Tossina botulinica precoce per la riduzione della rigidità muscolare nei pazienti con ictus per la prima volta: miglioramento del recupero e dell'indipendenza (EARLY BOT-SPAS)

Participants in the intervention group will receive early botulinum toxin type A (BoNT-A) injections in addition to a standard rehabilitation program. The botulinum toxin will be administered within the first 12 weeks following stroke onset, targeting muscles affected by spasticity. The injections aim to reduce abnormal muscle tone, prevent contractures, and improve functional mobility. Rehabilitation therapy will include physical exercises, range-of-motion activities, and muscle-strengthening interventions tailored to individual recovery needs. The combined therapy is designed to optimize motor function, promote neuroplasticity, and improve overall independence and quality of life.

This intervention involves the early administration of botulinum toxin type A (BoNT-A) within the first 12 weeks after a cerebrovascular event. The injections target muscles affected by spasticity, aiming to reduce abnormal tone, prevent contractures, and improve functional mobility. BoNT-A works by blocking acetylcholine release at the neuromuscular junction, resulting in muscle relaxation. Ultrasound guidance or anatomical landmarks will be used for accurate injection. This early intervention capitalizes on the neuroplastic window and is combined with standard rehabilitation to enhance motor recovery and prevent long-term complications.

• Abobotulinumtoxin A
• BoNT-A
• Neurotossina botulinica a

Participants in the control group will undergo a standard rehabilitation program without the early application of botulinum toxin. The rehabilitation will consist of physical therapy focused on improving muscle strength, range of motion, and functional independence. Treatment will be tailored to each participant's condition and recovery progress, following established post-stroke rehabilitation protocols. This group will serve as the comparator to evaluate the additional benefits of early botulinum toxin intervention.

The Modified Ashworth Scale (MAS) is a 6-point ordinal scale (0, 1, 1+, 2, 3, 4) used to assess spasticity by evaluating resistance during passive movement of a joint. The scoring system is as follows:

0: No increase in muscle tone.

1: Slight increase in tone, with a catch and release or minimal resistance at the end of the range of motion.

1+: Slight increase in tone, with a catch followed by minimal resistance throughout less than half of the range of motion.

2: More marked increase in tone through most of the range, but the joint moves easily.

3: Considerable increase in tone, making passive movement difficult. 4: Affected part is rigid in flexion or extension.

The Modified Tardieu Scale (MTS) assesses spasticity by measuring muscle response to passive stretching at different velocities. It evaluates both the angle of muscle reaction (R1) and the final range of motion (R2). The key feature of the MTS is its sensitivity to velocity-dependent resistance, distinguishing it from the Modified Ashworth Scale. Joint movement is tested at three speeds: slow (V1), normal (V2), and fast (V3). The difference between R1 and R2 reflects dynamic spasticity and muscle stiffness.

The scale assigns qualitative scores (0-5) based on the severity of the muscle reaction:

0: No resistance throughout the movement.

1. Slight resistance with no clear catch.
2. Clear catch at a precise angle, followed by release.
3. Fatigable clonus with fewer than 10 seconds of contraction.
4. Unfatigable clonus lasting more than 10 seconds.
5. Joint is immobile.

The Mini-Mental State Examination (MMSE) is a widely used screening tool to assess cognitive function, often employed in stroke rehabilitation studies to monitor neurological recovery. The test evaluates five cognitive domains: orientation, immediate memory, attention and calculation, recall, and language. It includes tasks such as recalling objects, following commands, and answering orientation questions. The MMSE is scored out of 30 points, with higher scores indicating better cognitive function.

A score of 24 or higher is generally considered normal, while scores below this threshold suggest varying degrees of cognitive impairment. The MMSE will be administered at different intervals to assess how early intervention with botulinum toxin and rehabilitation affects patients' cognitive recovery. Its role as a secondary outcome helps determine whether improvements in motor function correlate with cognitive benefits during stroke rehabilitation.

The Barthel Index is a standardized tool used to assess a patient's level of independence in performing basic activities of daily living (ADLs). It evaluates 10 tasks, including feeding, bathing, dressing, using the toilet, walking, and controlling bladder and bowel movements. Each task is scored based on the patient's ability to perform the activity independently or with assistance. The total score ranges from 0 to 100, with higher scores indicating greater independence.

0 points: Complete dependence 100 points: Full independence

The NIHSS Scale is a clinical tool used to assess the severity of neurological deficits in patients who have experienced a stroke. It evaluates multiple domains, including level of consciousness, motor function, sensory abilities, language, coordination, and visual fields. The scale consists of 15 items, each scored from 0 to 4, with a maximum score of 42 indicating severe stroke and a score of 0 indicating no neurological deficits.

Key categories assessed include:

Motor Function: Arm and leg movement Sensory Function: Response to tactile stimuli Language and Speech: Aphasia or dysarthria Level of Consciousness: Alertness and responsiveness

The Modified Rankin Scale (mRS) is a 7-point ordinal scale used to measure functional status and the degree of disability or dependence in activities of daily living following a stroke. It evaluates outcomes ranging from no symptoms (0) to severe disability or death (6). The scale is widely used in stroke rehabilitation to monitor recovery and assess long-term functional outcomes.

Scoring:

0: No symptoms.

1. No significant disability; able to carry out all usual activities.
2. Slight disability; unable to perform all previous activities but manages without assistance.
3. Moderate disability; requires some help but can walk without assistance.
4. Moderately severe disability; unable to walk or attend to bodily needs without assistance.
5. Severe disability; requires constant nursing care and attention.
6. Death.

The Fugl-Meyer Assessment (FMA) for Upper and Lower Extremities is a widely used, validated tool to evaluate motor recovery after stroke. It assesses motor function, balance, sensation, and joint movement through a series of tasks designed to measure impairments in the affected limbs. The assessment is divided into two parts:

1. Upper Extremity (FMA-UE) Focuses on shoulder, elbow, wrist, hand, and coordination tasks. Tasks are scored from 0 (no function) to 2 (normal function) based on movement ability, precision, and control.

   Maximum score: 66 points for the upper limb.

2. Lower Extremity (FMA-LE) Evaluates hip, knee, and ankle movement, including weight-bearing tasks and reflex activity.

Similar scoring from 0 to 2 per task, with a maximum score of 34 points for the lower limb.

Key Areas Assessed:

Voluntary Movement: Flexion, extension, and joint movement. Coordination and Speed: Smoothness and accuracy of movements.

Goal Attainment Scaling (GAS) is an individualized, patient-centered tool used to measure the extent to which a patient achieves predetermined rehabilitation goals. It involves setting specific, measurable goals tailored to the patient's condition, which can include improvements in motor function, independence, pain reduction, or daily activities. Each goal is rated on a 5-point scale, ranging from -2 to +2, where:

• 2: Much less than expected outcome.

• 1: Somewhat less than expected outcome. 0: Expected outcome achieved.

  • 1: Somewhat better than expected outcome.
  • 2: Much better than expected outcome.

The MRC Scale is a validated clinical tool used to assess muscle strength in patients with neurological or muscular impairments, such as after a stroke. It evaluates the ability of specific muscle groups to generate force against resistance. Each muscle group is tested, and strength is graded on a 6-point ordinal scale (0 to 5):

0: No muscle contraction observed.

1. Flicker of contraction, but no visible joint movement.
2. Active movement possible only with gravity eliminated.
3. Active movement against gravity, but no resistance.
4. Active movement against gravity and some resistance.
5. Normal strength, full movement against maximum resistance.