Figure 1.
Blink reflexes in a multiple sclerosis patient showing a unilateral enhancement of excitability (AbEx).
Recordings from bilateral orbicularis oculi (OOc; R = right and L = left) of the trigeminal (TBR) and the somatosensory blink reflexes (SBR). The graphs at the top of the figure (TBR) show both unilateral/early response (R1), and bilateral/late responses (R2 and R2c), to stimulation of the supraorbital nerve (SON) of either side (two traces are superimposed). The graphs at the bottom of the figure (SBR) show ipsilateral OOc responses to median nerve stimuli. The recordings of a healthy subject (A) are shown in the left side of the figure, and those corresponding to a representative patient with enhanced R2c/R2 ratio (AbEx, B) are shown in the right side. Note that the R2c is larger than the R2 to stimulation of the right SON in the patient but not in the healthy subject, i.e., the R2c/R2 ratio is below 1 in the healthy subject and above 1 in the patient. Note also the similar size of the SBR in responses of both sides in the healthy subject and the clear inter-side difference in the patient, who had a larger response in the left side (coincident asymmetry with the R2c/R2 ratio). Coincident enhanced unilateral OOc responses from both trigeminal and median nerve stimulation suggest left facial motoneuronal excitability enhancement.
Table 1.
Clinical, neuroimage and neurophysiological signs of brainstem involvement in all study patients.
Figure 2.
Trigeminal blink reflex and brainstem MRI of a patient with AbLat (n° 13).
In A (left), orbicularis oculi (OOc) responses in both sides (R = right and L = left) are recorded after bilateral supraorbital nerve stimulation (SON, R = right, L = left; two traces are superimposed). Vertical dashed lines indicate the normal upper cut-off values for the latency of R1 and R2 responses and arrows indicate response onset. Note the delay in response latency for R1 in both sides and for the R2 and R2c to L-SON stimulation while these responses could not be obtained to R-SON (mixed pattern). In B (right), relevant MRI images from this patient are shown: coronal T1-MPRAGE (upper), axial FLAIR (lower left) and T2-weighted (lower right) images show evidence for multiple bilateral lesions in the pons.
Figure 3.
Graphical representation of values for right and left side R2c/R2 ratios (upper graphs) and mean R2 area (µV x s; lower graphs) in healthy subjects and patients with multiple sclerosis.
The individual values for right (R) and left (L) sides are tied by a line to highlight the degree of between-sides asymmetry. Horizontal dashed lines indicate the normal upper cut-off values for both response size parameters. Note that healthy subjects show relatively more symmetrically distributed values with respect to patients for both the R2c/R2 ratio and the mean R2 area. A unilateral R2c/R2 ratio value above 1 was observed in 9 patients (lines reaching above 1 in panel B). Only 2 AbLat patients had a single value above 1 in the R2c/R2 ratio (marked with asterisks in B). Although no differences on the distribution of the mean R2 area values were apparent between both groups (lower graphs), 8 patients had a significant increase in the inter-side difference which was coincident with a unilateral enhancement on the R2c/R2 ratio (AbEx patients). These 8 subjects are identified in panel D because of their steeper slope in the inter-side.
Table 2.
Data on response size calculated in healthy subjects and in patients categorized as AbEx and no-AbEx.
Figure 4.
Blink reflex excitability abnormalities and brain MRI in a representative AbEx patient (n° 9).
In A, supratentorial demyelinating lesions are identified (sagital FLAIR sequence, upper image) in absence of brainstem lesions (axial T2-weighted and sagital T1-MPRAGE sequences, lower images). In the inserted figure (B), significant individual differences on BRER can be observed between the side with largest OOc response size (AbEx side; first and third traces) and the contralateral side (normal side; second and forth traces) at the 600 (upper traces) and 300 miliseconds-ISIs (lower traces). In C, the BRIP was examined on both orbicularis oculi (OOc; R = right and L = left) to ipsilateral prepulses. Upper traces show the R1 and R2 responses obtained to ipsilateral supraorbital nerve (SON) stimulus without a prepulse. In lower traces, normal inhibition of the R2 response to a somatosensory prepulse delivered 100 ms before is only observed in the right side, but not in the left. In D, bilateral OOc surface recording in the same subject showing myokymic discharges on the left side. The BRER curve of all AbEx patients (n = 9) is also represented plotting the mean value (plus standard error) of each paired-stimuli interval (ISI, in miliseconds) (B). Data from both normal and AbEx sides (see above) were employed to build two curves. A higher mean value in the response's recovery was obtained in the side with largest OOc response size, with respect to the opposite side from 200 to 600 ms, with statistically significant differences in the 500 and 600-ISIs (marked with an asterisk, p<0.05).
Figure 5.
Lesion probability map in patients with AbLat (upper sequences) and AbEx (lower sequences).
The distribution of lesions is shown at a supratentorial and brainstem level (representative sequences). In the probability map each voxel value (colored from deep blue to green) could be thought of as an estimate of the probability (from 0.0 to 0.4) that each subject of the subgroup had a lesion at that location. A different pattern of lesion distribution can be clearly distinguished between both groups.
Table 3.
Data on brain volume and brain lesion-load MRI-acquired in patients with multiple sclerosis separated by the abnormalities found on the TBR.