Faculty Bibliography

OBJECTIVE: The availability of non-invasive brain imaging permits the study of normal and abnormal brain development in childhood and adolescence. This paper summarizes current knowledge of brain abnormalities of two conditions, attention deficit hyperactivity disorder (ADHD) and childhood onset schizophrenia (COS), and illustrates how such findings are bringing clinical and preclinical perspectives closer together. METHOD: A selected review is presented of the pattern and temporal characteristics of anatomic brain magnetic resonance imaging (MRI) studies in ADHD and COS. These results are discussed in terms of candidate mechanisms suggested by studies in developmental neuroscience. RESULTS: There are consistent, diagnostically specific patterns of brain abnormality for ADHD and COS. Attention deficit hyperactivity disorder is characterized by a slightly smaller (4%) total brain volume (both white and grey matter), less-consistent abnormalities of the basal ganglia and a striking (15%) decrease in posterior inferior cerebellar vermal volume. These changes do not progress with age. In contrast, patients with COS have smaller brain volume due to a 10% decrease in cortical grey volume. Moreover, in COS there is a progressive loss of regional grey volume particularly in frontal and temporal regions during adolescence. CONCLUSIONS: In ADHD, the developmental pattern suggests an early non-progressive 'lesion' involving neurotrophic factors controlling overall brain growth and selected dopamine circuits. In contrast, in COS, which shows progressive grey matter loss, various candidate processes influencing later synaptic and dendritic pruning are suggested by human post-mortem and developmental animal studies

Several studies suggest hemispheric lateralization of autonomic cardiovascular control. There is controversy regarding which hemisphere dominates sympathetic or parasympathetic activity. Hemispheric influences on baroreflex sensitivity (BRS) have not yet been evaluated. To determine hemispheric autonomic control in epilepsy patients, we assessed cardiovascular and baroreflex modulation before and during hemispheric inactivation. For 15 patients with drug-refractory epilepsy, we analyzed autonomic heart rate (HR) and blood pressure (BP) modulation and BRS before and during left and right intracarotid amobarbital procedure (IAP). After Blackman-Tukey spectral analysis, we calculated the low-frequency (LF: 0.04-0.15 Hz) and high-frequency (HF: 0.15-0.5 Hz) power of HR and BP as well as BRS as the LF transfer function gain between BP and HR. Right hemispheric inactivation induced a significant decrease of BP and an increase of HF power of HR and BP (p < 0.05). Left inactivation increased HR, BP, and LF power of both signals and decreased BRS by nearly 30% (p < 0.05). The results confirm previous IAP studies showing sympathetic lateralization in the right hemisphere and, moreover, demonstrate parasympathetic predominance and up-regulation of BRS in the left hemisphere. In epilepsy patients, unilateral electrical activity might derange autonomic balance between both hemispheres and contribute to cardiovascular dysregulation and sudden fatalities

BACKGROUND AND PURPOSE: The management of broad-necked cerebral aneurysms by Guglielmi detachable coils (GDCs) is technically challenging owing to a variety of factors, including difficulty in defining the aneurysm/parent vessel interface angiographically and problems in achieving complete occlusion, later predisposing the aneurysm to regrowth/recanalization. We sought to determine whether the use of intraluminal balloons to remodel the parent vessel/aneurysm interface during GDC embolization would provide a safe means of improving the efficacy of endovascular treatment of broad-necked aneurysms. METHODS: Twenty-two saccular aneurysms of the internal carotid artery were treated with GDCs by using balloon remodeling techniques. All aneurysms were characterized by wide necks or were small with unfavorable neck/fundus ratios and required balloon assistance for coil embolization. Patients were followed up both clinically and angiographically. RESULTS: By using a microcatheter-mounted nondetachable balloon to provide a temporary barrier across the aneurysmal neck, we were able to deploy GDCs safely within a variety of aneurysms. Among the 22 patients treated, aneurysmal occlusion on follow-up angiography (mean, 19 months) was found in 17 of 20 patients (two patients died and no follow-up studies were available). Observed or suspected thromboembolic events occurred in four of 22 patients, resulting in one permanent deficit. Twenty of the 22 patients had good to excellent clinical outcomes. CONCLUSION: Although balloon-assisted coiling of cerebral aneurysms requires manipulation of a second microcatheter and an inflatable balloon, increasing its technical complexity, we believe that this method has utility in treating broad-necked aneurysms and small aneurysms that are otherwise suboptimally managed by conventional GDC deployment

BACKGROUND: For radiobiological experiments using the Gamma Knife model B, we constructed a stereotactic device to irradiate rat and mouse brains and verify the absorbed dose at the target using thermoluminescence dosimetry and a head phantom. METHODS: Our stereotactic device is primarily designed for rats using the fixation principles of a stereotactic atlas. A head-fixation adapter for a mouse was constructed to enable targeted irradiation of mouse brains. We built simple phantoms to simulate rat and mouse heads. We placed thermoluminescent dosimeters at various positions on the phantom for dose measurements. Dose planning employed the Leksell Gamma Plan version 4.11 software, assuming a spherical skull geometry for all calculations. FINDINGS: The measurements demonstrated that the actual absorbed dose agreed with our calculations within the errors of thermoluminescence dosimetry and the accuracy of our irradiation technique and dose calculations. INTERPRETATION: This device provides an accurate method for irradiating rat and mouse brains using the Gamma Knife model B

BACKGROUND AND PURPOSE: Wada testing may provide important information for surgical planning in pediatric patients with medically refractory epilepsy, but it is often not used because of the difficulties in performing the angiographic portion of the procedure in conscious children. We reviewed our experience using propofol, a short-acting IV administered anesthetic agent, for pediatric patients undergoing Wada testing. METHODS: In a retrospective review of Wada tests performed on patients younger than 18 years, we identified 24 cases in which propofol anesthesia was used. We reviewed the medical records of these patients, with particular reference to dose of propofol, physiological parameters during anesthesia, and adequacy of neuropsychological testing after emergence from anesthesia. RESULTS: Patients ranged in age from 6 to 16 years (mean age, 12.5 years). Propofol induced mild reductions in blood pressure (12.4% for systolic and 13.9% for diastolic blood pressure) and heart rate (mean reduction of 4.7%), which did not require specific treatment in any patient. Recovery from anesthesia was smooth and rapid, allowing initiation of Wada testing within 15 to 25 minutes of cessation of propofol. Wada testing was successfully accomplished in all patients. CONCLUSION: Propofol provided rapid induction of anesthesia, was administered without endotracheal intubation, and did not cause substantial changes in cardiorespiratory parameters. Propofol anesthesia allowed controlled angiography among patients as young as 6 years and did not interfere with neuropsychological testing

OBJECTIVE: To determine whether an arterial 'steal' from the ophthalmic artery accounts for the ocular manifestations associated with maxillofacial arteriovenous malformation (AVM) outside the orbit. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Seven patients with maxillofacial AVM who had been previously treated, unsuccessfully, with proximal ligation of the supplying external carotid artery branches were evaluated clinically and by superselective cerebral angiography. No cases had intraorbital arteriovenous shunting or abnormal venous drainage to the orbit. INTERVENTION: Endovascular embolization. MAIN OUTCOME MEASURES: Signs and symptoms of ocular ischemia were correlated with findings on cerebral/orbital angiography. RESULTS: Four of seven patients had signs of ocular ischemia. By selective angiography, these four patients were found to have a significant ophthalmic artery supply to the AVM. In contrast, the three patients without signs of ocular ischemia had minimal or no ophthalmic artery supply to the AVM. CONCLUSIONS: When the ophthalmic arterial blood supply is recruited, ophthalmic artery 'steal' phenomenon occurs in patients with maxillofacial AVMs that do not directly involve the orbit. This mechanism appears to be the cause of ocular ischemia. It is possible that this 'steal' is precipitated or worsened by previous surgical proximal ligation of external carotid arterial branches that are potential collaterals with the ophthalmic artery but fail to occlude the arteriovenous (AV) shunts

BACKGROUND: Familial arteriovenous malformations (AVMs) of the brain are rare. We present two sisters with the same parents who harbored AVMs that were successfully treated. METHODS: The elder sister presented with a unilateral migrainous type of headache overlying the right parietal area. The younger one suffered from exercise-induced headaches. Both were neurologically intact. Magnetic resonance imaging scans of the brain and cerebral angiography delineated the lesions. Both sisters underwent endovascular embolization followed by surgical resection. RESULTS: Postoperatively, aside from a left inferior quadrantanopsia in the elder sister, both were neurologically intact. CONCLUSIONS: We report the rare occurrence of familial AVMs in two siblings and review the literature of 14 reports. No genetic predisposition was found

We describe a young woman with a glioblastoma multiforme in whom angiography showed multiple intracranial stenoses. The resected tumour was found to be invading cerebral vessels

BACKGROUND AND PURPOSE: Progressive multifocal leukoencephalopathy (PML) is typically occult at angiography and fails to enhance on MR images. After observing angiographic abnormalities characterized by arteriovenous shunting and pathologic parenchymal blush in patients with AIDS-related PML, often in the absence of contrast enhancement on MR images, we hypothesized that there might be distinct changes in the cerebral microvasculature that account for the reduction in vascular transit time (arteriovenous shunting) in the absence of blood-brain barrier dysfunction. METHODS: The imaging studies and neuropathologic specimens of six patients with biopsy-proved PML were reviewed retrospectively. In all patients contrast-enhanced MR imaging and CT, followed by cerebral angiography, were performed before stereotactically directed biopsy. The angiograms were evaluated for the presence of vascular displacement, pathologic parenchymal blush, arteriovenous shunting, and neovascularity. The CT and MR studies were reviewed for the presence of enhancement of the PML lesions. Biopsy specimens were examined for the presence of necrosis, perivascular inflammation, and neovascularity. RESULTS: All patients had oligodendrocytic intranuclear inclusions diagnostic of PML, together with perivascular inflammation and neovascularity to a varying extent; no other neuropathologic processes were identified. Angiographic abnormalities, characterized by a pathologic parenchymal blush and arteriovenous shunting, were identified in four of the six patients. In only one of these cases, however, was abnormal enhancement identified on cross-sectional imaging studies (MR and CT), and this patient had florid perivascular inflammatory infiltrates histologically. CONCLUSION: The pathologic parenchymal blush and arteriovenous shunting seen angiographically in some patients with PML reflect small-vessel proliferation and perivascular inflammatory changes incited by the presence of the JC virus in infected oligodendrocytes

For many patients with cerebral aneurysms, endovascular therapy offers an acceptable alternative to aneurysm surgery. These neurointerventional methods are broadly classified as deconstructive or reconstructive procedures, depending on whether the parent vessel is preserved in treating the aneurysm. Results to date suggest that appropriately selected patients may be treated successfully with low technical morbidity and mortality. Whereas certain shortcomings are evident, developing technology has expanded the spectrum of aneurysms amenable to endovascular treatment and improved the effectiveness of such management