Characterizing the face in facioscapulohumeral muscular dystrophy.

OBJECTIVE: To evaluate facial weakness in patients with FSHD to better define clinical signs, and pilot a facial weakness severity score. METHODS: 87 FSHD patients and 55 controls were video recorded while performing seven facial tasks. The videos were assessed by three independent examiners to compile an overview of signs of facial weakness. Next, videos were semi-quantitatively assessed using a newly developed 4-point facial weakness score (FWS). This score was evaluated and correlated to other FSHD disease characteristics. RESULTS: Patients had lower scores on the total FWS than controls (mean score 43 ± 28, range 4-118, vs 14 ± 9, range 0-35, p < 0.001) and on all seven individual facial tasks (all p < 0.001). 54% of patients had FWS scores outside the range of controls. Patients had more asymmetry between the left and right side of the face than controls. About 10% of the patients had very mild facial weakness. These were mostly males (89%) with longer D4Z4 repeat sizes of 7-9 units. More severe facial weakness correlated to more severe overall disease severity and shorter D4Z4 repeat size, but not to disease duration. Interobserver agreement for the FWS between three raters was low with a Fleiss Kappa of 0.437. CONCLUSION: This study provides an overview of the clinical spectrum of facial weakness and its relation to other disease characteristics. The 4-point scale we introduced to grade the severity of facial weakness enables correlation of facial weakness to disease characteristics, but is not suited as clinical outcome measure for longitudinal studies.

The effect of voluntary lateral trunk bending on balance recovery following multi-directional stance perturbations.

Stabilising shifts of the centre of mass (COM) are observed during balance recovery when subjects simultaneously execute voluntary unilateral knee flexion or unilateral arm raising. Here, we examined whether voluntary lateral trunk bending provided more beneficial stabilising effects, and how motor programs of balance corrections are combined with those of the focal voluntary action. The upright balance of 24 healthy young subjects (19-33 years of age) was perturbed using multi-directional rotations of the support-surface. The perturbations consisted of combined pitch and roll rotations (7.5 degrees and 60 degrees/s) presented randomly in six different directions. Three conditions were tested: perturbation of stance only (PO); combined balance perturbation and cued uphill bending of the trunk (CONT); and combined perturbation and cued downhill bending of the trunk (IPS). For comparison, subjects were required to perform trunk bending alone (TO). Outcome measures were biomechanical responses and surface EMG activity of several muscles. Calculated predicted outcomes (PO + TO) were compared with combined measures (CONT or IPS). CONT trunk bending uphill showed two phases of benefit in balance recovery for laterally but, in contrast to voluntary knee bending, not for posterior directed components of the perturbations. IPS trunk bending had negative effects on balance. Early balance correcting muscle responses were marginally greater than PO responses. Prominent secondary balance correcting responses, having a similar timing as voluntary responses observed under TO conditions, were seen under CONT only in trunk muscles. These, and later stabilising, responses had amplitudes as expected from PO + TO conditions being significantly greater than PO responses. The ability with which different muscle synergies for balance corrections and voluntary trunk bending were integrated into one indicates a flexible adjustment of the CNS programs to the demands of both tasks.

Postural instability in cerebellar ataxia: correlations of knee, arm and trunk movements to center of mass velocity.

The aim of this study was to investigate the correlations between body segment movements and center of mass (COM) velocity during pathological balance corrections of spinocerebellar ataxia (SCA) patients compared with controls, and to relate correlations indicating instability to EMG activity differences. Eighteen SCA patients and 21 age-matched controls were tested. Upright standing was perturbed using rotations of the support surface. We recorded body motion and surface EMG. For lateral perturbations peaks in COM lateral velocity were larger in SCA patients than controls. These peaks were correlated with increased ("hypermetric") trunk roll downhill and reduced uphill knee flexion velocity. Subsequent arm abduction partially corrected the lateral instability. Early balance correcting responses in knee and paraspinal muscles showed reduced amplitudes compared with normal responses. Later responses were consistent with compensation mechanisms for the lateral instability created by the stiffened knee and pelvis. We conclude that truncal hypermetria coupled with insufficient uphill knee flexion is the primary cause of lateral instability in SCA patients. Holding the knees and pelvis more rigid possibly permits a reduction in the controlled degrees of freedom and concentration on arm abduction to improve lateral instability. For backwards perturbations excessive posterior COM velocity coincided with marked trunk hypermetric flexion forwards. We concluded that this flexion and the ensuing backwards shift of the pelvis result from rigidity which jeopardizes posterior stability. Timing considerations and the lack of confirmatory changes in amplitudes of EMG activity suggest that lateral and posterior instability in SCA is primarily a biomechanical response to pelvis and knee rigidity resulting from increased muscle background activity rather than changed evoked responses.

Trunk sway analysis to quantify the warm-up phenomenon in myotonia congenita patients.

OBJECTIVE: Patients with autosomal recessive myotonia congenita display myotonia and transient paresis that diminish with repetitive muscle contractions (warm-up phenomenon). A new approach is presented to quantify this warm-up phenomenon under clinically relevant gait and balance tasks. METHODS: Ten patients with DNA proven autosomal recessive myotonia congenita and 14 age-matched controls participated. Subjects performed six everyday gait and balance tasks. Balance control during these tasks was monitored using two angular velocity transducers that measured trunk movements in anterior-posterior (pitch) and medio-lateral (roll) directions at the level of the lumbar vertebral column. Tasks were performed under two conditions in randomised order: after a 10-minute seated rest period ("rested") and after having consecutively repeated the task five times ("warm-up"). Controls were also tested twice. RESULTS: "Rested" patients showed the greatest abnormalities (increased sway in pitch and roll) for tandem walking and walking stairs. Balance impairment was also evident for all other tasks. After "warm-up," balance was markedly improved in patients, as reflected by decreased trunk sway (especially during tandem walking) and reduced task duration for all tasks. These results were not only evident at the group level but also clearly present in individual patients. CONCLUSION: The results show that trunk sway analysis detects postural instability in myotonia congenita patients during everyday gait and balance tasks. Moreover, this technique provides a useful tool to quantify the warm-up phenomenon, suggesting a potential use as clinical endpoint in future clinical trials.

Epidemiology and pathophysiology of falls in facioscapulohumeral disease.

BACKGROUND AND AIMS: Muscle weakness is a potentially important, yet poorly studied, risk factor for falls. Detailed studies of patients with specific myopathies may shed new light on the relation between muscle weakness and falls. Here falls in patients with facioscapulohumeral disease (FSHD) who suffered from lower limb muscle weakness were examined. This study provides insights into the prevalence, relevance and pathophysiology of falls in FSHD. METHODS: A validated questionnaire was used as well as a prospective 3 month follow-up to examine the prevalence, circumstances and consequences of falls in 73 patients with FSHD and 49 matched healthy controls. In a subgroup of 28 subjects, muscle strength was also examined and balance was assessed electrophysiologically using body worn gyroscopes. RESULTS: In the questionnaire, 30% of the patients reported falling at least once a month whereas none of the controls did. Injuries occurred in almost 70% of the patients. The prospective study showed that patients fell mostly at home, mainly due to intrinsic (patient related) causes, and usually in a forward direction. Fallers were unstable while climbing stairs, rising from a chair and standing with eyes closed whereas non-fallers had normal balance control. Frequent fallers had greater muscle weakness than infrequent fallers. CONCLUSION: These findings demonstrate the high prevalence and clinical relevance of falls in FSHD. The relation between muscle weakness and instability among fallers is also highlighted. Because patients fell mainly at home, fall prevention strategies should focus on home adaptations. As mainly intrinsic causes underlie falls, the impact of adopting balance strategies or balance training should be explored in this patient group.

Control of roll and pitch motion during multi-directional balance perturbations.

Does the central nervous system (CNS) independently control roll and pitch movements of the human body during balance corrections? To help provide an answer to this question, we perturbed the balance of 16 young healthy subjects using multi-directional rotations of the support surface. All rotations had pitch and roll components, for which either the roll (DR) or the pitch (DP) component were delayed by 150 ms or not at all (ND). The outcome measures were the biomechanical responses of the body and surface EMG activity of several muscles. Across all perturbation directions, DR caused equally delayed shifts (150 ms) in peak lateral centre of mass (COM) velocity. Across directions, DP did not cause equally delayed shifts in anterior-posterior COM velocity. After 300 ms however, the vector direction of COM velocity was similar to the ND directions. Trunk, arm and knee joint rotations followed this roll compared to pitch pattern, but were different from ND rotation synergies after 300 ms, suggesting an intersegmental compensation for the delay effects. Balance correcting responses of muscles demonstrated both roll and pitch directed components regardless of axial alignment. We categorised muscles into three groups: pitch oriented, roll oriented and mixed based on their responses to DR and DP. Lower leg muscles were pitch oriented, trunk muscles were roll oriented, and knee and arm muscles were mixed. The results of this study suggest that roll, but not pitch components, of balance correcting movement strategies and muscle synergies are separately programmed by the CNS. Reliance on differentially activated arm and knee muscles to correct roll perturbations reveals a dependence of the pitch response on that of roll, possibly due to biomechanical constraints, and accounts for the failure of DP to be transmitted equally in time across all limbs segments. Thus it appears the CNS preferentially programs the roll response of the body and then adjusts the pitch response accordingly.

Identifying deficits in balance control following vestibular or proprioceptive loss using posturographic analysis of stance tasks.

OBJECTIVE: To distinguish between normal and deficient balance control due to vestibular loss (VL) or proprioceptive loss (PL) using pelvis and shoulder sway measures. METHODS: Body-worn gyroscopes measured pelvis and shoulder sway in pitch (anterior-posterior) and roll (side-to-side) directions in 6 VL, 6 PL and 26 control subjects during 4 stance tasks. Sway amplitudes were compared between groups, and were used to select optimal measures that could distinguish between these groups. RESULTS: VL and PL patients had greater sway amplitudes than controls when standing on foam with eyes closed. PL patients also swayed more when standing with eyes closed on firm support and eyes open on foam. Standard sensory analysis techniques only differentiated VL patients from controls. Stepwise discriminate analysis showed that differentiation required pitch measures for VL patients, roll measures for PL patients, and both measures for all three groups. Pelvis measures yielded better discrimination than shoulder measures. CONCLUSIONS: Distinguishing between normal and deficient balance control due to VL or PL required pitch and roll pelvis sway measures. SIGNIFICANCE: Accurate identification of balance deficits due to VL or PL may be useful in clinical practice as a functional diagnostic tool or to monitor balance improvements in VL or PL patients.

Respiratory function in facioscapulohumeral muscular dystrophy 1.

To test the hypothesis that wheelchair dependency and (kypho-)scoliosis are risk factors for developing respiratory insufficiency in facioscapulohumeral muscular dystrophy, we examined 81 patients with facioscapulohumeral muscular dystrophy 1 of varying degrees of severity ranging from ambulatory patients to wheelchair-bound patients. We examined the patients neurologically and by conducting pulmonary function tests: Forced Vital Capacity, Forced Expiratory Volume in 1 second, and static maximal inspiratory and expiratory mouth pressures. We did not find pulmonary function test abnormalities in ambulant facioscapulohumeral muscular dystrophy patients. Even though none of the patients complained of respiratory dysfunction, mild to severe respiratory insufficiency was found in more than one third of the wheelchair-dependent patients. Maximal inspiratory pressures and maximal expiratory pressures were decreased in most patients, with a trend that maximal expiratory pressures were more affected than maximal inspiratory pressures. Wheelchair-dependent patients with (kypho-)scoliosis showed the most restricted lung function. Wheelchair-dependent patients with (kypho-)scoliosis are at risk for developing respiratory function impairment. We advise examining this group of facioscapulohumeral muscular dystrophy patients periodically, even in the absence of symptoms of respiratory insufficiency, given its frequency and impact on daily life and the therapeutic consequences.

Incorporating voluntary unilateral knee flexion into balance corrections elicited by multi-directional perturbations to stance.

Positive effects on lateral center of mass (CoM) shifts during balance recovery have been seen with voluntarily unilateral arm raising but not with voluntarily bilateral knee flexion. To determine whether unilateral voluntary knee movements can be effectively incorporated into balance corrections we perturbed the balance of 30 young healthy subjects using multi-directional rotations of the support surface while they simultaneously executed unilateral knee flexion. Combined pitch and roll rotations (7.5 degrees and 60 degrees/s) were presented randomly in six different directions. Subjects were tested in four stance conditions: balance perturbation only (PO); cued flexion of one knee only (KO); combined support surface rotation and cued (at rotation onset) flexion of the uphill knee, contralateral to tilt (CONT), or of the downhill knee, ipsilateral to tilt (IPS). Outcome measures were CoM motion and biomechanical and electromyography (EMG) responses of the legs, arms and trunk. Predicted measures (PO+KO) were compared with combined measures (CONT or IPS). Unilateral knee flexion of the uphill knee (CONT) provided considerable benefit in balance recovery. Subjects rotated their pelvis more to the uphill side than predicted. Downhill knee bending (IPS) also had a positive effect on CoM motion because of a greater than predicted simultaneous lateral shift of the pelvis uphill. KO leg muscle activity showed anticipatory postural activity (APA) with similar profiles to early balance correcting responses. Onsets of muscle responses and knee velocities were earlier for PO, CONT, and IPS compared to KO conditions. EMG response amplitudes for CONT and IPS conditions were generally not different from the PO condition and therefore smaller than predicted. Later stabilizing responses at 400 ms had activation amplitudes generally equal to those predicted from the PO+KO conditions. Our results suggest that because EMG patterns of anticipatory postural activity of voluntary unilateral knee flexion and early balance corrections have similar profiles, the CNS is easily able to incorporate voluntary activation associated with unilateral knee flexion into automatic postural responses. Furthermore, the effect on movement strategies appears to be non-linear. These findings may have important implications for the rehabilitation of balance deficits.

Vestibular and proprioceptive contributions to human balance corrections: aiding these with prosthetic feedback.

Movement strategies controlling quiet stance and rapid balance corrections may have common characteristics. We investigated this assumption for lower leg proprioceptive loss (PL), peripheral vestibular loss (VL), and healthy controls. Our underlying hypothesis was that changes in movement-strategy modulation following sensory loss would improve with prosthetic biofeedback. Quiet stance was measured under different sensory conditions and compared to corrections induced by multidirection support-surface tilts. Response synergies were assessed using electromyography recordings from several muscles. Biofeedback of trunk sway during gait and stance tasks used lower trunk rotations to drive head-band-mounted vibro-tactile and auditory actuators. Strategies of quiet stance were different for roll and pitch, depending on sensory conditions. Simultaneously acting strategies were observed for low- and high-frequency sway. PL induced strategies different from those of VL and controls. VL strategies were identical to those of controls but with greater amplitudes. Tilt perturbation movement strategies were similar to high-frequency strategies of quiet stance--multisegmental. VL induced increased trunk pitch and roll responses with hypermetric trunk muscle responses and hypometric knee responses but unchanged synergies. Increasing PL up the legs caused changed synergies. Biofeedback reduced stance body sway in VL and elderly subjects. In conclusion, several movement strategies underlie quiet stance with high-frequency strategies being common to those of perturbed stance. PL changes both movement strategies and synergies, whereas VL only causes pathological changes to the modulation depth. Thus, VL is more easily rectified using trunk sway positional biofeedback.

Vestibular and proprioceptive influences on trunk movements during quiet standing.

We characterized upper trunk and pelvis motion in normal subjects and in subjects with vestibular or proprioceptive loss, to document upper body movement modes in the pitch and roll planes during quiet stance. Six bilateral vestibular loss (VL), six bilateral lower-leg proprioceptive loss (PL) and 28 healthy subjects performed four stance tasks: standing on firm or foam surface with eyes open or closed. Motion of the upper body was measured using two pairs of body-worn gyroscopes, one mounted at the pelvis and the other pair at the shoulders. Pitch and roll angular velocities recorded from the gyroscopes were analyzed separately for low-frequency (<0.7 Hz) and high-frequency (>3 Hz) motion. Low-frequency pitch motion was similar for all groups, consisting of in-phase pelvis and shoulder motion. High-frequency pitch motion in controls and VL subjects was dominated by pelvis motion with little shoulder motion, but vice versa in PL subjects. Low-frequency roll motion changed for all groups from mainly shoulder and little pelvis motion to in-phase pelvis and shoulder motion after moving from a firm to foam surface. In contrast, high-frequency roll motion changed from mainly shoulder motion to mainly pelvis motion with the change to a foam surface, except for PL subjects with eyes closed. Coherent low-frequency sway between pelvis and shoulder was only pronounced in VL patients. These results indicate that relative motion between the pelvis and shoulder depends on the support surface, the type of sensory loss, and whether the motion is in roll or pitch plane. Furthermore, relative motion between the pelvis and upper trunk is an integral part of movement modes used to control quiet stance. Vestibular loss patients showed very similar movement modes as controls, with larger amplitudes. Proprioceptive loss patients, however, used more shoulder motion and stabilized the pelvis for the high-frequency mode. We conclude that there is relative motion between the upper trunk and pelvis during quiet stance and suggest that it may contribute to balance control.

Balance control in patients with distal versus proximal muscle weakness.

Muscle weakness is consistently associated with falls in the elderly people, typically when present along with other risk factors. However, it remains unknown whether and how muscle weakness alone affects balance. This hampers development of more effective fall prevention strategies. Clinical observations suggest that the amount and distribution of muscle weakness influences balance control. We therefore investigated balance corrections in patients with either predominantly proximal (limb girdle muscular dystrophy (LGMD); n=8) or distal (distal spinal muscular atrophy; n=5) leg weakness, and 27 matched healthy controls. Balance was perturbed using surface tilt rotations that were delivered randomly in eight directions. Balance measures were full body kinematics and surface electromyographic activity (EMG) of leg, arm, and trunk muscles. Both patient groups were more unstable than controls, as reflected by greater excursions of the centre of mass (COM), especially in the pitch (anterior-posterior (AP)) plane. COM displacements were greater in distal weakness patients. Patients with distal weakness had excessive and unstable trunk, knee and ankle movements, and this was present following both forward and backward directed balance perturbations, possibly reflecting the greater use of distal leg muscles in these directions. In contrast, the less weak proximal weakness patients demonstrated unstable trunk and ankle movements only for backward directed balance perturbations. Both patient groups used arm movements to compensate for their instability. We conclude that primarily distal but also proximal muscle weakness leads to significant postural instability. This observation, together with the retained ability of patients to use compensatory arm movements, provides targets that may be amenable to improvement with therapeutic intervention.