A porcine model for sequential assessments of cerebral haemodynamics and metabolism

We present a physiologically stable porcine model designed for sequential assessments of pharmacological effects on mean hemispheric cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) at sustained normocapnia. The dynamic influence of continuously administered fentanyl (0.040 mg.kg-1.h-1 i.v.), nitrous oxide (70%) and pancuronium (0.30 mg.kg-1.h-1 i.v.) on these variables was studied in eight normoventilated pigs. CBF was reliably assessable at 10-min intervals by clearance of intra-arterially injected 133Xe, monitored by an extracranial scintillation detector. CMRO2 was calculated from CBF and the simultaneously measured cerebral arteriovenous difference in blood oxygen content. The intracerebral distribution of a contrast medium injected into the external and internal carotid arteries was studied by angiography, and the cerebral venous outflow was investigated by measurements of the distribution of an intra-arterially administered non-diffusible tracer, [99mTc]pertechnetate, to the internal and external jugular veins. After a 3-h equilibration period, CBF and CMRO2 were determined on six occasions over a study period lasting 1 h 40 min. The mean ranges of these variables were 56-60 and 1.9-2.0 ml.100 g-1.min-1, respectively. We conclude that the model enables repeated assessments of CBF and CMRO2 under stable physiological background conditions and thus valid cerebral pharmacodynamic investigations of drugs given for anaesthesia.     

Treatment of muscle spasticity in patients with cerebral palsy using BTX-A: a pilot study

This study was designed to verify the safety and efficacy of botulinum toxin type A (BTX-A) used as a neuromuscular block on spastic masticatory musculature of children with cerebral palsy. Six patients who had spastic-tetraplegic cerebral-palsy, aged 5 to 20 years were selected. All patients had spasticity of the jaw muscles, bruxism, lower lip trauma, limited mouth opening, and difficulties in cleaning the oral cavity. The patients were sedated under general anesthesia, while the dentist injected the masseter and temporalis muscles bilaterally with 150 and 75 units of BTX-A each. Clinical examinations were conducted at 7, 14, 30, and 90 days after the initial appointment. We found statistically significant decreases in muscle spasticity and bruxism ( p = 0.002), improved inter-incisal opening ( p = 0.002), improved oral hygiene ( p = 0.031), and less lower lip trauma ( p = 0.060) after the neuromuscular blocking.     

Ictal Single-Photon Emission Computed Tomography Imaging in Extra Temporal Lobe Epilepsy Using Statistical Parametric Mapping

PURPOSE: To examine the application of statistical parametric mapping (SPM) to analyze ictal single-photon emission computed tomography (SPECT) scans in surgical candidates with extratemporal lobe epilepsy. METHODS: The authors selected patients who underwent successful ictal SPECT acquisition in the process of surgical treatment of intractable partial epilepsy. Thirteen patients were identified who met inclusion criteria for confident seizure localization from either intracranial electroencephalogram recordings or epilepsy surgery outcome. In these cases, ictal scans were registered to an in-house-developed normal SPECT atlas composed of 14 spatially normalized brains of normal subjects. SPM96 was used to test on a voxel-by-voxel basis for statistically significant increases in blood flow associated with each patient's ictal scan. The results were then mapped back onto the patient's magnetic resonance image (MRI) for final interpretation. Statistical parametric mapping (SPM) analysis of ictal SPECT scans was compared to both conventional visual interpretation and the analysis of subtraction ictal SPECT co-registered to MRI (SISCOM). RESULTS: Ten of 13 patient scans showed localizing focal ictal increases in regional cerebral blood flow, all of which were concordant with ultimate epilepsy localization. Of the 3 cases not localized with SPM, 1 was localized by conventional visual interpretation and another, not localized by visual interpretation, was correctly localized with SISCOM. Two cases not localized by SISCOM were localized by both visual and SPM analysis. CONCLUSIONS: This work provides supportive evidence for proof of principle that SPM can be used to provide objective, accurate analysis of ictal SPECT scans in patients with extratemporal lobe epilepsy.     

Intensity-dependent regional cerebral blood flow during 1-Hz repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers studied with H215O positron emission tomography: I. Effects of primary motor cortex rTMS.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) affects the excitability of the motor cortex and is thought to influence activity in other brain areas as well. We combined the administration of varying intensities of 1-Hz rTMS of the motor cortex with simultaneous positron emission tomography (PET) to delineate local and distant effects on brain activity. METHODS: Ten healthy subjects received 1-Hz rTMS to the optimal position over motor cortex (M1) for producing a twitch in the right hand at 80, 90, 100, 110, and 120% of the twitch threshold, while regional cerebral blood flow (rCBF) was measured using H(2)(15)O and PET. Repetitive transcranial magnetic stimulation (rTMS) was delivered in 75-pulse trains at each intensity every 10 min through a figure-eight coil. The regional relationship of stimulation intensity to normalized rCBF was assessed statistically. RESULTS: Intensity-dependent rCBF increases were produced under the M1 stimulation site in ipsilateral primary auditory cortex, contralateral cerebellum, and bilateral putamen, insula, and red nucleus. Intensity-dependent reductions in rCBF occurred in contralateral frontal and parietal cortices and bilateral anterior cingulate gyrus and occipital cortex. CONCLUSIONS: This study demonstrates that 1-Hz rTMS delivered to the primary motor cortex (M1) produces intensity-dependent increases in brain activity locally and has associated effects in distant sites with known connections to M1.     

Cerebrovascular deaths before and after the appearance of oral contraceptives

The mortality of cerebrovascular diseases in Denmark was analysed for men and women 15-44 years of age, in a 14-year period before and after the appearance of oral contraceptives (OC) in 1966. 1,670 deaths were registered over 28 years, during which the female incidence of cerebrovascular deaths increased by 19% (P less than 0.025), while the male mortality was unchanged. Women showed a percentage increase in deaths from cerebral thromboembolic attacks (CTA) of 33%, men a fall of 14%. The increase of female CTA deaths was most pronounced in the young fertile group, the age group with a high OC use. A relative risk of CTA of 3.3-4.5 for OC users compared with non-users could explain the CTA trend difference between women and men. No other single risk factor responsible for the observed trends could be identified. Both women and men had a significant increase in the mortality of subarachnoidal hemorrhages, and a significant fall in the mortality of intracerebral hemorrhages.     

Triple lumen venous access for pediatric bone marrow transplantation candidates

Multiple routes of vascular access are required in children undergoing bone marrow transplantation to facilitate total parenteral nutrition (TPN); blood withdrawal; and administration of blood products, antibiotics, fluids, and immunosuppressive drugs. Placement of multiple catheters frequently requires multiple venotomies in separate vessels. We have found that both a Broviac catheter and pediatric dual-lumen Raaf catheter can be placed through separate venotomies in the external jugular vein, which provides sufficient routes of vascular access without complications. This technique places only one vessel at risk while minimizing the chance for infection by utilizing two exit sites. We consider this to be the procedure of choice in young patients requiring multiple routes of vascular access.     

Characterization of ramified microglia in tissue culture: pinocytosis and motility

Functional properties of ramified microglia were investigated in primary cultures of rat cerebral cortical cells. These microglia could be readily identified in both fixed and living cultures through previously established features. Based on their destruction by 5 mM L-leucine methyl ester, a high level of intrinsic endocytotic activity was established. When cultures were incubated with fluorescent latex beads to assess phagocytosis, little or no such activity was exhibited by ramified cells. However, when cultures were incubated with dyes or other soluble tracer compounds, these cells always exhibited labeling. This labeling was selective for ramified microglia in the cultures and was demonstrated using a variety of compounds, including trypan blue, lucifer yellow, horseradish peroxidase (HRP), and India ink. Intracellular label could be observed in vesicular structures; this localization corresponded to an active cellular process. Also, cellular labeling was inhibited by the presence of colchicine. These features supported the inference that the labeling was attributable to pinocytosis, and this process appeared to account for the vast majority of endocytotic activity in the ramified microglia. Possible physiological significance of this pinocytotic activity was indicated by the accumulation of various neurotransmitters/modulators: gamma-aminobutyric acid and vasoactive intestinal polypeptide (VIP). Ramified cells in these cultures have been previously noted to exhibit a constant and rapid pattern of motility, which was consistently observed here through time-lapse video recording; pinocytosis and rapid motility were shown to concur in individual cells. Based on their high intrinsic pinocytotic activity and pattern of cellular motility, the ramified microglia specifically are suggested to serve a constitutive function of fluid cleansing within the interstitial spaces of brain tissue.     

MAGNETIC RESONANCE IMAGING IN POSTERIOR CIRCULATION INFARCTION: IMPACT ON DIAGNOSIS AND MANAGEMENT

To compare the diagnostic yield of magnetic resonance imaging (MRI) with computed tomography (CT) in posterior circulation infarction, we used proton MRI with a 0.3 Tesla magnet and a 3rd generation CT scanner in 25 patients. Age-matched controls were compared in a blinded fashion. Seventeen patients (68%) showed relevant pathology on MRI not seen on CT, 11 with normal CT and six with more extensive lesions, chiefly in the brain stem. Evidence of abnormal vertebrobasilar blood flow was seen in 8/25 (32%) of patients, suggested by vascular high intensity signals on MRI. Two tissue and one flow abnormality were seen in the control group. MRI provides additional information concerning infarct site, extent and pathogenesis in posterior circulation infarction.     

Perfusion imaging by a flow-sensitive alternating inversion recovery (Fair) technique: Application to functional brain imaging

Perfusion is a crucial physiological parameter for tissue function. To obtain perfusion-weighted images and consequently to measure cerebral blood flow (CBF), a newly developed flow-sensitive alternating inversion recovery (FAIR) technique was used. Dependency of FAIR signal on inversion times (TI) was examined; signal is predominantly located in large vessels at short TI, whereas it is diffused into gray matter areas at longer TI. CBF of gray matter areas in the human brain is 71 ± 15 SD ml/100 g/min (n = 6). In fMRI studies, micro- and macrovessel inflow contributions can be obtained by adjusting TIs. Signal changes in large vessel areas including the scalp were seen during finger opposition at a TI of 0.4 s; however, these were not observed at a longer TI of 1.4 s. To compare with commonly used BOLD and slice selective inversion recovery techniques, FAIR and BOLD images were acquired at the same time during unilateral finger opposition. Generally, activation sites determined by three techniques are consistent. However, activation of some areas can be detected only by FAIR, not by BOLD, suggesting that the oxygen consumption increase couples with the CBF change completely. Relative and absolute CBF changes in the contralateral motor cortex are 53 ± 17% SD (n = 9) and 27 ± 11 SD ml/100 g/min (n = 9), respectively.