Motor-conduction failure in clinical isolated syndromes: sensitivity to detect clinically silent lesions with transcranial magnetic stimulation and the triple-stimulation technique

Objective: To compare the sensitivity to detect motor-conduction failure in patients with „clinical isolated syndromes“ (CIS) with transcranial magnetic stimulation (TMS) and the triplestimulation technique (TST) and to describe their pathophysiology.

Background: Patients with CIS like optic neuritis, myelitis, brainstem or cerebral inflammatory disease are at high risk to develop multiple sclerosis (MS). Magnetic resonance imaging (MRI) of the brain or spinal cord and neurophysiologic tests could demonstrate further lesions which are clinically silent in affected patients. TST examines the corticospinal tract by magnetic stimulation of cortical motor areas followed by sequential distal and proximal peripheral nerve electric stimulation. The emerging potential results from the collision of sequenced stimuli. Compared with sequential stimulation of peripheral nerves alone, the amplitude ratio quantifies central motor conduction failure. Lesions with conduction block/axonal pathology (CB) are detected by diminished TST-amplitude ratios, on the other hand demyelinating lesions (DL) display prolonged central motor conduction time in TMS.

Design/methods: Upper limb (to abductor digiti minimi muscle) and lower limb (to abductor hallucis muscle) TMS and TST was applied to 54 healthy controls to establish normal values (mean value –2.5 times standard deviation) and to 80 consecutive patients with CIS (19 with supratentorial, 15 with infratentorial lesions, 31 with myelitis and 15 with optic neuritis). Patients were examined including the Expanded disability status score (EDSS), spinal cord magnetic resonance imaging (MRI) and visual (VEP) and somatosensory (SEP) evoked potentials. MRI were analysed according to the criteria of Barkhoff/Tintore, VEP/SEP with our laboratory normal values.

Results: The EDSS of patients varied between 1 and 5.5. MRI demonstrated cerebral or spinal lesions in 95% of patients, 56% had an initial MRI typical for MS. TST was abnormal in 55% of patients, SEP in 42%, VEP in 27% and TMS in 20%. Motor conduction failure of CB-type was 2,75 times more frequent than DL and was detected in 48.8% of patients without any clinical motor finding.

Conclusions/Relevance: TST is a sensitive method to detect central motor conduction failure in patients with a high risk to develop MS. In comparison to TMS the TST-method is markedly more sensitive to detect clinically silent pyramidal tract lesions, mostly of the CB-type.