New Developments in Stroke Rehabilitation

Eugenio R. Rocksmith, MD, and Michael J. Reding, MD

AddressBurke Rehabilitation Hospital, 785 Mamaroneck Avenue, White Plains, NY 10605-2523, USA. E-mail: erocksmith@burke.orgCurrent Atherosclerosis Reports 2002, 4:277–284Current Science Inc. ISSN 1523–3804Copyright © 2002 by Current Science Inc.

IntroductionThere is increasing evidence that environmental and neu-ropharmacologic treatments enhance stroke recovery. Func-tional magnetic resonance imaging (fMRI) has allowed usto study the role of ipsilateral and contralateral primary,secondary, and tertiary motor control systems in the motorrecovery process. Magnetic coil stimulation has been usedto study primary and secondary motor cortex responsive-ness to stimulation before versus after passive manipula-tion of the paretic limb, or to drug versus placebointervention. Behavioral interventions, such as forced use ofthe paretic limb by constraining the normal hand and par-tial body weight-supported treadmill gait training of thehemiplegic patient, have a solid experimental base and arebecoming standard rehabilitation techniques for selectedpatients. Use of hemi-field ocular prisms or patching tech-niques is being studied for their effects on treating visualhemi-neglect following stroke. Important advances havealso been made in the prevention, recognition, and treat-

ment of common stroke complications, such as depression,dysphagia, venous thromboembolic complications, incon-tinence, and spasticity. This article examines these develop-ments and their effects on rehabilitation following stroke.

Advances in Stroke EpidemiologyThe American Heart Association has recently increased itsestimate of the number of new strokes in the UnitedStates population from 500,000 to 600,000 per year (105to 139 cases per 100,000 population). Their estimate ofthe number of stroke survivors in the United States hasalso been increased from 3 million to 4 million. [1] Thesechanges are due to the fact that previous estimates werebased on populations from white, middle class Rochester,Minnesota and Framingham, Massachusetts. The poor areless likely to seek medical attention, and blacks are 2.4times more likely to have a stroke than whites [2]. Strokeremains the most common debilitating neurologic disor-der of adults in the United States. It is the third leadingcause of mortality and is one of the leading causes oflong-term, severe disability. The cost of acute care plusrehabilitation services is estimated to total $30 billion peryear. Of all patients surviving 3 months after their stroke,approximately half will be alive in 5 years, and a thirdwill survive 10 years. Approximately 60% recover inde-pendence with self-care, and 75% recover the ability towalk independently. Approximately 19% will requirechronic institutional care. [3]

Advances in NeuroimagingWithin the past decade, the neuroscience community hasmade tremendous strides in understanding the complex-ities of the human brain. Positron emission tomography(PET) imaging became available in the late 1980s. Itrequires administration of a radioactive tracer, which isused to measure regional cerebral glucose metabolismboth at rest and while performing cognitive or behav-ioral tasks. Comparisons of rest with activation imagesprovide information about the role of specific neuroana-tomic structures in performance of the cognitive orbehavioral tasks. Its application in behavioral research islimited by the short half-life of the radioactive tracersused and by the total dosage of radiation that can besafely administered.

There is increasing evidence that environmental and neuro-pharmacologic treatments enhance stroke recovery. Func-tional magnetic resonance imaging and transcranial magnetic stimulation have significantly broadened our understanding of the neuroanatomic relationships involved in recovery from brain injury due to stroke. These tools have also demon-strated the role for pharmacologic enhancement of cortical plasticity coupled with behavioral interventions. Robot-assisted therapy and partial body weight-supported treadmill gait training have demonstrated the role for technologic intervention in the modern neuro-rehabilitation setting. Cur-rent research using hemi-field ocular prisms and patching techniques suggest a role in the rehabilitation of hemianopsia and visual neglect. Finally, many advances have been made in the understanding of common stroke complications, such as depression, dysphagia, venous thromboembolic disease, incontinence, and spasticity.

278 Cardiovascular Disease and Stroke

Functional MRI is a significant advance in neurobehav-ioral research that became available in the mid 1990s. It doesnot require radiation exposure. fMRI is based upon the con-cept that increased neuronal activity is coupled to increasedlocal blood flow. For example, flexion and extension of theright elbow is associated with increased blood flow in theregion of the left primary motor cortex devoted to elbowcontrol. With the use of fMRI, it has been shown that bilat-eral motor cortices and their association areas are recruited inlearning a novel motor task. In addition, the greater theamount of force generated, the larger the area of bilateralactivation. [4] As performance of the motor task is perfectedthrough repetition, the recruitment area becomes smallerand includes only contralateral primary motor cortex.

Functional MRI has also revealed that the same patternof recruitment occurs initially in some patients who havesustained a stroke. As with learning a novel task, a patientwith a subcortical stroke relearning how to grasp an objectwith the paretic hand initially activates bilateral motor cor-tices, posterior parietal regions, and prefrontal regions. Asthe ability to perform the task is refined, ipsilateral motorcortex activity decreases and contralateral activity increases[5••]. There is evidence that this neural plasticity can beenhanced through various techniques used in the neurore-habilitation setting.

Modulation of Neural PlasticityConstraint-induced (CI) therapy for motor recovery isbased on research in monkeys and demonstrates that deaf-ferentation of a limb results in either no movement or veryclumsy nonproductive movements. Through negative rein-forcement, the monkeys learn not to use the affected limb.They develop compensatory strategies using their intactlimb to achieve their goals. Forcing the animals to use theirdeafferented limb by restraining the intact upper extremityimproves motor performance in the affected limb. CI ther-apy was first studied in stroke survivors in 1981 [6]. Withinthe past several years, fMRI and transcranial magnetic stim-ulation (TMS) have enabled research neuroscientists tovisualize the changes that take place in the brain as a resultof CI therapy. The data support two effects of CI therapy:cortical reorganization via use-dependent plasticity, andreversal of learned nonuse of the paretic limb.

Intracortical microstimulation studies of monkeys witha surgically induced ischemic infarct in a portion of themotor strip responsible for hand function have demon-strated that cortical reorganization does occur. The areasurrounding the infarct, normally responsible for shoulderor elbow movement, can be shown to produce hand move-ment when electrically stimulated following a period ofintensive training focused on recovery of hand function[7]. The hand function represented in the area of infarctthat was lost is learned by an adjacent but spared region ofcortex. The training paradigm requires progressive model-ing of finger movements. Monkeys are first trained to

retrieve food pellets with gross four-finger grasp, then withsuccessively more precise finger movements.

Several studies have shown efficacy of CI rehabilitationtechniques of the upper extremity (UE) in selected patientsfollowing stroke. Patients must have some residual volun-tary wrist and hand movement (20 degrees of wrist exten-sion and 10 degrees of finger extension). CI therapyimprovements have led to functional and lasting gains asmeasured by improved performance of self-care activities[8•,9–11].

Brain imaging and TMS studies in stroke victims haveshown that CI therapy causes use-dependent cortical reor-ganization. This is evidenced by an increase in the area ofcortex involved in the control of movement of the affectedUE [12]. In a study by Levy et al. [13], two subjects whohad already undergone traditional therapy had a baselinefMRI performed that revealed minimal ipsilateral posteriorparietal activation. After 2 weeks of CI therapy for 6 hoursper day, follow-up fMRI in one subject demonstrated acti-vation bordering the lesion, bilateral activation in associa-tion motor cortices, and ipsilateral activation in theprimary motor cortex. In the second subject, activation wasdemonstrated adjacent to the lesion site. Additionally,these increases in areas of activation correlated withincreased strength and performance time [13]. TMS hasalso been used to map the region of the primary motor cor-tex involved in controlling the affected arm movements inhemiparetic patients. As the magnetic coil is applied tospecific regions of the motor strip, muscle activity isdetected in the affected hand via electromyelogram (EMG).After a trial of CI therapy, an enlargement of the corticalregion producing hand movements is noted, implying thatcortical reorganization has occurred [14].

Robot-assisted NeurorehabilitationAt the dawn of the 21st century, we have achieved a num-ber of technologic advances that have been applied tostroke rehabilitation. Our multimedia environment pro-vides us with new techniques to increase patient motiva-tion and participation in their therapy programs.Technology may also be used to reduce the cost of in-patient rehabilitation by more efficient use of therapisttime and skills. Robot-aided sensorimotor training, a varia-tion of CI rehabilitation, can deliver a quantifiable amountof patient therapy and can simultaneously measure patientperformance objectively. One therapist can oversee thetraining of several patients [15].

Several clinical trials have been completed with MIT-Manus, a device designed by the Bioengineering depart-ment of the Massachusetts Institute of Technology (MIT)for robotic manipulation of a hemiparetic-hemiplegic UEfollowing stroke (Fig. 1). In a recent trial, 50 patientsunderwent a training period of 5 days per week for 4 weeks,with each session lasting 45 minutes and requiring perfor-mance of 1024 flexion and extension movements in a hori-

New Developments in Stroke Rehabilitation • Rocksmith and Reding 279

zontal plane. Forty control patients spent only 1 to 2 hoursper week with the robot using their intact limb to move theaffected limb. In addition, all patients concurrently under-went a traditional multidisciplinary rehabilitation pro-gram. The results of this trial suggested that roboticmanipulation of the paretic arm enhanced motor recoveryin the proximal UE and that this improved outcome wassustained after 3 years. [16•,17] We are currently usingfMRI to study the cortical activation effects of robot-trainedversus traditional rehabilitation-trained stroke patients.

Physiologic Gait TrainingPartial body weight-supported treadmill training (PBW-STT) is a promising new technique for post-stroke gaittraining. It is based on the observation that the mamma-lian lumbosacral spinal cord contains a gait pattern genera-tor that can function independently of cortical activation.Cats and dogs with spinal cord transections placed on amoving treadmill and given lateral support to control bal-ance show rhythmical stepping movements of their hindlimbs that vary in stride length and cadence with the speedof the treadmill. This indicates that the spinal cord con-tains the neural circuitry for self-regulation of alternatingleg flexion-extension sufficient to produce an effective gait.Lesioning of the dorsal root proprioceptive input to thecord from the hind limb abolishes the responsiveness ofthe gait to treadmill speed, but does not eliminate rhyth-mic stepping movements once they are initiated by eitherelectrical or chemical stimulation of the spinal cord.

Human PBWSTT is an attempt to activate the spinalcord gait pattern generator in as physiologic a manner aspossible. Patients are supported by a modified parachuteharness from an overhead hoist system that gives them a

sense of comfort and safety (Fig. 2). While safely supportedover a slowly moving treadmill, the patient's therapist canassist with paretic leg and foot placement. The goal is forthe patient to provide at least 70% of his or her own bodyweight. PBWSTT allows the patient to practice as normal agait as possible. The alternative is either not to begin walk-ing or to use bracing and a quadruped cane plus physicalsupport by the therapist to walk the patient. Use of a braceand cane have been criticized as possibly inducing abnor-mal gait patterns that are later difficult or impossible forthe patient to correct [18].

Human PBWSTT can be considered a form of CI treat-ment for gait dysfunction following stroke. It is probablymost useful for low-level patients who are difficult to mobi-lize by other means. This opinion is supported by a recentstudy that compared PBWSTT with aggressive mobilizationwith bracing and use of rigid hemi-bar. The only significantbenefit of PBWSTT was in the subgroup of acute stroke reha-bilitation patients who had suffered a major hemisphericstroke (those with hemiparesis, hemianopic visual field def-icit, and hemihypesthesia). These patients were difficult tomobilize when randomized to aggressive bracing and use ofrigid hemi-bar [19••]. PBWSTT probably allowed these low-level patients the opportunity to practice gait earlier thanwas possible by less supportive treatment techniques. PBW-STT requires less oxygen consumption per meter thanunsupported gait training, thus allowing patients with car-diovascular problems to better tolerate therapy [20]. It isalso less strenuous for the therapist.

Human PBWSTT often requires one therapist to controlthe patient's pelvis and weight shifting while another ther-apist controls movement of the paretic leg. Newer, moremechanized PBWSTT systems provide mechanical footsupport on a footplate, and lateral pelvic movement andvertical control of center of gravity by cam and pulleycabling systems mechanically linked to movement of thefootplates within the gait cycle. Even with the most currentPBWSTT systems, one therapist is still required to monitorthe patient's leg motion and safety while training [21,22].

Visual Neglect and Homonymous HemianopsiaPatients with a stroke involving the optic radiations in thetemporal-parietal region or the occipital cortex often havehomonymous hemianopsia or unilateral visual neglect.These deficits can interfere with performance of activitiesof daily living (ADL), and thus may contribute to poorfunctional recovery.

The use of Fresnel prisms to shift the affected visualfield towards the intact side has resulted in improvementof patients' awareness of body-midline and visual percep-tion test scores [23,24]. Fresnel prisms have, however, notbeen shown to significantly improve ADL function [25].Fresnel prisms are usually applied only over the affectedhemi-field, with the base of the prisms towards the affected

Figure 1. MIT-Manus upper extremity robotic device. Note the patient's forearm, wrist, and hand supported by and attached to the manipulandum. The patient uses the manipulandum to guide a cursor on the video screen to the highlighted target. If the patient is unable to move the manipulandum, the robot will carry the limb through the desired movements.

280 Cardiovascular Disease and Stroke

hemi-field and the apex towards the intact hemi-field, buttrimmed back 2 mm from the pupil so as not to interferewith function within the intact hemi-field. Used in thismanner, they can be viewed as a means of optimizing func-tion within the impaired visual field. Their use is rationalin patients with either visual neglect or hemianopsia.

Monocular patching involves placing a patch over theeye on the side opposite the visual neglect. A variation ofthis technique requires only placing a hemi-field patchover the intact visual hemi-field opposite the side of visualneglect. Patches are usually placed on the patient's pre-scription glasses. Patching reduces visual neglect in dailyactivities, presumably by interfering with the tendency tosaccade towards the side of the intact visual hemi-field[26]. From this perspective, monocular patching representsa form of CI therapy, forcing a patient to explore their envi-ronment using their hemi-neglected visual field. There is atheoretical contraindication to use of monocular or hemi-field patching in patients with hemianopsia. This treat-ment deprives the hemianopic patient of the use of theirintact visual hemi-field. There are no published studies

comparing the relative efficacy of prisms versus patchingfor treatment of visual neglect following stroke.

Pharmacologic Enhancement of RecoveryRecent experiments have demonstrated that long-termpotentiation (LTP) resulting in use-dependent corticalplasticity in humans may occur via N-methyl-D-aspartate(NMDA) receptor-mediated activation. Gamma-amino-butyric acid (GABA)-A receptor-mediated activation caninhibit this use-dependent plasticity. These findings implythat pharmacologic manipulation in the rehabilitation set-ting may enhance cortical plasticity and recovery of func-tion in stroke patients undergoing therapy [27••].

In animal models of stroke, the use of dextro (d)-amphetamine has been shown to facilitate functionalrecovery. The mechanism is hypothesized to be via anincrease in the release of norepinephrine, perhaps resultingin a facilatory effect on use-dependent plasticity.

Transcranial magnetic stimulation studies in healthyvolunteers undergoing a training period of voluntary butnovel thumb movements appear to support this hypothesis[28]. A human study dating back to 1995 suggested theadministration of d-amphetamine in conjunction withphysical therapy was efficacious in improving motor recov-ery; however, the number of patients in the study was verysmall [29]. A follow-up to this study showed there were noadverse reactions to the administration of 10 mg of d-amphetamine to patients in a typical stroke population.The medication was administered 30 minutes prior to rele-vant therapies for a total of 10 sessions [30]. In a larger,double-blind, placebo-controlled study, these findingswere challenged. Using the same dosage of d-amphet-amine, also over a course of 10 sessions, the treatmentgroup did not show any increase in motor function ascompared with the control group [31]. Levodopa, adopamine and norepinephrine precursor, was also shownto enhance motor recovery when given in combinationwith daily physical therapy [32]. Again, the release of nor-epinephrine is believed to enhance functional recovery.Further research is needed to investigate the clinical effi-cacy of these adjunctive treatments in humans.

Several double-blinded, placebo-controlled studiesusing piracetam in conjunction with speech therapy sug-gest a positive effect on the recovery of aphasia [33•]. Onestudy used PET imaging to identify areas of significantlyincreased task-related flow activation in the eloquent areasof the dominant hemispheres. It is hypothesized that pirac-etam may enhance neurotransmitter release and may stabi-lize neuronal cell membranes in the ischemic penumbra[34]. Bromocriptine, a dopamine agonist, has yieldedmixed results as a treatment for aphasia [35,36]. Morerecently, there have been several studies that suggest a rolefor bromocriptine in the treatment of nonfluent aphasia[37–39]. A recent study looked at the efficacy of amphet-amine in the treatment of aphasia. The results suggested a

Figure 2. Partial body weight-supported treadmill gait trainer. The patient is supported by a modified parachute harness from an over-head hoist system. One therapist assists with paretic leg and foot placement. A therapist aide is often required to assist with control of the pelvis and with weight shifting during the gait cycle.

New Developments in Stroke Rehabilitation • Rocksmith and Reding 281

benefit when paired with aggressive speech and behavioraltherapy [40•].

As there is increasing evidence that monoamine medi-cations may enhance stroke recovery, there is growingawareness that other medications may inhibit recovery.These include many drugs commonly prescribed in theacute rehabilitation setting. Among these are clonidine,prazosin, benzodiazepines, neuroleptics and other dopam-ine receptor antagonists, phenytoin, and phenobarbital.Patients receiving any of these medications have poorermotor recovery compared with patients who do not [41••]This effect is seen even when one corrects for covariablessuch as severity of stroke and stroke-related comorbidities.

DepressionPost-stroke depression (PSD) occurs in 30% to 40% ofpatients following stroke. In the setting of recent stroke, thesigns and symptoms of depression are difficult to recog-nize because they are easily ascribed to stroke-related sideeffects. There is not yet a consensus about whether PSD ismore frequent in patients with left versus right hemispherelesions [42]. PSD may adversely affect functional outcome.There is a general consensus that PSD should be aggres-sively treated with antidepressants. In addition to improv-ing quality of life, treatment of PSD may also improvefunctional recovery and long-term survival. Patients exhib-iting signs of irritability, restlessness, and anxiety are bestserved by the use of an antidepressant such as trazodone orvenlafaxine. Venlafaxine is both an antidepressant and ananxiolytic. Patients exhibiting psychomotor retardation,fatigue, and apathy may benefit from an activating antide-pressant such as paroxetine or sertraline [43]. Both areselective serotonin reuptake inhibitors that have good side-effect profiles and have been recently shown to result infavorable clinical outcomes [44].

Medical Complications of DysphagiaApproximately 42% of patients with stroke will havesymptomatic dysphagia as determined by bedside swal-lowing evaluation, the 3-ounce water swallow test, orstructured observation [45]. Of those referred for videoflu-oroscopic modified barium swallow (VMBS), approxi-mately 40% will show evidence of aspiration of bariumbelow the level of the vocal folds. Aspiration is known tosignal an increased risk of developing pneumonia andother dysphagia-related complications such as dehydra-tion, calorie-nitrogen loss, and death. There is increasingawareness, however, that although many patients showevidence of aspiration, only a few will develop pneumo-nia. The absence of a laryngeal cough response is a moreimportant determinant of whether patients who aspiratewill develop pneumonia.

Two techniques have recently been developed to assesslaryngeal sensitivity: fiber-optic endoscopic swallowing

study with sensory testing (FEESST) and the nebulized tar-taric acid laryngeal cough reflex test. FEESST allows visual-ization of the pharynx and larynx. A jet of air of knownpressure and duration can be delivered through the endo-scope and used to stimulate the aryepiglotic folds. A nor-mal response to this mechanical stimulation is reflexadduction of the arytenoids with closure of the laryngealinlet. Patients with absence of an arytenoid adductionresponse to stimulation of the aryepiglotic fold on eitherside of the larynx are at greatest risk of developing pneu-monia [46]. Three inhalations of a 20% solution of nebu-lized tartaric acid normally induce a cough. Absence ofcough indicates compromise of the laryngeal cough reflex,and significantly increased risk of developing pneumonia.[47•]. The tartaric acid laryngeal cough reflex test may pro-vide a reliable screen for swallowing safety, especially dur-ing the first several days following stroke, before morediagnostic FEESST or VMBS studies can be performed. Itsapproval by the Food and Drug Administration as a diag-nostic test for airway protection following stroke isexpected by late 2002.

There is increasing awareness that dysphagia is associ-ated with medical complications other than pneumonia. Itis a major cause of dehydration, malnutrition, and upperairway obstruction. These factors may result in a weakenedimmune system, compromising the patient's ability tofight infection. Routine assessment of serum transferrinand prealbumin can serve as markers for negative nitrogenbalance. Weight loss and urinary ketones (without glyco-suria) signal inadequate calorie intake. Elevation of theblood urea nitrogen to creatinine ratio above 20 is com-monly used to indicate dehydration, but this may be anunreliable marker for dehydration in dysphagic patientswith very low protein intake. Serum sodium above 145mmol/L may serve as a better indicator of dehydration insuch patients.

Venous Thromboembolic ComplicationsThe incidence of deep venous thrombosis (DVT) is approx-imately 50% within the first 2 weeks post-stroke. Approxi-mately two thirds of cases are below the knee, and most areasymptomatic. In the acute rehabilitation setting, the riskfalls to approximately 33% as evidenced by bilateralvenography. The main concern with proximal DVT is itspotential to cause fatal pulmonary embolization (PE). Inaddition, with either proximal or distal DVT, one candevelop a post-phlebitic syndrome, characterized bychronic pain, swelling, and venous ulceration [48].

Development of the D-dimer assay has proven to be auseful screening tool for DVT in the stroke rehabilitationsetting. This can be readily obtained usually within anhour from most laboratories. There are a number of clini-cal conditions that may give falsely elevated values: stroke,myocardial infarction, atrial fibrillation, congestive heartfailure, and pneumonia [49••]. A normal D-dimer blood

282 Cardiovascular Disease and Stroke

concentration, however, effectively excludes active throm-bosis as the cause of edema in a plegic leg. Elevated D-dimer values require more definitive evaluation.

Use of impedance plethysmography is becoming anincreasingly popular bedside technique for DVT screening.The cost of the equipment is modest and the technique iseasily mastered by a trained nurse technician. It is easy toimplement in most rehabilitation clinic and inpatient set-tings. Compression ultrasonography requires more expen-sive instrumentation and a full-time technician to perform,but is more sensitive and specific for DVT diagnosis thanplethysmography. Compression ultrasonography is usuallyonly available in an acute-care hospital setting.

Currently, the standard of care for DVT prophylaxis isanticoagulation with either "minidose" heparin (5000 Usubcutaneously every 12 hours) or low-molecular weightheparin (30 mg subcutaneously every 12 hours). Low-molecular weight heparin is more effective and safer thanuse of unfractionated heparin, but is considerably moreexpensive. Thigh-length thromboembolic disease (TED)stockings are beneficial, but not well tolerated by inconti-nent stroke patients. Knee length TED hose are a reasonablecompromise. Pneumatic compression devices (eg, Kendallfoot-pumps [Kendall, Mansfield, MA] or Venodyne boots[Microtek Medical, Columbus, MS]) placed on both lowerextremities are useful for patients with hemorrhagic stroke,subarachnoid hemorrhage, or other contraindications toanticoagulation. Once the patient can walk a distance of 150feet, anticoagulants can be discontinued, as the risk of DVTdrops by 45% with this level of ambulation.

Urinary Incontinence, Retention, and InfectionApproximately 75% of patients suffering from stroke in theanterior circulation with resultant hemiplegia, hemihypes-thesia, and hemianopsia will be incontinent during thefirst month following stroke. Institutionalization rates andmortality are significantly higher in this subset of patients[50]. In addition, an age of 75 years or greater is indepen-dently associated with post-stroke incontinence and poorsubsequent recovery [51]. Only 5% of patients with puremotor hemiparesis due to lacunar infarction are expectedto be incontinent. Factors not associated with post-strokeurinary incontinence are sex, diabetes, hypertension, atrialfibrillation, and aphasia [52].

Intermittent, rather than indwelling, catheterizationrepresents a major advance in management of urinaryretention following stroke. Inexpensive bedside computer-ized ultrasound bladder scanners can be used by the nurs-ing staff to monitor bladder volume every 6 hours. Whenbladder volumes reach 350 mL or higher, a nonretainabledisposable catheter is inserted and the bladder drained.This greatly reduces the risk of recurrent urinary tract infec-tion or colonization seen with traditional indwelling cath-eters. Tolterodine, a new anticholinergic agent that is even

less able to cross the blood-brain barrier than oxybutynin,was recently approved for treatment of post-stroke urgeincontinence. The tolterodine-dosing schedule of 2 mgorally every 12 hours is also more convenient than use of 5mg of oxybutynin orally every 8 hours. Patients takingtolterodine are less likely to complain of peripheral anti-cholinergic side effects such as constipation and dry mouth[53]. When using an anticholinergic agent it is prudent tosubsequently check an occasional post-void residual urinevolume to exclude the development of pharmacologicallyinduced urinary retention.

Urinary retention due to detrussor sphincter dyssyn-ergy is rare with supratentorial stroke, but is occasionallyseen with brainstem stroke affecting the pontomesen-cephalic micturition center. Diagnosis is made bycystometrogram-electromyography evidence of synchro-nous contraction of both the detrussor and internalsphincter muscles. Treatment consists of an α-adrenergicblocking agent such as 0.4 mg of oral tamsulosin daily.Potential side effects include postural hypotension andreflex tachycardia.

SpasticityPost-stroke spasticity (PSS) can result in painful spasms,flexion contractures, decreased range of motion (ROM),and impaired ability to perform ADLs. It can also be ben-eficial, allowing patients to use their spasticity to standand walk on their paretic leg. Therefore, treatment shouldbe instituted only when spasticity interferes with thepatient's mobility or self-care. There are a limited numberof therapeutic modalities available to clinicians in thetreatment of PSS. Tizanidine is a recently approved α-2adrenergic agonist that reduces spasticity by increasingpolysynaptic inhibition of spinal cord motor neurons. Itsmajor advantage over baclofen, an older antispasticityagent, is that it is less likely to weaken spastic muscles.Tizanidine's major side effects are drowsiness and dizzi-ness [54,55]. Baclofen is a centrally acting GABA agonistthat also causes presynaptic inhibition of spinal motorneurons. When administered orally at dosages requiredto reduce spasticity, baclofen's side effects are confusion,drowsiness, and memory and attention problems. Sud-den withdrawal can lead to hallucinations and seizures.

Intrathecal baclofen administration via a chronicallyimplanted baclofen pump eliminates most of baclofen'scentral side effects. It is especially useful for lower extrem-ity spasticity because it is administered through an indwell-ing catheter in the lumbar spine. This allows for higherconcentrations in the lumbosacral region with lower cere-brospinal fluid levels in the cervical region and even lowerconcentrations at the level of the brainstem [56]. Patientswho rely on increased tone in the affected lower extremityfor performance of ADLs can have their infusion ratestitrated using the subcutaneous programmable infusionpump to maximize control of spasticity without adverse

New Developments in Stroke Rehabilitation • Rocksmith and Reding 283

effects on muscle strength. Because of its invasive nature,potential side effects, and required maintenance schedule,only carefully selected hemiplegic stroke patients areappropriate for intrathecal baclofen pump placement.

Botulinum toxin has recently been approved for thetreatment of focal spastic dystonia. Because of its expense(approximately $400 for 100 units), it has been used mostlyfor treatment of developing elbow, wrist, and finger contrac-tures in small upper extremity muscles. The cost of sufficientbotulinum toxin to produce a clinically significant effect inlarger lower extremity muscles, such as the gastrocnemius,soleus, or the tibialis posterior, has discouraged its use intreatment of developing dystonic equinovarus foot andankle deformities. Botulinum toxin injected into the spastic-dystonic muscle diffuses over a distance of several centime-ters. It is transported across the presynaptic nerve membraneand inhibits the docking of acetylcholine-containing synap-tic vesicles at the presynaptic motor endplate [57]. Its peakeffect is seen at 4 weeks and resolves by 8 to 12 weeks. Beforeinjecting a muscle, one must determine whether the risk ofincreasing the patient's weakness outweighs the benefit ofreducing spastic tone. Injecting a muscle with residualmovement may interfere with functional use of the limb.Repeated injections may lead to antibody production thatmay block its therapeutic effects. Should antibody-mediatedresistance develop, an alternate serotype of botulinum toxincan be administered.

ConclusionsThis article has examined new and exciting developments instroke rehabilitation. fMRI and TMS have allowed us to bet-ter understand the complex neuroanatomic relationshipsinvolved in recovery from brain injury due to stroke. Thesetools have also demonstrated the role for pharmacologicenhancement of cortical plasticity coupled with behavioralinterventions. The role for technologic intervention in strokerehabilitation has been bolstered by robot-assisted therapyand PBWSTT. Current research using hemi-field ocularprisms and patching techniques suggest a role in improve-ment of function in patients with hemianopsia and visualneglect. Finally, many advances have been made in the pre-vention, recognition, and treatment of common stroke com-plications: depression, dysphagia, venous thromboembolicdisease, incontinence, and spasticity.

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