Corticospinal excitability in idiopathic normal pressure hydrocephalus: a transcranial magnetic stimulation study

Abstract

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease with an unknown etiology. Disturbed corticospinal inhibition of the motor cortex has been reported in iNPH and can be evaluated in a noninvasive and painless manner using navigated transcranial magnetic stimulation (nTMS). This is the first study to characterize the immediate impact of cerebrospinal fluid (CSF) drainage on corticospinal excitability. Methods: Twenty patients with possible or probable iNPH (16 women and 4 men, mean age 74.4 years, range 67-84 years), presenting the classical symptom triad and radiological findings, were evaluated with motor function tests (10-m walk test, Grooved Pegboard and Box & Block test) and nTMS (silent period, SP, resting motor threshold, RMT and input-output curve, IO-curve). Evaluations were performed at baseline and repeated immediately after CSF drainage via lumbar puncture. Results: At baseline, iNPH patients presented shorter SPs (p < 0.001) and lower RMTs (p < 0.001) as compared to normative values. Positive correlation was detected between SP duration and Box & Block test (rho = 0.64, p = 0.002) in iNPH patients. CSF drainage led to an enhancement in gait velocity (p = 0.002) and a steeper IO-curve slope (p = 0.049). Conclusions: Shorter SPs and lower RMTs in iNPH suggest impaired corticospinal inhibition and corticospinal hyperexcitability. The steeper IO-slope in patients who improve their gait velocity after CSF drainage may indicate a higher recovery potential. Corticospinal excitability correlated with the motor function of the upper limbs implying that the disturbance in motor performance in iNPH extends beyond the classically reported gait impairment.

Upper limb dysfunction and activities in daily living in idiopathic normal pressure hydrocephalus

“…Therefore, the predictive role of upper limb motor function tests as a part of the preoperative TAP test is controversial and not generally used in clinical practice [ 28 , 29 ]. The underlying dysfunction and the effect of CSF drainage may differ between upper and lower limbs as suggested in our recent study, in which an initial change in corticospinal excitability after decreased intrathecal pressure was associated with improved walking speed but not with upper limb function [ 30 ].…”

Diabetes is associated with familial idiopathic normal pressure hydrocephalus: a case–control comparison with family members

“…By affecting the astrocytes diabetes has also been found to reduce the glutamate uptake in brain in rat models [ 50 , 51 ]. Interestingly, iNPH patients have been found to suffer from corticospinal hyperexcitability and it has been hypothesized to possibly derive from increased activity of glutamatergic system [ 52 , 53 ].…”

Input–Output Slope Curve Estimation in Neural Stimulation Based on Optimal Sampling Principles

“…Extensive research is covering the relationship between the IO curve parameters and medical conditions. For instance, IO curves can be used as biomarkers for movement disorders [6], [7], epilepsy [8], dementia [9], stroke [10], [11], idiopathic normal pressure hydrocephalus (iNPH) [12], neurodegenerative diseases [13], and various other neurological conditions [14]- [18].…”

“…The narrower the excitability distribution, the larger the available connections, which tends to result in a steeper slope of the IO curve, and vice versa. For instance, in [12], the IO curve of a number of iNPH patients were acquired by TMS before and after cerebrospinal fluid drainage through lumbar puncture. The results show significant increase of the slope of the IO curve after drainage in iNPH patients who had improved gait performance.…”