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1.
Neurology ; 100(11): e1177-e1192, 2023 03 14.
Article in English | MEDLINE | ID: mdl-36639237

ABSTRACT

BACKGROUND AND OBJECTIVES: Brain-computer interfaces (BCIs) are being developed to restore mobility, communication, and functional independence to people with paralysis. Though supported by decades of preclinical data, the safety of chronically implanted microelectrode array BCIs in humans is unknown. We report safety results from the prospective, open-label, nonrandomized BrainGate feasibility study (NCT00912041), the largest and longest-running clinical trial of an implanted BCI. METHODS: Adults aged 18-75 years with quadriparesis from spinal cord injury, brainstem stroke, or motor neuron disease were enrolled through 7 clinical sites in the United States. Participants underwent surgical implantation of 1 or 2 microelectrode arrays in the motor cortex of the dominant cerebral hemisphere. The primary safety outcome was device-related serious adverse events (SAEs) requiring device explantation or resulting in death or permanently increased disability during the 1-year postimplant evaluation period. The secondary outcomes included the type and frequency of other adverse events and the feasibility of the BrainGate system for controlling a computer or other assistive technologies. RESULTS: From 2004 to 2021, 14 adults enrolled in the BrainGate trial had devices surgically implanted. The average duration of device implantation was 872 days, yielding 12,203 days of safety experience. There were 68 device-related adverse events, including 6 device-related SAEs. The most common device-related adverse event was skin irritation around the percutaneous pedestal. There were no safety events that required device explantation, no unanticipated adverse device events, no intracranial infections, and no participant deaths or adverse events resulting in permanently increased disability related to the investigational device. DISCUSSION: The BrainGate Neural Interface system has a safety record comparable with other chronically implanted medical devices. Given rapid recent advances in this technology and continued performance gains, these data suggest a favorable risk/benefit ratio in appropriately selected individuals to support ongoing research and development. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT00912041. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that the neurosurgically placed BrainGate Neural Interface system is associated with a low rate of SAEs defined as those requiring device explantation, resulting in death, or resulting in permanently increased disability during the 1-year postimplant period.


Subject(s)
Brain-Computer Interfaces , Spinal Cord Injuries , Adult , Humans , Feasibility Studies , Prospective Studies , Quadriplegia , Spinal Cord Injuries/surgery
2.
Biomed Opt Express ; 11(8): 4666-4678, 2020 Aug 01.
Article in English | MEDLINE | ID: mdl-32923070

ABSTRACT

As the prevalence of diabetic retinopathy (DR) continues to rise, there is a need to develop computer-aided screening methods. The current study reports and validates an ordinary least squares (OLS) method to model optical coherence tomography angiography (OCTA) images and derive OLS parameters for classifying proliferative DR (PDR) and no/mild non-proliferative DR (NPDR) from non-diabetic subjects. OLS parameters were correlated with vessel metrics quantified from OCTA images and were used to determine predicted probabilities of PDR, no/mild NPDR, and non-diabetics. The classification rates of PDR and no/mild NPDR from non-diabetic subjects were 94% and 91%, respectively. The method had excellent predictive ability and was validated. With further development, the method may have potential clinical utility and contribute to image-based computer-aided screening and classification of stages of DR and other ocular and systemic diseases.

3.
Cell Tissue Res ; 382(1): 173-183, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32725425

ABSTRACT

The last decade has been a frustrating time for investigators who had envisioned major advances in the treatment of Parkinson's disease using neurotrophic factors. The first trials of glial cell line-derived neurotrophic factor for treating Parkinson's disease were very promising. Later blinded control trials were disappointing, not reaching the predetermined outcomes for improvement in motor function. Consideration of the problems in the studies as well as the biology of the neurotrophins used can potentially lead to more effective therapies. Parkinson's disease presents a multitude of opportunities for the cell biologist wanting to understand its pathology and to find possible new avenues for treatment.


Subject(s)
Glial Cell Line-Derived Neurotrophic Factor/genetics , Animals , Humans , Ligands , Signal Transduction
4.
J Ophthalmol ; 2019: 5171965, 2019.
Article in English | MEDLINE | ID: mdl-31341653

ABSTRACT

BACKGROUND AND OBJECTIVE: Diabetic retinopathy (DR) is a major complication of diabetes and the leading cause of blindness among US working-age adults. Detection of subclinical DR is important for disease monitoring and prevention of damage to the retina before occurrence of vision loss. The purpose of this retrospective study is to describe an automated method for discrimination of subclinical DR using fine structure analysis of retinal images. METHODS: Discrimination between nondiabetic control (NC; N = 16) and diabetic without clinical retinopathy (NDR; N = 17) subjects was performed using ordinary least squares regression and Fisher's linear discriminant analysis. A human observer also performed the discrimination by visual inspection of the images. RESULTS: The discrimination rate for subclinical DR was 88% using the automated method and higher than the rate obtained by a human observer which was 45%. CONCLUSIONS: The method provides sensitive and rapid analysis of retinal images and could be useful in detecting subclinical DR.

5.
Front Hum Neurosci ; 5: 40, 2011.
Article in English | MEDLINE | ID: mdl-21629859

ABSTRACT

Previous studies in non-human primates (NHPs) have shown that beta oscillations (15-30 Hz) of local field potentials (LFPs) in the arm/hand areas of primary motor cortex (MI) propagate as traveling waves across the cortex. These waves exhibited two stereotypical features across animals and tasks: (1) The waves propagated in two dominant modal directions roughly 180° apart, and (2) their propagation speed ranged from 10 to 35 cm/s. It is, however, unknown if such cortical waves occur in the human motor cortex. This study shows that the two properties of propagating beta waves are present in MI of a tetraplegic human patient while he was instructed to perform an instruction delay center-out task using a cursor controlled by the chin. Moreover, we show that beta waves are sustained and have similar properties whether the subject was engaged in the task or at rest. The directions of the successive sustained waves both in the human subject and a NHP subject tended to switch from one dominant mode to the other, and at least in the NHP subject the estimated distance traveled between successive waves traveling into and out of the central sulcus is consistent with the hypothesis of wave reflection between the border of motor and somatosensory cortices. Further, we show that the occurrence of the beta waves is not uniquely tied to periods of increased power in the beta frequency band. These results demonstrate that traveling beta waves in MI are a general phenomenon occurring in human as well as NHPs. Consistent with the NHP data, the dominant directions of the beta LFP waves in human aligned to the proximal to distal gradient of joint representations in MI somatotopy. This consistent finding of wave propagation may imply the existence of a hardwired organization of motor cortex that mediates this spatiotemporal pattern.

6.
J Neurosurg ; 115(1): 159-64, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21275563

ABSTRACT

OBJECT: The dynamics of fluid flow in normal pressure hydrocephalus (NPH) are poorly understood. Normally, CSF flows out of the brain through the ventricles. However, ventricular enlargement during NPH may be caused by CSF backflow into the brain through the ventricles. A previous study showed this reversal of flow; in the present study, the authors provide additional clinical data obtained in patients with NPH and supplement these data with computer simulations to better understand the CSF flow and ventricular wall displacement and emphasize its clinical implications. METHODS: Three NPH patients and 1 patient with aqueductal stenosis underwent cine phase-contrast MR imaging (cine MR imaging) for measurement of CSF flow and ventricle wall movement during the cardiac cycle. These data were compared to data previously obtained in 8 healthy volunteers. The CSF flow measurements were obtained at the outlet of the aqueduct of Sylvius. Calculation of the ventricular wall movement was determined from the complete set of cine MR images obtained axially at the middle of the lateral ventricle. The data were obtained before and after CSF removal with a ventriculoperitoneal shunt with an adjustable valve. To supplement the clinical data, a computational model was used to predict the transmural pressure and flow. RESULTS: In healthy volunteers, net CSF aqueductal flow was 1.2 ml/minute in the craniocaudal direction. In patients with NPH, the net CSF flow was in the opposite direction--the caudocranial direction--before shunt placement. After shunting, the magnitude of the abnormal fluid flow decreased or reversed, with the flow resembling the normal flow patterns observed in healthy volunteers. CONCLUSIONS: The authors' MR imaging-based measurements of the CSF flow direction and lateral ventricle volume size change and the results of computer modeling of fluid dynamics lead them to conclude that the directional pattern and magnitude of CSF flow in patients with NPH may be an indication of the disease state. This has practical implications for shunt design and understanding the mechanisms that produce hydrocephalus.


Subject(s)
Cerebral Ventricles/physiopathology , Cerebrospinal Fluid , Hydrocephalus, Normal Pressure/physiopathology , Hydrocephalus/physiopathology , Magnetic Resonance Imaging, Cine , Adult , Cerebrospinal Fluid/physiology , Female , Humans , Hydrocephalus/surgery , Hydrocephalus, Normal Pressure/surgery , Hydrodynamics , Male , Middle Aged , Treatment Outcome , Ventriculoperitoneal Shunt
7.
Pediatr Neurosurg ; 45(3): 161-74, 2009.
Article in English | MEDLINE | ID: mdl-19440003

ABSTRACT

This article reviews our previous work on the dynamics of the intracranial cavity and presents new clinically relevant results about hydrocephalus that can be gained from this approach. Simulations based on fluid dynamics and poroelasticity theory are used to predict CSF flow, pressures and brain tissue movement in normal subjects. Communicating hydrocephalus is created in the model by decreasing CSF absorption. The predictions are shown to reflect dynamics demonstrated by structural MRI and cine-MRI studies of normal subjects and hydrocephalus patients. The simulations are then used to explain unilateral hydrocephalus and how hydrocephalus could occur without CSF pulsations. The simulations also predict the known pressure/volume relationships seen on bolus infusions of CSF, and the small transmural pressure gradients observed in animal experiments and in patients with hydrocephalus. The complications and poor performance of shunts based on pressure-sensitive valves are explained and a system of feedback control is suggested as a solution.


Subject(s)
Cerebrospinal Fluid/physiology , Computer Simulation , Hydrocephalus/physiopathology , Intracranial Pressure/physiology , Models, Biological , Child , Humans
8.
Mov Disord ; 24(7): 1048-53, 2009 May 15.
Article in English | MEDLINE | ID: mdl-19353721

ABSTRACT

To report a novel treatment approach, pallidotomy and deep brain stimulation (DBS), in two sisters with dystonic storm due to Batten's disease. This study is based on long-term follow-up of two sisters, presenting with dystonic storm and their response to pallidotomy and DBS. These sisters, who had visual loss, seizures, and progressive psychomotor decline, experienced progressive disabling abnormal movements culminating in dystonic storm at the age of 15 and 17 years, respectively. In addition to intubation and sedation, multiple medications, including botulinum toxin injections and intrathecal baclofen infusion were tried in both patients without any benefit. The old sister underwent bilateral pallidotomy. Within 10 days postoperatively, there was marked improvement in dystonic storm. She was free of abnormal movements for 9 months. Then she started having opisthotonus lasting 20 seconds to an hour several times/day, but over 6 years abnormal movements are markedly improved, and not returned to pre-pallidotomy level. The young sister underwent both bilateral pallidotomy and DBS, 3 weeks apart. She was free of abnormal movements for 7 months and able to maintain reduction in the abnormal movements by adjusting DBS settings. Pallidotomy and DBS should be considered in dystonic storm due to Batten's disease.


Subject(s)
Deep Brain Stimulation/methods , Dystonia/etiology , Dystonia/therapy , Neuronal Ceroid-Lipofuscinoses/complications , Pallidotomy/methods , Adult , Female , Humans , Longitudinal Studies , Young Adult
9.
J Neurosurg ; 109(3): 405-9, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18759568

ABSTRACT

OBJECT: The aim of this study was to provide an objective assessment of deep brain stimulation (DBS) for groups of patients with mixed secondary dystonia and primary torticollis syndromes by a blinded evaluation of 13 consecutive patients who underwent ineffective medical treatment and botulinum toxin injections. METHODS: Nine patients with secondary dystonia and 4 with cranial dystonia involving prominent spasmodic torticollis were selected for a DBS implant after they underwent unsuccessful medical treatment. Preoperative videos and neurological assessments were obtained and the DBS implant was inserted into the globus pallidus internus. Postoperatively, DBS parameters were adjusted to provide optimal benefit. Postoperative videotapes and quality of life scores were obtained. Blinded randomized evaluation of videotapes was performed by a neurologist specializing in movement disorders. Videos were scored using the Unified Dystonia Rating Scale, Toronto Western Spasmodic Torticollis Rating Scale, Burke-Fahn-Marsden Dystonia Rating Scale, or Abnormal Involuntary Movement Scale. Quality of life scoring was assessed using a standardized 7-point Global Rating Scale. RESULTS: All 13 patients completed preoperative videotaping, medical assessment, and surgery. Optimal DBS programming was completed in 6.5 visits over 5.9 months. Seven patients reported marked improvement, 3 reported moderate improvement, 2 reported slight improvement or no change, and 1 was lost to follow-up. Examiner scores on the Global Rating Scale reflected patient self-reported scores. CONCLUSIONS: Global subjective gains and notable objective improvement were observed in 11 of 13 patients. Although the benefits were variable and not fully predictable, they were of sufficient magnitude to justify offering the procedure when medications and botulinum toxin injections have failed.


Subject(s)
Deep Brain Stimulation , Dystonic Disorders/therapy , Torticollis/therapy , Adolescent , Adult , Aged , Follow-Up Studies , Globus Pallidus , Humans , Middle Aged , Prospective Studies , Single-Blind Method , Syndrome , Treatment Outcome
10.
IEEE Trans Biomed Eng ; 55(9): 2303-13, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18713700

ABSTRACT

Several treatment modalities for neurodegenerative diseases or tumors of the central nervous system involve invasive delivery of large molecular weight drugs to the brain. Despite the ample record of experimental studies, accurate drug targeting for the human brain remains a challenge. This paper proposes a systematic design method of administering drugs to specific locations in the human brain based on first principles transport in porous media. The proposed mathematical framework predicts achievable treatment volumes in target regions as a function of brain anatomy and infusion catheter position. A systematic procedure to determine the optimal infusion and catheter design parameters that maximize the penetration depth and volumes of distribution will be discussed. The computer simulations are validated with agarose gel phantom experiments and rat data. The rigorous computational approach will allow physicians and scientists to better plan the administration of therapeutic drugs to the central nervous system.


Subject(s)
Brain/metabolism , Drug Therapy, Computer-Assisted/methods , Macromolecular Substances/administration & dosage , Macromolecular Substances/pharmacokinetics , Models, Neurological , Pharmaceutical Preparations/administration & dosage , Pharmacokinetics , Animals , Brain/drug effects , Brain Chemistry , Computer Simulation , Macromolecular Substances/chemistry , Models, Chemical , Pharmaceutical Preparations/chemistry , Porosity , Rats
11.
J Biomech ; 41(10): 2176-87, 2008 Jul 19.
Article in English | MEDLINE | ID: mdl-18550067

ABSTRACT

Effective drug delivery for many neurodegenerative diseases or tumors of the central nervous system is challenging. Targeted invasive delivery of large macromolecules such as trophic factors to desired locations inside the brain is difficult due to anisotropy and heterogeneity of the brain tissue. Despite much experimental research, prediction of bio-transport phenomena inside the brain remains unreliable. This article proposes a rigorous computational approach for accurately predicting the fate of infused therapeutic agents inside the brain. Geometric and physiological properties of anisotropic and heterogeneous brain tissue affecting drug transport are accounted for by in-vivo diffusion tensor magnetic resonance imaging data. The three-dimensional brain anatomy is reconstructed accurately from subject-specific medical images. Tissue anisotropy and heterogeneity are quantified with the help of diffusion tensor imaging (DTI). Rigorous first principles physical transport phenomena are applied to predict the fate of a high molecular weight trophic factor infused into the midbrain. Computer prediction of drug distribution in humans accounting for heterogeneous and anisotropic brain tissue properties have not been adequately researched in open literature before.


Subject(s)
Anisotropy , Biological Transport/physiology , Brain/drug effects , Brain/metabolism , Adult , Algorithms , Brain/anatomy & histology , Calibration , Computational Biology/methods , Diffusion , Drug Delivery Systems , Humans , Image Processing, Computer-Assisted/methods , Kinetics , Models, Biological , Models, Theoretical , Software
12.
IEEE Trans Biomed Eng ; 54(2): 291-302, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17278586

ABSTRACT

Advances in magnetic resonance (MR) imaging techniques enable the accurate measurements of cerebrospinal fluid (CSF) flow in the human brain. In addition, image reconstruction tools facilitate the collection of patient-specific brain geometry data such as the exact dimensions of the ventricular and subarachnoidal spaces (SAS) as well as the computer-aided reconstruction of the CSF-filled spaces. The solution of the conservation of CSF mass and momentum balances over a finite computational mesh obtained from the MR images predict the patients' CSF flow and pressure field. Advanced image reconstruction tools used in conjunction with first principles of fluid mechanics allow an accurate verification of the CSF flow patters for individual patients. This paper presents a detailed analysis of pulsatile CSF flow and pressure dynamics in a normal and hydrocephalic patient. Experimental CSF flow measurements and computational results of flow and pressure fields in the ventricular system, the SAS and brain parenchyma are presented. The pulsating CSF motion is explored in normal and pathological conditions of communicating hydrocephalus. This paper predicts small transmantle pressure differences between lateral ventricles and SASs (approximately 10 Pa). The transmantle pressure between ventricles and SAS remains small even in the hydrocephalic patient (approximately 30 Pa), but the ICP pulsatility increases by a factor of four. The computational fluid dynamics (CFD) results of the predicted CSF flow velocities are in good agreement with Cine MRI measurements. Differences between the predicted and observed CSF flow velocities in the prepontine area point towards complex brain-CSF interactions. The paper presents the complete computational model to predict the pulsatile CSF flow in the cranial cavity.


Subject(s)
Cerebral Ventricles/physiopathology , Cerebrospinal Fluid Pressure , Hydrocephalus/physiopathology , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Manometry/methods , Pulsatile Flow , Adult , Cerebrospinal Fluid , Humans , Hydrocephalus/diagnosis , Middle Aged , Rheology/methods
13.
J Magn Reson Imaging ; 24(4): 756-70, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16958068

ABSTRACT

PURPOSE: To develop quantitative MRI techniques to measure, model, and visualize cerebrospinal fluid (CSF) hydrodynamics in normal subjects and hydrocephalic patients. MATERIALS AND METHODS: Velocity information was obtained using time-resolved (CINE) phase-contrast imaging of different brain regions. A technique was developed to measure the change of lateral ventricle (LV) size. The temporal relationships between the LV size change, CSF movement, and blood flow could then be established. The data were incorporated into a first-principle CSF hydrodynamic model. The model was then used to generate specific predictions about CSF pressure relationships. To better-visualize the CSF flow, a color-coding technique based on linear transformations was developed that represents the magnitude and direction of the velocity in a single cinematic view. RESULTS: The LV volume change of the eight normal subjects was 0.901+/-0.406%. Counterintuitively, the LV decreases as the choroid plexus expands, so that they act together to produce the CSF oscillatory flow. The amount of oscillatory flow volume is 21.7+/-10.6% of the volume change of the LV from its maximum to its minimum. CONCLUSION: The quantification and visualization techniques, together with the mathematical model, provide a unique approach to understanding CSF flow dynamics.


Subject(s)
Brain Mapping/methods , Cerebrospinal Fluid/physiology , Hydrocephalus/cerebrospinal fluid , Hydrocephalus/physiopathology , Lateral Ventricles/physiopathology , Magnetic Resonance Imaging, Cine/methods , Adult , Artifacts , Cerebrospinal Fluid Pressure , Cerebrovascular Circulation , Female , Humans , Male , Middle Aged , Models, Statistical , Phantoms, Imaging
14.
Neurosurg Focus ; 21(2): e5, 2006 Aug 15.
Article in English | MEDLINE | ID: mdl-16918226

ABSTRACT

Medical management of adult spasticity, a condition of increased muscle tone and deep tendon reflexes, is often challenging and complex. Oral medications such as baclofen often have unacceptable supraspinal side effects at effective doses. Intrathecal baclofen delivered by an implanted catheter and pump system provides good relief of spasticity while overcoming these limitations. In this paper the authors survey the use of oral and intrathecal baclofen therapy, detail the surgical process, and explain the risks and benefits of the procedure.


Subject(s)
Baclofen/administration & dosage , Muscle Relaxants, Central/administration & dosage , Muscle Spasticity/drug therapy , Administration, Oral , Humans , Infusion Pumps, Implantable , Injections, Spinal/methods , Risk
15.
Nature ; 442(7099): 164-71, 2006 Jul 13.
Article in English | MEDLINE | ID: mdl-16838014

ABSTRACT

Neuromotor prostheses (NMPs) aim to replace or restore lost motor functions in paralysed humans by routeing movement-related signals from the brain, around damaged parts of the nervous system, to external effectors. To translate preclinical results from intact animals to a clinically useful NMP, movement signals must persist in cortex after spinal cord injury and be engaged by movement intent when sensory inputs and limb movement are long absent. Furthermore, NMPs would require that intention-driven neuronal activity be converted into a control signal that enables useful tasks. Here we show initial results for a tetraplegic human (MN) using a pilot NMP. Neuronal ensemble activity recorded through a 96-microelectrode array implanted in primary motor cortex demonstrated that intended hand motion modulates cortical spiking patterns three years after spinal cord injury. Decoders were created, providing a 'neural cursor' with which MN opened simulated e-mail and operated devices such as a television, even while conversing. Furthermore, MN used neural control to open and close a prosthetic hand, and perform rudimentary actions with a multi-jointed robotic arm. These early results suggest that NMPs based upon intracortical neuronal ensemble spiking activity could provide a valuable new neurotechnology to restore independence for humans with paralysis.


Subject(s)
Bionics/methods , Prostheses and Implants , Quadriplegia/physiopathology , Quadriplegia/rehabilitation , Adult , Electrodes , Humans , Male , Middle Aged , Movement , Robotics/methods , User-Computer Interface
18.
Magn Reson Med ; 54(3): 725-31, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16086307

ABSTRACT

Brain T1 mapping has important clinical applications in detecting brain disorders. Conventional T1 mapping techniques are usually based on inversion recovery spin echo (IRSE) imaging or its more time-efficient counterpart inversion recovery fast spin echo (IRFSE) imaging because they can deliver good image quality. Multiple inversion times are required to accurately estimate T1 over a wide range of values. Without acquisition optimization, both the IRSE and the IRFSE T1 mapping techniques require long scan times to image the whole brain. To reduce the scan time and maintain the quality of the T1 maps, we propose a new full-brain T1 mapping pulse sequence based on a multislice inversion recovery fast spin echo imaging using a time-efficient slice ordering technique.


Subject(s)
Brain Mapping/methods , Magnetic Resonance Imaging/methods , Adult , Female , Humans , Linear Models , Male , Phantoms, Imaging
19.
J Neurosurg ; 102(6): 1069-75, 2005 Jun.
Article in English | MEDLINE | ID: mdl-16028766

ABSTRACT

OBJECT: The goal of this investigation was to establish whether pressure gradients exist between the ventricles, brain tissue, and subarachnoid space when acute or chronic hydrocephalus develops. Such gradients are hypothesized by many models of hydrocephalus, but considerable controversy continues about their existence. METHODS: A stereotactic frame was used for surgery in dogs to implant pressure sensors within the right lateral ventricle, the frontal lobe, and forward in the subarachnoid space. The dogs were allowed to recover for 10 to 14 days postoperatively. Then, 800 mg of sterile kaolin in water was injected into the cisterna magna region by using a percutaneous approach. Both real-time and long-term intracranial pressures were measured. Of the six dogs, one experienced an intracranial hemorrhage, one dog displayed status epilepticus after a second injection of kaolin and was killed, one experienced acute hydrocephalus, and three experienced mild chronic hydrocephalus. No consistent pressure differences were found in any dog between the ventricle, brain, and subarachnoid space before kaolin administration or afterward when hydrocephalus developed. In addition, no pulse pressure gradients occurred between the brain and the ventricle or subarachnoid space. CONCLUSIONS: Precise monitoring of pressure before and during the development of hydrocephalus did not detect pressure gradients between the ventricle, brain, and subarachnoid space. This was true for long-term measurements over weeks and for real-time measurements that allowed accurate assessment of pulse pressures. Theories predicting pressure gradients greater than the resolution of these sensors (0.5 mm Hg) across brain tissue have to be reevaluated in light of these findings.


Subject(s)
Cerebral Ventricles/physiology , Hydrocephalus/physiopathology , Intracranial Pressure/physiology , Subarachnoid Space/physiology , Acute Disease , Animals , Blood Pressure/physiology , Chronic Disease , Disease Models, Animal , Dogs , Kaolin , Monitoring, Physiologic
20.
Neurosurg Clin N Am ; 14(3): 381-7, 2003 Jul.
Article in English | MEDLINE | ID: mdl-14567139

ABSTRACT

This brief review of intrathecal pain medication delivery has emphasized the unusual but useful pharmacology of CSF drug delivery, the new study definitely showing that the method is helpful in cancer pain, and the rare complication of mass formation at the catheter tip. As new medications are developed for intrathecal delivery, this field is likely to expand, especially if a wider range of dorsal horn receptor mechanisms underlying pain processing can be modified. The changes in spinal cord signaling that are induced by chronic pain states are being investigated, and new possibilities for intervention are likely. the availability of a reliable well-understood way of delivering such new therapies by implanted drug pumps will speed the process. Intrathecal morphine for chronic pain has an important role in helping many patients with a wide variety of pain conditions and, as with all pain treatment, is woefully underused.


Subject(s)
Analgesics/administration & dosage , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/adverse effects , Drug Delivery Systems/adverse effects , Drug Delivery Systems/instrumentation , Granuloma/etiology , Humans , Infusion Pumps/adverse effects , Injections, Spinal , Morphine/administration & dosage , Morphine/adverse effects , Spinal Cord Diseases/etiology , Treatment Outcome
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