Spinal inhibition and motor function in adults with spastic cerebral palsy

Abstract

Key points: Abnormal activation of motoneurons in the spinal cord by sensory pathways is thought to contribute to impaired movement control and spasticity in individuals with cerebral palsy. Here we use single motor unit recordings to show how individual motoneurons in the spinal cord respond to sensory inputs in a group of participants with cerebral palsy having different degrees of motor dysfunction. In participants who had problems walking independently and required assistive devices such as wheelchairs, sensory pathways only excited motoneurons in the spinal cord. In contrast, in participants with cerebral palsy who walked independently for long distances, sensory inputs both inhibited and excited motoneurons in the spinal cord, similar to what we found in uninjured control participants. These findings demonstrate that in individuals with severe cerebral palsy, inhibitory control of motoneurons from sensory pathways is reduced and may contribute to motor dysfunction and spasticity.

Abstract: Reduced inhibition of spinal motoneurons by sensory pathways may contribute to heightened reflex activity, spasticity and impaired motor function in individuals with cerebral palsy (CP). To measure if the activation of inhibitory post-synaptic potentials (IPSPs) by sensory inputs is reduced in CP, the tonic discharge rate of single motor units from the soleus muscle was plotted time-locked to the occurrence of a sensory stimulation to produce peri-stimulus frequencygrams (PSFs). Stimulation to the medial arch of the foot was used to activate cutaneomuscular afferents in 17 adults with bilateral spastic CP and 15 neurologically intact (NI) peers. Evidence of IPSP activation from the PSF profiles, namely a marked pause or reduction in motor unit firing rates at the onset of the cutaneomuscular reflex, was found in all NI participants but in only half of participants with CP. In the other half of the participants with CP, stimulation of cutaneomuscular afferents produced a PSF profile indicative of a pure excitatory post-synaptic potential, with firing rates increasing above the mean pre-stimulus rate for 300 ms or more. The amplitude of motoneuron inhibition during the period of IPSP activation, as measured from the surface EMG, was less in participants with poor motor function as evaluated with the Gross Motor Functional Classification System (r = 0.72, P < 0.001) and the Functional Mobility Scale (r = -0.82, P < 0.001). These findings demonstrate that in individuals with CP, reduced activation of motoneuron IPSPs by sensory inputs is associated with reduced motor function and may contribute to enhanced reflexes and spasticity in CP.

Figure 1. Components of the cutaneomuscular reflex

A, example of CMR that started with an EMG suppression (I1). The onset of I1 is marked by the first black vertical line and its termination by the dashed vertical grey line as the EMG falls below and returns to the mean pre‐stimulus EMG as marked by the dashed horizontal line. The pre‐stimulus EMG is expressed as a 0% Change (Δ) BKD EMG value. The maximum suppression of EMG activity between reflex onset and before 80 ms (I1_max) is marked by the open circle taken from the moving‐window average (solid grey line). The termination of the CMR is marked by the second black vertical line when the EMG response returns to the pre‐stimulus baseline. B, same as in A but for a CMR with no EMG suppression and only an excitatory response with the onset of the early component (E1) marked by the first black vertical line. Here I1_max is marked by the lowest point on the moving‐window average between the onset of the reflex and 80 ms. I1 = first inhibitory response; I1_max = maximal amount of EMG suppression within I1; E1 = first excitatory response.

Figure 2. MRI scans

Example axial FLAIR slices from each participant with CP imaged. Slices were selected at similar axial locations across participants except for those with cerebral malformations (CM) or deep grey matter injury (DGMI) where the slice was chosen to best display the abnormality. All participants with abnormal imaging had evidence of mild (+), moderate (++) or severe (+++) periventricular white matter injury (PVWMI) on both sides of the brain.  Five participants had additional findings: CP‐2 has partial agenesis of the posterior corpus callosum (a type of cerebral malformation) and evidence of a shunt tract; CP‐10 and CP‐11 have polymicrogyria (a type of cerebral malformation); CP‐8 has injury to the deep grey matter on the left; and CP‐15 has evidence of a perinatal cerebral vascular accident (CVA).

Figure 3. Representative PSFs in NI participants

Representative examples of the two main types of PSFs measured in NI participants evoked from cutaneomuscular stimulation (at time = 0 ms). Within the PSF (bottom panel), each dot corresponds to the instantaneous firing rate of a motor unit and the thick black line is a moving‐window average of those rates. Unrectified intramuscular EMG and an inset of the superimposed, isolated motor unit are displayed in the top panel (duration of motor unit waveforms 2–3 ms). A, an initial IPSP is indicated by a pause in firing ∼60 ms following stimulation in the PSF. A pause in firing was noted when there was a break in the PSF and low to no counts in the PSTH (third panel). Dashed horizontal lines indicate mean pre‐stimulus EMG (second panel) and firing rates (bottom panel). B, PSF demonstrating an initial EPSP that preceded the IPSP with increased firing probability and rate near 50 ms following stimulation. Subsequent IPSP is indicated by a pause in firing starting at 60 ms and a resumption of firing near 120 ms with firing rates slightly below baseline. PSF = peri‐stimulus frequencygram; PSTH = peri‐stimulus time histogram.

Figure 4. Representative PSFs in participants with CP

Same as in Fig. 3 but for representative PSFs from four participants with CP. A, PSF indicating a strong initial IPSP with a pause in firing starting near 60 ms and followed by an EPSP (CP‐2). Note the line in the PSF marking the moving‐window average is white for better visualization. B, PSF indicating a weak IPSP as marked by a decrease in the firing rate beginning near 45 ms following stimulation (CP‐17). C and D, pure EPSP indicated by increases in the firing rate starting near 50 ms following stimulation and continuing to 300 ms (CP‐13, CP‐6). PSF = peri‐stimulus frequencygram.

Figure 5. Cutaneomuscular reflexes: surface EMG

A, black lines represent the averaged surface EMG response (25 trials) to cutaneomuscular stimulation at time = 0 ms for three representative NI participants (i to iii). The grey line represents the moving‐window average from response onset to 80 ms following stimulation with the lowest point on the moving‐window average (I1_max) indicated by the open circle. EMG values are normalized to the mean pre‐stimulation EMG (marked by the dotted horizontal line) and expressed as an absolute change (Δ) from that value (mean pre‐stimulation EMG = 0% Δ). B, same as in A but for three representative participants with CP showing progressively lower amounts of EMG suppression (i to ii) and EMG facilitation (iii). I1_max = maximal amount of EMG suppression within the first inhibitory response.

Figure 6. Spinal inhibition and motor function

The magnitude of I1_max is plotted against FMS_TOTAL (left panel) and GMFCS (right panel) in the CP group (n = 17). The box plot in the middle panel illustrates the median (thick black line), 25th and 75th percentiles (box bounds), and 95th and 5th percentiles (whiskers) of I1_max in the NI group. The scatter of all data points for the NI group (n = 14) is also displayed over the box plot. FMS_TOTAL = total Functional Mobility Scale, GFMCS = Gross Motor Functional Classification System, I1_max = maximal amount of EMG suppression within the first inhibitory response.