New Developments in Rehabilitation Eugenio R. Rocksmith, MD, and Michael J. Reding, MD

Address ment of common stroke complications, such as , Burke Rehabilitation Hospital, 785 Mamaroneck Avenue, dysphagia, venous thromboembolic complications, incon- White Plains, NY 10605-2523, USA. tinence, and . This article examines these develop- E-mail: [email protected] ments and their effects on rehabilitation following stroke. Current Atherosclerosis Reports 2002, 4:277–284 Current Science Inc. ISSN 1523–3804 Copyright © 2002 by Current Science Inc. Advances in Stroke Epidemiology The American Heart Association has recently increased its There is increasing evidence that environmental and neuro- estimate of the number of new in the United pharmacologic treatments enhance stroke recovery. Func- States population from 500,000 to 600,000 per year (105 tional magnetic resonance imaging and transcranial magnetic to 139 cases per 100,000 population). Their estimate of stimulation have significantly broadened our understanding of the number of stroke survivors in the United States has the neuroanatomic relationships involved in recovery from also been increased from 3 million to 4 million. [1] These brain injury due to stroke. These tools have also demon- changes are due to the fact that previous estimates were strated the role for pharmacologic enhancement of cortical based on populations from white, middle class Rochester, plasticity coupled with behavioral interventions. Robot- Minnesota and Framingham, Massachusetts. The poor are assisted therapy and partial body weight-supported treadmill less likely to seek medical attention, and blacks are 2.4 gait training have demonstrated the role for technologic times more likely to have a stroke than whites [2]. Stroke intervention in the modern neuro-rehabilitation setting. Cur- remains the most common debilitating neurologic disor- rent research using hemi-field ocular prisms and patching der of adults in the United States. It is the third leading techniques suggest a role in the rehabilitation of hemianopsia cause of mortality and is one of the leading causes of and visual neglect. Finally, many advances have been made in long-term, severe disability. The cost of acute care plus the understanding of common stroke complications, such as rehabilitation services is estimated to total $30 billion per depression, dysphagia, venous thromboembolic disease, year. Of all patients surviving 3 months after their stroke, incontinence, and spasticity. approximately half will be alive in 5 years, and a third will survive 10 years. Approximately 60% recover inde- pendence with self-care, and 75% recover the ability to Introduction walk independently. Approximately 19% will require There is increasing evidence that environmental and neu- chronic institutional care. [3] ropharmacologic treatments enhance stroke recovery. Func- tional magnetic resonance imaging (fMRI) has allowed us to study the role of ipsilateral and contralateral primary, Advances in Neuroimaging secondary, and tertiary motor control systems in the motor Within the past decade, the neuroscience community has recovery process. Magnetic coil stimulation has been used made tremendous strides in understanding the complex- to study primary and secondary motor cortex responsive- ities of the human brain. Positron emission tomography ness to stimulation before versus after passive manipula- (PET) imaging became available in the late 1980s. It tion of the paretic limb, or to drug versus placebo requires administration of a radioactive tracer, which is intervention. Behavioral interventions, such as forced use of used to measure regional cerebral glucose metabolism the paretic limb by constraining the normal hand and par- both at rest and while performing cognitive or behav- tial body weight-supported treadmill gait training of the ioral tasks. Comparisons of rest with activation images hemiplegic patient, have a solid experimental base and are provide information about the role of specific neuroana- becoming standard rehabilitation techniques for selected tomic structures in performance of the cognitive or patients. Use of hemi-field ocular prisms or patching tech- behavioral tasks. Its application in behavioral research is niques is being studied for their effects on treating visual limited by the short half-life of the radioactive tracers hemi-neglect following stroke. Important advances have used and by the total dosage of radiation that can be also been made in the prevention, recognition, and treat- safely administered. 278 Cardiovascular Disease and Stroke

Functional MRI is a significant advance in neurobehav- retrieve food pellets with gross four-finger grasp, then with ioral research that became available in the mid 1990s. It does successively more precise finger movements. not require radiation exposure. fMRI is based upon the con- Several studies have shown efficacy of CI rehabilitation cept that increased neuronal activity is coupled to increased techniques of the upper extremity (UE) in selected patients local blood flow. For example, flexion and extension of the following stroke. Patients must have some residual volun- right elbow is associated with increased blood flow in the tary wrist and hand movement (20 degrees of wrist exten- region of the left primary motor cortex devoted to elbow sion and 10 degrees of finger extension). CI therapy control. With the use of fMRI, it has been shown that bilat- improvements have led to functional and lasting gains as eral motor cortices and their association areas are recruited in measured by improved performance of self-care activities learning a novel motor task. In addition, the greater the [8•,9–11]. amount of force generated, the larger the area of bilateral Brain imaging and TMS studies in stroke victims have activation. [4] As performance of the motor task is perfected shown that CI therapy causes use-dependent cortical reor- through repetition, the recruitment area becomes smaller ganization. This is evidenced by an increase in the area of and includes only contralateral primary motor cortex. cortex involved in the control of movement of the affected Functional MRI has also revealed that the same pattern UE [12]. In a study by Levy et al. [13], two subjects who of recruitment occurs initially in some patients who have had already undergone traditional therapy had a baseline sustained a stroke. As with learning a novel task, a patient fMRI performed that revealed minimal ipsilateral posterior with a subcortical stroke relearning how to grasp an object parietal activation. After 2 weeks of CI therapy for 6 hours with the paretic hand initially activates bilateral motor cor- per day, follow-up fMRI in one subject demonstrated acti- tices, posterior parietal regions, and prefrontal regions. As vation bordering the lesion, bilateral activation in associa- the ability to perform the task is refined, ipsilateral motor tion motor cortices, and ipsilateral activation in the cortex activity decreases and contralateral activity increases primary motor cortex. In the second subject, activation was [5••]. There is evidence that this neural plasticity can be demonstrated adjacent to the lesion site. Additionally, enhanced through various techniques used in the neurore- these increases in areas of activation correlated with habilitation setting. increased strength and performance time [13]. TMS has also been used to map the region of the primary motor cor- tex involved in controlling the affected arm movements in Modulation of Neural Plasticity hemiparetic patients. As the magnetic coil is applied to Constraint-induced (CI) therapy for motor recovery is specific regions of the motor strip, muscle activity is based on research in monkeys and demonstrates that deaf- detected in the affected hand via electromyelogram (EMG). ferentation of a limb results in either no movement or very After a trial of CI therapy, an enlargement of the cortical clumsy nonproductive movements. Through negative rein- region producing hand movements is noted, implying that forcement, the monkeys learn not to use the affected limb. cortical reorganization has occurred [14]. They develop compensatory strategies using their intact limb to achieve their goals. Forcing the animals to use their deafferented limb by restraining the intact upper extremity Robot-assisted Neurorehabilitation improves motor performance in the affected limb. CI ther- At the dawn of the 21st century, we have achieved a num- apy was first studied in stroke survivors in 1981 [6]. Within ber of technologic advances that have been applied to the past several years, fMRI and transcranial magnetic stim- stroke rehabilitation. Our multimedia environment pro- ulation (TMS) have enabled research neuroscientists to vides us with new techniques to increase patient motiva- visualize the changes that take place in the brain as a result tion and participation in their therapy programs. of CI therapy. The data support two effects of CI therapy: Technology may also be used to reduce the cost of in- cortical reorganization via use-dependent plasticity, and patient rehabilitation by more efficient use of therapist reversal of learned nonuse of the paretic limb. time and skills. Robot-aided sensorimotor training, a varia- Intracortical microstimulation studies of monkeys with tion of CI rehabilitation, can deliver a quantifiable amount a surgically induced ischemic infarct in a portion of the of patient therapy and can simultaneously measure patient motor strip responsible for hand function have demon- performance objectively. One therapist can oversee the strated that cortical reorganization does occur. The area training of several patients [15]. surrounding the infarct, normally responsible for shoulder Several clinical trials have been completed with MIT- or elbow movement, can be shown to produce hand move- Manus, a device designed by the Bioengineering depart- ment when electrically stimulated following a period of ment of the Massachusetts Institute of Technology (MIT) intensive training focused on recovery of hand function for robotic manipulation of a hemiparetic-hemiplegic UE [7]. The hand function represented in the area of infarct following stroke (Fig. 1). In a recent trial, 50 patients that was lost is learned by an adjacent but spared region of underwent a training period of 5 days per week for 4 weeks, cortex. The training paradigm requires progressive model- with each session lasting 45 minutes and requiring perfor- ing of finger movements. Monkeys are first trained to mance of 1024 flexion and extension movements in a hori- New Developments in Stroke Rehabilitation • Rocksmith and Reding 279

sense of comfort and safety (Fig. 2). While safely supported over a slowly moving treadmill, the patient's therapist can assist with paretic leg and foot placement. The goal is for the patient to provide at least 70% of his or her own body weight. PBWSTT allows the patient to practice as normal a gait as possible. The alternative is either not to begin walk- ing or to use bracing and a quadruped cane plus physical support by the therapist to walk the patient. Use of a brace and cane have been criticized as possibly inducing abnor- mal gait patterns that are later difficult or impossible for the patient to correct [18]. Human PBWSTT can be considered a form of CI treat- ment for gait dysfunction following stroke. It is probably most useful for low-level patients who are difficult to mobi- lize by other means. This opinion is supported by a recent study that compared PBWSTT with aggressive mobilization Figure 1. MIT-Manus upper extremity robotic device. Note the patient's forearm, wrist, and hand supported by and attached to the with bracing and use of rigid hemi-bar. The only significant manipulandum. The patient uses the manipulandum to guide a cursor benefit of PBWSTT was in the subgroup of acute stroke reha- on the video screen to the highlighted target. If the patient is unable to bilitation patients who had suffered a major hemispheric move the manipulandum, the robot will carry the limb through the stroke (those with , hemianopic visual field def- desired movements. icit, and hemihypesthesia). These patients were difficult to mobilize when randomized to aggressive bracing and use of zontal plane. Forty control patients spent only 1 to 2 hours rigid hemi-bar [19••]. PBWSTT probably allowed these low- per week with the robot using their intact limb to move the level patients the opportunity to practice gait earlier than affected limb. In addition, all patients concurrently under- was possible by less supportive treatment techniques. PBW- went a traditional multidisciplinary rehabilitation pro- STT requires less oxygen consumption per meter than gram. The results of this trial suggested that robotic unsupported gait training, thus allowing patients with car- manipulation of the paretic arm enhanced motor recovery diovascular problems to better tolerate therapy [20]. It is in the proximal UE and that this improved outcome was also less strenuous for the therapist. sustained after 3 years. [16•,17] We are currently using Human PBWSTT often requires one therapist to control fMRI to study the cortical activation effects of robot-trained the patient's pelvis and weight shifting while another ther- versus traditional rehabilitation-trained stroke patients. apist controls movement of the paretic leg. Newer, more mechanized PBWSTT systems provide mechanical foot support on a footplate, and lateral pelvic movement and Physiologic Gait Training vertical control of center of gravity by cam and pulley Partial body weight-supported treadmill training (PBW- cabling systems mechanically linked to movement of the STT) is a promising new technique for post-stroke gait footplates within the gait cycle. Even with the most current training. It is based on the observation that the mamma- PBWSTT systems, one therapist is still required to monitor lian lumbosacral spinal cord contains a gait pattern genera- the patient's leg motion and safety while training [21,22]. tor that can function independently of cortical activation. Cats and dogs with spinal cord transections placed on a moving treadmill and given lateral support to control bal- Visual Neglect and ance show rhythmical stepping movements of their hind Homonymous Hemianopsia limbs that vary in stride length and cadence with the speed Patients with a stroke involving the optic radiations in the of the treadmill. This indicates that the spinal cord con- temporal-parietal region or the occipital cortex often have tains the neural circuitry for self-regulation of alternating homonymous hemianopsia or unilateral visual neglect. leg flexion-extension sufficient to produce an effective gait. These deficits can interfere with performance of activities Lesioning of the dorsal root proprioceptive input to the of daily living (ADL), and thus may contribute to poor cord from the hind limb abolishes the responsiveness of functional recovery. the gait to treadmill speed, but does not eliminate rhyth- The use of Fresnel prisms to shift the affected visual mic stepping movements once they are initiated by either field towards the intact side has resulted in improvement electrical or chemical stimulation of the spinal cord. of patients' awareness of body-midline and visual percep- Human PBWSTT is an attempt to activate the spinal tion test scores [23,24]. Fresnel prisms have, however, not cord gait pattern generator in as physiologic a manner as been shown to significantly improve ADL function [25]. possible. Patients are supported by a modified parachute Fresnel prisms are usually applied only over the affected harness from an overhead hoist system that gives them a hemi-field, with the base of the prisms towards the affected 280 Cardiovascular Disease and Stroke

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

Pharmacologic Enhancement of Recovery Recent experiments have demonstrated that long-term potentiation (LTP) resulting in use-dependent cortical plasticity in humans may occur via N-methyl-D-aspartate (NMDA) receptor-mediated activation. Gamma-amino- butyric acid (GABA)-A receptor-mediated activation can inhibit this use-dependent plasticity. These findings imply that 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 functional recovery. The mechanism is hypothesized to be via an increase in the release of , perhaps resulting in a facilatory effect on use-dependent plasticity. Transcranial magnetic stimulation studies in healthy volunteers undergoing a training period of voluntary but novel thumb movements appear to support this hypothesis [28]. A human study dating back to 1995 suggested the administration of d-amphetamine in conjunction with was efficacious in improving motor recov- ery; however, the number of patients in the study was very small [29]. A follow-up to this study showed there were no adverse reactions to the administration of 10 mg of d- amphetamine to patients in a typical stroke population. Figure 2. Partial body weight-supported treadmill gait trainer. The The medication was administered 30 minutes prior to rele- patient is supported by a modified parachute harness from an over- vant therapies for a total of 10 sessions [30]. In a larger, head hoist system. One therapist assists with paretic leg and foot double-blind, placebo-controlled study, these findings placement. A therapist aide is often required to assist with control of the pelvis and with weight shifting during the gait cycle. were challenged. Using the same dosage of d-amphet- amine, also over a course of 10 sessions, the treatment group did not show any increase in motor function as hemi-field and the apex towards the intact hemi-field, but compared with the control group [31]. Levodopa, a trimmed back 2 mm from the pupil so as not to interfere dopamine and norepinephrine precursor, was also shown with function within the intact hemi-field. Used in this to enhance motor recovery when given in combination manner, they can be viewed as a means of optimizing func- with daily physical therapy [32]. Again, the release of nor- tion within the impaired visual field. Their use is rational epinephrine is believed to enhance functional recovery. in patients with either visual neglect or hemianopsia. Further research is needed to investigate the clinical effi- Monocular patching involves placing a patch over the cacy of these adjunctive treatments in humans. eye on the side opposite the visual neglect. A variation of Several double-blinded, placebo-controlled studies this technique requires only placing a hemi-field patch using piracetam in conjunction with speech therapy sug- over the intact visual hemi-field opposite the side of visual gest a positive effect on the recovery of aphasia [33•]. One neglect. Patches are usually placed on the patient's pre- study used PET imaging to identify areas of significantly scription glasses. Patching reduces visual neglect in daily increased task-related flow activation in the eloquent areas activities, presumably by interfering with the tendency to of the dominant hemispheres. It is hypothesized that pirac- saccade towards the side of the intact visual hemi-field etam may enhance neurotransmitter release and may stabi- [26]. From this perspective, monocular patching represents lize neuronal cell membranes in the ischemic penumbra a form of CI therapy, forcing a patient to explore their envi- [34]. Bromocriptine, a dopamine agonist, has yielded ronment using their hemi-neglected visual field. There is a mixed results as a treatment for aphasia [35,36]. More theoretical contraindication to use of monocular or hemi- recently, there have been several studies that suggest a role field patching in patients with hemianopsia. This treat- for bromocriptine in the treatment of nonfluent aphasia ment deprives the hemianopic patient of the use of their [37–39]. A recent study looked at the efficacy of amphet- intact visual hemi-field. There are no published studies amine in the treatment of aphasia. The results suggested a New Developments in Stroke Rehabilitation • Rocksmith and Reding 281 benefit when paired with aggressive speech and behavioral study with sensory testing (FEESST) and the nebulized tar- therapy [40•]. taric acid laryngeal cough reflex test. FEESST allows visual- As there is increasing evidence that monoamine medi- ization of the pharynx and larynx. A jet of air of known cations may enhance stroke recovery, there is growing pressure and duration can be delivered through the endo- awareness that other medications may inhibit recovery. scope and used to stimulate the aryepiglotic folds. A nor- These include many drugs commonly prescribed in the mal response to this mechanical stimulation is reflex acute rehabilitation setting. Among these are , adduction of the arytenoids with closure of the laryngeal prazosin, benzodiazepines, neuroleptics and other dopam- inlet. Patients with absence of an arytenoid adduction ine receptor antagonists, phenytoin, and phenobarbital. response to stimulation of the aryepiglotic fold on either Patients receiving any of these medications have poorer side of the larynx are at greatest risk of developing pneu- motor recovery compared with patients who do not [41••] monia [46]. Three inhalations of a 20% solution of nebu- This effect is seen even when one corrects for covariables lized tartaric acid normally induce a cough. Absence of such as severity of stroke and stroke-related comorbidities. cough indicates compromise of the laryngeal cough reflex, and significantly increased risk of developing pneumonia. [47•]. The tartaric acid laryngeal cough reflex test may pro- Depression vide a reliable screen for swallowing safety, especially dur- Post-stroke depression (PSD) occurs in 30% to 40% of ing the first several days following stroke, before more patients following stroke. In the setting of recent stroke, the diagnostic FEESST or VMBS studies can be performed. Its signs and symptoms of depression are difficult to recog- approval by the Food and Drug Administration as a diag- nize because they are easily ascribed to stroke-related side nostic test for airway protection following stroke is effects. There is not yet a consensus about whether PSD is expected by late 2002. more frequent in patients with left versus right hemisphere There is increasing awareness that dysphagia is associ- lesions [42]. PSD may adversely affect functional outcome. ated with medical complications other than pneumonia. It There is a general consensus that PSD should be aggres- is a major cause of dehydration, malnutrition, and upper sively treated with . In addition to improv- airway obstruction. These factors may result in a weakened ing quality of life, treatment of PSD may also improve immune system, compromising the patient's ability to functional recovery and long-term survival. Patients exhib- fight infection. Routine assessment of serum transferrin iting signs of irritability, restlessness, and anxiety are best and prealbumin can serve as markers for negative nitrogen served by the use of an such as trazodone or . Weight loss and urinary ketones (without glyco- venlafaxine. Venlafaxine is both an antidepressant and an suria) signal inadequate calorie intake. Elevation of the anxiolytic. Patients exhibiting psychomotor retardation, blood urea nitrogen to creatinine ratio above 20 is com- , and apathy may benefit from an activating antide- monly used to indicate dehydration, but this may be an pressant such as paroxetine or sertraline [43]. Both are unreliable marker for dehydration in dysphagic patients selective serotonin reuptake inhibitors that have good side- with very low protein intake. Serum sodium above 145 effect profiles and have been recently shown to result in mmol/L may serve as a better indicator of dehydration in favorable clinical outcomes [44]. such patients.

Medical Complications of Dysphagia Venous Thromboembolic Complications Approximately 42% of patients with stroke will have The incidence of deep venous thrombosis (DVT) is approx- symptomatic dysphagia as determined by bedside swal- imately 50% within the first 2 weeks post-stroke. Approxi- lowing evaluation, the 3-ounce water swallow test, or mately two thirds of cases are below the knee, and most are structured observation [45]. Of those referred for videoflu- asymptomatic. In the acute rehabilitation setting, the risk oroscopic modified barium swallow (VMBS), approxi- falls to approximately 33% as evidenced by bilateral mately 40% will show evidence of aspiration of barium venography. The main concern with proximal DVT is its below the level of the vocal folds. Aspiration is known to potential to cause fatal pulmonary embolization (PE). In signal an increased risk of developing pneumonia and addition, with either proximal or distal DVT, one can other dysphagia-related complications such as dehydra- develop a post-phlebitic syndrome, characterized by tion, calorie-nitrogen loss, and death. There is increasing chronic pain, swelling, and venous ulceration [48]. awareness, however, that although many patients show Development of the D-dimer assay has proven to be a evidence of aspiration, only a few will develop pneumo- useful screening tool for DVT in the stroke rehabilitation nia. The absence of a laryngeal cough response is a more setting. This can be readily obtained usually within an important determinant of whether patients who aspirate hour from most laboratories. There are a number of clini- will develop pneumonia. cal conditions that may give falsely elevated values: stroke, Two techniques have recently been developed to assess myocardial infarction, atrial fibrillation, congestive heart laryngeal sensitivity: fiber-optic endoscopic swallowing failure, and pneumonia [49••]. A normal D-dimer blood 282 Cardiovascular Disease and Stroke concentration, however, effectively excludes active throm- less able to cross the blood-brain barrier than oxybutynin, bosis as the cause of edema in a plegic leg. Elevated D- was recently approved for treatment of post-stroke urge dimer values require more definitive evaluation. incontinence. The tolterodine-dosing schedule of 2 mg Use of impedance plethysmography is becoming an orally every 12 hours is also more convenient than use of 5 increasingly popular bedside technique for DVT screening. mg of oxybutynin orally every 8 hours. Patients taking The cost of the equipment is modest and the technique is tolterodine are less likely to complain of peripheral anti- easily mastered by a trained nurse technician. It is easy to cholinergic side effects such as constipation and dry mouth implement in most rehabilitation clinic and inpatient set- [53]. When using an anticholinergic agent it is prudent to tings. Compression ultrasonography requires more expen- subsequently check an occasional post-void residual urine sive instrumentation and a full-time technician to perform, volume to exclude the development of pharmacologically but is more sensitive and specific for DVT diagnosis than induced urinary retention. plethysmography. Compression ultrasonography is usually Urinary retention due to detrussor sphincter dyssyn- only available in an acute-care hospital setting. ergy is rare with supratentorial stroke, but is occasionally Currently, the standard of care for DVT prophylaxis is seen with brainstem stroke affecting the pontomesen- anticoagulation with either "minidose" heparin (5000 U cephalic micturition center. Diagnosis is made by subcutaneously every 12 hours) or low-molecular weight cystometrogram-electromyography evidence of synchro- heparin (30 mg subcutaneously every 12 hours). Low- nous contraction of both the detrussor and internal molecular weight heparin is more effective and safer than sphincter muscles. Treatment consists of an α-adrenergic use of unfractionated heparin, but is considerably more blocking agent such as 0.4 mg of oral tamsulosin daily. expensive. Thigh-length thromboembolic disease (TED) Potential side effects include postural hypotension and stockings are beneficial, but not well tolerated by inconti- reflex tachycardia. nent stroke patients. Knee length TED hose are a reasonable compromise. Pneumatic compression devices (eg, Kendall foot-pumps [Kendall, Mansfield, MA] or Venodyne boots Spasticity [Microtek Medical, Columbus, MS]) placed on both lower Post-stroke spasticity (PSS) can result in painful spasms, extremities are useful for patients with hemorrhagic stroke, flexion , decreased range of motion (ROM), subarachnoid hemorrhage, or other contraindications to and impaired ability to perform ADLs. It can also be ben- anticoagulation. Once the patient can walk a distance of 150 eficial, allowing patients to use their spasticity to stand feet, anticoagulants can be discontinued, as the risk of DVT and walk on their paretic leg. Therefore, treatment should drops by 45% with this level of ambulation. be instituted only when spasticity interferes with the patient's mobility or self-care. There are a limited number of therapeutic modalities available to clinicians in the Urinary Incontinence, Retention, treatment of PSS. is a recently approved α-2 and Infection adrenergic agonist that reduces spasticity by increasing Approximately 75% of patients suffering from stroke in the polysynaptic inhibition of spinal cord motor neurons. Its anterior circulation with resultant hemiplegia, hemihypes- major advantage over , an older antispasticity thesia, and hemianopsia will be incontinent during the agent, is that it is less likely to weaken spastic muscles. first month following stroke. Institutionalization rates and Tizanidine's major side effects are drowsiness and dizzi- mortality are significantly higher in this subset of patients ness [54,55]. Baclofen is a centrally acting GABA agonist [50]. In addition, an age of 75 years or greater is indepen- that also causes presynaptic inhibition of spinal motor dently associated with post-stroke incontinence and poor neurons. When administered orally at dosages required subsequent recovery [51]. Only 5% of patients with pure to reduce spasticity, baclofen's side effects are confusion, motor hemiparesis due to lacunar infarction are expected drowsiness, and memory and attention problems. Sud- to be incontinent. Factors not associated with post-stroke den withdrawal can lead to hallucinations and seizures. urinary incontinence are sex, diabetes, hypertension, atrial Intrathecal baclofen administration via a chronically fibrillation, and aphasia [52]. implanted baclofen pump eliminates most of baclofen's Intermittent, rather than indwelling, catheterization central side effects. It is especially useful for lower extrem- represents a major advance in management of urinary ity spasticity because it is administered through an indwell- retention following stroke. Inexpensive bedside computer- ing catheter in the lumbar spine. This allows for higher ized ultrasound bladder scanners can be used by the nurs- concentrations in the lumbosacral region with lower cere- ing staff to monitor bladder volume every 6 hours. When brospinal fluid levels in the cervical region and even lower bladder volumes reach 350 mL or higher, a nonretainable concentrations at the level of the brainstem [56]. Patients disposable catheter is inserted and the bladder drained. who rely on increased tone in the affected lower extremity This greatly reduces the risk of recurrent urinary tract infec- for performance of ADLs can have their infusion rates tion or colonization seen with traditional indwelling cath- titrated using the subcutaneous programmable infusion eters. Tolterodine, a new anticholinergic agent that is even pump 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, 2. Sacco RL, Boden-Albala B, Gan R, et al.: Stroke incidence potential side effects, and required maintenance schedule, among white, black, and Hispanic residents of an urban community: the Northern Manhattan Stroke Study. Am J Epi- only carefully selected hemiplegic stroke patients are demiol 1998, 147:259–268. appropriate for intrathecal baclofen pump placement. 3. Ancheta JI, Reding MJ: Stroke diagnosis and treatment: a mul- has recently been approved for the tidisciplinary effort. In Principles of Geriatric Medicine and Ger- ontology. Edited by Hazzard WR, Blass JP. New York: McGraw- treatment of focal spastic dystonia. Because of its expense Hill; 1999:1239–1256. (approximately $400 for 100 units), it has been used mostly 4. Cramer SC, Nelles G, Schaechter JD: A functional MRI study of for treatment of developing elbow, wrist, and finger contrac- three motor tasks in the evaluation of stroke recovery. Neu- tures in small upper extremity muscles. The cost of sufficient rorehabil Neural Repair 2001, 15:1–8. 5.•• Marshall RS, Perera GM, Lazar RM: Evolution of cortical acti- botulinum toxin to produce a clinically significant effect in vation during recovery from corticospinal tract infarction. larger lower extremity muscles, such as the gastrocnemius, Stroke 2000, 31:656–661. soleus, or the tibialis posterior, has discouraged its use in An in-depth description of the cortical activation patterns in patients with lacunar stroke as evidenced by functional magnetic treatment of developing dystonic equinovarus foot and resonance imaging. ankle deformities. Botulinum toxin injected into the spastic- 6. Ostendorf CG, Wolf SL: Effect of forced use of the upper dystonic muscle diffuses over a distance of several centime- extremity of a hemiplegic patient on changes in function. A ters. It is transported across the presynaptic nerve membrane single case design. Phys Ther 1981, 61:1022–1028. 7. Nudo RJ, Wise BM, Sifuentes F: Neural substrates for the and inhibits the docking of -containing synap- effects of rehabilitative training on motor recovery after tic vesicles at the presynaptic motor endplate [57]. Its peak ischemic infarct. Science 1996, 272:1791–1794. effect is seen at 4 weeks and resolves by 8 to 12 weeks. Before 8.• Taub E, Morris DM: Constraint-induced movement therapy for motor recovery in chronic stroke patients. Arch Phys Med injecting a muscle, one must determine whether the risk of Rehabil 1999, 80:624–628. increasing the patient's weakness outweighs the benefit of An overwiew of constraint-induced therapy including basic animal reducing spastic tone. Injecting a muscle with residual research, human studies, neuroimaging, and transcranial magnetic stimulation evidence of cortical reorganization and impacts movement may interfere with functional use of the limb. on rehabilitation. Repeated injections may lead to antibody production that 9. Van der Lee JH, Wagenaar RC, Lankhorst GJ, et al.: Forced use may block its therapeutic effects. Should antibody-mediated of the upper extremity in chronic stroke patients: results from a single-blind randomized clinical trial. Stroke 1999, resistance develop, an alternate serotype of botulinum toxin 30:986–988. can be administered. 10. Dromerick AW, Edwards DF, Hahn M: Does the application of constraint-induced movement therapy during acute rehabili- tation reduce arm impairment after ischemic stroke. Stroke 2000, 31:2984–2988. Conclusions 11. Miltner WH, Bauder H, Sommer M, et al.: Effects of constraint- This article has examined new and exciting developments in induced movement therapy on patients with chronic motor stroke rehabilitation. fMRI and TMS have allowed us to bet- deficits after stroke: a replication. Stroke 1999, 30:586–592. 12. Taub E, Morris DM: Constraint-induced movement therapy to ter understand the complex neuroanatomic relationships enhance recovery after stroke. Curr Atheroscler Rep 2001, involved in recovery from brain injury due to stroke. These 3:279–286. tools have also demonstrated the role for pharmacologic 13. Levy CE, Nichols DS, Schmalbrock PM, et al.: Functional MRI enhancement of cortical plasticity coupled with behavioral evidence of cortical reorganization in upper-limb stroke hemiplegia treated with constraint-induced movement ther- interventions. The role for technologic intervention in stroke apy. Am J Phys Med Rehabil 2001, 80:4–12. rehabilitation has been bolstered by robot-assisted therapy 14. Morris DM, Taub E: Constraint-induced therapy approach to and PBWSTT. Current research using hemi-field ocular restoring function after neurological injury. Top Stroke Rehabil 2001, 8:16–30. prisms and patching techniques suggest a role in improve- 15. Volpe BT, Krebs HI, Hogan N: Is robot-aided sensorimotor ment of function in patients with hemianopsia and visual training in stroke rehabilitation a realistic option? Curr Opin neglect. Finally, many advances have been made in the pre- Neurol 2001, 14:745–752. vention, recognition, and treatment of common stroke com- 16.• Volpe BT, Krebs HI, Hogan N, et al.: Robot training enhanced motor outcome in patients with stroke maintained over 3 plications: depression, dysphagia, venous thromboembolic years. 1999, 53:1874–1876. disease, incontinence, and spasticity. A study correlating goal-directed sensorymotor therapy with decreases in impairment measures of the upper extremity. These improvements continued over a 3-year period. 17. Volpe BT, Krebs HI, Hogan N: Is robot-aided sensorimotor References and Recommended Reading training in stroke rehabilitation a realistic option?” Curr Opin Papers of particular interest, published recently, have been Neurol 2001, 14:745–752. highlighted as: 18. Visintin M, Barbeau H, Korner-Bitensky N, et al.: A new • Of importance approach to retrain gait in stroke patients through body weight support and treadmill stimulation. Stroke 1998, •• Of major importance 29:1122–1128. 1. American Stroke Association: 2001 Stroke Statistics. Accessible at http://www.strokeassociation.org. Accessed February 29, 2001. 284 Cardiovascular Disease and Stroke

19.•• Kosak MC, Reding MJ: Comparision of partial body weight- 37. Raymer AM, Bandy D, Adair JC: Effects of bromocriptine in a supported treadmill gait training versus aggressive bracing patient with crossed nonfluent aphasisa: a case report. Arch assisted walking post stroke. Neurorehabil Neural Repair 2000, Phys Med Rehabil 2001, 82:139–144. 14:13–19. 38. Bragoni M, Altieri M, DiPietro V, et al.: Bromocriptine and A study that demonstrated that partial body weight-supported speech therapy in non-fluent chronic aphasia after stroke. treadmill gait training (PBWSTT) and aggressive brace-assisted Neurol Sci 2000, 21:19–22. walking are equally effective gait training techniques except for a 39. Gold M, VanDam D, Silliman ER: An open label trial of bro- subset of patients with major hemispheric stroke. This subset of mocriptine in nonfluent aphasia: a qualitative analysis of patients were easier to mobilize with PBWSTT, and thus showed word storage and retrieval. Brain Lang 2000, 74:141–156. better over-ground endurance. 40.• Walker-Batson D, Curtis S, Natarajan R, et al.: A double blind, 20. Danielsson A, Sunnerhagen KS: Oxygen consumption during placebo controlled study of the use of amphetamine in the treadmill walking with and without body weight support in treatment of aphasia. Stroke 2001, 32:2093–2098. patients with hemiparesis after stroke and in healthy sub- A prospective, double-blind study of 21 aphasic patients given dextro- jects. Arch Phys Med Rehabil 2000, 81:953–957. amphetamine paired with speech and language therapy. Dextroam- 21. Hesse S, Werner C, Bardeleben A, et al.: Body weight-supported phetamine facilitated recovery in these patients. treadmill training after stroke. Curr Atheroscler Rep 2001, 41.•• Goldstein LB: Effects of amphetamines and small related 3:287–294. molecules on recovery after stroke in animals and man. Neu- 22. Hesse S, Uhlenbrock D: A mechanized gait trainer for restora- ropharmacology 2000, 39:852–859. tion of gait. J Rehab Res and Dev 2000, 37:701–708. A review article that focuses on the impact of various drugs on func- 23. Rosetti Y, Rode G, Pisella L, et al.: Prism adaptation to a right- tional recovery after focal brain injury. ward optical deviation rehabilitates left hemispatial neglect. 42. Gawronski DW, Reding MJ: Post-stroke depression: an update. Nature 1998, 10:166–169. Curr Atheroscler Rep 2001, 3:307–312. 24. Rossi PW, Kheyfets S, Reding MJ: Fresnel prisms improve 43. Gawronski DW, Reding MJ: Post-stroke depression: an update. visual perception in stroke patients with homonymnous Curr Atheroscler Rep 2001, 3:307–312. hemianopia or unilateral visual neglect. Neurology 1990, 44. Huff W, Ruhrmann S, Sitzer M: Post-stroke depression: diag- 40:1597–1599. nosis and therapy. Fortschr Neurol Psychiatr 2001, 69:581–591. 25. Rossi PW, Kheyfets S, Reding MJ: Fresnel prisms improve 45. AU: PROVIDE AUTHOR NAMES: Clinical assessment of swal- visual perception in stroke patients with homonymnous lowing and dysphagia severity. Am J Speech Lang Pathol 1997, hemianopia or unilateral visual neglect. Neurology 1990, 6:17–24. 40:1597–1599. 46. Kidd D, Lawson J, Nesbitt R, et al.: Aspiration in acute stroke: a 26. Butter CM, Kirsch N: Combined and separate effects of eye clinical study with videofluoroscopy. Q J Med 1993, 86:825–829. patching and visual stimulation on unilateral neglect follow- 47.• Addington WR, Stephens RE, Gilliland K, et al.: Assessing the ing stroke. Arch Phys Med Rehabil 1992, 73:1133–1139. laryngeal cough reflex and the risk of developing pneumonia 27.•• Butefisch CM, Davis BC, Wise SP, et al.: Mechanisms of use- after stroke. Arch Phys Med Rehabil 1999, 80:150–154. dependent plasticity in the human motor cortex. Proc Natl A description of a new technique using nebulized tartaric acid to eval- Acad Sci 2000, 97:3661–3665. uate the laryngeal cough reflex and the associated risk of developing A description of the mechanisms underlying use-dependent plasticity aspiration pneumonia.. and long-term potentiation. 48. Kelly J, Rudd A, Lewis R, et al.: Venous thromboembolism after 28. Butefisch CM, Davis BC, Sawaki L, et al.: Modulation of use- acute stroke. Stroke 2001, 32:262–267. dependent plasiticity by d-Amphetamine. Ann Neurol 2002, 49.•• Sadosty AT, Goyal DG, Boie ET, et al.: Emergency department 51:59–68. D-dimer testing. J Emerg Med 2001, 21:423–429. 29. Walker-Batson D, Smith P, Curtis S, et al.: Amphetamine paired A review of the physiologic, pathologic, and chemical bases for the use with physical therapy accelerates motore recovery after of D-dimer assays in screening for venous thromboembolic disease. stroke. Further Evidence. Stroke 1995, 26:2254–2259. 50. Patel M, Coshall C, Rudd AG, et al.: Natural history and effects 30. Unwin H, Walker-Batson D: No side effects after low-dose on 2 yr outcomes of urinary incontinence after stroke. Stroke amphetamine administration in stroke rehabilitation. Stroke 2001, 32:122–127. 2000, 31:1785. 51. Patel M, Coshall C, Lawrence E, et al.: Recovery from post- 31. Sonde L, Nordstrom M, Nilsson CG, et al.: A double-blind pla- stroke urinary incontinence: associated factors and impact cebo-controlled study of the effects of amphetamine and on outcome. J Am Geriatr Soc 2001, 49:1229–1233. physiotherapy after stroke. Cerevrovasc Dis 2001, 12:253–257. 52. Patel M, Coshall C, Rudd AG, et al.: Natural history and effects 32. Scheidtmann K, Fries W, Muller F, et al.: Effect of levodopa in on 2 yr outcomes of urinary incontinence after stroke. Stroke combination with physiotherapy on functional motor recov- 2001, 32:122–127. ery after stroke: a prospective, randomised, double-blind 53. Cranall C: Tolterodine: a clinical review. J Womens Health Gend study. Lancet 2001, 358:787–790. Based Med 2001, 10:735–743. 33.• Greener J, Enderby P, Whurr R: Pharmacological treatment for 54. Gelber DA, Good DC, Dromerick A, et al.: Open-label dose- aphasia following stroke (Cochrane Review). Cochrane Data- titration safety and efficacy study of tizanidine hydrochloride base Syst Rev 2001, 4:CD000424. in the treatment of spasticity associated with chronic stroke. An extensive and comprehensive review of the Cochrane Stroke Stroke 2001, 32:1841–1846. Group Register to assess the effect of drugs on language abilities in 55. Meythaler JM, Guin-Renfroe S, Johnson A: Prospective assess- patients with aphasia secondary to stroke. ment of tizanidine for spasticity due to acquired brain injury. 34. Kessler J, Thiel A, Karbe H, et al.: Piracetam improves activated Arch Phys Med Rehabil 2001, 82:1155–1163. blood flow and facilitates rehabilitation of poststroke apha- 56. Meythaler JM, Guin-Renfroe S, Brunner RC: Intrathecal sic patients. Stroke 2002, 31:2112–2116. baclofen for spastic hypertonia from stroke. Stroke 2001, 35. Sabe L, Salvarezza F, Garcia Cuerva A, et al.: A randomized, 32:2099–2109. double-blind, placebo controlled study of bromocriptine in 57. McGuire JR: Effective use of chemodenervation and chemical nonfluent aphasia. Neurology 1995, 45:2272–2274. neurolysis in the management of poststroke pasticity. Top 36. Gupta SR, Mlcoch AG, Scolaro C, et al.: Bromocriptine treat- Stroke Rehabil 2001, 8:47–55. ment of nonfluent aphasia. Neurology 1995, 45:2170–2173.