Practice parameter: pharmacologic treatment of spasticity in children and adolescents with cerebral palsy (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society.

OBJECTIVE: To evaluate published evidence of efficacy and safety of pharmacologic treatments for childhood spasticity due to cerebral palsy. METHODS: A multidisciplinary panel systematically reviewed relevant literature from 1966 to July 2008. RESULTS: For localized/segmental spasticity, botulinum toxin type A is established as an effective treatment to reduce spasticity in the upper and lower extremities. There is conflicting evidence regarding functional improvement. Botulinum toxin type A was found to be generally safe in children with cerebral palsy; however, the Food and Drug Administration is presently investigating isolated cases of generalized weakness resulting in poor outcomes. No studies that met criteria are available on the use of phenol, alcohol, or botulinum toxin type B injections. For generalized spasticity, diazepam is probably effective in reducing spasticity, but there are insufficient data on its effect on motor function and its side-effect profile. Tizanidine is possibly effective, but there are insufficient data on its effect on function and its side-effect profile. There were insufficient data on the use of dantrolene, oral baclofen, and intrathecal baclofen, and toxicity was frequently reported. RECOMMENDATIONS: For localized/segmental spasticity that warrants treatment, botulinum toxin type A should be offered as an effective and generally safe treatment (Level A). There are insufficient data to support or refute the use of phenol, alcohol, or botulinum toxin type B (Level U). For generalized spasticity that warrants treatment, diazepam should be considered for short-term treatment, with caution regarding toxicity (Level B), and tizanidine may be considered (Level C). There are insufficient data to support or refute use of dantrolene, oral baclofen, or continuous intrathecal baclofen (Level U).

A novel approach to stroke rehabilitation: robot-aided sensorimotor stimulation.

OBJECTIVE: In patients with stroke, the authors tested whether additional sensorimotor training of the paralyzed or paretic upper limb delivered by a robotic device enhanced motor outcome. METHODS: Fifty-six patients with stroke and hemiparesis or hemiplegia received standard poststroke multidisciplinary rehabilitation, and were randomly assigned either to receive robotic training (at least 25 hours) or exposure to the robotic device without training. Outcomes were assessed by the same masked raters, before treatment began and at the end of treatment, with the upper extremity component of the Fugl-Meyer Motor Assessment, the Motor Status score, the Motor Power score, and Functional Independence Measurement. RESULT: The robot treatment and control group had comparable clinical characteristics, lesion size, and pretreatment impairment scores. By the end of treatment, the robot-trained group demonstrated improvement in motor outcome for the trained shoulder and elbow (Motor Power score, p < 0.001; Motor Status score, p < 0. 01) that did not generalize to untrained wrist and hand. The robot-treated group also demonstrated significantly improved functional outcome (Functional Independence Measurement-Motor, p < 0. 01). CONCLUSION: Robot-delivered quantitative and reproducible sensorimotor training enhanced the motor performance of the exercised shoulder and elbow. The robot-treated group also demonstrated improved functional outcome. When added to standard multidisciplinary rehabilitation, robotics provides novel therapeutic strategies that focus on impairment reduction and improved motor performance.

Increasing productivity and quality of care: robot-aided neuro-rehabilitation.

This paper presents an overview of our research in robot-aided stroke neuro-rehabilitation and recovery. At the onset of this research we had to confront squarely (and solve!) a critical question: If anatomy is destiny, can we influence it? Our efforts over the last five years have been focused on answering this question and we will present a few of our clinical results from over 2,000 hours of robot-aided therapy with 76 stroke patients. To determine if exercise therapy influences plasticity and recovery of the brain following a stroke, we needed the appropriate "microscope" that would allow us to concomitantly control the amount of therapy delivered to a patient, while objectively measuring patient's performance. Back-driveable robots are the key enabling technology. Our results to date using common clinical scales suggest that robot-aided sensorimotor training does have a genuinely positive effect on reduction of impairment and the reorganization of the adult brain. Yet while clinical scales can help us to examine the impact in the neuro-recovery process, their coarse nature requires extensive and time-consuming trials, and on top of that they fail to show us details important for optimizing therapy. Alternative, robot-based scales offer the potential benefit of new finer measurements-and deeper insight into the process of recovery from neurological injury. We also plan to use present technology to establish the practicality and economic feasibility of clinician-supervised, robot-administered therapy, including classroom therapy. We feel quite optimistic that the march of progress will accelerate substantially in the near future and allow us to transfer this technology from the research realm to the everyday treatment of stroke survivors.

Robot training enhanced motor outcome in patients with stroke maintained over 3 years.

In an attempt to improve motor recovery of the upper limb after stroke, we added a robot (MIT-Manus) experience that provided additional goal-directed sensorimotor activity to standard rehabilitation treatments. The first trial produced a significant decrease in motor impairment in the upper limb for the treated group. In re-evaluating 12 of those 20 patients, nearly 3 years later, robot-trained patients showed further significant decreases in impairment measures of the affected limb. The groups were comparable at the start of the study.

Quantization of continuous arm movements in humans with brain injury.

Segmentation of apparently continuous movement has been reported for over a century by human movement researchers, but the existence of primitive submovements has never been proved. In 20 patients recovering from a single cerebral vascular accident (stroke), we identified the apparent submovements that composed a continuous arm motion in an unloaded task. Kinematic analysis demonstrated a submovement speed profile that was invariant across patients with different brain lesions and provided experimental verification of the detailed shape of primitive submovements. The submovement shape was unaffected by its peak speed, and to test further the invariance of shape with speed, we analyzed movement behavior in a patient with myoclonus. This patient occasionally made involuntary shock-like arm movements, which occurred near the maximum capacity of the neuromuscular system, exhibited speed profiles that were comparable to those identified in stroke patients, and were also independent of speed.

Overview of clinical trials with MIT-MANUS: a robot-aided neuro-rehabilitation facility.

We are applying robotics and information technology to assist, enhance, and quantify neuro-rehabilitation. Our goal is a new class of interactive, user-affectionate clinical devices designed not only for evaluating patients, but also-for delivering meaningful therapy via engaging "video games". Notably, the novel robot MIT-MANUS has been designed and programmed for clinical neurological applications, and has undergone extensive clinical trials for more than four years at Burke Rehabilitation Hospital - White Plains, NY. This paper will review results of the first clinical trial of 20 patients, which showed that: - Stroke patients treated daily with additional robot-aided therapy during acute rehabilitation had improved outcome in motor activity at hospital discharge, when compared to a control group that received only standard acute rehabilitation treatment. - This improved outcome was sustained after three years. - The neuro-recovery process continued far beyond the commonly accepted 3 months post-stroke interval.

Robot-aided neurorehabilitation.

Our goal is to apply robotics and automation technology to assist, enhance, quantify, and document neurorehabilitation. This paper reviews a clinical trial involving 20 stroke patients with a prototype robot-aided rehabilitation facility developed at the Massachusetts Institute of Technology, Cambridge, (MIT) and tested at Burke Rehabilitation Hospital, White Plains, NY. It also presents our approach to analyze kinematic data collected in the robot-aided assessment procedure. In particular, we present evidence 1) that robot-aided therapy does not have adverse effects, 2) that patients tolerate the procedure, and 3) that peripheral manipulation of the impaired limb may influence brain recovery. These results are based on standard clinical assessment procedures. We also present one approach using kinematic data in a robot-aided assessment procedure.

A comparison of low molecular weight heparin and low dose unfractionated heparin prophylaxis in subacute myelopathy.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are common life threatening complications of acute myelopathy. Prophylaxis with low dose unfractionated heparin (LDUH) has been the standard of care. Studies suggest that low molecular weight heparin (LMWH) has superior efficacy, but advantages may be offset by higher expense. Since LMWH (enoxaparin sodium) became available, standard practice at our institution has been to treat all inpatients with myelopathy with LMWH. To examine the impact of this practice, all inpatients diagnosed with myelopathy and treated with LMWH were sequentially matched by diagnosis and compared in a retrospective review with inpatients treated with LDUH. In each group, 11 patients had traumatic injury, four had transverse myelitis, four had neoplasms and five had spinal stenosis. Characteristics of the LMWH/LDUH groups were: mean age--48.5/50.4; spinal level--cervical 13/7, thoracic 9/12, lumbar 2/5; American Spinal Injury Association impairment scale-A, 8/9; B, 2/2; C, 8/5; D, 6/8. There were five DVTs and two PEs in five patients taking LDUH; there were no cases of DVT or of PE in the LMWH group (p = 0.04, two-tailed chi-square test). Isolated DVTs occurred in two patients with traumatic injuries and in one patient with transverse myelitis; PE + DVT occurred in one patient with a primary and one patient with a metastatic tumor. All developed within 3.5 months of the onset of spinal dysfunction. One patient with a traumatic injury on ibuprofen and dexamethasone had a gastrointestinal hemorrhage while receiving LMWH. The cost of administration of LMWH was $24,499 compared with $5,700 for LDUH. The LDUH group spent a total of 57 days in an acute care facility, costing $57,000.00 and patients treated with LMWH spent nine days, costing $9,000.00. We conclude that treatment with LMWH was associated with a significant decrease in incidence of DVT/PE and an overall decline in health care costs of approximately $30,000 or approximately $1,250 per patient.

The effect of robot-assisted therapy and rehabilitative training on motor recovery following stroke.

BACKGROUND: We used MIT-Manus, a robot designed to provide interactive, goal-directed motor activity for clinical neurologic applications. OBJECTIVE: To test whether this robotic manipulation of the impaired limb influenced motor recovery in patients with hemiplegia. METHODS: Sequential patients with a history of a single stroke and hemiplegia (N = 20) hospitalized on the same acute care rehabilitation floor were enrolled in a standard rehabilitation program supplemented by either robot-aided therapy or sham robot-aided therapy. These 2 groups were comparable in age, initial physical impairment, and time between onset of the stroke and enrollment in the trial. Patients, clinical team members, and the clinical evaluator were blinded to the treatment group assignments. Standardized assessment tools measured outcomes. RESULTS: Impairment and disability declined in both groups between hospital admission and discharge. The robot-treated group showed a greater degree of improvement in all 3 measures of motor recovery, and the change in motor status measured in the proximal upper limb musculature was significant (P = .002). No adverse events resulted from robot-assisted therapy. CONCLUSIONS: These results suggest that robotic manipulation of the impaired limb may favorably add to recovery following stroke and that robotics may provide new strategies for neurologic rehabilitation.

A double-blind placebo-controlled study of 3,4-diaminopyridine in amytrophic lateral sclerosis patients on a rehabilitation unit.

3,4-Diaminopyridine (DAP) enhances acetylcholine release from the nerve terminal and improves conduction in demyelinated axons. In this double-blinded placebo controlled cross over study we examined the effects of DAP combined with inpatient rehabilitation in nine patients with disabling motor weakness due to amyotrophic lateral sclerosis (ALS). A single dose of DAP or placebo was increased daily to the maximum (range: 10-80 mg) tolerated dose; after patients were assessed on the first treatment, the alternate drug was given in the same manner. Functional Independence Measurement (FIM), Ashworth, grip strength, limb strength measurements, nerve conduction studies and speech assessments were initiated 1/2 h after receiving the maximum tolerated dose of DAP or placebo. DAP was tolerated in all patients, but limited by gastrointestinal side effects in four patients. The mean peak serum level was 20.11 (S.D. = 5.11) ng/ml, occurring 1.25 (S.D. = 0.56) h after dose. A statistically significant improvement in FIM and speech assessment scores between admission and discharge occurred. However, no significant differences in clinical or electrophysiologic measures were seen between DAP and placebo treatments. This study suggests that intensive inpatient rehabilitation has a role in the management of patients with ALS, but DAP does not diminish motor impairment.

The sympathetic skin response in the shoulder-hand syndrome complicating tetraplegia.

To determine the utility of the sympathetic skin response (SSR) in studying sympathetic outflow in cervical spinal cord injury (CSCI) patients who develop features of reflex sympathetic dystrophy, we studied seven consecutive CSCI patients with the shoulder-hand syndrome (SHS), and seven patients with similar injuries but without the manifestations of the SHS. The mean SSR amplitude was more than three times greater in patients with the SHS, a statistically significant difference. We restudied six patients with a SHS after symptoms had improved following steroid treatment: the mean amplitude fell significantly, approaching the mean for the control group. When pain was asymmetric, the SSR amplitude was higher in the arm with greater pain. Four of the seven SHS patients demonstrated an unusual pattern of spontaneous cyclical electrical activity during a period of severe pain. We conclude that a SHS complicating CSCI is associated with increased amplitude of the SSR, supporting the theory that sympathetic hyperactivity is important in the pathophysiology of reflex sympathetic dystrophy in this setting.

3,4-diaminopyridine as a treatment for amyotrophic lateral sclerosis.

The slow potassium channel blocker 3,4-diaminopyridine (DAP) enhances acetylcholine release from the nerve terminal and improves conduction in unmyelinated nerve. In this open label pilot study, we examined the effect of DAP combined with inpatient rehabilitation in seven patients with motor weakness due to amyotrophic lateral sclerosis (ALS). A single daily 20 mg oral dose of DAP was gradually increased to the maximum tolerated dose, and serum DAP concentrations were measured. Videotaped motor examination (for subsequent "blinded" review and assignment of a quantitative motor score), Functional Independence Measure (FIM) assessment, nerve conduction studies and neuropsychological evaluations were performed on admission, 1 h after maximum DAP dose, and post-treatment. DAP was tolerated in all patients, though dose was limited by gastrointestinal side effects in five patients. The mean peak serum level was 128 (+/- 50) ng/ml, occurring 1.0 (+/- 0.50) h after dose. A modest but statistically significant (p = 0.045) peak in motor score occurred on DAP. A significant (p = 0.045) improvement from baseline in FIM performance was apparent with DAP. Nerve conduction studies showed small increases in evoked response amplitudes and conduction velocities on DAP, but they did not reach statistical significance. No cognitive or affective changes were apparent. This unblinded pilot study shows that DAP is tolerated in ALS patients, and may be associated with functional and electrophysiologic improvement.

Design of a controlled-energy-dissipation orthosis (CEDO) for functional suppression of intention tremors.

Conventional neurological practice is generally not successful in restoring independent upper extremity function to people with disabiling tremors. The authors have been investigating an orthotic approach, the application of energy-dissipating loads to affected limbs, to allow voluntary intent to be expressed while attenuating tremor. CEDO 1 is a prototype Controlled-Energy-Dissipation Orthosis, which permits the 3 degrees of freedom (dof) needed for table-top activities. It mounts to the user's chair or table and applies velocity-proportional resistance to his/her forearm by means of computer-controlled magnetic particle brakes. The design incorporates a stiff linkage transmission to the elbow brake of the orthosis, allowing it to be fixed in the frame of reference. This eliminates its inertia from the moving linkage and provides virtually direct drive in all 3 dof. Initial experimental results show selective clinically significant tremor reduction during experimental tracking tasks.

Falls on a neurorehabilitation unit: reassessment of a prevention program.

We conducted a retrospective case-control study of falls over a four year period on a 30 bed neurorehabilitation unit at the Burke Rehabilitation Hospital to characterize the nature of falls and identify factors associated with falling. The most common diagnoses treated on the unit were traumatic spinal cord injury, brain injury, and multiple sclerosis; stroke patients are treated on another service. Falls represented 72 percent of all incident reports made to the Nursing Office during the study period. One hundred seventeen (117) falls occurred in 82 patients during a time when the unit census was 28,622 patient days, yielding a rate of 1,439 falls per 1,000 patient years. One hundred fourteen (114) patients admitted with no history of falling during the same period were selected randomly for comparison. Most falls were associated with no injury (n = 96) or minor injury (n = 18). The most significant injuries occurred in three cases with lacerations requiring sutures. Falls occurred with greatest frequency during the first and fourth quartiles of the hospital stay, during the evening and while bed transfers were being performed. No association between falling and patient age, sex, diagnosis, number of medications, use of sedating medications, presence of motor, visual or cognitive impairment or orthostatic hypotension was evident. An increased risk of falling was associated with physician orders for Posey restraints. The implication of these findings for falls prevention programs is discussed.

Shoulder-hand syndrome in cervical spinal cord injury.

To characterize the occurrence of shoulder-hand syndrome (SHS) complicating the rehabilitation of patients with cervical spinal cord injury, we reviewed the medical records of 43 consecutive patients admitted to the Burke Rehabilitation Center with cervical spinal cord injury, focusing on the clinical features of SHS: shoulder pain, hand/wrist pain, edema, vasomotor changes, trophic changes and osteoporosis on x-ray. Twenty-seven patients (63%) had three or more features of SHS. The number of features correlated with age (r = 0.495, p = 0.0007), but not with the presence of upper or lower motor neuron findings in the arms, or with autonomic dysfunction. Twenty-three of 25 (92%) SHS patients with adequate follow up had satisfactory resolution of symptoms with conservative therapy (i.e. neither systemic corticosteroids nor stellate ganglion block), but only after a mean of 121 days (range 42-274 days).

Properties of cutaneous afferents during recovery from Guillain-Barré syndrome.

The technique of percutaneous microneurography was used to record from 60 mechanosensitive cutaneous afferents in patients (n = 5) who were recovering from acute Guillain-Barré syndrome (GBS) and who displayed residual sensory deficits in the hands. Recordings were obtained from median and ulnar nerves, between 1 and 31 months following plasma exchange therapy. The behaviour of all four types of cutaneous afferents known to innervate the glabrous skin of the normal hand (rapidly adapting types RA and PC and slowly adapting types SAI and SAII) was studied in response to mechanical skin stimulation. Some of the units could not be fully classified. Additionally, intradermal electrical stimulation was used to study conduction velocity and absolute refractory period. Abnormal response behaviour was encountered in RA, PC and slowly adapting afferents. The abnormalities consisted of a generation of only a single action potential to above threshold stimuli (RA), inability to follow high frequency vibration (PC) and, in slowly adapting afferents, reduced discharge rates during sustained skin indentations or cessation of discharge during indentation. Abnormally responding units were more frequently found in patients with marked, than in those with mild, clinical sensory symptoms. In the former, half of all units in each patient responded abnormally (12 out of 23 in total). In patients with mild symptoms, most units (33 out of 37) were normal in response behaviour as well as in other measures made: threshold to mechanical stimuli, static discharge rate, receptive field size, conduction velocity, absolute refractory period. Spontaneous activity of unknown origin was also encountered in some patients. The activity consisted of highly regular discharge bursts or relatively regular unitary discharges. The data indicate that the encoding capabilities of all types of cutaneous afferents (RA, PC, SAI and SAII) may be affected in GBS, contributing to the sensory deficits of the disease. The abnormal encoding most likely reflects a limited ability of the axons to conduct trains of action potentials.