multiple organ systems through infiltration and characteristically causing multifocal osteosclerosis. Central nervous system involvement, particularly of the spine, is rare.

Role of fever in ventriculoperitoneal shunt placement after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Central fever is common after aneurysmal subarachnoid hemorrhage (aSAH) and may delay ventriculoperitoneal shunt (VPS) placement. OBJECTIVE: We hypothesize that drain-dependent aSAH patients with central fever or persistent fever after treatment of an identifiable cause are not at an increased risk of infectious VPS failure. METHODS: Patient demographics, radiographic characteristics, temperature, incidence of infection, and shunt failure were prospectively recorded in a consecutive cohort of aSAH patients. Central fever was defined as temperature higher than 38.3°C with no identifiable cause. RESULTS: Of 580 patients, 61 (11%) were drain dependent. Central fever developed in 18, 35 had fever of known etiology, and 8 remained afebrile. There was no shunt failure at discharge, and 2 failures (3.2%) at follow-up were attributed to infection. One patient with central fever (6%), none with fever of identifiable etiology, and 1 (13%) with no fever had infectious shunt failures at a median follow-up of 10.2 ± 3.6 months (P > .05). Nine patients with central fever (50%) and 6 (17%) who were treated for fever of known etiologies had persistent fever at shunt placement. Patients who were febrile on the day of surgery had similar infectious shunt failure rates at discharge compared with those who were afebrile (0% vs 0%; P = 1.0). Similarly, febrile and afebrile patients at VPS insertion had comparable rates of infectious shunt failure at follow-up (7% vs 2%; P = .43). CONCLUSION: aSAH patients with central fever or persistent fever after treatment of fever of identifiable etiology are not at an increased risk of infectious VPS failure.

Glioblastoma biomarkers from bench to bedside: advances and challenges.

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumour, with few available therapies providing significant improvements in mortality. Biomarkers, which are defined by the National Institutes of Health as 'characteristics that are objectively measured and evaluated as indicators of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention', have the potential to play valuable roles in the diagnosis and treatment of GBM. Although GBM biomarker research is still in its early stages because of the tumour's complex pathophysiology, a number of potential markers have been identified which can be measured in either brain tissue or blood serum. In conjunction with other clinical data, particularly neuroimaging modalities such as MRI, these proteins could contribute to the clinical management of GBM by helping to classify tumours, predict prognosis and assess treatment response. In this article, we review the current understanding of GBM pathophysiology and recent advances in GBM biomarker research, and discuss the potential clinical implications of promising biomarkers. A better understanding of GBM pathophysiology will allow researchers and clinicians to identify optimal biomarkers and methods of interpretation, leading to advances in tumour classification, prognosis prediction and treatment assessment.

Alterations in systemic complement component 3a and 5a levels in patients with cerebral arteriovenous malformations.

The role of the complement cascade in the pathophysiology of cerebral arteriovenous malformation (AVM) is largely undefined. Complement subcomponents, C3a and C5a, are potent anaphylatoxins and key mediators of immuno-inflammatory response. Complement activation may contribute to the pro-inflammatory state observed in AVM. Thus, we sought to determine the systemic levels of C3a and C5a and their response to treatments in patients with AVM. Blood samples of 18 patients undergoing treatment for unruptured AVM, and from 30 healthy control participants, were obtained at four times: (i) pre-treatment, (ii) 24-hours post-embolization, (iii) 24-hours post-resection, and at 1-month follow-up. Plasma concentrations of C3a and C5a were measured using enzyme-linked immunosorbent assay. The pre-treatment mean plasma C3a level was significantly higher in patients with AVM (1817±168 ng/mL) compared to controls (1126±151 ng/mL). The mean C3a level decreased 24-hours after embolization (1482±170 ng/mL) and remained at statistically similar levels 24-hours after resection (1511±149 ng/mL) and at 1-month follow-up (1535±133 ng/mL). Mean C3a levels at the three time points were higher than control levels.The baseline mean plasma C5a level was significantly elevated in patients with AVM (13.1±2.2 ng/mL) compared to controls (3.9±1.5 ng/mL).Mean C5a level decreasedpost-embolization (8.2±2.3 ng/mL) and remained at similar levels post-resection (8.5±3.0 ng/mL) and at 1-month follow-up (7.7±2.9 ng/mL). Mean C5a levels at the three time points were significantly higher than the control levels. We conclude that systemic C3a and C5a levels in patients with AVM are elevated at baseline, decrease significantly after embolization, and remain at the new baseline levels after surgery and 1-month follow-up.

Polymorphisms in complement component 3 (C3F) and complement factor H (Y402H) increase the risk of postoperative neurocognitive dysfunction following carotid endarterectomy.

BACKGROUND: Up to 28% of patients undergoing carotid endarterectomy (CEA) are estimated to experience neurocognitive dysfunction following surgery. The complement cascade plays a central role in ischaemia-reperfusion injury. The authors investigated the effect of common polymorphisms in the complement component 3 (C3F) and complement factor H (CFH Y402H) genes on incidence of neurocognitive dysfunction post-CEA. METHODS: This study examined a nested cohort of prospectively recruited patients receiving elective CEA, who were genotyped for the C3F or Y402H polymorphisms. Each patient underwent a standard battery of eight neuropsychometric tests before, and 1 day and 30 days after, surgery. RESULTS: 57 of 142 (40%) CEA patients had at least one copy of the C3F allele (C3F+), and 17 of 137 (12%) patients had two copies of the CFH Y402H allele (Y402H++). At postoperative day 1, patients were three times (OR 3.05, p=0.045) or six times (OR 6.41, p=0.006) more likely to experience moderate-to-severe neurocognitive dysfunction if they carried the C3F+ or Y402H++ genotype, respectively. Patients with both risk genotypes had an almost eightfold risk of dysfunction (OR 7.67, p=0.046). Right-hand-dominant C3F+ subjects undergoing right-side CEA performed significantly worse on tests of visuospatial function than C3F- subjects. At day 30, C3F+ and Y402H++ genotypes trended towards significance as predictors of dysfunction (p=0.07 and p=0.22, respectively). CONCLUSION: The C3F and Y402H polymorphisms are strong independent predictors of moderate-to-severe neurocognitive dysfunction at 1 day following CEA. Furthermore, patients undergoing right-sided CEA are predisposed to deficits associated with cortex ipsilateral to the operative carotid artery.

A phase I clinical trial of tiopronin, a putative neuroprotective agent, in aneurysmal subarachnoid hemorrhage.

BACKGROUND: The neurotoxic aldehyde 3-aminopropanal (3-AP) contributes to brain injury following cerebral ischemia. Tiopronin (N-2-mercaptopropionyl-glycine[N-2-MPG]) is a US Food and Drug Administration (FDA)-approved drug for the treatment of cystinuria and a putative neuroprotective agent that has been shown to bind and neutralize 3-AP and reduce infarct volumes. OBJECTIVE: The objective of this trial was to establish the safety of tiopronin administration in patients with aneurysmal subarachnoid hemorrhage (aSAH) in preparation for further trials of its efficacy as a neuroprotective agent in this disease process. METHODS: This Phase I dose-escalation trial enrolled three-patient cohorts using a conventional "3+3" study design. Tiopronin dose began at 1 g/d until aSAH Day 14. Each subsequent cohort received a dose of tiopronin based on predetermined guidelines. A maximum dose of 3 g/d was selected, because this is the maximum FDA-approved dose for long-term cystinuria treatment. Subjects were monitored for known side effects of tiopronin. RESULTS: Nine patients were enrolled, the minimum number required based on the study design. None of these patients experienced serious side effects attributable to tiopronin, and no adverse events were noted that could not be attributed to the pathophysiology of aSAH. CONCLUSION: The administration of 3 g/d of tiopronin following aSAH for up to 14 days appears to be safe and without the side effects associated with long-term use. Plans for a randomized, placebo-controlled Phase II trial of tiopronin for neuroprotection following aSAH are underway.

Systemic expression of matrix metalloproteinase-9 in patients with cerebral arteriovenous malformations.

OBJECTIVE: Increased expression angiogenic factors, such as matrix metalloproteinases (MMPs), are associated with the formation of cerebral arteriovenous malformations (AVMs). The objective of this study was to determine plasma levels of MMP-9 of patients with AVMs. METHODS: Blood samples were drawn from 15 patients with AVMs before treatment, 24 hours postembolization, 24 hours postresection, and 30 days postresection. Blood samples were also obtained from 30 healthy controls. Plasma MMP-9 concentrations were measured via enzyme-linked immunosorbent assay. RESULTS: The mean plasma MMP-9 level in AVM patients at baseline was significantly higher than in control patients: 108.04 +/- 16.11 versus 41.44 +/- 2.44 ng/mL, respectively. The mean plasma MMP-9 level 1 day after embolization increased to 172.35 +/- 53.76 ng/mL, which was not significantly elevated over pretreatment levels. One day after resection, plasma MMP-9 levels increased significantly over pretreatment levels to 230.97 +/- 51.00 ng/mL. Mean plasma MMP-9 concentrations 30 days after resection decreased to 92.8 +/- 18.7 ng/mL, which was not different from pretreatment levels but was still significantly elevated over control levels. MMP-9 levels did not correlate with patient sex, age, presentation, or AVM size. CONCLUSION: Plasma MMP-9 levels are significantly elevated over controls at baseline, increase significantly immediately after surgery, and decrease to pretreatment levels during follow-up.

A comprehensive review of radiosurgery for cerebral arteriovenous malformations: outcomes, predictive factors, and grading scales.

The management of cerebral arteriovenous malformations (AVMs) continues to present a challenge to neurosurgeons. The natural history of this condition, as well as the morbidity and mortality of therapeutic interventions, remains incompletely elucidated. Predictive factors and grading scales in AVM management allow risk-benefit analysis of treatment options and comparison of outcomes. Stereotactic radiosurgery is one of the established treatment modalities for AVMs and is generally used to treat lesions that are high risk for surgical resection. Radiosurgery aims to obliterate AVMs and thus prevent hemorrhage or seizure without any new or worsening of existing symptoms. Lesion characteristics and postsurgical complications differ markedly in patientstreated by radiosurgery versus microsurgery. Radiosurgery-based grading systems account for factors that have been associated with various aspects of radiosurgical outcomes including obliteration, hemorrhage, and postoperative complications, particularly those induced by radiation. The purpose of this paper is to describe the most current predictive factors and grading systems for radiosurgical treatment of cerebral AVMs.