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Hereditary spastic paraplegia (HSP) is the name given to a heterogeneous group of rare neurodegenerative disorders of the motor system characterised by slowly progressive spasticity and weakness of the lower limbs. About one third of patients with autosomal dominant pure spastic paraplegia (ADPSP) linked to chromosome 2p have lower urinary tract symptoms (LUTS) and additionally most of these patients also experience rectal urgency/urge incontinence (RUI) as well as sexual dysfunction.1
The direct motor pathway to the external anal sphincter may be studied by transcranial magnetic stimulation (TMS), evoking compound muscle action potentials (CMAPs) with cortical and sacral stimulation.2 3
This study was conducted to evaluate the motor evoked potentials (MEPs) from the external anal sphincter in patients with ADPSP linked to chromosome 2p and to obtain norminative data.
After informed consent was obtained 11 definitely affected patients from six different families with ADPSP linked to chromosome 2p and 12 normal controls were included. The median age for the patients was 41 (range 20–64) years, and for the controls 40 (range 21–60) years. Six patients had LUTS and RUI, five of whom previously underwent urodynamic evaluation including measures of the bulbocavernosus reflex (patient numbers A2, C4, C6, K10, and L11 in Neerup Jensenet al 1). Five patients were without LUTS and RUI. Family details, clinical features, and urodynamic findings have been previously described.1-4 The investigator was blinded to the urinary and bowel symptoms. The study was approved by the ethics committee.
Motor evoked potentials (MEPs) were elicited by cortical stimulation using a parabolic shaped coil, diameter 14 cm with a Twintop Magnetic Stimulator, and EMG responses obtained with a Keypoint EMG-machine (Dantec Medical Inc, Denmark). The compound motor action potentials (CMAPs) were recorded from the external anal sphincter using a disposable sphincter electrode (Dantec 13L81, Dantec Medical Inc, Denmark). The position of the electrode was anteroposterior to avoid cancelling of the motor potentials because of bilateral contraction from the right and left side of the external anal sphincter induced by cortical and sacral stimulations.
The cortical stimuli were applied near to the vertex in the area representing the lowest threshold for a motor contraction in the lower limbs measured in the right abductor hallucis (AH) muscle. The motor threshold (MT) was determined as the minimal stimulus intensity applied to the relevant cortical representation evoking at least three motor action potentials of five trials with an amplitude exceeding 50 μV. In some patients the MEP amplitudes were very small, and therefore MT determination was difficult. To ensure a sufficient stimulus intensity the AH muscle was selected for MT measures. The stimulus intensity was increased to 50% above MT for the AH muscle or to a level sufficient to evoke a reproducible contraction of the external anal sphincter. The patients and the controls were instructed not voluntary to contract the sphincter (“relaxed MEPs”). The cortical latency (CL) and amplitude of the CMAP were identified. The sacral stimulation was applied to the S2-S4 area using magnetic stimulation (maximum output) and the sacral latency (SL) and the central motor conduction time (CMCT=CL-SL) were calculated. The stimulations were performed in at least three individual trials with two runs to ensure reproducibility. In four patients the motor action potentials were hardly reproducible, and therefore an averaging technique was used in those patients. The results of MEPs obtained in upper and lower limb muscles are presented elsewhere.4
The results are presented as median (range), and the distributions were compared by the Kruskal-Wallis test. The level of significance was taken as 0.05.
Examples of cortical and sacral stimulation and CMAP from the external anal sphincter evoked in a control person and in a patient with LUTS and RUI are shown in figure 1. The results are shown in table1.
The CL and the CMCT were significantly longer and the amplitude of CMAP at cortical stimulation was significantly lower in the patients with ADPSP with LUTS and RUI compared with the patients without these symptoms. The patients without LUTS and RUI presented no significant differences in CL, CMCT, or amplitude of the CMAP compared with the controls. The patients with LUTS and RUI presented significantly longer CL and CMCT and lower amplitudes of the CMAP than the control subjects. No significant differences in SL or amplitudes of CMAP at sacral stimulation were seen between the patients with ADPSP and the controls.
In this study we found that reproducible CMAPs could be obtained from the external anal sphincter using surface electrodes with cortical and sacral stimulation. Our normative values were similar to former studies.2-3 Using TMS we showed that patients with LUTS and RUI presented longer CMCT and reduced amplitudes of the cortical evoked CMAPs, whereas patients without these symptoms showed no differences. As shown in table 1, there is little overlap between the two groups. The number of patients are small, but the results suggest that measurement of MEPs to the external anal sphincter may be a method to be used as a part of the evaluation of patients with supranuclear lesions and sphincter symptoms.
In neuropathological studies axonal degeneration was found to be maximal in the terminal portions of the longest descending and ascending tracts. Dorsal root ganglia, posterior roots, and peripheral nerves were normal.5 Axonal degeneration of the corticospinal neurons, however, cannot solely explain the pathogenesis of the disease. Patients without LUTS and RUI presented normal CMCTs and only non-significantly reduced CMAsPs, despite the presence of severe spasticity. A reduced CMAP is suggestive of selective large fibre loss in the relevant spinal cord pathways; however, other mechanisms may be involved in the reduced CMAP, including a raised cortical threshold to TMS.
We conclude that MEPs from the external anal sphincter in patients with ADPSP linked to chromosome 2p with LUTS and RUI present longer CMCTs and lower CMAPs at cortical stimulation. These results may in part be related to the pathogenesis of the disease. MEPs from the external anal sphincter can be relatively easily evoked and may be a new useful method in the evaluation of patients with supranuclear lesions and RUI.
Financial support was obtained from Hartmann's Foundation, the Danish Medical Research Council, and the Danish Medical Association Research Fund.
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