**3. Hemorrhagic versus non-hemorrhagic stroke**

Stroke prognosis between hemorrhagic and non-hemorrhagic stroke, is another area of controversy17-19. It is largely attributed to the timing of outcome measurement and scopes of outcome. Not only matched comparison studies20,21, but also large population retrospective ones22-24 consistently showed better and faster functional recovery in hemorrhagic versus non-hemorrhagic stroke at short term outcomes. For long-term outcomes (one year poststroke), one study reported that there was no difference between hemorrhagic and nonhemorrhagic stroke22, but another study observed better outcome in non-hemorrhagic stroke23. For further study, it is to be considered that 20-40% of initial ischemic infarction may develop hemorrhagic transformation within one week after initial stroke onset. Hemorrhagic transformation may blur the distinction between hemorrhagic and nonhemorrhagic strokes and therefore, the classification based on initial imaging studies can be a source of significant bias.

perceptual abilities. Stroke patients with right hemisphere lesion often demonstrate lack of safety awareness and impulsive behaviors. With these complex impairments, they have difficulties in re-learning ADL (activities of daily living). For example, they are unable to read or copy letters, forget to clean their left side body, or ignore to wear assistive devices for activity. Even though they can maintain speech-language function better than patients

Major functions of the left hemisphere are to control the movements of the right side of the body and to maintain speech-language function. Patients with left hemispheric strokes sustain right hemiplegia and aphasia. They behave cautiously and need more time to complete the same task compared with right hemispheric stroke patients. Different types of

It is controversial whether rehabilitation outcomes differ depending on which hemisphere the lesion is occurs6-8. Possible reasons for the controversy are different outcome scales, measurement domain, presence of hemi-neglect, and evaluation timing. For example, if the outcome compared is vocational rehabilitation, patients with right hemisphere lesion show better outcome9. The higher percentage of patients returning to work with a right hemispheric lesion largely can be explained by preserved speech-language function. However patients with right hemispheric lesions more frequently develop social defects than those with left hemispheric lesions10. In contrast, if regaining arm function is measured as a rehabilitation outcome, poorer outcome is reported in right hemispheric lesions11.

Hemi-neglect develops more commonly in stroke patients who have right hemispheric lesion compared to the left. There is a wide range of incidence reported, because of different evaluation tools and evaluation timing12,13. Among patients with right hemispheric lesions, patients with hemi-neglect are more disabled and stay longer at rehabilitation facilities than those without hemi-neglect14. Again, one possible reason of controversy in outcomes of patients with stroke between right and left hemispheric lesions is that patients with a concurrent right hemispheric lesion with hemi-neglect has more disability than would be with a right hemispheric lesion alone15. Future studies excluding hemi-neglect patients may

help clarify the difference in disability between right and left hemiplegia patients16.

Stroke prognosis between hemorrhagic and non-hemorrhagic stroke, is another area of controversy17-19. It is largely attributed to the timing of outcome measurement and scopes of outcome. Not only matched comparison studies20,21, but also large population retrospective ones22-24 consistently showed better and faster functional recovery in hemorrhagic versus non-hemorrhagic stroke at short term outcomes. For long-term outcomes (one year poststroke), one study reported that there was no difference between hemorrhagic and nonhemorrhagic stroke22, but another study observed better outcome in non-hemorrhagic stroke23. For further study, it is to be considered that 20-40% of initial ischemic infarction may develop hemorrhagic transformation within one week after initial stroke onset. Hemorrhagic transformation may blur the distinction between hemorrhagic and nonhemorrhagic strokes and therefore, the classification based on initial imaging studies can be

**3. Hemorrhagic versus non-hemorrhagic stroke** 

a source of significant bias.

aphasia can occur depending on the specific site of the lesion in the left hemisphere.

with left hemisphere stroke patients, they may make errors in grammar.

In summary, hemorrhagic stroke has higher mortality rate than non-hemorrhagic in acute phase and often requires emergent surgical intervention for survival. However, hemorrhagic stroke survivors without significant surgical complications make better functional improvement in early phase of rehabilitation than those with non-hemorrhagic stroke.

#### **4. Impairments and disabilities sequelae to stroke**

Severity and types of impairments resulted from a stroke depend on stroke site and lesion size. Most common impairments are 1) motor dysfunction (paralysis of extremity, face, and oropharyngeal muscles), 2) sensory dysfunction (decreased sensation, perception disorder, abnormal sensation), 3) sphincter dysfunction (bowel and bladder incontinence), 4) cognitive dysfunction (anomia, aphasia, dementia), 5) emotional disturbance (depression, apathy).

1. Paralysis of one side of body (hemiplegia): It develops in very early phase of stroke. If stroke lesion is in the right hemisphere, paralysis develops in the left face and the extremity. But stroke lesion located in the right brainstem, develops paralysis in the right face and left extremity. Most patients with stroke complain of flaccid extremity as an initial symptom. The flaccid extremity usually evolves to spastic extremity as part of its natural course. Details of motor function recovery will be described in the follow section (Motor function recovery).

One side of bulbar muscle paralysis results in oropharyngeal dysfunction (dysphagia). Stroke patient with dysphagia needs non-oral feeding until safe swallowing recovered. Depending on the severity of dysphagia, stroke patient needs nasogastric or gastrostomy/jejunostomy tube feeding. VFSS (videofluorographic swallowing study), also called videofluorographic modified barium swallowing study, is a standard diagnostic test to evaluate swallowing function. Penetration is defined when a bolus moves aberrantly down to the vestibule above the true vocal fold. This may trigger a coughing or a choking reflex after swallowing the bolus. Aspiration occurs when a bolus passes farther down through the true vocal folds and enter into the trachea and lungs. Most of patients with dysphagia return to a regular diet in early post-stroke phase25, 26. Compared to other lesions, dysphagia develops more common and less favorable outcome in brainstem stroke, however 88% returned to regular oral intake 4 months after stroke27. Tracheostomy increases the risk of aspiration because of the limitation of laryngeal elevation during swallowing. Selection of adequate texture of meals and meticulous monitoring of swallowing are critical to prevent aspiration.

2. Sensory impairment: stroke patients have sensory impairment of peripheral and/or central sensation. Peripheral sensory impairments include hypesthesia/paresthesia, loss of proprioception and position, or loss of pain/temperature. Agraphesthesia and astreognosis is seen in central sensory impairment. Those impairments cause stroke patients to needs more assistance for learning motor and cognitive skills. Reception is the processing of registration of sensations or stimuli which are collected through sensory organs (nose, eye, ear, skin, tongue, joint, or internal organs). Received sensations or stimuli are conveyed to the corresponding primary sensory cortexes. For example, visual sensation reaches occipital cortex via optic pathways. Perception is the next process to interpret the received sensations or stimuli. Perception is higher cortical function than reception and many parts of brain are involved. Details of perception disorder will be discussed in the following perception disorder.

Stroke Rehabilitation 25

Perception is the conscious mental process through the senses of existence and external sensory stimulus. Visual perception disorders are manifested as agnosia, alexia, apraxia, hemi-neglect, spatial disorientation. Hemispatial neglect is synonymous with hemiagnosia, hemi-neglect, unilateral neglect, unilateral inattention. Homonymous hemianopsia differs from visual hemi-neglect. While the former is resulted from the lesion of the visual track and the patient with this impairment uses compensate strategy (for example, head turning), the latter is spatial inattention to one side of body resulted from parietal cortex and one with this impairment does not compensate. Perception disorders impede not only functional recovery, but safety awareness. For example, perceptual disorder of position leads the patient stands with asymmetric weight bearing and affects gross motor function recovery. Patients with right hemisphere stroke predominantly sustain spatial perception disorders. Perceptual training with mirror therapy, prism adaption, eye patch, reportedly improves functional outcomes after stroke, but one large review article showed insufficient supportive data of perceptual intervention (visual field deficits, neglect/inattention, and apraxia were

Apraxia is the inability to carry out familiar, purposeful tasks without sensory or motor impairment, especially difficult is proper use of an object. Patients with speech apraxia demonstrate incomplete speech with repetition, omission, or distorted words. They are doing well with short simple conversations (How are you? Are you OK?...), but the impairment is exaggerated with long complex sentences. Patients with ideational apraxia have difficulties in coordination of sequential performance. For example, he/she knows how to hold a letter, to put it into an envelope, and to attach a stamp. But when he/she is requested to do these three steps sequentially, he/she cannot do this in the proper order. Clinically, it is manifested as difficulties in eating, dressing, and bathing. A patient with ideomotor apraxia is unable to respond properly to a request or command. He/she knows the name of an object, but not able to use properly. For example, when he/she is asked to brush hair with a comb, the patient demonstrates improper usage of the comb. Constructional apraxia is the inability to copy, draw, or construct simple figures. The patient with this impairment draws a face unproportionally. Dressing apraxia, difficulty in wearing cloths, is a misnomer (not true apraxia). This is resulted from the impairment of spatial perception, which makes it difficult to recognize and match the parts of the body and the

Pain perception disorder: Central post-stroke pain syndrome (CPSP) is one of devastating complications and formerly called thalamic pain syndrome. It is understood that damaged spinothalamic track may play a key role in pathogenesis, but not always. It may develop independently or jointly with complex regional pain syndrome (CRPS). Clinical findings are very similar to CRPS, however, CPSP is confined to hemiplegic face or limbs only. Both the presence of sensory disturbances and neurpathic pain differentiates CPSP from CRPS. It usually develops 1-3 months after stroke onset, but sometimes develops in a chronic phase. Plain radiographic study is recommended to rule out musculoskeletal lesion of the shoulder or hand. In order to rule out deep vein thrombosis, Doppler ultrasound study is useful. Triple phase bone scan is to be considered if CRPS suspected. Therapeutic options are similar to CRPS. Magnetic motor cortex stimulation50, vestibular stimulation51,52, or deep

**5. Perception disorder** 

excluded in this study) 48, 49.

cloth correctly.

vein stimulations53 are being tried in some cases.


Post-stroke depression is a strong negative factor for functional recovery, however there is no standard pharmacological treatment. A double-blind controlled study with fluoxetine and nefiracetam did not support therapeutic effectiveness for either agent44, 45, however, a matched comparison study with milnacipran revealed effectiveness46. The controversy is in part ascribed to uncovered pharmacodynamics of anti-depressant in stroke. Systemic review of pharmacological management of post-stroke depression concludes there is insufficient evidence to support anti-depressant administration for prevention or to improve recovery, but the medications may improve mood in poststroke depression47.

3. Sphincter dysfunction: Double incontinence (both urinary and fecal incontinence) is more common than isolated urinary or fecal incontinence in stroke patients28. Even though this impairment resolved during early post-stroke period, persistent urinary incontinence was reported 10-20% at the time of discharge from rehabilitation28, 29. The most common type of bladder dysfunction is uninhibited type. It is usually resolved with timed voiding training. Sometimes anti-cholinergic agents (oxybutynin, tolterodine) are indicated to relax bladder. Most of sphincter dysfunction is restored as other functional recovery occurs. Nocturnal incontinence may persist in chronic phase. Unawareness of bladder is a strong negative prognostic factor for urinary incontinence, in addition to cognitive impairment and lower limb dysfunction. It may be a lifelong

4. Cognitive dysfunction is the most powerful negative factor for outcome. This is most commonly and severely impaired in patients with left hemisphere lesion with aphasia. It is also very closely negatively correlated with returning to work. 38% of stroke patients were found to have cognitive impairment assessed by Mini-Mental State Examination at 3 month post-stroke and more common in elderly (>75 years), low socioeconomic status, and left hemisphere lesion30. It has strong correlations with longterm outcome. 30-50% of stroke survivors were categorized in lower levels on most measures of neuropsychological testing and information processing is the most common and the worst deficit31. Cognitive impairment and dementia after a stroke can be reduced by adequate treatment of hypertension and acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine), prescribed to alzheimer's disease, and may be beneficial for cognitive rehabilitation32, 33. A randomized placebo-controlled double blind study reports that greater improvement of language function in verbal fluency and repetition was found in patients receiving levedopa than placebo34. One open label case study shows rapid improvement in cognitive as well as physical function in three

5. Emotional disturbance: Right hemispheric stroke patients sustain behavioral changes, which in turn caused family conflicts with this altered behaviors36. A 5 year longitudinal study shows about 30% of stroke survivors sustained depression and 48% were not depressed at any time of evaluation31, 37. Also depression was not static, but resolved and newly developed at any time in the 5 year follow-up37. High risk factors of depression include stroke severity, unemployment, and cognitive impairment. A patient with depression prior to stroke has 9 times higher risk of post-stroke depression38. The frequency of post-stroke apathy is reported 20-25% and commonly conjunct with cognitive impairment and depression39. Dopaminergics or neurostimulants

Post-stroke depression is a strong negative factor for functional recovery, however there is no standard pharmacological treatment. A double-blind controlled study with fluoxetine and nefiracetam did not support therapeutic effectiveness for either agent44, 45, however, a matched comparison study with milnacipran revealed effectiveness46. The controversy is in part ascribed to uncovered pharmacodynamics of anti-depressant in stroke. Systemic review of pharmacological management of post-stroke depression concludes there is insufficient evidence to support anti-depressant administration for prevention or to improve recovery, but the medications may improve mood in post-

(methylphenidate, dexamphetamine) is reportedly beneficial to apathy40-43.

disability in those with significantly cognitive impaired.

chronic stroke patients with perispinal etanercept35.

stroke depression47.

#### **5. Perception disorder**

Perception is the conscious mental process through the senses of existence and external sensory stimulus. Visual perception disorders are manifested as agnosia, alexia, apraxia, hemi-neglect, spatial disorientation. Hemispatial neglect is synonymous with hemiagnosia, hemi-neglect, unilateral neglect, unilateral inattention. Homonymous hemianopsia differs from visual hemi-neglect. While the former is resulted from the lesion of the visual track and the patient with this impairment uses compensate strategy (for example, head turning), the latter is spatial inattention to one side of body resulted from parietal cortex and one with this impairment does not compensate. Perception disorders impede not only functional recovery, but safety awareness. For example, perceptual disorder of position leads the patient stands with asymmetric weight bearing and affects gross motor function recovery. Patients with right hemisphere stroke predominantly sustain spatial perception disorders. Perceptual training with mirror therapy, prism adaption, eye patch, reportedly improves functional outcomes after stroke, but one large review article showed insufficient supportive data of perceptual intervention (visual field deficits, neglect/inattention, and apraxia were excluded in this study) 48, 49.

Apraxia is the inability to carry out familiar, purposeful tasks without sensory or motor impairment, especially difficult is proper use of an object. Patients with speech apraxia demonstrate incomplete speech with repetition, omission, or distorted words. They are doing well with short simple conversations (How are you? Are you OK?...), but the impairment is exaggerated with long complex sentences. Patients with ideational apraxia have difficulties in coordination of sequential performance. For example, he/she knows how to hold a letter, to put it into an envelope, and to attach a stamp. But when he/she is requested to do these three steps sequentially, he/she cannot do this in the proper order. Clinically, it is manifested as difficulties in eating, dressing, and bathing. A patient with ideomotor apraxia is unable to respond properly to a request or command. He/she knows the name of an object, but not able to use properly. For example, when he/she is asked to brush hair with a comb, the patient demonstrates improper usage of the comb. Constructional apraxia is the inability to copy, draw, or construct simple figures. The patient with this impairment draws a face unproportionally. Dressing apraxia, difficulty in wearing cloths, is a misnomer (not true apraxia). This is resulted from the impairment of spatial perception, which makes it difficult to recognize and match the parts of the body and the cloth correctly.

Pain perception disorder: Central post-stroke pain syndrome (CPSP) is one of devastating complications and formerly called thalamic pain syndrome. It is understood that damaged spinothalamic track may play a key role in pathogenesis, but not always. It may develop independently or jointly with complex regional pain syndrome (CRPS). Clinical findings are very similar to CRPS, however, CPSP is confined to hemiplegic face or limbs only. Both the presence of sensory disturbances and neurpathic pain differentiates CPSP from CRPS. It usually develops 1-3 months after stroke onset, but sometimes develops in a chronic phase. Plain radiographic study is recommended to rule out musculoskeletal lesion of the shoulder or hand. In order to rule out deep vein thrombosis, Doppler ultrasound study is useful. Triple phase bone scan is to be considered if CRPS suspected. Therapeutic options are similar to CRPS. Magnetic motor cortex stimulation50, vestibular stimulation51,52, or deep vein stimulations53 are being tried in some cases.

Stroke Rehabilitation 27

stroke, underlying health status,…), treatment options are determined. It is suggested that early rehabilitation intervention is necessary, even if diagnostic or therapeutic plan are not completed. At this phase, rehabilitation starts with less intensive approach. Passive range of motion, position changes, stimulation control, safe feeding, and joint contracture prevention

Functional improvement is not always parallel with neurological recovery in patients with stroke. Analysis of the Uniform Data System for Medical Rehabilitation (UDSMR) for stroke patients in US from 2000 to 2007 shows decreased a mean length of rehabilitation unit stay from 19.6 days to 16.5 days, decrease a mean FIM (functional independence measurement) at rehabilitation unit from 62.5 to 55.1 (means more functionally dependent patients were admitted to rehabilitation unit), decrease a mean FIM at discharge from rehabilitation unit from 86.4 to 79.8 (means less functionally independent patients were discharged from rehabilitation unit), but the FIM change during rehabilitation stay remained relatively stable59. These results reflect that patients with stroke in US admit and discharge earlier than before. Patients with stroke may benefit from early discharge, but by the other hand, early

From an ADL (activities of daily living) standpoint, stair walking (downward more difficult than upward) is the hardest to be improved, and then tub/shower transfer, ambulation, and lower body dressing follow. In contrast, eating is the easiest to be improved, and then

Poor sitting balance, poor trunk control, urinary incontinence, severity of disability, and old age (>74 years) are poor predictors for independent walking61. Standing balance ability is

In cognitive rehabilitation, problem solving is the most severely impaired and the least potential for recovery after stroke. Learning and memory impairments are most common10. Comprehension and expression are less impaired and better improved than memory. Patients with right hemiplegia are more impaired and less likely to improve in cognitive

Cognitive and speech-language impairment prevents patients with stroke from participation in social activities. Patients with higher cognitive level recover much better than ones with lower level. A study of return to work reports 1) no significant racial differences in left hemisphere infarction, but whites were more likely to return to work in right hemisphere infarction, 2) no significant difference of returning to work between whites and non-whites with left hemisphere infarction, 3) whites with right hemisphere infarction are most likely to return to work, while non-whites with right hemisphere infarction are least likely, 4) patients employed premorbidly at professional or managerial position, younger age group, less severe disability, white race, right hemisphere lesion were more likely to return to work

**8. Traditional and new therapeutic approaches to stroke rehabilitation** 

Traditional physical therapy and occupation therapy are still largely mainstays of the rehabilitation. Many therapeutic techniques to facilitate movement of paralyzed side, based on motor developmental hierarchy, repetition of motor pattern, and task-oriented training.

more important than lower extremity strength to achieve better ambulation62.

are important to prevent impending complications.

discharge from rehabilitation unit increased the mortality60.

grooming, and sphincter control follow.

functions than those with left hemiplegia.

following a cerebral infarction9.
