Interim Safety Profile From the Feasibility Study of the BrainGate Neural Interface System.

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.

Classification of advanced and early stages of diabetic retinopathy from non-diabetic subjects by an ordinary least squares modeling method applied to OCTA images.

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.

Improving therapeutic potential of GDNF family ligands.

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.

Detection of Subclinical Diabetic Retinopathy by Fine Structure Analysis of Retinal Images.

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.

Propagating waves in human motor cortex.

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.

Ventricle wall movements and cerebrospinal fluid flow in hydrocephalus.

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.

The physics of hydrocephalus.

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.

Dystonic storm due to Batten's disease treated with pallidotomy and deep brain stimulation.

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.

A prospective blinded evaluation of deep brain stimulation for the treatment of secondary dystonia and primary torticollis syndromes.

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.

Rigorous mathematical modeling techniques for optimal delivery of macromolecules to the brain.

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.

Computational methods for predicting drug transport in anisotropic and heterogeneous brain tissue.

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.

Cerebrospinal fluid flow in the normal and hydrocephalic human brain.

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.

Dynamics of lateral ventricle and cerebrospinal fluid in normal and hydrocephalic brains.

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.

Intrathecal baclofen in the treatment of adult spasticity.

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.

Neuronal ensemble control of prosthetic devices by a human with tetraplegia.

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.

Full-brain T1 mapping through inversion recovery fast spin echo imaging with time-efficient slice ordering.

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.

Pressure gradients in the brain in an experimental model of hydrocephalus.

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.

Intrathecal medication delivery.

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.

Continuous intrathecal clonidine and tizanidine in conscious dogs: analgesic and hemodynamic effects.

Unlabelled: Alpha-2-adrenergic agonists, such as clonidine, produce antinociception in animal pain models after intrathecal administration. However, clinical usage is limited by cardiovascular side effects. To investigate alternative alpha(2)-adrenergic agonists as analgesics, we implanted six dogs with an intrathecal catheter and infusion pump.

Reaction time is not impaired by stimulation of the ventral-intermediate nucleus of the thalamus (Vim) in patients with tremor.

We studied the effect of high-frequency electrical stimulation of the ventral-intermediate nucleus of the thalamus (Vim) in four patients implanted with chronic stimulators to determine whether this procedure adversely affects reaction time to a proprioceptive stimulus. Two patients had undergone this surgery for treatment of tremor resulting from Parkinson's disease insufficiently responsive to levodopa therapy and two patients for treatment of essential tremor. Reaction times to auditory, visual, cutaneous, and proprioceptive stimuli were tested in a simple motor task requiring flexion of the elbow joint to a visual target in response to each stimulus.

Effects of age and size on development of allodynia in a chronic pain model produced by sciatic nerve ligation in rats.

Sciatic nerve constriction injury in rats has been used by various investigators as a model of chronic pain exhibiting allodynia and hyperalgesia. Although rats ranging between 200 and 350 g (40-70 days old) at the time of operation have been used by various investigators, the effect of rat age and weight on the model has not been previously studied. We noted that a group of older rats failed to develop all the characteristics of the model and designed the present study to determine the effect of age and weight on the development of allodynia and hyperalgesia.

Octreotide: a potent new non-opiate analgesic for intrathecal infusion.

Somatostatin-14 has been reported to relieve severe cancer pain when given intraspinally. We have studied a stable analog, octreotide, which is suitable for long-term infusion by a drug pump. In preclinical trials in dogs, chronic intrathecal and intraventricular perfusion at 40 micrograms/h did not produce neurotoxicity.

Effect of intrathecal tizanidine on antinociception and blood pressure in the rat.

Experiments were performed in rats to determine if the alpha 2-adrenergic agonist tizanidine has an antinociceptive effect when injected intrathecally, and whether the analgesia is accompanied by changes in blood pressure. Rats were chronically implanted with catheters in the lumbar subarachnoid space. Antinociception was evaluated in conscious rats with the tail-flick test.