Chronic lymphocytic leukemia and the central nervous system: a clinical and pathological study.

Chronic lymphocytic leukemia is the most common human leukemia but infrequently causes neurologic symptoms. We have reviewed all previously reported cases of chronic lymphocytic leukemia in the CNS along with three new cases; one patient was diagnosed antemortem and treated with immediate improvement and 4-year survival. In addition, we reviewed all autopsy cases since 1972 and available lumbar puncture data on patients with chronic lymphocytic leukemia admitted to the Massachusetts General Hospital. Invasion of the CNS by chronic lymphocytic leukemia often leads to confusional state, meningitis with cranial nerve abnormalities, optic neuropathy, or cerebellar dysfunction. Lumbar puncture shows a lymphocytosis consisting of monoclonal B cells, but CSF cytology studies are of limited value in establishing the diagnosis. Long-term survival may be related to the stage of chronic lymphocytic leukemia at the time of CNS disease and may be associated with intrathecal chemotherapy. A mild, asymptomatic infiltration of the brain, frequently noted in late-stage chronic lymphocytic leukemia in autopsy series, may explain the CSF lymphocytosis in some patients with late-stage chronic lymphocytic leukemia

Colocalization of GLUT2 glucose transporter, sodium/glucose cotransporter, and gamma-glutamyl transpeptidase in rat kidney with double-peroxidase immunocytochemistry.

Glucose is reabsorbed from the glomerular filtrate in the proximal segment of the renal tubule in two stages. The first stage is uphill transport across the brush border membrane by Na(+)-glucose cotransport and the second stage is downhill transport across the basolateral membrane by facilitated diffusion. Genes for both a renal Na(+)-glucose cotransporter (SGLT1) and a renal facilitated glucose transporter (GLUT2) have been cloned and sequenced. To examine whether SGLT1 and GLUT2 colocalize to the same tubular epithelial cells in rat kidney, double-immunoperoxidase studies with dual chromogens and paraformaldehyde perfusion-fixed frozen sections of rat kidney were performed. Antipeptide antisera were prepared against rat GLUT2 (amino acids 510-522) and rabbit SGLT1 (amino acids 402-420). Proximal tubules were identified immunocytochemically with an antiserum raised against a synthetic peptide corresponding to the 21 amino acids at the COOH-terminal of the heavy chain of rat gamma-glutamyl transpeptidase, which is a proximal tubule-specific enzyme. The anti-GLUT2 antiserum strongly stained the basolateral membrane of 46% of cortical tubules, whereas the SGLT1 antiserum stained the brush border of 56% of the cortical tubules. The gamma-glutamyl transpeptidase antiserum also stained the brush border of 51% of the cortical tubules. GLUT2 and SGLT1 colocalized to 40% of cortical epithelium, but 16% of cortical epithelial cells were immunopositive for brush border SGLT1 and immunonegative for basolateral GLUT2. These gamma-glutamyl transpeptidase staining results suggest that at least 50% of the tubules in the cortex are proximal tubules and that SGLT1 and GLUT2 colocalize to most proximal tubules. The fact that SGLT1 antiserum immunoreacted with tubules unreactive to the GLUT2 antiserum suggests that either the SGLT1 epitope is conserved on a related brush border protein or that there is another GLUT transporter responsible for the exit of sugar from these proximal tubule cells

A robotic device for hand motor therapy after stroke

This paper describes the design of a robotic device - the Hand-Wrist Assisting Robotic Device, or HWARD ("Howard") - that can assist functional grasping and releasing movements of the stroke-impaired hand. The 3 degrees-of-freedom device is pneumatically-actuated and backdriveable. The design of HWARD was guided by neurobiological principles of motor learning, such as sensorimotor integration, movement repetition, environmental complexity, and attention. Specifically, HWARD can assist repetitive grasping and releasing movements while allowing the subject to feel real objects during therapy. The use of real objects having rich sensory and functional characteristics can stimulate sensorimotor cortex activation while enhancing subject motivation and attention - features hypothesized to reduce impairment and disability. A pilot study will test the safety and efficacy of HWARD, with endpoints that include established motor function scales as well as brain mapping with functional MRI (fMRI). © 2005 IEEE

Correlation between genetic polymorphisms and stroke recovery: analysis of the GAIN Americas and GAIN International Studies.

Background and purposeRecovery after stroke occurs on the basis of specific molecular events. Genetic polymorphisms associated with impaired neural repair or plasticity might reduce recovery from stroke and might also account for some of the intersubject variability in stroke recovery. This study hypothesized that the ApoE ε4 polymorphism and the val(66) met polymorphism for brain-derived neurotrophic factor (BDNF) are each associated with poorer outcome after stroke. Associations with mitochondrial genotype were also explored.MethodsGenotypes were determined in 255 stroke patients who also received behavioral evaluations in the Glycine Antagonist In Neuroprotection (GAIN) clinical trials. The primary outcome measure was recovery during the first month post-stroke, as this is the time when neural repair is at a maximum and so when genetic influences might have their largest impact. Two secondary outcome measures at 3 months post-stroke were also examined.Results  Genotype groups were similar acutely post-stroke. Presence of the ApoE ε4 polymorphism was associated with significantly poorer recovery over the first month post-stroke (P = 0.023) and with a lower proportion of subjects with minimal or no disability (modified Rankin score 0-1, P = 0.01) at 3 months post-stroke. Indeed, those with this polymorphism were approximately half as likely to achieve minimal or no disability (18.2%) versus those with polymorphism absent (35.5%). Findings were confirmed in multivariate models. Results suggested possible effects from the val(66) met BDNF polymorphism and from the R0 mitochondrial DNA haplotype.Conclusions  Genetic factors, particularly the ApoE ε4 polymorphism, might contribute to variability in outcomes after stroke

Haptic Augmented Reality to monitor human arm's stiffness in rehabilitation

Augmented Reality (AR) is a live, direct or indirect, view of a physical, real-world environment whose elements are overlaid by virtual, computer generated objects. In this paper, AR is combined with haptics in order to observe human arm's stiffness. A haptic, hand-held device is used to measure the human arm's impedance. While a computer vision system tracks and records the position of the hand, a computer screen displays the impedance diagrams superimposed on the hand in a real-time video feed. The visual augmentation is also performed using a video projector that project's the diagrams on the hand as it moves. © 2012 IEEE

An assistive tabletop keyboard for stroke rehabilitation

We propose a tabletop keyboard that assists stroke patients in using computers. Using computers for purposes such as paying bills, managing bank accounts, sending emails, etc., which all include typing, is part of Activities of Daily Living (ADL) that stroke patients wish to recover. To date, stroke rehabilitation research has greatly focused on using computer-assisted technology for rehabilitation. However, working with computers as a skill that patients need to recover has been neglected. The conventional human computer interfaces are mouse and keyboard. Using keyboard stays the main challenge for hemiplegic stroke patients because typing is usually a bimanual task. Therefore, we propose an assistive tabletop keyboard which is not only a novel computer interface that is specially designed to facilitate patient-computer interaction but also a rehab medium through which patients practice the desired arm/hand functions. © 2013 Authors

Real-time computer modeling of weakness following stroke optimizes robotic assistance for movement therapy

This paper describes the development of a novel control system for a robotic arm orthosis for assisting patients in motor training following stroke. The robot allows naturalistic motion of the arm and is as mechanically compliant as a human therapist's arms. This compliance preserves the connection between effort and error that appears essential for motor learning, but presents a challenge: accurately creating desired movements requires that the robot form a model of the patient's weakness, since the robot cannot simply stiffly drive the arm along the desired path. We show here that a standard model-based adaptive controller allows the robot to form such a model of the patient and complete movements accurately. However, we found that the human motor system, when coupled to such an adaptive controller, reduces its own participation, allowing the adaptive controller to take over the performance of the task. This presents a problem for motor training, since active engagement by the patient is important for stimulating neuroplasticity. We show that this problem can be solved by making the controller continuously attempt to reduce its assistance when errors are small. The resulting robot successfully assists stroke patients in moving in desired patterns with very small errors, but also encourages intense participation by the patient. Such robot assistance may optimally provoke neural plasticity, since it intensely engages both descending and ascending motor pathways. © 2007 IEEE

A multimodal approach to understanding motor impairment and disability after stroke

Many different measures have been found to be related to behavioral outcome after stroke. Preclinical studies emphasize the importance of brain injury and neural function. However, the measures most important to human outcomes remain uncertain, in part because studies often examine one measure at a time or enroll only mildly impaired patients. The current study addressed this by performing multimodal evaluation in a heterogeneous population. Patients (n = 36) with stable arm paresis 3-6 months post-stroke were assessed across 6 categories of measures related to stroke outcome: demographics/medical history, cognitive/mood status, genetics, neurophysiology, brain injury, and cortical function. Multivariate modeling identified measures independently related to an impairment-based outcome (arm Fugl-Meyer motor score). Analyses were repeated (1) identifying measures related to disability (modified Rankin Scale score), describing independence in daily functions and (2) using only patients with mild deficits. Across patients, greater impairment was related to measures of injury (reduced corticospinal tract integrity) and neurophysiology (absence of motor evoked potential). In contrast, (1) greater disability was related to greater injury and poorer cognitive status (MMSE score) and (2) among patients with mild deficits, greater impairment was related to cortical function (greater contralesional motor/premotor cortex activation). Impairment after stroke is most related to injury and neurophysiology, consistent with preclinical studies. These relationships vary according to the patient subgroup or the behavioral endpoint studied. One potential implication of these results is that choice of biomarker or stratifying variable in a clinical stroke study might vary according to patient characteristics. © 2014 Springer-Verlag Berlin Heidelberg