Functional effects of botulinum toxin in patients with HSP
(4, 5). However, despite the high prevalence of hip
adductor spasticity in patients with HSP, there are no
studies that have systematically investigated the effects
of BTX-A injections in these muscles, either on clinical
indicators of spasticity, or with respect to balance and
gait capacity. In a few previous studies with limited
numbers of patients with HSP, the hip adductors were
injected in some of the participants (n = 5–12), yet often
in combination with other muscle groups (i.e. calves,
tibialis posterior, iliopsoas and rectus femoris) (6, 8, 9).
Furthermore, these studies did not include stretching
exercises following BTX-A treatment, as recommended
by international consensus (10). Hence, the specific
effects of BTX-A injections in the hip adductors with
subsequent stretching exercises remain to be established.
This exploratory study focused on the effects of
BTX-A injections in spastic hip adductors and subse-
quent stretching exercises in patients with pure HSP,
using 2 primary outcomes: (i) gait width; and (ii)
the quality of sideways reactive stepping responses
following lateral balance perturbations. In addition,
comfortable and fast gait speed, success rates of the
lateral stepping responses, and various clinical (phy-
sical and functional) tests served as secondary outcome
measures. The physiological effect of BTX-A usually
reaches its maximum 6 weeks after the injections (11)
and diminishes progressively until approximately 16
weeks after the injections. Therefore, we hypothesized
that reduced hip adductor tone would translate into
improvements in both gait width and lateral stepping
at 6 weeks post-treatment, whereas a reduction in these
effects was expected at 16 weeks after treatment.
METHODS
Participants
Participants were recruited from all patients with HSP and hip
adductor spasticity known at the expert centre for genetic mo-
vement disorders of the Donders Institute for Brain, Cognition
and Behaviour, Radboud University Medical Center, Nijmegen,
The Netherlands. In addition, active recruitment took place
through the national patient organization “Spierziekten Neder-
land”. Inclusion criteria were: (i) a “pure” form of autosomal
dominant HSP (either genetically proven, or based on family
history); (ii) 18 years of age or older; (iii) bilateral hip adductor
spasticity (Modified Ashworth Scale (MAS) score 1–4); (iv)
balance- and/or gait-related activity limitations in daily life; (v)
able to walk > 50 m independently with (adapted) shoes and/or
orthoses (but without walking aids, such as crutches or a wal-
ker); and (vi) comfortable gait velocity > 0.4 m/s. Participants
were excluded if they had any cognitive impairment, or they
had any comorbidity affecting their gait capacity. In addition,
the final BTX-A treatment of the hip adductors should have
been administered longer than 6 months before the first mea-
surement. Regular BTX-A treatments of other muscle groups
should have been performed either within 3–4 weeks or longer
than 4 months before the first measurement in order to have
435
either an optimal or, otherwise, an absent effect of these prior
injections during the study period.
For participants recruited at the outpatient departments, all
inclusion criteria were checked by the attending physician.
Participants who responded to the recruitment letters via the
patient organization were interviewed by telephone by the pri-
mary investigator to check inclusion criteria i, ii and iv, whereas
inclusion criteria ii, v and vi were checked by a physiotherapist
at the first visit for the study. Out of 75 patients, 25 fulfilled the
inclusion criteria and were included. Their demographic and
clinical characteristics are listed in Table I.
Ethics statement
All subjects gave their written informed consent prior to partici-
pation. The study was approved by the regional medical-ethics
committee and conducted in accordance with the Declaration
of Helsinki. Due to lack of prior research on gait width and
quality of reactive sidesteps in patients with HSP, no formal
power calculation could be performed. Given the exploratory
nature of the current study, a required number of 25 patients
seemed optimal, feasible and justified, and was agreed upon by
the medical ethics committee.
Intervention
Each participant was treated with bilateral BTX-A injections
in the hip adductors by 1 of 3 rehabilitation physicians of our
university hospital. A solution of 100 U Xeomin® (Botulinum
toxin type A, Merz Pharmaceuticals GmbH, Frankfurt am Main,
Germany) per 5 ml saline 0.9% was used. A dose of 150 or 200
U per leg was injected, depending on the degree of hypertonia
(Modified Ashworth Scale (MAS) 1: 150 U; MAS ≥ 2: 200 U).
Table I. Patient characteristics before the intervantion (T0)
Characteristics
Sex, male/female, n
Gene, n
SPG-4
SPG-10
SPG-17
SPG-31
AD, genotype not confirmed
Tibialis anterior, median (range)
MAS
MRC
Triceps surae, median (range)
MAS
knee extended
knee flexed
MRC
Hip adductors, median (range)
MAS
MRC
Hip abductors, median (range)
MRC
BBS, median (range)
Age, years, mean (range)
Hip abduction, mean (range)
ROM
6MWT, mean (range)
TUG, mean (range)
ABC, mean (range)
12/13
12
2
1
2
8
0 (0–1)
5 (2–5)
2.5 (1–4)
2.5 (0–4)
5 (2–5)
3 (1–4)
5 (2–5)
5 (2–5)
49.5 (27–56)
53.5 (26–72)
38.8 (20.0–52.5)
367.5 (196–515)
11.1 (6.3–23.0)
49.83 (17–95.3)
AD: autosomal dominant inheritance; MAS: Modified Ashworth Scale; MRC:
Medical Research Council scale; BBS: Berg Balance Scale; ROM: range of motion;
6MWT: 6-min Walk Test; TUG: Timed Up and Go test; ABC: Activities-specific
Balance Confidence scale.
J Rehabil Med 51, 2019