Functional tremor developing after successful MRI-guided focused ultrasound thalamotomy for essential tremor.

OBJECTIVE: To describe a case of functional tremor occurring after a successful MR-guided focused ultrasound thalamotomy (MRgFUS) for essential tremor. METHODS: A 71-year-old right-handed man with essential tremor was referred to us for consideration of deep brain stimulation surgery for worsening bilateral upper limb tremor after a successful left MRgFUS for essential tremor. RESULTS: On clinical exam, signs compatible with a functional tremor were noted, including entertainability and suppressibility. Electrophysiological studies were consistent with essential tremor and superimposed tremor fulfilling the laboratory-supported criteria for functional tremor. DISCUSSION: We describe the first reported case of a functional movement disorder occurring after successful MRgFUS procedure for essential tremor. Recognising this entity and its development after such therapeutic interventions is essential to avoid further unnecessary invasive therapies.

Active MR-temperature feedback control of dynamic interstitial ultrasound therapy in brain: in vivo experiments and modeling in native and coagulated tissues.

PURPOSE: The recent clinical emergence of minimally invasive image-guided therapy has demonstrated promise in the management of brain metastasis, although control over the spatial pattern of heating currently remains limited. Based on experience in other organs, the delivery of high-intensity contact ultrasound energy from minimally invasive applicators can enable accurate spatial control of energy deposition, large treatment volumes, and high treatment rate. In this acute study, the feasibility of active MR-Temperature feedback control of dynamic ultrasound heat deposition for interstitial thermal ablation in brain was evaluatedin vivo. METHODS: A four-element linear ultrasound transducer (f=8.2 MHz) originally developed for transurethral ultrasound therapy was used in a porcine model for generating thermal ablations in brain interstitially. First, the feasibility of treating and retreating preciselyin vivo brain tissues using stationary (non-rotating device) ultrasound exposures was studied in two pigs. Experimental results were compared to numerical simulations for maximum surface acoustic intensities ranging from 5 to 20 W cm(-2). Second, active MRT feedback-controlled ultrasound treatments were performed in three pigs with a rotating device to coagulate target volumes of various shapes. The acoustic power and rotation rate of the device were adjusted in real-time based on MR-thermometry feedback control to optimize heat deposition at the target boundary. Modeling of in vivo treatments were performed and compared to observed experimental results. RESULTS: Overall, the time-space evolution of the temperature profiles observedin vivo could be well estimated from numerical simulations for both stationary and dynamic interstitial ultrasound exposures. Dynamic exposures performed under closed-loop temperature control enabled accurate elevation of the brain tissues within the targeted region above the 55 °C threshold necessary for the creation of irreversible thermal damage. Treatment volumes ranging from 1 to 9 cm3 were completed within 8±3 min with a radial targeting error<2 mm on average (treatment rate: 0.7±0.5 cm3/min). Tissue changes were visible on T1-weighted contrast-enhanced (T1w-CE) images immediately after treatment. These changes were also evident on T2-weighted (T2w) images acquired 2 h after the 1st treatment and correlated well with the MR-thermometry measurements. CONCLUSIONS: These results support the feasibility of active MRT feedback control of dynamic interstitial ultrasound therapy ofin vivo brain tissues and confirm the feasibility of using simulations to predict spatial heating patterns in the brain.

Management and clinical outcome of posterior fossa arteriovenous malformations: report on a single-centre 15-year experience.

OBJECTIVES: Posterior fossa brain arteriovenous malformations (PFbAVMs) are rare lesions. Management is complicated by eloquence of adjacent neurological structures, multimodality treatment is often necessary, and obliteration is not always possible. We describe a 15-year experience in the management of posterior fossa brain AVMs with a focus on clinical outcome. METHODS: From 1989 to 2004, prospectively collected information on 106 patients with diagnosis of a PFbAVMs was obtained. Clinical and angioarchitectural characteristics, management options and complications are described and reviewed to evaluate their impact on final outcome as measured by the Modified Rankin Score (mRS). RESULTS: Ninety-eight patients were followed for an average of 3.3 years (1-14.6). The male-to-female ratio was 1:1. Ninety-five out of 98 patients (96.9%) were symptomatic at presentation, with 61 (62.2%) intracranial haemorrhages. Sixty-two patients were treated (46 cerebellar, 16 brainstem). Ten haemorrhages occurred in follow-up (4.1%/year). The mRS was obtained in 62 patients and was classified as low (good, mRSor=3). Haemorrhage was the only predictor of poor mRS at presentation (p = 0.0229). A poor clinical outcome was correlated with the presence of AA (p = 0.0276), a poor initial mRS (p<0.0001) and the number of treatments needed (p = 0.0434). Patients were significantly more likely to improve than to deteriorate over time (p = 0.0201). CONCLUSION: The final clinical outcome in PFbAVMs relates directly with the presence of associated aneurysms, number of treatments needed to obliterate the AVM and mRS at presentation. Despite the fact that patients tend to improve after brain AVM haemorrhage, the relationship of MRS at presentation and final outcome suggests that an expedited, more definitive treatment is probably a better choice, especially in patients with good grades after the initial bleeding.

The Toronto traumatic brain injury study: injury severity and quantified MRI.

OBJECTIVE: To assess the relationship between regional brain volume changes and traumatic brain injury (TBI) severity in patients with and without focal lesions. METHODS: Sixty-nine chronic-phase TBI patients spanning the full range of severity were recruited from consecutive hospital admissions. Patients received high-resolution structural MRI a minimum of 1 year after injury. Multivariate statistical analyses assessed covariance patterns between volumes of gray matter, white matter, and sulcal/subdural and ventricular CSF across 38 brain regions and TBI severity as assessed by depth of coma at the time of injury. Patients with diffuse and diffuse plus focal injury were analyzed both separately and together. RESULTS: There was a stepwise, dose-response relationship between parenchymal volume loss and TBI severity. Patients with moderate and severe TBI were differentiated from those with mild TBI, who were in turn differentiated from noninjured control subjects. A spatially extensive pattern of volume loss covaried with TBI severity, with particularly widespread effects in white matter volume and sulcal/subdural CSF. The most reliable effects were observed in the frontal, temporal, and cingulate regions, although effects were observed to varying degrees in nearly every brain region. Focal lesions were associated with greater volume loss in frontal and temporal regions, but volume loss remained marked even when analyses were restricted to patients with diffuse injury. CONCLUSIONS: Patterns of parenchymal volumetric changes can differentiate among levels of traumatic brain injury (TBI) severity, even in mild TBI. TBI causes a spatially extensive pattern of volume loss that reflects independent but overlapping contributions of focal and diffuse injury.

Liquid embolisation material reduces the delivered radiation dose: a physical experiment.

OBJECTIVE: To test a new hypothesis that the glue/contrast admixture used for embolisation reduces the dose delivered to AVMs using an experimental model. METHOD: A model was created using a block of "solid water" (6 x 5 x 2 cm) with twelve wells of different depths. Different concentrations of the glue admixture (Enbucrilate + Lipiodol) were used. The model was irradiated using a 5MV beam with a clinical LINAC system and the dose was checked upstream and downstream. Dose was measured using Kodak XV film, a Vidar 16 bit film scanner and software for therapeutic film dosimetry measurements (RIT software). RESULTS: The radiation dose varied with the distance beyond the glue solid water interface. For distances of 0, 2 and 5 mm to the film, the mean reduction was 13.65% (SD = 2.94), 6.87% (SD = 1.95) and 1.75% (SD = 1.14), respectively. There was also correlation with the Lipiodol concentration in the mixture. The maximum reductions for 80, 50 and 20% Lipiodol concentrations were 16.1% (SD = 1.32), 14.85% (SD = 0.98) and 10% (SD = 1.21), respectively. There was no correlation between the glue depth and the dose delivered. CONCLUSION: The hypothesis that the glue mixture used for embolisation reduces the radiation dose delivered was experimentally confirmed with this study.

Fractionated (split dose) radiosurgery in patients with recurrent brain metastases: implications for survival.

Radiosurgery is conventionally prescribed for brain metastases with a single dose of radiation. Fractionation has been advocated to improve tumour control. A multivariate analysis of prognostic factors including fractionation has been performed in two consecutive prospective radiosurgery protocols with and without fractionation in order to identify an association, if any, between fractionation and survival. A surgically applied stereotactic head frame was used. Radiosurgery planning was based on a contrast-enhanced CT. Sixty-nine patients underwent the two-fraction regimen and 35 patients had a single treatment. Multivariate analysis showed that the presence of extracranial malignancy, performance status, multiple brain metastases, patient gender and the time from the initial treatment to radiosurgery were independent determinants for survival. Fractionation was also an independent determinant with two-fraction patients surviving a median of 30 weeks versus single fraction patients who survived a median of 16 weeks. Fractionated radiosurgery was associated with improved survival and deserves further investigation.

Chronic hypoxia up-regulates fibroblast growth factor ligands in the perinatal brain and induces fibroblast growth factor-responsive radial glial cells in the sub-ependymal zone.

A number of signaling molecules have been implicated in the acute response to hypoxia/ischemia in the adult brain. In contrast, the reaction to chronic hypoxemia is largely unexplored. We used a protocol of chronic hypoxia in rat pups during the first three postnatal weeks, encompassing the period of cellular plasticity in the cerebral cortex. We find that the levels of fibroblast growth factor 1 (FGF1) and FGF2, two members of the FGF family, increase after 2 weeks of chronic hypoxia. In contrast, members of the neurotrophin family are unaffected. FGF2 is normally expressed in the nucleus of mature, glial fibrillary acidic protein (GFAP)-containing astrocytes. Under hypoxia, most FGF2-containing cells do not express detectable levels of GFAP, suggesting that chronic low O(2) induces their transformation into more immature glial phenotypes. Remarkably, hypoxia promotes the appearance of radial glia throughout the sub-ventricular and ependymal zones. Most of these cells express vimentin and brain lipid binding protein. A subset of these radial glial cells expresses FGF receptor 1, and are in close contact with FGF2-positive cells in the sub-ventricular zone. Thus, FGF receptor signaling in radial glia may foster cell genesis after chronic hypoxic damage. From the results of this study we suggest that after the chronic exposure to low levels of oxygen during development, the expression of radial glia increases in the forebrain periventricular region. We envision that astroglia, which are the direct descendants of radial glia, are reverting back to immature glial cells. Alternatively, hypoxia hinders the normal maturation of radial glia into GFAP-expressing astrocytes. Interestingly, hypoxia increases the levels of expression of FGF2, a factor that is essential for neuronal development. Furthermore, chronic hypoxia up-regulated FGF2's major receptor in the periventricular region. Because radial glia have been suggested to play a key role in neurogenesis and cell migration, our data suggests that hypoxia-induced FGF signaling in radial glia may represent part of a conserved program capable of regenerating neurons in the brain after injury.

Predictors of outcome of biventricular repair in infants with multiple left heart obstructive lesions.

BACKGROUND: Decisions regarding surgical strategy in patients with multiple left heart obstructive or hypoplastic lesions often must be made in the newborn period and are seldom reversible. Predictors of outcome of biventricular repair have not been well defined in this heterogeneous group of patients, and risk factors described for critical aortic valve stenosis have been shown to be inapplicable to patients with other left heart obstructive lesions. The goal of this study was to identify echocardiographic predictors of outcome of biventricular repair for infants with multiple left heart obstructive lesions. METHODS AND RESULTS: Patients with >/=2 areas of left heart obstruction or hypoplasia, diagnosed at

Uterine artery embolization for the treatment of uterine fibroids: an outpatient procedure.

OBJECTIVE: Our objectives were to establish an outpatient program for uterine artery embolization of fibroids and to monitor the following: percentage of patients who required immediate hospitalization or admission within 2 weeks, outcomes in terms of the degree of ultrasound regression of the fibroids, patient satisfaction, reduction of pressure symptoms, and reduction of bleeding. STUDY DESIGN: Patients were screened by a gynecologist with the use of a designed care algorithm; they then underwent uterine embolization, performed by an interventional radiologist. Patients were evaluated at 6 weeks and 6 months after the procedure, and ultrasound studies were performed both before and at 2 to 6 months after the procedure. RESULTS: Of 35 patients, 29 (83%) went home on the day of the procedure, whereas 6 were observed overnight. Three (9%) patients required admission within 1 week. Of 26 patients, 24 (92%) were satisfied with the reduction of bleeding, and 14 of 18 (78%) were satisfied with the reduction in pressure symptoms. The mean decrease in uterine volume was 36%, and the mean decrease in the size of the dominant fibroid was 49%. CONCLUSIONS: Uterine artery embolization for the treatment of uterine fibroids might be done on an outpatient basis with a low rate of same-day admissions and delayed admissions. Patient satisfaction was high, and uterine artery embolization might become an accepted option for the treatment of uterine fibroids.

Intracranial arteriovenous malformations: real-time auto-triggered elliptic centric-ordered 3D gadolinium-enhanced MR angiography--initial assessment.

Auto-triggered elliptic centric-ordered three-dimensional (3D) gadolinium-enhanced magnetic resonance (MR) angiography was compared with 3D multiple overlapping thin-slab acquisition time-of-flight (TOF) MR angiography in the evaluation of intracranial arteriovenous malformations (AVMs) in 10 patients. Intraarterial digital subtraction angiography (DSA) was the reference standard. Gadolinium-enhanced MR angiograms were found to be equivalent to DSA images in AVM component depiction in 70%--90% of cases and were consistently superior to TOF MR angiograms.

Adding magnesium to the silver-gill binding model for rainbow trout (Oncorhynchus mykiss).

Rainbow trout (Oncorhynchus mykiss; 2-17 g) were exposed to approximately 0.1 microM silver as AgNO3 for 3 to 4 h in synthetic, ion-poor water (20 microM Ca, 100 microM Na, 150 microM Cl, pH 7) to which was added Mg, Ca, or thiosulfate (S2O3). Gills were extracted and assayed for Ag using graphite furnace atomic absorption spectrophotometry. Up to 210 mM Mg (fourfold the concentration of Mg in seawater) did not reduce accumulation of Ag by trout gills. The conditional equilibrium stability constant (K) for Mg at silver-binding sites on the gills was calculated to be log K(Mg-gillAg) = 3.0, or approximately half-as-strong binding as for Ca at these sites. The inclusion of the Mg-gill stability constant into the original Ag-gill binding model increases the flexibility of the model, although the competitive effects of Mg are only important in sodium-poor systems.

DYN 12, a small molecule inhibitor of the enzyme amadorase, lowers plasma 3-deoxyglucosone levels in diabetic rats.

3-Deoxyglucosone (3DG) is a highly reactive alpha-dicarbonyl sugar and potent protein cross-linker that is important in the formation of advanced glycation end products (AGEs), which have been postulated to lead to the development of diabetic complications. (1) Reducing 3DG levels in diabetics is a potentially effective therapy to slow the development of diabetic complications. Standard biochemical methods were used to isolate, identify, and characterize the enzyme responsible for the production of 3DG, in order to develop an effective therapeutic agent against this target. We have purified and characterized Amadorase, a fructosamine-3-kinase, and demonstrated both in vitro and in vivo that it is responsible for the production of 3-deoxyglucosone (3DG). A small molecule inhibitor of Amadorase, DYN 12, significantly lowered plasma levels of 3DG in diabetic (by 46%, p = 0.0116) and normal (by 43%, p = 0.0024) rats. These data are the first indications that it is possible to significantly reduce 3DG production in diabetics and thus possibly reduce the development of diabetic complications.

Unruptured intracranial aneurysms: appraisal of the literature and suggested recommendations for surgery, using evidence-based medicine criteria.

OBJECTIVE: The literature on unruptured intracranial aneurysms is reviewed, and an attempt is made to stratify it according to the weight of the evidence. Recommendations for surgery are suggested, using evidence-based criteria. METHODS: A MEDLINE search was performed for 1966 to 1999. The focus was restricted to surgical management rather than other types of management, such as endovascular treatments. Each article was classified as Class I, II, or III according to the weight of the evidence. Some articles, such as literature reviews and data analyses, did not fit this classification and were grouped separately. Recommendations are based on the evidence available. RESULTS: Forty-five articles were reviewed. Thirteen articles contained information on the natural history, 19 contained data on the risks of surgery, and 2 contained information on both. In addition, 11 contained analyses of costs and benefits. None met the criteria for Class I evidence. Seven articles on the natural history and 7 on the risks of surgery met the criteria for Class II evidence, and 6 and 12, respectively, met those for Class III evidence. The remainder of the articles were analyses or review articles. CONCLUSION: There is insufficient evidence to recommend a standard of management. As a therapeutic guideline, conservative treatment is recommended for small aneurysms (<10 mm) and asymptomatic nongiant aneurysms in older people, whereas surgery is recommended for larger aneurysms in younger people and symptomatic aneurysms in fit patients. Other recommendations can be justified only as therapeutic options, using evidence-based criteria. Areas for future investigation are discussed.

Assessment of strategic self-regulation in traumatic brain injury: its relationship to injury severity and psychosocial outcome.

Standard neuropsychological tests administered in a constrained and artificial laboratory environment are often insensitive to the real-life deficits faced by patients with traumatic brain injury (TBI). The Revised Strategy Application Test (R-SAT) creates an unstructured environment in the laboratory in which environmental cues and internal habits oppose the most efficient strategy, thus mimicking the real-life situations that are problematic for patients with TBI. In this study, R-SAT performance was related both to severity of TBI (i.e., depth of coma) sustained 2-3 years earlier and to quality of life outcome as assessed by the Sickness Impact Profile. This relationship held after accounting for variance attributable to TBI-related slowing and inattention. These findings support the validity of the R-SAT and suggest that behavioral correlates of quality of life outcome in TBI can be assessed in the laboratory with unstructured tasks.

Heterotopic calcification and tears of the ulnar collateral ligament: radiographic and MR imaging findings.

OBJECTIVE: The purpose of this paper is to describe the radiographic and MR imaging appearance of heterotopic calcification in the ulnar collateral ligament. MATERIALS AND METHODS: Retrospective radiographic review of 710 patients examined for elbow pain yielded 42 individuals (age range, 16-38 years) with heterotopic calcification in the ulnar collateral ligament. Radiographic and MR imaging findings were compared with surgical findings. RESULTS: Fifty-one heterotopic calcifications were identified in 42 patients; nine patients had two sites of heterotopic calcification. Average initial calcification size in the craniocaudal dimension was 4 mm (range, 1-12 mm) and in the transverse dimension was 1 mm (range, 1-4 mm). Five of 42 patients had enlargement of the calcification on follow-up radiography. The largest heterotopic calcification that was not visualized on MR imaging measured 5 x 4 mm in craniocaudal and transverse dimensions. Of 34 patients with heterotopic calcification who underwent surgery, 26 patients (76%) had either partial or complete tears of the ulnar collateral ligament. CONCLUSION: Heterotopic calcification in the ulnar collateral ligament may be associated with partial or complete tears. The MR imaging detection of heterotopic calcification is less sensitive than that of radiography of the elbow.

Differential modulation of proliferation in the neocortical ventricular and subventricular zones.

Recent studies have implicated the classical neurotransmitters GABA and glutamate in the regulation of neural progenitor proliferation. We now show that GABA and glutamate have opposite effects on the two neural progenitor populations in the ventricular zones (VZs) and subventricular zones (SVZs) of the embryonic cerebrum. Application of either molecule to organotypic slice cultures dramatically increases proliferation in the VZ by shortening the cell cycle, whereas proliferation in the SVZ is decreased. These disparate effects, measured both by bromodeoxyuridine uptake and the expansion of retrovirally labeled progenitor clones, are mimicked by the application of specific GABA and glutamate agonists and are blocked by antagonists. Thus, the relative contributions of the VZ and SVZ to neocortical growth may be regulated by differential responsiveness to GABA and glutamate.

Basic fibroblast growth factor (Fgf2) is necessary for cell proliferation and neurogenesis in the developing cerebral cortex.

Little is known about regionally specific signals that control the number of neuronal progenitor cells in vivo. We have previously shown that the germline mutation of the basic fibroblast growth factor (Fgf2) gene results in a reduction in the number of cortical neurons in the adult. We show here that Fgf2 is expressed in the pseudostratified ventricular epithelium (PVE) in a dorsoventral gradient and that Fgf2 and its receptor, Fgfr-1, are downregulated by mid to late stages of neurogenesis. In Fgf2 knockout mice, the volume and cell number of the dorsal PVE (the cerebral cortical anlage) are substantially smaller, whereas the volume of the basal PVE is unchanged. The dorsal PVE of Fgf2 knockout mice has a 50% decrease in founder cells and a reduced expansion of the progenitor pool over the first portion of neurogenesis. Despite this reduction, the degree of apoptosis within the PVE is not changed in the Fgf2 knockouts. Cortical neuron number was decreased by 45% in Fgf2 knockout mice by the end of neurogenesis, whereas the number of neurons in the basal ganglia was unaffected. Microscopically, the frontal cerebral cortex of neonatal Fgf2 null mutant mice lacked large neurons in deep cortical layers. We suggest that Fgf2 is required for the generation of a specific class of cortical neurons arising from the dorsal PVE.

Prediction of recovery of continuous memory after traumatic brain injury.

OBJECTIVE: To evaluate the ability of measures of initial severity, tests of attention, and demographic characteristics to predict recovery of continuous memory for words over a 24-hour period in patients with acute traumatic brain injury. METHODS: Recovery of continuous memory was assessed prospectively in 94 patients with nonpenetrating traumatic brain injury. A classification and regression tree analysis identified a hierarchical subset of variables that may be used as a simple guideline for predicting recovery of continuous memory. Weibull regression models evaluated and compared the predictive ability of multiple variables. RESULTS: Four groups of patients were identified based on measures of severity of injury and demographic characteristics. These four groups had recovery profiles that were more precise than could be obtained by using the Glasgow Coma Scale alone: mild, about 1 week to recovery of continuous memory; moderate, 1 to 4 weeks; severe, 2 to 6 weeks; and extremely severe, 4 to 8 weeks. Regression analysis confirmed that measures of capacity (inherent resources such as indicated by age) and compromise (general functional brain state measured neuropsychologically) improved prediction over models based only on injury severity measures, such as the Glasgow Coma Scale. CONCLUSIONS: Approaches to predicting recovery of continuous memory in the acute period after traumatic brain injury that take into account multiple measures provide a more sensitive predictive index.

Characteristics of injuries to the cervical spine and spinal cord in polytrauma patient population: experience from a regional trauma unit.

STUDY DESIGN: Retrospective analysis of a prospectively collected trauma database of a Level 1 (tertiary) trauma center. OBJECTIVE: To define the features of the cervical spinal injuries in polytrauma population admitted to the regional trauma unit. SETTING: Canada, Ontario Province, Toronto, Sunnybrook Health Sciences Center. METHODS: All trauma admissions between 1987 and 1996 entered prospectively into a trauma registry database were studied for incidence, demographic and epidemiological details of cervical spine (cord and column) injuries. RESULTS: A total of 468 patients (66% male) with cervical spinal injury (CSI) from 1198 spinal injuries admitted to the regional trauma center were identified. Seventy-five per cent of the CSI involved were aged less than 50 years; nearly 30% were in the third decade alone. Overall, the commonest spinal level injured was C2 (27%) followed by C5 (22%). Older population (above 60 years of age) had C1 + 2 involved more often than the young (P=0.02). Motor vehicular crashes (MVC) accounted for 71%, followed by pedestrian trauma (10%), sport injuries (7%). Spinal cord injury (SCI) was noted in 27%; complete in 16% and incomplete in 11% and more frequently at C4 or C5 level compared with C1, C2 (P<0.00001); the former level had more often a complete SCI (P=0.06). Though MVC produced 74% of SCI, only 27% had neurological deficits. Recreational trauma produced SCI in 45%, motor cycle crashes (MCC) in 37% and a rear passenger in MVC in 34% that was complete in 78%, 71% and 73% respectively. Front seat passenger and driver in MVC had a C5 level injury while a rear seat passenger had at C4 (P<0.001). The C1 level injury had high association with severe and life threatening head and neck and facial injuries compared with the more frequently injured spinal levels; either C2 (P=0.03) or C5 (P=0.004). Similarly C1 injuries had higher ISS compared with C2 (P<0.0001) and C5 (P<0.008). CONCLUSIONS: C2 was the commonest fractured spine while SCI was more frequent at C5. Older and pedestrian population had higher incidences of injuries at C1 and C2. Sport and MCC resulted in severe SCI. The level of spine injured was different between a front and a rear seat occupant in MVC.