INTRODUCTION:
Hereditary Spastic Paraplegia (HSP) is a heterogeneous group of inherited neurological
disorders characterized by progressive weakness and spasticity in the lower limbs, which
significantly impairs walking abilities (endurance and speed). Despite several specific
interventions for particular deficits already having been studied, there is currently a
lack of comprehensive and structured neurorehabilitation programs designed to improve
walking function in these patients. Therefore, this protocol aims to explore the
feasibility and effectiveness of a composite training approach focused on improving
flexibility, muscle strength, motor control, balance, and aerobic capacity.
STUDY OBJECTIVES:
Primary endpoint: Feasibility of the study, assessed by the following:
Sufficient recruitment rate, with 20 patients enrolled within 24 months from the study's
initiation.
Adequate adherence to the treatment plan, defined by the completion of at least 75% of
the planned treatment sessions, with a minimum of 10 treatment sessions.
Sufficient patient retention, defined as at least 75% of enrolled patients completing the
study with adequate treatment adherence.
Absence of serious adverse events related to patient participation in the study.
Patient satisfaction with the healthcare received during the study.
Secondary endpoint: Therapeutic efficacy of the study, assessed by:
Improvement in walking endurance (6-Minute Walk Test). Improvement in walking speed
(10-Meter Walk Test).
Exploratory objectives:
Improvement in overall functional condition (Spastic Paraplegia Rating Scale and the
Hereditary Spastic Paraplegia - Self Notion and Perception Questionnaire).
Improvement in passive joint range of motion in the lower limbs (goniometer). Improvement
in lower limb muscle strength (5 Times Sit-to-Stand Test). Improvement in standing
balance (Functional Reach Test and stabilometric platform).
STUDY DESIGN: Open-label, non-randomized, uncontrolled interventional study.
STUDY POPULATION: Hereditary Spastic Paraplegia patients
SAMPLE SIZE: 20 patients
ELIGIBILITY:
Inclusion criteria:
Adults diagnosed with Hereditary Spastic Paraplegia. Presence of any functional deficit
in the lower limbs affecting walking, such as muscle weakness, hypertonia, or balance
issues.
Ability to walk independently, without physical assistance from another person, defined
by a Functional Ambulation Category score of 3 or higher.
Ability to understand simple instructions, comprehend the purpose of the study,
willingness to participate, commitment to at least 10 treatment sessions, and suitability
for signing the informed consent.
Exclusion criteria:
Use of botulinum toxin or surgery to treat lower limb hypertonia within six months prior
to study enrollment.
Contraindications for moderate physical activity, including stretching exercises, muscle
strengthening, and aerobic training.
Withdrawal Criteria:
Voluntary withdrawal by the patient. Occurrence of adverse events or health issues that
prevent continuation of the treatment plan.
Patient Replacement:
Recruitment will continue until 20 subjects are enrolled. Any patients who withdraw from
the study will not be replaced.
METHODS:
Twenty adults diagnosed with HSP will participate in 10 to 16 therapist-guided sessions,
each lasting 60 or 120 minutes, occurring once or twice a week depending on individual
choice and capabilities. At the conclusion of the study, participants will receive an
information package (manual and video tutorials) to support long-term home exercise.
Evaluations will take place at three time points: before the intervention (T0),
immediately after the intervention (T1), and three months post-intervention (T2). The
primary objectives will focus on assessing the study's feasibility (recruitment,
retention, adherence, absence of adverse events, and patient satisfaction). Secondary
outcomes will evaluate improvements in walking ability and specific contributing factors,
such as reduced spasticity, increased muscle strength, and improved balance.
INTERVENTION:
FRAME training is composed of four key components:
Component 1: Flexibility. To decrease muscle tone and enhance mobility, the therapist
will apply a combination of stretching exercises and electrical stimulation, targeting
areas such as the triceps surae, adductors, rectus femoris, and hamstrings. Electrical
stimulation will utilize biphasic, high-frequency sensory stimulation (100 Hertz, pulse
width 200 µs, and intensity just below the motor threshold) for a duration of 30 minutes,
combined with stretching activities.
Component 2: Resistance Training (and Balance). The resistance training will focus on
strengthening muscles typically weakened in individuals with Hereditary Spastic
Paraplegia (HSP), especially the proximal muscles of the hip and trunk. To promote muscle
engagement and improve balance and coordination, core stability and resistance exercises
will be performed under conditions of mild instability. These exercises will be carried
out in sitting or standing positions, rather than lying down, to optimize muscle
activation.
Component 3: Movement Execution (and Balance). Gait training will be based on motor
learning principles such as repetitive, task-oriented practice, variable practice, and
graded practice. Graded practice involves breaking down a complex movement into simpler
segments, practicing each segment until proficiency is achieved, and then progressively
combining them into more complex sequences. Patients will be challenged with standing
balance exercises while working on specific gait impairments. Gait training will involve
varying walking patterns, including fast, slow, sidewalk walking, walking backward, and
stair climbing.
Component 4: Aerobic Training via High-Intensity Interval Training (HIIT). HIIT consists
of brief, intense aerobic efforts using large muscle groups, followed by rest periods of
equal length. HIIT has been found to produce better cardiovascular results with a lower
perceived level of effort compared to moderate-intensity aerobic exercise. In this
protocol, patients will perform 30-second high-intensity intervals followed by 30 seconds
of passive rest, repeated 10 times in two sets. Each session will begin with a 5-minute
warm-up, include a 5-minute rest between sets, and conclude with a 5-minute cool-down.
Patients will participate in the modality most suitable for consistent training, such as
walking, running, cycling, or squatting.
RELEVANCE:
This protocol is significant for providing clinicians with valuable insights into the
feasibility and potential effectiveness of a comprehensive, clinically-oriented program
designed to improve walking ability in adults with Hereditary Spastic Paraplegia. It also
aims to inform future translational research studies in the field.