EVALUATION OF THE EFFECTS OF EARLY APPLICATION OF BOTULINUM TOXIN IN PATIENTS WITH A FIRST CEREBRAL VASCULAR EVENT.
Phase: EARLY_PHASE1
Conditions: Spasticity, Stroke, Neurological Rehabilitation
Sponsor: Instituto Mexicano del Seguro Social

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EVALUATION OF THE EFFECTS OF EARLY APPLICATION OF BOTULINUM TOXIN IN 
PATIENTS WITH A FIRST CEREBRAL VASCULAR EVENT. 
 
NCT ID not yet assigned] 
 
MERIDA, YUCATAN, MEXICO 
JANUARY 2025 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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I Summary  
Theoretical Framework: Cerebrovascular disease is the second leading cause of death 
worldwide and the leading neurological cause of disability. Damage to the pyramidal tract and 
the accompanying cortico-reticulospinal fibers results in upper motor neuron syndrome. 
Spasticity is a positive feature of upper motor neuron syndrome that occurs as a result of 
alterations in the balance between excitatory and inhibitory signals from the spinal motor 
neuron pool leading to chronic changes in soft tissue and muscle fiber density. Early detection 
of risk factors for spasticity and management with botulinum toxin not only reduces this 
complication but may also improve function and increase patient independence. 
 
Objectives: To evaluate the effects of early application of botulinum toxin in patients with 
cerebrovascular event. 
Material and methods: Patients entitled to the General Regional Hospital No. 1 “Lic. Ignacio 
García Téllez” IMSS Yucatán Delegation, currently active with a diagnosis of cerebrovascular 
disease admitted to hospitalization by the Internal Medicine and Emergency services in a 
period of three years. The sampling will be non-probabilistic, for convenience, and all patients 
with a diagnosis of stroke hospitalized who meet the inclusion criteria will be included (>18 
years, entitled to stroke within the first 7 days of evolution). 
Patients will be selected, a first assessment will be carried out by the Rehabilitation service in 
the first seven days after the onset of the stroke, where the patient will be invited to take part 
in the study, expressing the reason, intention and structure of the work plan, upon confirming 
their participation they will sign informed consent and the following will be done: 
1. Assignment of a folio number to structure your file. 
2. Recording of sociodemographic data. 
3. Capturing data obtained through clinical records. 
4. Neurological physical examination. 
The information will be captured in an Excel 2019 spreadsheet (Microsoft ©, Redmont, 
Washington) and IBM® SPSS Statistics® version 22 to create the database. The analysis and 
results presentation plan will comprise two phases: a) Descriptive phase. b) Inferential phase. 
The results of quantitative variables will be compared with the Student t test for paired samples 
if their distribution is normal or with the Wilcoxon rank test otherwise. Qualitative variables will 
be compared with the Chi square test. In all cases, a p value <0.05 will be considered 
statistically significant.  
 
 

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II Background  
CEREBROVASCULAR DISEASE: EPIDEMIOLOGY IN MEXICO AND AT THE HGR No. 1 
IN MÉRIDA 
Cerebrovascular disease is the second cause of death worldwide and the first neurological 
cause of disability. It most frequently affects people over 65 years of age. The available 
literature in Mexico describes that ischemic stroke is the most frequent form of cerebral 
vascular disease in our country and causes between 50 and 70% of cases (PARRA, 2019), 
followed by intraparenchymal hemorrhage, subarachnoid hemorrhage, transient ischemic 
attack and cerebral venous thrombosis. 1,2 
The estimated incidence in Mexico according to the BASID (Brain Attack in Corpus 
Christi) study (CANTU-BRITO et al, 2010)is 230 cases per 100,000 inhabitants, mainly 
affecting older adults over 64 years of age. The most important risk factor in our population for 
suffering a cerebrovascular event is hypertension, followed by diabetes mellitus. Mortality from 
this condition in Mexico is 28.3 per 100,000 inhabitants. 2 
The typical evolution of a stroke follows an ascending curve with a progressively lower 
slope. In a patient with a favorable recovery, early improvement is due to the recovery of the 
penumbra tissue of the periphery of the ischemic area and the resolution of diaschisis 
(transynaptic failure of surrounding areas). Long-term improvement is attributed to neuronal 
plasticity. 3 95% of recovery will have been achieved by the third month after the stroke, with 
the fastest recovery occurring in the first month and a half (85%). Between the fourth and sixth 
months the recovery slope is slight, almost plateauing, and from the sixth month onwards there 
is hardly any improvement. 3,4 
Stroke is characterized by the sudden onset of clinical signs related to the brain site 
where the injury occurs. Damage to the pyramidal tract and accompanying cortico-
reticulospinal fibers results in upper motor neuron syndrome, which includes both positive and 
negative signs. 4 Positive signs include spasticity and abnormal postures; negative signs 
include those that have been lost, such as strength and dexterity. Initially, about 80% of all 
stroke patients experience motor deficits in the contralateral limb(s), i.e., hemiparesis with 
marked decrease in muscle tone. 
 
SPASTICITY: DEFINITION, PATHOPHYSIOLOGY 
Spasticity has been defined as a velocity-dependent increase in muscle tone and 
represents a motor dysfunction arising from upper motor neuron lesions. 
Spasticity is a positive feature of upper motor neuron syndrome that arises as a result 
of alterations in the balance between excitatory and inhibitory signals from the spinal motor 
neuron pool leading to chronic changes in soft tissue and muscle fiber density. 

4 
 
  
The most recent definitions of spasticity include all positive symptoms of upper motor 
neuron syndrome (increased tendon reflexes, presence of pathological reflexes, clonus, 
spasms, spastic dystonia and velocity-dependent increased tone) excluding complications 
(contractures, loss of muscle fibers). 5 
Other motor deficits related to spasticity include abnormal synergies, inappropriate 
muscle activation, and abnormal muscle coactivation. Spasticity manifests only in muscles at 
rest, whereas the other related motor impairments arise during activation. 6 
 
NEUROMECHANICAL CONSEQUENCES OF SPASTICITY 
Spasticity can worsen the consequences of weakness. Weakness often leads to 
immobility. Spasticity-related involuntary muscle hyperactivity and synergistic activation tend 
to immobilize joints in abnormal positions. In turn, this potentiates the development of tendon 
shortening and muscle contracture over time, leading to abnormal posture, for example, 
stereotypical presentations of ankle equinus-varus deformity and clenched fist. 6 
Abnormal posture of a joint can have mechanical effects on other joints through the 
kinetic chain, particularly in the leg during walking.6,7 
The severity of muscle hyperactivity can be described using the modified Ashworth 
scale, the Tardieu scale and the Resistance to Passive Movement Scale (REPAS). 7 
 
DEVELOPMENT AND EVOLUTION OF SPASTICITY IN RELATION TO TIME 
The onset of spasticity is highly variable and may occur in the short, medium or long 
term after stroke or brain injury. 8 
Electroneuromyography (EMG) studies have shown that reflex-mediated increases in 
muscle tone peak between 1 and 3 months after stroke. 9,10,11 After 3 months, eventual 
increases in muscle endurance are attributed to intrinsic changes in the muscles. 11 
Lundstrom et al. in their sample of 49 subjects observed early development of spasticity 
in 27% of patients at 1 month and 23% at 6 months. 12 Wissel et al. presented a study of 94 
subjects without preexisting spasticity after the stroke in which they observed early 
development of spasticity, with 24.5% within 2 weeks after the stroke and among all subjects 
who developed spasticity at any time during the course of the study, 98% exhibited spasticity 
with a median presentation of 6 weeks. 13 
In a meta-analysis, Zeng et al. reported the prevalence of spasticity in relation to the time of 
evolution of the cerebrovascular event, in the first month of 4-46%, from the first to the third 
month of 4.16-48%, from 3 to 6 months of 6.3-63% and beyond 6 months of 7.6-46% and the 
prevalence of patients who developed severe spasticity in 2-2.6% during the first month, 5% 
from the first to the third month, 8-15.6% in the 6 months after the cerebrovascular event and 
12.5%-18% after 6 months. 14 

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Figure 1. Prevalence of post-stroke spasticity. Image taken from Wissel Jorg et al. 21 
 
RISK FACTORS FOR THE DEVELOPMENT OF SPASTICITY 
Early identification of spasticity, together with the identification of predictors of its onset, 
allows us to identify patients at higher risk with the aim of initiating early treatment and thereby 
preventing long-term complications. 15,16 
The SALGOT study evaluated spasticity in the upper limbs following a first stroke, 
concluding that reduced sensorimotor function was the most important predictor of spasticity 
at 12 months after the cerebrovascular event and that spasticity could be predicted with high 
sensitivity at 10 days post-stroke. 17 
Lundström et al. included 49 subjects with any paresis after their first stroke and 
examined them at baseline (day 2-10 after stroke) and at two follow-up time points, at 1 and 6 
months. They assessed muscle tone (assessed by MAS), global disability (assessed by MRS), 
stroke severity, paresis severity, and sensory disturbance (all assessed by the National 
Institutes of Health Stroke Scale [NIHSS]). They found that severe arm paresis (more than 2 
points on point 5 of the NIHSS) during the first month after stroke was associated with an 
increased risk of spasticity (P < 0.001). All six patients who developed disabling spasticity over 
the follow-up period had severe initial arm paresis (P < 0.002). 12 
Wissel et al. presented a study of 94 subjects without preexisting spasticity who were 
examined at 6 days post-stroke, 6 weeks, and 16 weeks. At all time points, muscle tone (MAS), 
pain, paresis, and Barthel Index score were recorded. The presence of hemiparesis correlated 
with spasticity at the first (P = 0.02) and second (P = 0.005) follow-up. Hemi-spasticity and 
increased muscle tone (MAS score ≥1) in more than two joints at 6 weeks, and more severe 
degrees of paresis at 16 weeks, were risk factors for permanent spasticity. A lower Barthel 
Index at baseline predicted the development of more severe spasticity at the final follow-up (P 
= 0.002). 13 

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Kong et al. investigated patients admitted to a rehabilitation unit after a first-time 
ischemic stroke (N = 163). They used the Modified Ashworth Scale to assess upper limb 
spasticity. Upper limb function was assessed and basic activities of daily living were assessed 
using the Barthel Index. Upper limb spasticity was defined as MAS of 1 or greater. In this 
sample, upper limb spasticity occurred in 1/3 of patients (54 patients) at 3 months after stroke. 
As predictive factors, poor upper limb function was the most important factor for the 
development of moderate to severe spasticity (MAS ≥ 2). 18 
Leitsner et al. conducted a study evaluating patients in the acute phase after stroke (<7 
days). Spasticity was assessed with the Resilience to Passive Movement Scale (REPAS) for 
major joint movements in the upper and lower extremities, according to the Ashworth scale, 
within 7 days after stroke and at 3 months of progression. Of the 145 patients evaluated with 
first stroke, 34 patients (23.4%) exhibited spasticity. The Modified Rankin Scale (MRS), the 
National Institutes of Health Stroke Scale (NIHSS), and the Mini-Mental State Examination 
(MMSE) were found to be strong clinical predictors of spasticity. The combination of an MRS 
>2, NIHSS >2, and MMSE <27 showed a positive predictive value (95.2%) for the prediction 
of spasticity (sensitivity 94.4%, specificity 93.3%). 13 
Opheim et al conducted a study in which they included 117 patients who had 
experienced a stroke for the first time and with documented arm paresis on day 3 post stroke. 
Assessments were performed at admission, at 3 and 10 days, 4 weeks and 12 months post 
stroke. They considered spasticity as an increase in muscle tone assessed through MAS 
greater than 1, and severe spasticity was considered as MAS greater than 2 in any of the 
muscles. Sensorimotor function, pain and joint range of motion in the upper limb were 
assessed with the Fugl-Meyer assessment scale. Demonstrating that spasticity was best 
predicted with variables collected on day 10 post stroke and severe spasticity was best 
predicted with variables collected 4 weeks post stroke. The lowest sensorimotor function 
score, identified with the FMA-UE, consistently and significantly predicted both any spasticity 
and severe spasticity at 12 months post-stroke. The presence of upper limb spasticity 4 weeks 
post-stroke was a significant predictor of severe spasticity. 16 
Zeng et al. analyzed 23 studies in a meta-analysis. The incidence of spasticity after first 
stroke with paresis was 39.5%. The prevalence of disabling or severe spasticity (MAS ≥ 3) in 
stroke patients with paresis was 9.4%. Mild paresis was defined as NIHSS score less than or 
equal to 1 on item 5 or 6, or British Medical Research Council (BMRC) scale grade 4, while 
moderate to severe paresis was greater than or equal to 2 on NIHSS or BMRC grades 0–3. A 
subgroup of four studies showed that only moderate to severe paresis was a risk factor for 
spasticity. In subgroup analysis, sensory disturbance was found to predict the development of 
spasticity in the 3–6 months after stroke, but not at other times. 14 

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Nam et al conducted a retrospective study of 861 stroke patients and found that the 
median time from stroke presentation to presentation of upper extremity spasticity was 34 
days. Approximately half of the patients developed spasticity within 1 month after stroke. They 
concluded that in general, the time of onset of spasticity is 3 days to 6 weeks after stroke, 
mostly within 1 month. 19 
 
Table 1. Predictors of post-stroke spastic movement disorder 
ACUTE PHASE, FIRST WEEK POST-EVC 
POST-ACUTE PHASE 
Severe paresis (leading to spasticity within 6 months) 
Paresis (leads to spasticity within 6 months) 
Low score on the Fugl-Meyer scale (leads to spasticity within 
12 months) 
Increased muscle tone (leading to spasticity within 12 
months) 
Increased muscle tone (Ashworth scale greater than 1), 
leading to spasticity within 3-6 months 
Hemiparesis and low Barthel Index score (leads to spasticity 
within 12 months) 
Moderate increase in muscle tone (Ashworth scale greater 
than 2), leading to spasticity within 3-6 months 
Low Barthel Index score + Left paresis (leading to spasticity 
within 12 months) 
Low Barthel Index and EQ-5D scores (leads to spasticity 
within 3-6 months) 
High NIHSS score + Low Motor Index (leads to spasticity 
within 3 months) 
Hemihypoesthesia (leads to spasticity within 6 months) 
Extensive lesions on CT or MRI (leading to spasticity within 
5 days to 1 year). 
High MRS + NIHSS score + low MMST score (leads to 
spasticity within 3 months) 
Severe paresis (leading to spasticity within 12 months) 
 
RATING SCALES 
Appropriate assessments for spastic muscle tone, as well as the consequences of post-stroke 
spastic movement disorder for activities of daily living and motor performance, are well 
established and include the Ashworth scale (modified), Tardieu scale, active and passive 
range of motion, Modified Rankin Scale (MRS), National Institutes of Health Stroke Scale 
(NIHSS), Fugl-Meyer Upper and Lower Extremity Scale, Barthel Index, cognitive tests such as 
the Mini-Mental State Examination (MMSE). 21 
 
1.1 NIHSS SCALE (National Institute of Health Stroke Score) 
The NIHSS scale numerically scores the severity of stroke. It should be applied at the 
beginning and during the evolution of the stroke. Minimum score 0, maximum 42 points. It 
assesses level of consciousness, conjugate gaze, confrontation visual fields, facial paresis, 
arm paresis, leg paresis, dysmetria, sensitivity, language, dysarthria, neglect. 
 
Ryu et al evaluated 245 patients with the aim of examining the prevalence of spasticity and 
predictors of the condition. In their evaluation they used the National Institutes of Health Stroke 
Scale (NIHSS) and found that the score on the scale was significantly predictive of spasticity 
after a stroke. 20 
 

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Leitsner et al. also managed to highlight the value of applying the scale in predicting the 
development of spasticity by observing 145 patients during the acute phase of the 
cerebrovascular event in whom the combination of an MRS >2, NIHSS >2 and MMSE <27 
showed a positive predictive value (95.2%) for the prediction of spasticity (sensitivity 94.4%, 
specificity 93.3%). 13 
 
1.2 MINI MENTAL STATE EXAMINATION (MMSE) 
This is a screening test for dementia, which is also useful for monitoring the disease. It 
scores a maximum of 30 points and the items are grouped into 5 sections, which include 
orientation, immediate memory, attention, calculation, delayed recall, language and 
construction. The cut-off point for dementia is set at 24 points. 
 
1.3 ASHWORTH SCALE 
The Ashworth Scale is used to assess tone in neurological patients. It is a qualitative scale 
and, according to the definition of each of its values, the measurements are ordinal. It is based 
on the assessment of resistance to passive stretching. The score for this test ranges from 0 
(there is no resistance to stretching) to 4 (there is complete resistance). 
 
1.4 MODIFIED TARDIEU SCALE 
Scale that assesses spasticity according to the notion of speed as a parameter that 
participates in the evaluation. First, the maximum angle of joint mobilization is determined, 
which is obtained at the slowest possible speed (to free oneself as much as possible from the 
stretch reflex, speed V1). Secondly, the joint is mobilized at the fastest speed possible for the 
examiner and the angle at which it appears is noted (speed V3). The spasticity angle is the 
difference between the angle at V1 and the angle at V3. The intensity of the response is 
indicated on a scale from 0 to 4. The scale retains the reference position of Tardieu, where 0° 
is the joint amplitude at which the muscle is shortest. 
1.5 BARTHEL INDEX 
 
The Barthel Index is a generic measure that assesses the patient's level of independence 
with respect to carrying out some basic activities of daily living, through which different scores 
and weights are assigned according to the ability of the subject examined to carry out these 
activities. 
The values assigned to each activity depend on the time spent performing it and the need 
for assistance to carry it out. The basic activities of daily living included in the index are ten: 

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eating, transferring between chair and bed, personal hygiene, using the toilet, 
bathing/showering, moving around (walking on a smooth surface or in a wheelchair), going 
up/down stairs, dressing/undressing, stool control and urine control. The activities are valued 
differently, and can be assigned 0, 5, 10 or 15 points. The overall range can vary between 0 
(completely dependent) and 100 points (completely independent). 
Wissel et al demonstrated that a lower Barthel Index at baseline predicted the development 
of more severe spasticity at the final follow-up, 16 weeks post-stroke (P = 0.002) .13 
 
1.6 RANKIN SCALE 
The Rankin Scale assesses the patient's functional status and allows for obtaining partial 
results regarding quality of life (asymptomatic patient, mild, moderate, severe disability or 
death) since it excludes important assessment items such as mental status or motor functions. 
 
1.7 MEDICAL RESEARCH COUNCIL (MRC) SCALE MUSCLE STRENGTH EVALUATION 
The MRC scale is a validated and easy-to-use clinical scale at the bedside, which allows 
the assessment of muscle strength in 3 muscle groups of each upper and lower limb, in a 
range from 0 (paralysis) to 5 (normal strength) for each muscle group. The final result obtained 
ranges from 0 (total paralysis) to 60 (normal muscle strength in all 4 limbs). A value below 48 
is considered to define acquired weakness. 
 
1.8 FUGL-MEYER ASSESSMENT SCALE 
It is a tool that, through direct observation, evaluates motor performance based on 33 
items that are rated from 0 to 2 (0 = cannot do it, 1 = does it partially, 2 = maximum 
performance). The FMA-EU It takes about 30 min to complete and has a final score ranging 
from 0 (no functional limitation) to 66 (maximum limitation/disability). This scale has shown 
excellent reliability and construct validity, and has been validated for use in Spanish (Barbosa 
et al. 2019). A reduced version of the FMA-UE has recently been implemented, which includes 
6 of the original items. This version is quicker and easier to administer and appears to have 
good psychometric properties (Amano et al. 2020). 
 
1.9 GAS (Goal Attainment Scaling) 
It is an individualized, criterion-based measure of change, and its application involves defining 
a set of unique goals for the patient and then a range of outcomes that reflect specific 
therapeutic interventions. Kiresuk et al. (1994) strongly recommend the use of scales 
consisting of five levels of achievement, represented by f scores ranging from -2 to +2. It is 

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useful for measuring individual goals, functional goals, reflects a patient-centered perspective, 
and generates a numerical score for analyzing the performance of the multidisciplinary medical 
team. 23 
 
THERAPEUTIC OPTIONS AND EARLY INTERVENTION. 
Management of PSS includes physical modalities (e.g., stretching, range of motion 
exercises, ultrasound) (Duncan et al. 2005; Francisco and McGuire 2012) and pharmacologic 
therapies (e.g., intrathecal and oral baclofen, gabapentin, dantrolene, and botulinum toxins) 
(Duncan et al. 2005; Thibaut et al. 2013). OnabotulinumtoxinA is a type of botulinum toxin 
approved for the treatment of upper extremity spasticity in the United States and most regions 
of the world. 
Botulinum toxin A (BoNT-A) has been in clinical use for the treatment of post-stroke 
spasticity for approximately 30 years and is the accepted standard treatment for post-stroke 
focal spasticity. 1 BoNT-A treatment is now known to be safe and effective in both upper and 
lower limb spasticity, where it can result in both active and passive functional gains. 2 
Furthermore, BoNT-A is a first-line pharmacological treatment in the management of post-
stroke focal and multifocal spasticity, which together with a multidisciplinary team, should be 
part of a rehabilitation program to promote optimal clinical effect. 10 
BoNT-A has been shown to provide sustained reduction in upper limb spasticity after 
stroke when combined with rehabilitation in patients as early as 2 to 12 weeks post-stroke 
(Rosales, Kong et al 2012). 
The acute and early subacute phase after the first stroke is a phase of neuroplasticity 
that allows for effective intervention before maladaptation to severely altered muscle tone and 
spastic motor pattern, which generate deforming paresis and, in addition, tissue changes. 
Based on these assumptions, this transition from the early to the late subacute phase after the 
first stroke marks the boundary for the term "early versus late treatment with BoNT." 
In their ONTIME 2018 study Rosales et al investigated whether early injection of 
abobotulinumtoxinA after stroke delays the onset or progression of upper limb spasticity 
symptoms. They included 42 patients with a mean time post stroke of 6.18-6.52 weeks. With 
the application of abobotulinumtoxinA they obtained the greatest statistically significant 
decrease in tone between weeks 6 and 8 post-application compared to the placebo group who 
in no assessment between 4-12 weeks post-application achieved statistically significant tone 
decrease values. 14 
Although the ONTIME study suggests that early injection of abobotulinumtoxinA delays the 
development of symptomatic spasticity, the effects may not be restorative of maladaptive 
changes in the brain, due to the finite duration of the treatment effect. However, early treatment 
may modify disease progression before secondary local biomechanical changes occur. 14 

11 
 
Picelli et al. conducted a longitudinal, multicenter cohort study in which they aimed to 
determine whether the time elapsed between the stroke and the initial injection of BoNT-A had 
an effect on the management of spasticity. They included patients with an evolution time since 
the stroke of less than 12 months who had spasticity and who had received BoNT-A according 
to standard clinical practice. They evaluated them at 4, 12, and 24 weeks. They observed that 
those patients with more than 90 days of disease evolution had higher Ashworth scores at 4, 
12, and 24 weeks after the application of the drug compared to patients who underwent 
surgery less than 90 days after the stroke, suggesting the convenience of starting the 
management of spasticity with botulinum toxin within 3 months after the presentation of the 
stroke in order to obtain a greater reduction in muscle tone. 15 
Woo et al conducted a retrospective study in which their primary objective was to 
compare early versus late use of botulinum toxin for the management of spasticity after the 
first cerebrovascular event, they included 189 patients who received botulinum toxin within 15 
months after the first cerebrovascular event, in 68 of them toxin was applied within the first 12 
months of evolution, the mean time of evolution in which the drug was first applied was 
between 4.7 and 8.6 weeks and for the late application group of 49.6 weeks, they observed 
that the subsequent application intervals were significantly longer in the early use group (M = 
23.1 weeks) compared to the late start group (M = 14.6 weeks) reflecting better control of 
spasticity in the early start group. 16 
Rosales et al in 2012 conducted a double-blind study with the aim of studying the 
effectiveness of early use of toxin in patients with upper limb spasticity after a stroke, they 
included 163 patients of which, 80 were applied toxin and 83 were in the placebo group, all of 
them were within the first 12 weeks of evolution after the first stroke, they found that the 
application of toxin achieves a significantly greater decrease in muscle tone assessed by the 
Ashworth scale at 4 and 24 weeks compared to placebo, they did not observe significant 
differences in terms of function despite achieving good control of muscle tone, however, the 
long duration of the effect of the toxin on muscle tone is noteworthy, which could be attributable 
to the early modification of the changes in the rheological properties of spastic muscles. 17 
These interventions in the early stage of stroke recovery could potentially break the vicious 
cycle of the interaction of weakness and spasticity and reduce further development of 
spasticity. 16 
 
2. METHODS OF APPLICATION OF BOTULINUM TOXIN 
Santamato et al. evaluated spasticity in stroke patients after BoNT-A administration to the 
wrist and finger flexor muscles using ultrasound guidance and surface anatomical landmarks 
plus palpation. After one month of the treatment session, the patient group treated under 

12 
 
ultrasound guidance reported a statistically significant greater reduction in MAS compared to 
the group injected using manual needle placement with surface anatomical landmarks plus 
palpation to identify the target muscles. Ultrasound is well established as a reliable and 
reproducible imaging method in muscle anatomy. 22 
Picelli and colleagues, comparing three injection techniques for localizing forearm muscles 
in patients with upper limb spasticity after stroke, showed that instrumental guidance 
(ultrasound or electrical stimulation) compared with manual needle placement also improved 
clinical outcomes in these patients one month after injection. 
Ultrasound guidance allows injection into the muscles of the forearm, avoiding areas of fat 
and fibrosis, as well as assessing muscle depth and thickness, reducing the risk of needle 
insertion above the target thickness. Particularly useful in cases of decreased muscle trophism 
and for application to small and superficial muscles. 
Problem statement: 
Stroke is a leading cause of mortality and morbidity in adults in most countries. 
Spasticity is a common condition in stroke patients. 
Spasticity after stroke is often associated with pain, soft tissue stiffness, and joint 
contracture, and can lead to abnormal limb posture, decreased quality of life, increased 
treatment cost, and increased caregiver burden. Early detection of risk factors for spasticity 
and management of post-stroke spasticity not only reduces these complications, but may also 
improve function and increase independence in patients with spasticity. 
This pathology is responsible for a significant health expenditure due to the number of 
resources used in health services, which is why the disease is considered a priority health 
problem in our country. In our country, in 2015, just over 21 thousand cases of this disease 
were registered, and around 5 thousand deaths occurred in the main health institutions. Most 
of the survivors have moderate to severe sequelae. 5 
Justification 
In 2021, stroke in Mexico was the seventh cause of death in the general population, causing 
37,453 deaths, the majority in men over 65 years of age, according to data from the National 
Institute of Statistics and Geography (INEGI). In the world, it is the leading cause of disability 
in 
adults.  
In our country, there are 118 cases per 100,000 inhabitants, which represents 170,000 new 
patients per year, of which 20 percent may die in the first 30 days, and seven out of 10 will be 
left with some disability, with spasticity being one of the most disabling long-term sequelae. 21 
Zeng et al published a meta-analysis in which the prevalence of spasticity ranged from 4% to 
46% in the first month, 4.16% to 48% in 1–3 months, 6.9% to 63% in the 3–6 months of onset, 
and 7.6% to 49% beyond 6 months. 2%–2.6% of patients developed disabling or severe 

13 
 
spasticity within the first month of onset, 5% in 1–3 months, 8%–15.6% in 6 months, and 
12.5%–18% beyond 6 months. 
Currently, early treatment of PS-SMD in the early subacute phase after stroke is recommended to 
prevent or reduce the development of post-stroke complications, disability, and improve rehabilitation 
outcomes. 
Research question  
What are the effects of early application of botulinum toxin in patients with cerebrovascular 
events? 
 
HYPOTHESIS. 
Ho: Early application of botulinum toxin will have no effect on the development of spasticity in 
patients with stroke. 
Hi: Early application of botulinum toxin will have effects on patients with cerebrovascular 
events. 
GOALS 
General objective:  To evaluate the effects of early application of botulinum toxin in patients 
with cerebrovascular event 
 
Specific objectives: 
1. To describe the sociodemographic and clinical characteristics of patients with a 
cerebrovascular event in the first three months of evolution. 
2. To identify clinical risk factors that predict spasticity in the first 10 days of a 
cerebrovascular event. 
3. To measure the frequency of spasticity in patients suffering from stroke during the first 
three months of evolution. 
4. Recognize clinical risk factors predicting severe spasticity (MAS greater than 3) in the 
twelve weeks following the onset of stroke. 
5. To describe the short-, medium-, and long-term effects of early application of botulinum 
toxin plus rehabilitation on muscle tone, functionality, and quality of life in patients who 
suffer a first cerebrovascular event with a high risk of developing spasticity. 
6. To describe the short-, medium-, and long-term effects of early rehabilitation on muscle 
tone, functionality, and quality of life in patients who suffer a first stroke with a high risk 
of developing spasticity. 
7. To compare the short, medium and long-term effects on muscle tone, functionality and 
quality of life in patients who suffer a first cerebrovascular event with a high risk of 

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developing spasticity in the group treated with early rehabilitation and the group to which 
early application of botulinum toxin is added. 
 
Material and methods: 
Following approval by the Local Committee for Research and Ethics in Health Research 
(CLIES) of the Regional General Hospital Number 1 of the National Medical Center "Ignacio 
García Téllez" of the IMSS, Mérida, Yucatán, this study will be carried out with the following 
methodology: 
 
TYPE AND STUDY DESIGN.  
This study is a prospective, longitudinal, comparative controlled clinical trial. 
Universe of study: 
Patients entitled to the Regional General Hospital No. 1 “Lic. Ignacio García Téllez” 
IMSS Yucatán Delegation, currently active with a diagnosis of cerebrovascular disease 
admitted to hospitalization by the Internal Medicine and Emergency service of the Regional 
General Hospital No. 1 “Lic. Ignacio García Téllez”, in a period of three years. 
 
Sample: 
The sampling will be non-probabilistic, for convenience, and will include all patients 
diagnosed with stroke hospitalized in the Internal Medicine and Emergency Department of 
HGR1 of the Mexican Social Security Institute in Yucatan in a period of three years, who meet 
the inclusion criteria. 
SAMPLE SIZE 
It will be a census type and the sample will be determined by the total number of cases, 
that is, 100% of patients diagnosed with stroke hospitalized on the Internal Medicine and 
Emergency floor of HGR1 of the Mexican Social Security Institute in Yucatan in a period of 
three years, who meet the inclusion criteria. 
 
DEFINITION OF OBSERVATION UNITS 
Patients diagnosed with stroke hospitalized on the Internal Medicine and Emergency 
Department of HGR1 of the Mexican Social Security Institute in Yucatan in a three-year period, 
who meet the inclusion criteria. 
 
Inclusion criteria: 
• Men and women ≥18 years old. 

15 
 
• Beneficiaries who are treated in the Emergency and/or Internal Medicine service of HGR 
N°1, IMSS Mérida Yucatán, affected by an acute stroke with clinical symptoms and a new 
ischemic lesion in magnetic resonance imaging or computed tomography within 7 days of evolution. 
 
Exclusion criteria: 
• 
Severe cognitive deficits. 
• 
Severe language comprehension disorders. 
• 
Lack of capacity to give informed consent. 
• 
Physical disability already existing before the acute stroke. 
• 
Subarachnoid hemorrhage. 
• 
Transient ischemic attack. 
• 
Any other neurological disorder that could affect muscle tone (Conditions related to the spine, 
brain infection and traumatic brain injury). 
• 
Any amputation of the limb on the affected side. 
• 
Peripheral neuropathy of upper and/or lower limbs. 
• 
Patients who have suffered a previous stroke. 
Elimination criteria 
• 
Death. 
• 
Subsequent assessments are missing.  
• 
Presentation of a second cerebrovascular event. 
  
DEFINITION OF VARIABLES AND UNITS OF EXTENT. 
 
Dependent variables: Functional status, independence in daily living activities, pain, degree 
of spasticity, muscle stretch reflexes, muscle strength, alteration in superficial sensitivity, 
cognitive alteration, paresis, motor performance, achievement of goals. 
 
Independent variables: Age, sex, location of the lesion, chronic degenerative history (type 2 
diabetes mellitus, systemic arterial hypertension, smoking, heart disease, lung disease, kidney 
disease, liver disease, neurological disease, metabolic diseases, immunological disease, 
rheumatological disease), time of evolution, location of the lesion, type of cerebrovascular 
disease, clinical risk factors predicting spasticity. 
Table 1. Operational definition of the variables 
Variable 
Conceptual Definition 
Operational 
Definition 
Indicator 
Measuring scale 
Functional status 
Measuring how well a patient 
can carry out usual tasks and 
daily activities. 
 
It will be assessed 
using the Rankin scale 
score, which allows 
obtaining 
partial 
results 
about 
the 
patient's quality of life, 
Asymptomatic patient 
Mild disability 
Moderate disability 
Severe disability 
Death 
Qualitative nominal 

16 
 
since 
it 
excludes 
important assessment 
items such as mental 
state 
or 
motor 
functions. 
Independence 
in 
activities of daily 
living. 
Limitation of health-related 
attributes that allow a person 
to be and do what is important 
to him or her with the affected 
upper extremity 
It is obtained from the 
total sum of the scores 
obtained in the Barthel 
index, to obtain an 
average value that will 
be transformed into a 
final score. 
0-100%, a score close 
to 
0% 
indicates 
greater dependency 
Discrete quantitative 
Pain 
Unpleasant 
sensory 
and 
emotional 
experience 
associated with an actual or 
potential injury or described in 
terms of such injury. 
A 
10-centimeter 
horizontal line, at the 
ends of which are the 
extreme 
expressions 
of pain. On the left is 
the absence or lesser 
intensity and on the 
right is the greatest 
intensity. 
0 to 10 
Discrete quantitative 
Age 
Conceptual: 
time 
that 
a 
person has lived from birth to 
a certain moment 
It will be the age in 
years recorded in the 
file. 
Number of years 
Continuous quantitative 
Sex 
Conceptual: 
Set 
of 
peculiarities that characterize 
the individuals of a species, 
dividing them into male and 
female. 
It will be the sex 
according 
to 
the 
phenotypic 
assignment recorded 
in 
the 
file. 
 
 
Categorized 
as 
female or male. 
Dichotomous  
Nominal 
 
Chronic 
degenerative 
history 
Conceptual: 
A 
generally 
chronic 
condition 
during 
which a continuous process 
based 
on 
degenerative 
changes in cells takes place , 
in which the function or 
structure 
of 
the 
affected 
tissues or organs worsen 
over time. 
 
 
Operational: Presence 
of 
chronic 
degenerative 
diseases: 
(Diabetes 
Mellitus 
type 
2, 
Systemic 
arterial 
hypertension, 
Smoking, 
Heart 
disease) 
Disease 
(renal, 
hepatic, neurological, 
metabolic, 
immunological, 
rheumatological) 
reported in the file. 
But: 
Type 
2 
Diabetes 
Mellitus 
Systemic 
arterial 
hypertension 
Smoking 
Heart disease 
Lung disease 
Kidney disease 
Liver disease 
Neurological disease 
Metabolic diseases 
Immunological 
disease. 
Rheumatological 
disease 
Dichotomous 
Nominal 
 
 
 
 
 
Time of evolution 
(Duration 
of 
stroke) 
Conceptual: Time elapsed 
from the moment of onset of 
symptoms until a specific 
moment. 
 
 
Operational: 
Time 
(measured in days) 
elapsed 
from 
the 
moment of onset of 
symptoms associated 
with stroke until the 
moment of admission 
to 
the 
emergency 
department. 
 
Number of days 
 
Continuous quantitative 
Location 
of 
the 
lesion 
Area in the brain where the 
blood supply to part of the 
brain 
is 
interrupted 
or 
reduced, 
preventing 
brain 
tissue from receiving oxygen 
and nutrients. 
Site of the brain that 
suffers 
ischemia 
or 
hemorrhage, irrigated 
mainly by one of its 
three large arteries. 
Anterior 
cerebral 
artery territory. 
Middle cerebral artery 
territory 
Territory of posterior 
cerebral artery 
Qualitative Nominal 
Type 
of 
cerebrovascular 
disease 
Cerebrovascular disease is a 
clinical 
syndrome 
characterized by the rapid 
development 
of 
focal 
neurological 
signs, 
which 
persist for more than 24 
hours, 
with 
no 
apparent 
cause other than vascular 
origin. 
Cerebral ischemia is 
the consequence of 
the occlusion of a 
blood 
vessel. 
In 
intracerebral 
hemorrhage, 
the 
rupture of a vessel 
results in a collection 
of blood in the brain 
parenchyma. 
Ischemic/Hemorrhagi
c 
Dichotomous 

17 
 
Degree 
of 
Spasticity 
Conceptual: Motor disorder 
characterized 
by 
a 
rate-
dependent increase in tonic 
stretch reflexes (muscle tone) 
with 
exaggerated 
tendon 
spasms, 
as 
a 
result 
of 
hyperexcitability of the stretch 
reflex, as a component of 
upper 
motor 
neuron 
syndrome. 
 
Operational: It will be 
the 
presence 
of 
alteration of the tone 
measured 
on 
the 
modified 
Ashworth 
scale. 
Categorized 
according to modified 
Ashworth scale: 
0: No increase in 
muscle tone. 
1: Mild spasticity. 
2: Moderate spasticity 
3: Severe spasticity 
 
Qualitative ordinal 
 
Muscle 
stretch 
reflexes (MSR) 
Conceptual: 
Spinal 
reflex 
where the skeletal muscle, 
with intact innervation, is 
contracted 
involuntarily, 
immediately and briefly when 
a certain tendon is struck. 
 
Operational: It will be 
the grading of the 
motor 
response 
according 
to 
its 
intensity 
of 
the 
bicipital, 
tricipital, 
styloradial, 
patellar 
and Achilles muscle 
stretching 
reflexes, 
reported in the note of 
the first rehabilitation 
assessment 
in 
the 
patient's electronic file. 
Categorized 
according 
to 
REM 
grading scale: 
- 0 Normal 
-1 
Decreased 
response 
-2Increased response 
Qualitative nominal 
Muscle strength 
Conceptual: It is the result of 
the 
manual 
muscular 
examination, it is recorded in 
the form of a numerical score, 
variable between zero (0), 
which indicates absence of 
activity and five (5), which 
corresponds to a "normal" 
response. 
 
Operational: It will be 
the 
result 
of 
the 
manual 
muscle 
examination by muscle 
groups of shoulder, 
elbow, wrist, hip, knee 
and ankle, reported in 
the note of the first 
rehabilitation 
assessment 
of 
the 
patient's electronic file. 
Muscle strength grade 
(0-5) 
according 
to 
Medical 
Research 
Council Scale. 
- Presence of paresis:  
0 
Absent: 
total 
paralysis. 
1 
Minimal: 
visible 
muscle 
contraction 
without 
movement  
2 
Poor: 
movement 
without 
gravity. 
3 
Regular: 
partial 
movement 
against 
gravity only. 4 Good -: 
complete 
movement 
against gravity and 
minimal 
resistance. 
Good: 
complete 
movement 
against 
gravity and moderate 
resistance. 
- Normal/no paresis:  
5 
Normal: 
full 
movement 
against 
total resistance. 
Qualitative ordinal 
Altered superficial 
sensitivity 
Conceptual: 
Sensitivity, 
function 
of 
the 
nervous 
system through which the 
organism 
acquires 
information 
from 
the 
environment around it, having 
superficial 
free 
nerve 
terminals as receptors. 
 
Operational: It will be 
the 
presence 
of 
alterations 
in 
superficial 
tactile 
sensitivity 
by 
nerve 
segments/territories 
explored by means of 
a 
test 
with 
an 
exploration brush or 
swab, reported in the 
note 
of 
the 
first 
rehabilitation 
assessment 
in 
the 
patient's electronic file. 
But 
Nominal 
Dichotomous 
Cognitive 
impairment 
Conceptual:  
Intellectual 
or 
cognitive 
functions. 
 
Operational: It will be 
the score obtained in 
the Mini-Mental State 
Examination (MMSE) 
test for the evaluation 
of 
higher 
mental 
But 
Nominal 
Dichotomous 
 
 

18 
 
functions, reported in 
the note of the first 
rehabilitation 
assessment 
in 
the 
patient's electronic file. 
The maximum total 
MMSE score is 35 
points. 
Cognitive 
impairment 
is 
considered to occur 
with a score less than 
or equal to 23 points 
and 27 in geriatric 
patients. 
Paresis 
Decreased 
strength 
or 
absence 
of 
voluntary 
movement. 
Decreased strength or 
lack of movement in 
upper 
and/or 
lower 
limbs assessed with 
the NIHSS scale. 
Mild 
paresis 
was 
defined as a score of 1 
on item 5 and/or 6 of 
the NIHSS scale. 
Severe paresis was 
defined as a score ≥ 2 
on item 5 and/or 6 of 
the NIHSS scale. 
 
Qualitative ordinal 
Engine 
performance 
Motor skills aimed at 
achieving physical and 
functional independence. 
 
It will be evaluated 
through 
direct 
observation 
and 
application of the Fugl-
Meyer tool, which has 
shown 
excellent 
reliability and validity 
and 
has 
been 
validated in Spanish. 
0 
(no 
functional 
limitation) 
and 
66 
(maximum 
limitation/disability) 
 
Continuous quantitative. 
Scope 
of 
objectives 
It 
is 
an 
individualized, 
criterion-based measure of 
change, 
its 
application 
involves defining a set of 
unique goals for the patient 
and then a range of outcomes 
that 
reflect 
specific 
therapeutic interventions. 
Numerical 
score 
obtained by applying 
the GAS. 
-2 Much less 
-1 A little less 
0 Expected result 
1 A little more 
2 Much more 
Nominal qualitative. 
Clinical 
risk 
factors predicting 
spasticity 
These are parameters, signs 
and symptoms that appear 
early and help predict the 
presence of spasticity in 
patients who have had a 
stroke. 
Answer 
to 
the 
question: Do you have 
any clinical risk factors 
that predict spasticity? 
But 
Qualitative Dichotomous 
 
METHODS, TECHNIQUES AND PROCEDURES FOR COLLECTING INFORMATION. 
Patients who are eligible for the General Regional Hospital No. 1 “Lic. Ignacio García Téllez” 
IMSS Yucatán Delegation, currently active with a diagnosis of cerebrovascular disease 
admitted to hospital by the Internal Medicine/Emergency service, will be selected. An initial 
assessment will be carried out by the Rehabilitation service within the first seven days after 
the onset of the stroke, where the patient will be invited to take part in the study, expressing 
the reason, intention, and structure of the work plan, upon confirming their participation they 
will sign informed consent (Annexes) and the following will be done: 
1. Assignment of a folio number to structure your file. 
2. Record of sociodemographic data (ANNEXES). 
3. Capture of data obtained through clinical records (ANNEXES). 
4. Neurological physical examination. 
4.1 Assessment of spasticity 

19 
 
Spasticity will be assessed using the Modified Ashworth Scale (MAS). This is a 6-point ordinal 
scale with documented reliability. Technique: The patient will be assessed in a resting position. 
The assessment includes passive flexion and extension movements around the upper joints 
(shoulder, elbow, wrist, and fingers) and lower extremities (hip, knee, and ankle) performed by 
a Physical Therapy Resident. Spasticity will be defined as a MAS score ≥ 1 for any of the 
passive movements performed, in accordance with most previous studies on spasticity after 
stroke. Moderate spasticity was defined as MAS ≥ 2, and severe spasticity as MAS ≥ 3+. 
4.2 Application of Barthel index (ANNEXES). 
4.3 Application of Modified Rankin Scale (ANNEXES). 
4.4 Application of Mini Mental State Examination (ANNEXES). 
4.5 Application of NIHSS Scale (ANNEXES), will be used for the following 3 purposes: 
• 
Assess stroke severity (total NIHSS score). 
• 
To assess the severity of paresis. Severe paresis was defined as a score ≥ 2 on item 5 
and/or 6. 
• 
Assess the presence of sensory disturbance, defined as a score ≥ 1 in item 8. 
4.6 Muscle strength assessment 
The main muscle groups of the upper limbs (shoulder abductors, elbow flexors and wrist 
extensors) and lower limbs (hip flexors, knee extensors, ankle flexors) will be assessed. The 
assessment will be made using the Medical Research Council (MRC) scale for the examination 
of muscle strength, the final result obtained ranges from 0 (total paralysis) to 60 (normal 
muscle strength in all 4 limbs). Technique: 
•The muscle groups involved in 1) shoulder abduction, 2) elbow flexion, 3) wrist dorsiflexion, 
4) hip flexion, 5) knee extension, and 6) ankle dorsiflexion will be assessed bilaterally and 
systematically. 
•Each muscle group will be evaluated with a score of 0 to 5 based on the following criteria: 
Grade 0 No contraction visible or palpable. Grade 1 Mild contraction visible or palpable, 
although no movement of the limb is observed. Grade 2 Movement performed without weight 
through all or more than half of the range of motion. Grade 3 Movement against gravity through 
all or more than half of the range of motion. Grade 4 Movement against mild-moderate 
resistance through the entire range of motion. Grade 5 Normal contraction power (heavy 
resistance). 
 •Muscle assessment will be initiated for an MRC grade of 3 and progressed to grade 2 or 4 
depending on the results. 
•First, the Resident Physician will reproduce the movement passively and then ask the patient 
to do the active movement. 
•A muscle group will be evaluated bilaterally in order to move on to the next muscle group. 

20 
 
•Up to 3 attempts will be made for each muscle group. 
•Rest periods between measurements will be a maximum of 30 seconds unless the patient 
needs more time to recover. 
•The patient will be stimulated to maintain the contraction for 5-6 seconds. 
4.7 Application of the Fugl-Meyer Scale for assessing upper and lower limb functionality 
(ANNEX VII). 
6. The patient will be admitted to an intervention group (early neurological rehabilitation vs 
early neurological rehabilitation + application of botulinum toxin). 
7. APPLICATION OF BOTULINUM TOXIN. Patients who meet high-risk criteria for developing 
spasticity in the first twelve weeks following a first cerebrovascular event will be administered 
botulinum toxin type A under ultrasound guidance to the affected limbs according to the degree 
of spasticity. 
8. Three subsequent assessments will be carried out to evaluate the development of spasticity 
and the factors associated with its onset at four, eight and twelve weeks, as well as the early 
initiation of neurological rehabilitation and the early application of botulinum toxin with 
subsequent quarterly reassessments until two years after the onset of the cerebrovascular 
event. Patient recruitment will be carried out at the HGR1 Hospital of the Mexican Social 
Security Institute in Yucatan over a period of three years, and the follow-up time until the last 
patient will complete five years in total. 
 
STATISTICAL ANALYSIS  
The information will be captured in an Excel 2019 spreadsheet (Microsoft ©, Redmont, 
Washington) and IBM® SPSS Statistics® version 22 to create the database. The analysis 
and results presentation plan will comprise two phases: 
a) Descriptive phase. Simple frequencies, percentages, measures of central tendency 
(mean, median and mode) will be calculated for data with abnormal distribution, and 
dispersion (range, standard deviation) for data with normal distribution, according to the 
distribution of the variables, using Excel 2019 (Microsoft ©, Redmont, Washington) and 
IBM® SPSS Statistics® version 22. The description will be complemented with tables 
and graphs depending on the nature of the variables. 
b) Inferential phase. The results of quantitative variables The qualitative variables will be 
compared with the Student t test for paired samples if their distribution is normal or with 
the Wilcoxon rank test otherwise. The qualitative variables will be compared with the 
Chi square test. In all cases, a p value <0.05 will be considered statistically significant. 

21 
 
ETHICAL CONSIDERATIONS.  
The design of this study complies with the national and international institutional regulations 
governing health research, as well as those corresponding to research on human beings. 
Including the Regulation that establishes the provisions for Health research at the Mexican 
Social Security Institute 2000-001-009 31; the General Health Law and the Declaration of 
Helsinki (Fortaleza, Brazil, 2014). According to the regulations of the General Health Law, 
second title "Ethical Aspects of Research on Human Beings", chapter I, this research protocol 
is considered as research with greater than minimum risk, since random methods of 
assignment to therapeutic schemes will be used, for which reason a letter of informed consent 
will be requested. Annex V The principles of bioethics are respected. It will be considered 
equitable, since the results obtained in the present study will allow us to guide the management 
of patients with spasticity due to a cerebrovascular event and guide it in order to better obtain 
various aspects of their lives. There is justice, since there will be an adequate balance between 
the investment made and the knowledge obtained. The integrity of the subject is not put at 
risk, so the principle of non-maleficence is respected. The aim is to obtain results that improve 
the care of this type of patient (beneficence). The necessary measures will be taken to protect 
patient data through coding, so as not to identify the name or personal data of patients that 
may compromise their integrity. The research project will be submitted to the local committee 
for Research and Ethics of Health Research No. 3401, where it will be evaluated and verified 
that the necessary criteria are met to be able to carry it out, and if necessary, authorize it. 
 
Human Resources 
Physicians and resident physicians in the specialty of rehabilitation medicine qualified 
to perform ultrasound-guided botulinum toxin application procedures.  
 
Material resources 
- Botulinum toxin 100U 
- 500 needles 20g 
- 800 alcohol swabs 
- 2 liters of 70% ethyl alcohol 
- 800 syringes of 1 ml 
- 300 syringes of 3 ml 
- conductive gel 
- Marshall portable ultrasound Mod. M9 version 2022 with linear transducer with frequency up 
to 12-15MHz. 
- white sheets 

22 
 
- desktop computer 
 
Feasibility 
This study has a high probability of completion because it is a high referral hospital for 
neurological patients. 
 
Schedule of activities 
Year 
1st 
2nd 3rd 4th 5th 6th 
Choice of topic 
 
 
 
 
 
 
Protocol development 
 
 
 
 
 
 
Protocol registration 
 
 
 
 
 
 
Patient identification, 
application of treatments and 
assessment. 
 
 
 
 
 
 
Capturing information 
 
 
 
 
 
 
Database development 
 
 
 
 
 
 
Data analysis 
 
 
 
 
 
 
Presentation of results 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

23 
 
LITERATURE 
1. Parra, JA (2019). Ischemic stroke: an extensive review of the literature for the primary 
care physician. Med Int Méx, 61-63. 
 
2. Cantu-Brito. (2015). Hospitalized Stroke Surveillance in the Community of Durango, 
Mexico. VA MONTH CTR BOISE, 877-884. 
 
 
3. Cuadrado, A. (2009). Stroke rehabilitation: assessment, prognosis and treatment. 
Galicia Clínica/Sociedad Galeaga de Medicina Interna, 25-34. 
 
4. Marlenne, RS (2015). In-hospital mortality due to cerebrovascular diseases in the main 
public health institutions in Mexico. CONAMED-PAHO BULLETIN, 7-11. 
 
 
5. Glaess-Leistner, S. (2020). Early clinical predictors of post-stroke spasticity. Topics in 
Stoke Rehabilitation, 1-10. 
 
6. Li, M. P. (2021). A new definition of poststroke spasticity and the interference of 
spasticity with motor recovery from acute to chronic stages. Neurorehabilitation and 
Neural Repair, 601-607. 
 
7. Jacky, G. (2021). Muscle Tone Physiology and Abnormalities. Toxins, 1-20. 
 
 
8. Sunnerhagen, K. (2018). Onset, time course and prediction of spasticity after stroke or 
traumatic brain injury. Annals of Physicial and Rehabilitation Medicine, 1-4. 
 
9. Huangling, Z. (2021). Prevalence and Risk Factors fos Spasticity After Stroke: A 
Systematic Review and Meta-Analysis. Frontiers in Neurology, 1-12. 
 
 
10. Gerard E, FM (2020). A practical guide to optimizing the benefits of post-stroke 
spasticity interventions with botulinum toxin: An international group consensus. Journal 
of Rehabilitation Medicine, 2-14. 
 
11. Stephen, AD (n.d.). Spasticity in adults: management using botulinum toxin. Royal 
College of Physicians, 3-22. 
 
 
12. Atul, P.T. (2020). Impact of early intervention with onabotulinumtoxinA treatment in 
adult patients with post-stroke lower limb spasticity: results from the double-blind, 
placebo controlled, phase 3 REFLEX study. Journal of Neural Transmission, 1-11. 
13. Raymond, R.L. (2016). Botulinum toxin as early intervention for spasticity after stroke 
or non-progressive brain injury: A meta-analysis. . Journal of Neurological Sciences, 6-
14. 
 
14. Zeng, H. (2021). Prevalence and Risk Factors After Stroke: A Systematic Review and 
Meta-Analysis. Frontiers in Neurology, 1-12. 
 
 

24 
 
15. Katharina, S. S. (2016). Predictors of Spasticity After Stroke. Stroke Rehabilitation, 182-
185. 
 
16. Arve, O. (2015). Early prediction of long-term upper limb spasticity after stroke. 
American Academy of Neurology, 873-880. 
 
 
17. Kong, K. H. (2012). Occurrence and Temporal Evolution of Upper Limb Spasticity in 
Stroke Patients Admitted to a Rehabilitation Unit. Arch Phys Med Rehabil, 143-148. 
 
18. Nam, K. E. (2019). When does spasticity in the upper limb develop after a first stroke? 
A nationwide observational study on 861 stroke patients. Journal of Clinical 
Neuroscience, 144-148. 
 
 
19. Elliot, J. (2016). Predictive Factors of Spasticity and Their Effects on Motor Recovery 
and Functional Outcomes in Stroke Patients. Topics in Stroke Rehabilitation, 380-388. 
 
20. Farah-Góngora, NA (2021). Cerebrovascular event in a young patient in the Internal 
Medicine Hospitalization Service during 2020-2021 in a Second Level Center in Mérida, 
Yucatán. Revista Ictus, 16-24 
 
21. Wissel Jorg (2023). Early versus late injections of Botulinumtoxin type A in post-stroke 
spastic movement disorder: A literature review. Toxicon 229, 107150. Elsevier Ltd. 
https://doi.org/10.1016/j.toxicon.2023.107150 . 
 
22. Santamatoa Andrea, Micello Maria Francesca, et al. (2014). Can botulinum toxin type 
A injection technique influence the clinical outcome of patients with post-stroke upper 
limb spasticity? A randomized controlled trial comparing manual needle placement and 
ultrasound-guided injection techniques. Journal of the Neurological Sciences 347, 39–
43. http://dx.doi.org/10.1016/j.jns.2014.09.016 . 
 
23. McDougall, Janette Ph.D. (2007). GOAL ATTAINMENT SCALING: Description, Utility, 
and Applications in Pediatric Therapy Services. Research Associate, Thames Valley 
Children's Centre. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

25 
 
ANNEXES 
EXHIBIT YO. CONSENT INFORMED. 
 
 
                   MEXICAN INSTITUTE OF SOCIAL SECURITY 
                   EDUCATION, RESEARCH AND HEALTH POLICIES UNIT. 
                   HEALTH RESEARCH COORDINATION. 
 
INFORMED CONSENT LETTER. 
(ADULTS) 
INFORMED CONSENT LETTER TO PARTICIPATE IN RESEARCH PROTOCOLS. 
 
Study name: 
Evaluation of the effects of early application of 
botulinum toxin in patients with a first 
cerebrovascular event 
Place and date: 
HGR No. 1, IMSS, Merida, Yucatan. 2024-
2028. 
 
Justification and objective of the study: 
To evaluate the effects of early application of 
botulinum toxin in patients with a first 
cerebrovascular event. 
Procedures: 
Patients who have suffered a stroke during the 
first seven days of their illness and who meet 
risk factors for developing spasticity will be 
selected and divided into two groups: one of 
which will receive botulinum toxin in the 
affected arm and/or leg plus a rehabilitation 
program and the other only the rehabilitation 
program. Assessments will be carried out at 
four, eight and twelve weeks and subsequently 
every 3 months. 
Possible risks or discomforts 
Pain at the application site, muscle or joint pain 
typical of any rehabilitation exercise program. 
Possible benefits you will receive by 
participating in this study: 
Decreased spasticity in the affected body, 
decreased pain when moving, improved 
quality of life. 
Information on results and treatment 
alternatives: 
The results of each patient will be reported 
individually to the patient and family. 
Participation or withdrawal: 
I have been informed that I am free to decide 
whether or not to participate in this study and 
that I may withdraw from it at any time without 
this affecting the care I receive from the 
Institute. 
Privacy and confidentiality: 
I was told that my personal data will be 
encrypted and protected in such a way that it 
can only be identified by the Researchers of 
this study or, where appropriate, future studies. 
 
In case of doubts or clarifications related to the study, you can contact: 
Principal Investigator: 
Dr. Roberto Carlos Pech Argüelles. 
Contributors: 
Dr. Giovanna Gómez Arredondo, Dr. Jezabel 
Xitlalic Figueroa Flores, Dr. Omar Eligio 

26 
 
Huchin Cámara, Dr. Abigail Mariela Arriaga 
Coria, Dr. Maria Eugenia Galindo Gonzalez. 
 
In case of doubts or clarifications regarding your rights as a participant, you may contact: 
Research Ethics Commission of the CNIC of the IMSS: Avenida Cuauhtémoc 330 4th floor 
Block “B” of the Congress Unit, Colonia Doctores. Mexico City, CP 06720. Telephone (55) 56 
27 69 00 extension 21230, Email: comision.etica@imss.gob.mx 
 
 
___________________________________ 
Name and signature of the subject. 
 
 
 
___________________________________ 
Name and signature of the person obtaining 
consent. 
 
 
 
___________________________________ 
Name and signature of Witness 1 
 
 
 ___________________________________ 
Name and signature of Witness 2 
 
Key: 2810-009-013 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

27 
 
ANNEX II. Data collection instrument 
Institute Mexican Of the Sure Social (IMSS).  
DATE OF ADMISSION: 
Delegation State Yucatan.  
FOLIO: 
HGR No.1 “Lic. Ignacio Garcia “Tellez”. 
 
Medicine of Rehabilitation. 
 
EVALUATION OF THE EFFECTS OF EARLY APPLICATION OF BOTULINUM TOXIN IN PATIENTS WITH A 
FIRST CEREBRAL VASCULAR EVENT 
 
SHEET OF COLLECTION OF DATA (Instrument of harvest) 
 
 
Sociodemographic 
Name: 
Number of security social: 
Age: 
Sex: 
State civil: 
Place of residence: 
Level of schooling: 
Laterality: 
Occupation current: 
Activity physics either sport: 
Activity recreational current: 
Phone cellular: 
 Mail electronic: 
 
Background personal pathological of importance. 
Smoking: 
Styling: 
Hypertension Arterial Systemic 
(HAS). 
Diabetes Mellitus Guy 2 (DM2) 
Others pathologies: 
 
 
 
 
 
 
 
 
 
 
 
• 
Symptomatology current. 
Pain 
Paresis 
Spasticity 
Cognitive impairment 
Change in 
sensitivity 
Language disorders 
 
• 
Exploration physics. 
Weight: 
Size: 
BMI: 
 
Complement 
 
• 
Variables: 
Income. 
/  
/ 
4 
weeks. 
/  
/ 
8 
weeks. 
/  
/ 
12 
weeks. 
/  
/ 
Suffering current. 
Date of start: 
Etiology: 
Treatment initial (date, guy and time): 
Days of delay in he treatment or Others 
complications: 
CT date: 
Type of injury: 
EVOLUTION 

28 
 
Pain (ENA) 
Manual muscle examination of upper and lower limbs (right/left) 
Upper 
limb 
Shoulder 
flexion 
Shoulder 
abduction 
Elbow flexion 
Clamp 
Lower limb 
Hip flexion 
Knee 
extension 
Ankle flexion 
Trunk control (Yes/No) 
 
Income. 
/  
/ 
4 
weeks. 
/  
/ 
8 
weeks. 
/  
/ 
12 
weeks. 
/  
/ 
Upper and lower limb spasticity (right/left). Modified Ashworth Scale 
Upper limb 
Shoulder 
abductors 
Elbow flexors 
Finger flexors 
Lower limb 
Hip adductors 
Knee flexors 
Ankle 
plantarflexors 
 
 
 
REMS 
 
Bicipital 
Tricipital 
Radial style 
Patellar 
Achilles 
Decreased (+) 
 
 
 
 
 
Normal (++) 
 
 
 
 
 
Increased (+++) 
 
 
 
 
 
 
 
Barthel Index Score 
Modified Rankin Scale Score 
Mini Mental State Examination Score 
NIHSS Scale Score 
Stroke severity: 
Severity of 
paresis: 
Sensory 
disturbance: 
Fugl-Meyer Assessment Scale Score (Upper 
Extremity) 
 
 
 
 
 
NOTAS: 

29 
 
ANNEX III. BARTHEL INDEX 
Institute Mexican Of the Sure Social (IMSS).  
DATE: 
Delegation State Yucatan.  
FOLIO: 
HGR No.1 “Lic. Ignacio Garcia “Tellez”. 
 
Medicine of Rehabilitation. 
 
EVALUATION OF THE EFFECTS OF EARLY APPLICATION OF BOTULINUM 
TOXIN IN PATIENTS WITH A FIRST CEREBRAL VASCULAR EVENT 
 
Barthel index 
Activity 
Description 
Punctuation 
Eat 
1. Dependent 
0 
2. Needs help cutting, spreading butter, using 
condiments, etc. 
5 
3. Independent (able to use any instrument) 
10 
Transferring 
between  
chair and bed 
1. Dependent, does not sit still 
0 
2. Requires significant assistance (1 trained person 
or 2 people), can be seated 
5 
3. Needs some help (a little physical help or verbal 
help) 
10 
4. Independent 
15 
Personal 
hygiene 
1. Dependent 
0 
2. Independent for washing face, hands and teeth, 
combing hair and shaving 
5 
Using the 
toilet 
1. Dependent 
0 
2. Needs some help, but can do something alone 
5 
3. Independent (getting in and out, cleaning and 
dressing) 
10 
Bathing or  
showering 
1. Dependent 
0 
2. Independent for bathing or showering 
5 
Commute 
1. Motionless 
0 
2. Independent in wheelchair in 50 m 
5 
3. Walks with a little help from a person (physical or 
verbal) 
10 
4. Independent for at least 50 m, with any type of 
crutch, except a walker 
15 

30 
 
Going up and 
down  
stairs 
1. Dependent 
0 
2. Needs physical or verbal assistance, can use any 
type of crutch 
5 
3. Independent for up and down 
10 
Dressing and  
undressing 
1. Dependent 
0 
2. Needs help, but can do about half of it without 
help 
5 
3. Independent, including buttons, zippers, laces, 
etc. 
10 
Stool control 
1. Incontinent (or requires enema) 
0 
2. Exceptional accident (one/week) 
5 
3. Continent 
10 
Urine control 
1. Incontinent, or catheterized and unable to change 
the bag 
0 
2. Exceptional accident (maximum one/24 hours) 
5 
3. Continent, for at least 7 days 
10 
 
INTERPRETATION OF THE BARTHEL INDEX 
 
Punctuation 
Classification 
<20 
Total dependency 
21 – 60 
Severe dependency 
61 – 90 
Moderate dependence 
91 – 99 
Mild dependency 
100 
Independence 
 
• Cabañero-Martínez MJ. et al. Arch Gerontol Geriatr. 2009;49(1):e77, PMID: 18990459. 
 
 
 
 
 
 

31 
 
ANNEX IV. MODIFIED RANKIN SCALE 
Institute Mexican Of the Sure Social (IMSS).  
DATE: 
Delegation State Yucatan.  
FOLIO: 
HGR No.1 “Lic. Ignacio Garcia “Tellez”. 
 
Medicine of Rehabilitation. 
 
EVALUATION OF THE EFFECTS OF EARLY APPLICATION OF BOTULINUM TOXIN IN PATIENTS 
WITH A FIRST CEREBRAL VASCULAR EVENT 
 
MODIFIED RANKIN SCALE 
0. Asymptomatic 
1. Without significant disability. 
Has some symptoms and signs but no limitations in carrying out normal activities or work. 
Questions: Does the patient have difficulty reading or writing, speaking or finding the right 
word, problems with stability or coordination, visual disturbances, numbness (face, arms, 
legs, hands, feet), loss of mobility (face, arms, legs, hands, feet), difficulty swallowing or 
other symptoms after the stroke? 
2. Mild disability 
The patient has limitations in his/her usual activities and previous work, but is independent 
in basic activities of daily living (BADL). Questions: Has there been any change in the 
patient's ability to perform usual activities or work or caregiving compared to before the 
stroke? Has there been any change in the patient's ability to participate in social or leisure 
activities? Does the patient have problems with personal relationships with others or has 
he/she become socially isolated? 
3. Moderate disability 
Needs help with some instrumental activities but not with basic activities of daily living. Walks 
without help from another person. Needs a caregiver at least twice a week. Questions Do 
you need help with meal preparation, housekeeping, money management, shopping, or 
using public transportation? 
4. Moderately severe disability 
Unable to adequately care for self, requiring assistance with walking and basic activities. 
Requires caregiver at least once a day, but not continuously. May be left home alone for a 
few hours. Questions: Does he/she require assistance with eating, using the bathroom, daily 
hygiene, or walking? Could he/she be left alone for a few hours a day? 
5. Severe disability. 
Needs constant attention. Bedridden. Incontinent. Cannot be left alone. 
6. Death/Success. 
 
 
 
 

32 
 
APPENDIX V. MINI MENTAL STATE EXAMINATION (MMSE) 
Institute Mexican Of the Sure Social (IMSS). 
 
Delegation State Yucatan 
HGR No.1 “Lic. Ignacio Garcia “Tellez”. 
 
Medicine of Rehabilitation. 
EVALUATION OF THE EFFECTS OF EARLY APPLICATION OF BOTULINUM 
TOXIN IN PATIENTS WITH A FIRST CEREBRAL VASCULAR EVENT. 
 
MINI MENTAL STATUS EXAMINATION (MMSE) 
 
 
ORIENTATION IN TIME 
0 
1 
What Day is it (date): 
 
 
In which month: 
 
 
In which year: 
 
 
On what day of the week: 
 
 
What time is it approximately? 
 
 
 
SCORE (max. 5) 
ORIENTATION IN SPACE 
 
0 
1 
Where are we now? 
 
 
What floor or apartment are we on now? 
 
 
What neighborhood or parish is this? 
 
 
What city are we in? 
 
 
What country are we in? 
 
 
 
SCORE:(max. 5) 
MEMORY 
INSTRUCTION: “I am going to tell you the names of three objects. When I finish, I would like you to please 
repeat them.” 
*Pronounce the words clearly, one every second, then ask the older adult to repeat them. Give one point for 
each correct answer. Repeat the words until the person learns them (max. 6 attempts) but only the first 
repetition or attempt is scored. 
 
0 
1 
Paper 
 
 
Bicycle 
 
 
Spoon 
 
 
 
SCORE: (max. 3) 
ATTENTION AND CALCULATION: 
INSTRUCTION: “I am going to ask you to subtract 7 at a time starting from 100.” 
0 
1 
93 
 
 
86 
 
 
79 
 
 
72 
 
 
65 
 
 
 
 
1 Taken from: Reyes, S., Beaman, P, García-Peña, C., Villa, MA, Heres, J., Córdova, A. and Jagger, C. (2004). Validation of a modified version of the Mini-
Mental State Examination (MMSE) in Spanish. Aging Neuropsychology and Cognition, 11, 1-11 
 
MINI MENTAL STATUS EXAMINATION1 
(Folstein et al. 1975) 
CARD NO. 3c 
Name 
From the User: 
Area: 
District: 
Type of Care: 
Name of the Care Unit: 
 
Age 
Years: 
Months: 
Application date: 
Applied by: 
 

33 
 
SCORE: (max. 5) 
DEFERRED MEMORY 
INSTRUCTION: “Tell me the 3 objects I mentioned at the beginning.” 
0 
1 
Paper 
 
 
Bicycle 
 
 
Spoon 
 
 
 
SCORE:(max. 3) 
DENOMINATION 
0 
1 
Show him a pencil or a pen and ask, “What is this?” 
 
 
Show him a clock and ask, what is this? 
 
 
 
SCORE:(max. 2) 
REPETITION OF A PHRASE 
INSTRUCTION: “ Now I am going to tell you a sentence that you will have to repeat after 
me. I can only say it once, so pay close attention.” 
0 
1 
"neither yes, nor no, nor but" 
 
 
 
SCORE:(max. 1) 
UNDERSTANDING – EXECUTION OF ORDER 
INSTRUCTION: “I am going to give you some instructions. Please follow them in the order in which I am going 
to say them. I can only say them once”: 
“TAKE THIS PAPER WITH YOUR RIGHT HAND, FOLD IT IN HALF AND LEAVE IT ON THE FLOOR” 
 
0 
1 
Take this paper with your right hand 
 
 
Fold it in half 
 
 
Leave it on the ground 
 
 
 
SCORE:(max. 3) 
READING. 
0 
1 
Write legibly on a piece of paper "close your eyes." Ask the older adult to read it and do 
what the phrase says. 
 
 
 
SCORE:(max. 1) 
WRITING. 
0 
1 
INSTRUCTION: “I would like you to please write a sentence that conveys a message.” 
 
 
 
 
SCORE:(max. 1) 
COPY OF A DRAWING. 
0 
1 
INSTRUCTION: “Please copy this drawing as is” 
 
 
 
SCORE:(max. 1) 
TOTAL SCORE: (max. 30 points) 
  
                                                                                       
 
 
EVALUATOR'S SIGNATURE 
 
REFERENCE SCORES: 
 
27-30 
Normal 

34 
 
24 - 26 
Pathological 
suspicion 
12-23 
Deterioration 
9-11 
Dementia 
 
INTERPRETATION OF THE RESULT ACCORDING TO AGE AND LEVEL OF EDUCATION 
In the event that this test is applied to elderly people who are illiterate or have a low level of education, the 
score must be adapted using the following table: 
 
 
Age (years) 
Schooling 
Less 
than 
50 
51-75 
More 
than 75 
Less than 8 years of study 
0 
+1 
+2 
From 9 to 17 years of study 
-1 
0 
+1 
More than 17 years of study 
-2 
-1 
0 
 
* In these cases, what should be done is to take the total score and add or subtract the values indicated in the 
table taking into account the age and level of education or schooling of the older adult. And then this result is 
compared with the reference scores. For example: 
 
If the user is 78 years old, has 4 years of education and obtained a final score of 22 points, taking into account 
what is indicated in the table, 2 points must be added to his final score which would give him a total of 24 points 
which within the reference scores corresponds to a state of pathological suspicion. 
 
Mini-Mental State Examination (MMSE or Mini-Mental) according to the version by Reyes et al. (2004) 
INSTRUCTIVE2 
REAGENTS 
INSTRUCTIONS FOR ADMINISTRATION 
ORIENTATION IN TIME 
(5 points)  
ORIENTATION IN PLACE 
(5 points) 
Ask for today's date. Then ask specifically about the omitted data. 
Score: 1 point for each correct answer 
 
MEMORY (3 points) 
 
Say the three words clearly and slowly, one per second. When 
you finish, ask for them to be repeated and award one point for 
each word correctly repeated on the first attempt. 
When you finish, continue saying them until the patient can 
repeat them (minimum 3 repetitions, maximum 6). 
If after six repetitions you still cannot learn them, do not apply 
the memory. 
 
ATTENTION AND CALCULATION (5 
points) 
You can use the question “What is 100 minus 7?... minus 7?” etc. 
to support this question. Avoid mentioning the number from 
which you are subtracting, i.e. “93 minus 7 or 86 minus 7”, etc., 
unless it is essential for the test to continue. Give one point for 
each correct subtraction. 
DEFERRED MEMORY (3 points) 
 
Award one point for each word correctly recalled. 
 
DENOMINATION (1 POINT) 
 
Prevent the user from picking up objects unless there is 
significant visual weakness; try to ensure that information 
reaches the user only through the visual pathway. 
One point is awarded for each correctly named object. 
 
2 Taken from: https://www.villaneuropsicologia.com/uploads/1/4/4/5/14457670/mini_examen_del_estado_mental.pdf                                                                               
 

35 
 
REPETITION OF A PHRASE (1 point) 
Say the sentence once, clearly and slowly, but without breaking 
up the sentence. Grade based on this one attempt. Give one 
point for correct repetition. 
UNDERSTANDING – EXECUTION OF 
ORDER (3 points) 
While giving the command, keep the paper in view of the patient, 
but do not allow him to take it before you finish giving the 
commands. Perform only one trial and award one point for each 
action correctly performed. 
READING (1 point) 
Award a point only if the older adult performs the action. If he or 
she only reads the sentence, score 0. 
WRITING (1 point) 
Use a blank sheet of paper. The sentence must be written 
spontaneously, do not dictate any sentence. It must contain a 
subject, verb and predicate. Do not grade spelling. 
COPY OF A DRAWING. 
10 angles and two intersections must be present. Ignore wobble 
or rotation. 
 
 
• 
Beaman, Sandra Reyes de, Peter E. Beaman, Carmen García-Peña, Miguel Ángel Villa, Julieta Heres, 
Alejandro Córdova, and Carol Jagger, 2004. “Validation of a modified version of the Mini-Mental State 
Examination (MMSE) in Spanish.” Aging, Neuropsychology and Cognition 11 (1): 1-11. 
http://doi.org/10.1076/anec.11.1.1.29366 
 
 
 
 
 
 
 
 

36 
 
ANNEX VI. NIHSS SCALE 
Institute Mexican Of the Sure Social (IMSS). 
 
Delegation State Yucatan 
HGR No.1 “Lic. Ignacio Garcia “Tellez”. 
 
Medicine of Rehabilitation. 
 
EVALUATION OF THE EFFECTS OF EARLY APPLICATION OF BOTULINUM 
TOXIN IN PATIENTS WITH A FIRST CEREBRAL VASCULAR EVENT 
 
NIHSS scale "National Institute of Health Stroke Scale" 
1. LEVEL OF CONSCIOUSNESS 
1st. Alert 
Alert with answers normal 
0 
No alert, but reply to minima stimuli verbal 
1 
No alert, but reply to stimuli repeated either painful (No highlights) 
2 
No reply to stimuli painful either only with movements highlights 
3 
1b. Questions oral 
Ask he month current and the age. Rate only the first one answer. 
Both answers are correct 
0 
Only a Answer is correct, IOT, very dysarthric or barrier idiomatic 
1 
None is correct 
2 
1c. Orders motor 
Close - open the eyes and close – open the hand (side No paretic) 
Both answers are correct 
0 
Only a Answer is correct 
1 
None is correct 
2 
2. LOOK CONJUGATED 
It means that both eyes do the same thing and at rest the eyes are in a central position. Explore 
only the look horizontal voluntary either with highlights oculocephalic 1 in comatose 
Normal 
0 
Paresis partial of the look either paresis peripheral of an oculomotor nerve 2 
1 
Paresis total either deviation forced of the look conjugated 
2 
3. FIELDS VISUALS BY CONFRONTATION 
TO one meter of distance of the patient and cover he eye that is not going to be 
explored Explore the upper quadrants and inferior 
Vision No altered 
0 
Hemianopia 3 partial either visual extinction 4 
1 
Hemianopia complete 
2 
Blindness total 
3 
4. PARESIS FACIAL 
Teach the teeth, Yeah No collaborate HE can explore with a stimulus painful 
Motion normal (symmetry of the hemicaras) 
0 
Minimum asymmetry 
1 
Paralysis of the area lower of a hemiface 
2 
Paralysis of the areas lower and superior of a hemiface 
3 
5. ARM PARESIS First the 
non-paretic arm Get up and 
extend he arm to 90º 
Patient in decubitus, extend he arm to 45º 
5a. Side right 
Maintains the position during 10 seconds, amputation either immobilization 
0 
Claudica in less of 10 seconds without tap the bed 
1 
Claudica in under 10 seconds and the tip touch the bed 
2 
There is motion but No reaches the position either falls immediately 
3 
Paralysis of the tip 
4 
5b. Side left . 
Equal that he side right 

37 
 
6. PARESIS OF THE LEG 
First the non-paretic leg Get up the 
leg extended to 30º 
6a. Side right 
Maintains the position during 5 seconds, amputation proximal either immobilization 
0 
Claudica in under 5 seconds without tap the bed 
1 
Claudica in under 5 seconds and the tip touch the bed 
2 
There is motion but No reaches the position either falls immediately 
3 
Paralysis of the tip 
4 
6b. Side left. 
Equal that he side right 
7. DYSMETRIA (Ataxia: incoordination in he motion) 
Finger-nose and heel-knee, carry out with the eyes open 
Absent, amputation, deficit engine or fusion of the joint 
0 
Ataxia in a tip 
1 
Ataxia in two limbs 
2 
8. SENSITIVITY 
With needle explore the face, the arms, the trunk, the abdomen and the legs (No hands neither feet) In 
patient dazed evaluate the withdrawal to stimulus painful 
Normal 
0 
Mild hypoesthesia (it note) 
1 
Anesthesia either patient in coma 
2 
9. LANGUAGE 
Describe a drawing either read a list of words and phrases In 
patient dumb either IOT explore according to your writing 
Normal 
0 
Aphasia mild either moderate (can understand) 
1 
Aphasia serious (No HE can understand) 
2 
Comprehension null either in coma 
3 
10. DYSARTHRIA 
Appreciate only the joint 
Normal either IOT 
0 
Mild either moderate (HE can understand) 
1 
Serious, unintelligible either dumb 
2 
11. Extinction and Inattention, Negligence 
Extinction: in case of stimuli bilateral simultaneous, he patient it's not able to perceive in he side 
contralateral to the injury 
Negligence: he patient is unable of orient either reply in view of a stimulus in he side contralateral to 
the injury 
Inattention: he patient ignore the stimuli in he side contralateral to the injury 
Without alterations 
0 
Inattention either extinction in a mode (visual, tactile, space either bodily) 
1 
Inattention or extinction in further of a mode. No recognizes his own hand either 
only recognizes a part from space 
2 
 
 
 
 
 
 
 
 

38 
 
ANNEX VII. FUGL-MEYER UPPER EXTREMITY ASSESSMENT (FMA-ES) 
Institute Mexican Of the Sure Social (IMSS). 
 
Delegation State Yucatan 
HGR No.1 “Lic. Ignacio Garcia “Tellez”. 
 
Medicine of Rehabilitation. 
 
EVALUATION OF THE EFFECTS OF EARLY APPLICATION OF BOTULINUM 
TOXIN IN PATIENTS WITH A FIRST CEREBRAL VASCULAR EVENT 
FUGL-MEYER UPPER EXTREMITY ASSESSMENT (FMA-ES) 
 
Assessment of sensorimotor function 
TO. TIP SUPERIOR, position seated 
YO. Activity reflects 
none. 
could be 
caused 
Flexors : Biceps and flexors of the fingers (to the less one) 
Extenders : Triceps 
0 
0 
2 
2 
Subtotal Yo (max. 4) 
II. Motion volunteer inside of synergies , without aid gravitational 
none
. 
partial 
total 
Synergy flexor : Hand from knee contralateral until ear 
ipsilateral. From the synergy extender (adduction of 
shoulder/rotation internal, extension of the elbow, 
pronation of the forearm) until the synergy flexor 
(abduction of the shoulder /rotation external, flexion of 
the elbow, supination of the forearm). 
Synergy extender : Hand from he ear 
ipsilateral until the knee contralateral 
Shoulder 
Retraction 
0 
1 
2 
Elevation 
0 
1 
2 
Abduction (90°) 
0 
1 
2 
Rotation external 
0 
1 
2 
Elbow 
Flexion 
0 
1 
2 
Forearm 
Supination 
0 
1 
2 
Shoulder 
Adduction/rotation inter 
0 
1 
2 
Elbow 
Extension 
0 
1 
2 
Forearm 
Pronation 
0 
1 
2 
Subtotal II (max. 18) 
III. Motion volunteer mixing synergies , without compensation 
none
. 
partial 
total 
Hand to the column 
lumbar 
No can carry out, hand in forehead to thorn iliac antero- 
superior 
0 
1 
2 
Hand about lap 
Hand behind of thorn iliac anterior-superior (without 
compensation) 
Hand until the column lumbar (without compensation) 
Flexion shoulder 0°-90° 
Abduction immediate either flexion of elbow 
0 
1 
2 
Elbow to 0° 
Abduction either flexion of elbow during motion 
Pronation-supination 0° 
90° of flexion, No abduction of shoulder neither flexion of 
elbow 
Pronation-supination 
No pronation/supination, impossible position start 
0 
1 
2 
Elbow to 90° 
Pronation/supination limited, maintains position of start 
Shoulder at 0° 
Pronation/supination complete, maintains position of start 
Subtotal III (max. 6) 
IV. Motion volunteer with little either none synergy 
none
. 
partial 
total 
Abduction of shoulder 0°-90° 
Supination immediate either flexion of elbow 
0 
1 
2 
Elbow at 0° 
Supination either flexion of elbow during motion 
Forearm pronated 
90° of abduction, maintains extension and pronation 
Flexion of shoulder 90°-180° 
Abduction immediate either flexion of elbow 
0 
1 
2 
Elbow at 0° 
Abduction either flexion of elbow during motion 
Pronation-supination 0° 
Flexion of 180°, No abduction of shoulder either flexion of 
elbow 
Pronation/supination 
No pronation/supination, impossible position start 
0 
1 
2 
Elbow at 0° 
Pronation/supination limited, maintains position of start 
Shoulder to flexion of 30°-90° 
Pronation/supination complete, maintains position of start 
Subtotal IV (max. 6) 
V. Reflex activity normal evaluated only Yeah is achieved score total of 6 in Part IV 
Biceps, Triceps, 
Flexors of fingers 
0 points in part IV either 2 of 3 highlights markedly hyperactive 
0 
1 
2 
1 reflection markedly hyperactive either to the less 2 highlights 
energetic 
Maximum of 1 reflection energetic, none hyperactive 
Subtotal V (max. 2) 

39 
 
Total TO. TIP UPPER (max. 36) 
B. DOLL HE can give support in he elbow for adopt either keep the position, No support in doll, 
check range passive of motion before of take test 
none. partial 
total 
Stability to flexion dorsal of 15° 
Flexion dorsal active minor of 15° 
0 
1 
2 
Elbow to 90°, forearm pronated 
15° of Flexion dorsal, No tolerates endurance 
Shoulder to 0° 
Maintains flexion dorsal against endurance 
Flexion dorsal/volar repeated 
No can carry out voluntarily 
0 
1 
2 
Elbow to 90°, forearm pronated 
Range of motion asset limited 
Shoulder to 0° mild (flexion of the fingers) 
Range of motion asset complete, fluent 
Stability to flexion dorsal of 15° 
Flexion dorsal active minor of 15° 
0 
1 
2 
Elbow to 0°, forearm pronated 
15° of flexion dorsal, without endurance 
Mild flexion/abduction of shoulder 
Maintains position against endurance 
Flexion dorsal/volar repeated 
No can carry out voluntarily 
0 
1 
2 
Elbow to 0°, forearm pronated 
Range of motion asset limited 
Mild flexion/abduction of shoulder 
Range of motion asset complete, fluent 
Circumduction 
No can carry out voluntarily 
0 
1 
2 
Elbow to 90°, forearm pronated, shoulder to 0° 
Motion rude either incomplete 
Circumduction complete and gentle 
Total B (max. 10) 
C. HAND support can be given on the elbow to maintain 90° flexion, no support on the wrist, 
compare with hand No affected, the objects are interposed, grip asset 
none. 
partial 
total 
Flexion in mass 
From extension total active either passive 
0 
1 
2 
Extension in mass 
From flexion total active either passive 
0 
1 
2 
GRIP 
to. Grip of hook 
flexion in IFP and IFD (digits II – 
V) Extension in MCF II-V 
No can carry out 
0 
1 
2 
Can keep position but weak 
Maintains position against endurance 
b. Adduction of thumb 
1st CMC, MCF, IFP to 0°, piece of 
paper Between thumb and 2nd joint MCF 
No can carry out 
0 
1 
2 
Can hold paper but No against jerk 
Can hold paper against jerk 
c. Grip guy clamp, opposition 
Pulpejo of the thumb, against pulp of the 2 
do finger, HE strip either hala he pencil 
toward above 
No can carry out 
0 
1 
2 
Can hold pencil but No against jerk 
Can hold pencil against jerk 
d. Grip cylindrical 
Object in shape cylindrical (small can) HE 
strip either hala toward above with 
opposition in digits Yo and II 
No can carry out 
0 
1 
2 
Can hold cylinder but No against jerk 
Can hold cylinder against jerk 
and. Grip spherical 
Fingers in abduction/flexion, thumb 
opposite, ball of tennis 
No can carry out 
0 
1 
2 
Can hold ball but No against jerk 
Can hold ball against jerk 
Total C (max. 14) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

40 
 
ASSESSMENT OF FUGL-MEYER LIMB LOWER (FMA-EI) 
Assessment of the sensorimotor function  
 
AND. TIP LOWER 
I. Activity reflects , position supine 
none
. 
could be 
caused 
Flexors : Flexors of knee 
Extenders : Reflection Patellar and Aquilian (to the less one) 
0 
0 
2 
2 
Subtotal Yo (max. 4) 
II. Motion volunteer inside of synergies , position supine 
none
. 
partial 
total 
Synergy flexor : Flexion of hip maximum 
(abduction/rotation external), maximum flexion kneel and 
joint of ankle (feel tendons distal for ensure flexion 
active of knee) 
Hip 
Flexion 
0 
1 
2 
Knee 
Flexion 
0 
1 
2 
Ankle 
Flexion dorsal 
0 
1 
2 
Synergy extender : From the synergy flexor until the 
adduction/extension of the hip, extension of the knee 
and flexion plant of ankle. HE apply endurance for 
ensure motion asset, assess motion and strength 
(compare with he side No affected) 
Hip 
Extension 
0 
1 
2 
Adduction 
0 
1 
2 
Knee 
Extension 
0 
1 
2 
Ankle 
Flexion plant 
0 
1 
2 
Subtotal II (max. 14) 
III. Motion mixed volunteer with synergies , position sitting, 
knee to 10 cm of the edge of the chair/bed 
none
. 
partial 
total 
Knee flexion from 
knee extended active 
either passively 
No motion asset 
0 
1 
2 
Flexion No active minor of 90°, feel tendons hamstrings 
Flexion active further of 
90° 
Dorsal flexion of 
ankle 
Compare with 
side No affected 
No motion asset 
0 
1 
2 
Flexion dorsal limited 
Flexion dorsal complete 
Subtotal III (max. 4) 
IV. Motion volunteer with little either no synergy , position of 
foot, hip to 0° 
none
. 
partial 
total 
Knee flexion at 90° Hip 
at 0°, can hold on to 
balance 
Motion No asset either immediate, flexion of hip simultaneous 
0 
1 
2 
Flexion of knee of to the less 90° either flexion of hip during 
motion 
Flexion of knee of to the less 90° without flexion of hip simultaneous. 
Dorsal flexion of 
ankle 
Compare with side no 
affected 
No motion asset 
0 
1 
2 
Flexion dorsal limited 
Flexion dorsal complete 
Subtotal IV (max.4) 
V. Reflex activity normal position supine, HE evaluate only Yeah HE 
achieves he 
score total of 4 points in the first part IV, compare with side No 
affected 
none
. 
partial 
total 
Reflex activity 
Knee flexors, 
tendon Aquilliano 
and 
Patellar 
0 points in part IV either 2 of 3 highlights markedly hyperactive 
0 
1 
2 
1 reflection markedly hyperactive either to the less 2 highlights energetic 
Maximum of 1 reflection energetic, none hyperactive 
Subtotal V (max. 2) 
Total AND: TIP LOWER (max. 28) 
 
 
 
F. COORDINATION/ SPEED position supine, after of a 
proof with both legs, with the eyes bandaged, bead to the patella of 
the leg opposite, 5 times so fast as sea possible. 
marked 
mild 
none 
Shaking 
To the less 1 motion complete 
0 
1 
2 
Pronounced either unsystematic 
0 

41 
 
Dysmetria 
Mild and systematic 
1 
2 
No dysmetria 
>6s 
2-5s 
<2s 
Time 
To the less 6 sec. Slower that he side No affected 
0 
1 
2 
2-5 sec. further slow that he side No affected 
Less of 2 sec. of difference 
Total F (max. 6) 
 
H. SENSATION , lower extremity, blindfolded, 
compare with he side No affected 
anesthesi
a 
hypoesthes
ia 
Dysesthesi
a 
normal 
Touch Gentle 
Leg 
Plant of the foot 
0 
0 
1 
1 
2 
2 
less than ¾ 
correct or 
Absence 
¾ correct or 
considerable 
difference 
correct 100% 
little or none 
difference 
Position 
Small alteration in the 
position 
Hip 
0 
1 
2 
Knee 
0 
1 
2 
Ankle 
0 
1 
2 
Finger fat of the foot (joint - IF) 
0 
1 
2 
Total H. (max. 12) 
 
YO. MOTION ARTICULATE PASSIVE, tip lower 
J. PAIN ARTICULATE during passive movement, tip 
lower 
compare with side No affected 
only 
few 
degrees 
diminished 
normal 
severe pain during 
motion or pain very 
marked to the end of the motion 
some 
pain 
No pain 
Hip 
Flexion 
0 
1 
2 
0 
1 
2 
Abduction 
0 
1 
2 
0 
1 
2 
Rotation external 
0 
1 
2 
0 
1 
2 
Rotation internal 
0 
1 
2 
0 
1 
2 
Knee 
Flexion 
0 
1 
2 
0 
1 
2 
Extension 
0 
1 
2 
0 
1 
2 
Ankle 
Flexion dorsal 
0 
1 
2 
0 
1 
2 
Flexion plant 
0 
1 
2 
0 
1 
2 
Foot 
Pronation 
0 
1 
2 
0 
1 
2 
supination 
0 
1 
2 
0 
1 
2 
Total (max. 20) 
Total (max. 20) 
 
AND. TIP LOWER 
/28 
F. COORDINATION/ SPEED 
/6 
TOTAL EF (function motorboat) 
/34 
 
H. SENSATION 
/12 
YO. MOTION ARTICULATE PASSIVE 
/20 
J. PAIN ARTICULATE 
/20 
 
 
 
 
 
 
 
 
 
 
 
 

42 
 
ANNEX VII I. GOAL ATTAINMENT SCALE 
 
Mexican Social Security Institute (IMSS). 
Yucatan State Delegation 
HGR No. 1 “Lic. Ignacio Garcia Tellez”. 
Rehabilitation Medicine. 
 
EVALUATION OF THE EFFECTS OF EARLY APPLICATION OF BOTULINUM TOXIN IN 
PATIENTS WITH A FIRST CEREBRAL VASCULAR EVENT 
 
Setting the objectives 
 
 
 
Objective 1: (main) 
 
Objective 2: 
 
Objective 3: 
 
Objective 4: 
 
 
EVALUATION OF OBJECTIVES IN 5 POINTS 
 
 
 
Aim 1: 
-2 
-1 
0 
+1 
+2 
Mucho menos 
Un poco menos 
Resultado esperado 
Un poco más 
Mucho más 
Descripción : 
Descripción : 
Descripción : 
Descripción : 
Descripción : 

43 
 
43 
 
Aim 2: 
 
 
 
 
 
 
 
 
 
 
Aim 3: 
 
 
 
 
 
 
 
 
 
 
Aim 4: 
 
 
 
 
 
 
 
 
 
WEIGHTING OF OBJECTIVES: 
 
Weight = Importance x Difficulty 
Importance 
(for he patient and the family) 
Difficulty 
(evaluated by he 
equipment) 
None 
0 
None 
0 
Little 
1 
Little 
1 
Moderately 
2 
Moderately 
2 
A lot 
3 
A lot 
3 
 
 
 
-2 
-1 
0 
+1 
+2 
Mucho menos 
Un poco menos 
Resultado esperado 
Un poco más 
Mucho más 
Descripción : 
Descripción : 
Descripción : 
Descripción : 
Descripción : 
-2 
-1 
0 
+1 
+2 
Mucho menos 
Un poco menos 
Resultado esperado 
Un poco más 
Mucho más 
Descripción : 
Descripción : 
Descripción : 
Descripción : 
Descripción : 
-2 
-1 
0 
+1 
+2 
Mucho menos 
Un poco menos 
Resultado esperado 
Un poco más 
Mucho más 
Descripción : 
Descripción : 
Descripción : 
Descripción : 
Descripción : 

44 
 
44 
 
Aim 1: 
 
 
 
 
 
 
 
 
 
Aim 2: 
 
 
 
 
 
 
 
 
Aim 3: 
 
 
 
 
 
 
 
 
 Objective 4: 
Importancia 
(para el paciente y la familia) 
Dificultad 
(evaluada por el equipo) 
Ninguna 
0 
Ninguna 
0 
Poca 
1 
Poca 
1 
Moderadamente 
2 
Moderadamente 
2 
Mucha 
3 
Mucha 
3 
Importancia 
Dificultad 
Ninguna 
0 
Ninguna 
0 
Poca 
1 
Poca 
1 
Moderadamente 
2 
Moderadamente 
2 
Mucha 
3 
Mucha 
3 
Importancia 
Dificultad 
Ninguna 
0 
Ninguna 
0 
Poca 
1 
Poca 
1 
Moderadamente 
2 
Moderadamente 
2 
Mucha 
3 
Mucha 
3 
Importancia 
Dificultad 
Ninguna 
0 
Ninguna 
0 
Poca 
1 
Poca 
1 
Moderadamente 
2 
Moderadamente 
2 
Mucha 
3 
Mucha 
3