Abstract
Paired associative stimulation (PAS) with high-frequency peripheral nerve stimulation (PNS), called “high-PAS”, induces motor-evoked potential (MEP) potentiation in healthy subjects and ...improves muscle activity and independence in incomplete spinal cord injury patients. Data on optimal PNS intensity in PAS are scarce. In a high-PAS protocol, PNS intensity is defined as “minimal intensity required to produce F-responses”. We sought to further refine this definition and to investigate how PNS intensity affects PAS outcome. Two experiments were performed on 10 healthy subjects where MEP amplitude change was measured 0, 30, and 60 min after PAS. In the first experiment, the intensity required to achieve 7/10 persistence of F-responses was used to define PNS intensity level. In the second experiment, we used the intensity required to achieve 1/10 persistence (“baseline”). In addition, we applied this intensity at + 25%, − 25%, and − 50% levels. In the first experiment, PAS did not produce significant MEP potentiation. In the second experiment, PAS produced statistically significant MEP potentiation, with PNS intensity of “baseline” and “baseline − 25%” levels but not at + 25% or − 50% levels. In conclusion, for PAS utilizing high-frequency PNS, the intensity required to achieve 1/10 F-response persistence or the intensity 25% lower produces significant MEP potentiation in healthy subjects.
The intracarotid amobarbital procedure (IAP) is the current "gold standard" in the preoperative assessment of language lateralization in epilepsy surgery candidates. It is, however, invasive and has ...several limitations. Here we tested a simple noninvasive language lateralization test performed with magnetoencephalography (MEG).
We recorded auditory MEG responses to pairs of vowels and pure tones in 16 epilepsy surgery candidates who had undergone IAP. For each individual, we selected the pair of planar gradiometer sensors with the strongest N100m response to vowels in each hemisphere and-from the vector sum of signals of this gradiometer pair-calculated the vowel/tone amplitude ratio in the left (L) and right (R) hemisphere and, subsequently, the laterality index: LI = (L-R)/(L+R). In addition to the analysis using a single sensor pair, an alternative analysis was performed using averaged responses over 18 temporal sensor pairs in both hemispheres.
The laterality index did not correlate significantly with the lateralization data obtained from the IAP. However, an MEG pattern of stronger responses to vowels than tones in the left hemisphere and stronger responses to tones than vowels in the right hemisphere was associated with left-hemispheric language dominance in the IAP in all the six patients who showed this pattern. This results in a specificity of 100% and a sensitivity of 67% of this MEG pattern in predicting left-hemispheric language dominance (p = 0.01, Fisher's exact test). In the analysis using averaged responses over temporal channels, one additional patient who was left-dominant in IAP showed this particular MEG pattern, increasing the sensitivity to 78% (p = 0.003).
This simple MEG paradigm shows promise in feasibly and noninvasively confirming left-hemispheric language dominance in epilepsy surgery candidates. It may aid in reducing the need for the IAP, if the results are confirmed in larger patient samples.
A large proportion of spinal cord injuries (SCI) are incomplete. Even in clinically complete injuries, silent non-functional connections can be present. Therapeutic approaches that can strengthen ...transmission in weak neural connections to improve motor performance are needed. Our aim was to determine whether long-term delivery of paired associative stimulation (PAS, a combination of transcranial magnetic stimulation TMS with peripheral nerve stimulation PNS) can enhance motor output in the hands of patients with chronic traumatic tetraplegia, and to compare this technique with long-term PNS. Five patients (4 males; age 38-68, mean 48) with no contraindications to TMS received 4 weeks (16 sessions) of stimulation. PAS was given to one hand and PNS combined with sham TMS to the other hand. Patients were blinded to the treatment. Hands were selected randomly. The patients were evaluated by a physiotherapist blinded to the treatment. The follow-up period was 1 month. Patients were evaluated with Daniels and Worthingham's Muscle Testing (0-5 scale) before the first stimulation session, after the last stimulation session, and 1 month after the last stimulation session. One month after the last stimulation session, the improvement in the PAS-treated hand was 1.02 ± 0.17 points (p < 0.0001, n = 100 muscles from 5 patients). The improvement was significantly higher in PAS-treated than in PNS-treated hands (176 ± 29%, p = 0.046, n = 5 patients). Long-term PAS might be an effective tool for improving motor performance in incomplete chronic SCI patients. Further studies on PAS in larger patient cohorts, with longer stimulation duration and at earlier stages after the injury, are warranted.
Central poststroke pain (CPSP), a neuropathic pain condition, is difficult to treat. Repetitive transcranial magnetic stimulation (rTMS) targeted to the primary motor cortex (M1) can alleviate the ...condition, but not all patients respond. We aimed to assess a promising alternative rTMS target, the secondary somatosensory cortex (S2), for CPSP treatment.
This prospective, randomized, double-blind, sham-controlled three-arm crossover trial assessed navigated rTMS (nrTMS) targeted to M1 and S2 (10 sessions, 5050 pulses per session at 10 Hz). Participants were evaluated for pain, depression, anxiety, health-related quality of life, upper limb function, and three plasticity-related gene polymorphisms including Dopamine D2 Receptor (DRD2). We monitored pain intensity and interference before and during stimulations and at one month. A conditioned pain modulation test was performed using the cold pressor test. This assessed the efficacy of the descending inhibitory system, which may transmit TMS effects in pain control.
We prescreened 73 patients, screened 29, and included 21, of whom 17 completed the trial. NrTMS targeted to S2 resulted in long-term (from baseline to one-month follow-up) pain intensity reduction of ≥30% in 18% (3/17) of participants. All stimulations showed a short-term effect on pain (17–20% pain relief), with no difference between M1, S2, or sham stimulations, indicating a strong placebo effect. Only nrTMS targeted to S2 resulted in a significant long-term pain intensity reduction (15% pain relief). The cold pressor test reduced CPSP pain intensity significantly (p = 0.001), indicating functioning descending inhibitory controls. The homozygous DRD2 T/T genotype is associated with the M1 stimulation response.
S2 is a promising nrTMS target in the treatment of CPSP. The DRD2 T/T genotype might be a biomarker for M1 nrTMS response, but this needs confirmation from a larger study.
Objectives
To use pre- and post-operative diffusion tensor imaging (DTI) to monitor median nerve integrity in patients suffering from carpal tunnel syndrome (CTS).
Methods
Diffusivity and anisotropy ...images along the median nerve were compared among 12 patients, 12 age-matched and 12 young control subjects and correlated with electrophysiological neurography results. Slice-wise DTI parameter values were calculated to focus on local changes.
Results
Results of pre-operative patients and age-matched control subjects differed only in the distal nerve. Moreover, pre-operative patients differed significantly from young controls and post-operative patients. The main abnormalities were increased diffusivity and decreased anisotropy in the carpal tunnel and distal median nerve. Post-operative clinical improvement was reflected in diffusivity, but not in anisotropy. Slice-wise analysis showed high pre-operative diffusivity at the distal nerve. All groups had relatively large inter-subject variation in both diffusivity and anisotropy.
Conclusions
DTI can provide information complementary to clinical examination, electrophysiological recordings and anatomical MRI of diseases and injuries of peripheral nerves. However, similar age-related changes in diffusivity and anisotropy may weaken DTI specificity. Slice-wise analysis is necessary for detection of local changes in nerve integrity.
Key Points
• Diffusion tensor magnetic resonance imaging provides information complementary to conventional diagnostic methods.
• Age caused similar changes to diffusivity and anisotropy as carpal tunnel syndrome.
• Post-operative clinical improvement was reflected in diffusivity, but not in anisotropy.
• Inter-subject variation in diffusivity and anisotropy was considerable.
Recovery of lower-limb function after spinal cord injury (SCI) is dependent on the extent of remaining neural transmission in the corticospinal pathway. The aim of this proof-of-concept pilot study ...was to explore the effects of long-term paired associative stimulation (PAS) on leg muscle strength and walking in people with SCI. Five individuals with traumatic incomplete chronic tetraplegia (>34 months post-injury, motor incomplete, 3 females, mean age 60 years) with no contraindications to transcranial magnetic stimulation (TMS) received PAS to one or both legs for 2 months (28 sessions in total, 5 times a week for the first 2 weeks and 3 times a week thereafter). The participants were evaluated with the Manual Muscle Test (MMT), AIS motor and sensory examination, Modified Asworth Scale (MAS), and the Spinal Cord Independence Measure (SCIM) prior to the intervention, after 1 and 2 months of PAS, and after a 1-month follow-up. The study was registered at
clinicaltrials.gov
(NCT03459885). During the intervention, MMT scores and AIS motor scores increased significantly (
p
= 0.014 and
p
= 0.033, respectively). Improvements were stable in follow-up. AIS sensory scores, MAS, and SCIM were not modified significantly. MMT score prior to intervention was a good predictor of changes in walking speed (
R
adj
2
= 0.962). The results of this proof-of-concept pilot study justify a larger trial on the effect of long-term PAS on leg muscle strength and walking in people with chronic incomplete SCI.
Because of the premalignant nature of intraductal papillary mucinous neoplasms (IPMNs), patients should undergo surveillance as long as they remain fit for surgery. This surveillance, with imaging ...and laboratory tests every 6 to 12 months, is expensive and may psychologically burden patients. This study aimed to determine the effects of IPMN surveillance on patients´ health-related quality of life (HRQoL) and anxiety levels.
We included a random subgroup of all IPMN patients undergoing a follow-up check-up at Helsinki University Hospital (HUH) between August 2017 and November 2018. Patients were asked to complete the 15D HRQoL and state-trait anxiety inventory (STAI) questionnaires just before and three months after an IPMN control.
Among 899 patients in IPMN follow-up, 232 participated. The 15D HRQoL results showed differences in some IPMN patients' 15 analyzed dimensions compared to a sex- and age-standardized general population cohort, but the clinical relevance of these differences appear doubtful. We detected no significant difference in the anxiety levels determined using the STAI questionnaires before or three months after the IPMN control.
Surveillance should be less harmful than the risk of disease. Among our patients, the recommended IPMN follow-up carried minimal negative impact on patients' HRQoL or anxiety levels. This result is important, because the number of patients under IPMN surveillance is rapidly increasing and the cancer risk among the majority of these patients remains small.
The Surgical Ethics Committee of Helsinki University Hospital approved this study (Dnro HUS 475/2017) and it was registered at ClinicalTrials.gov (NCT03131076) before patient enrollment began.
Highlights ► Motor cortex excitability, modulated by afferent input, is increased in the affected hemisphere in the acute phase after stroke and decreases subsequently during recovery. ► Motor cortex ...excitability correlates with strength of secondary somatosensory cortex (SII) activation, suggesting that modulatory afferent input may reach the motor cortex via SII. ► Afferent input modulated motor cortex excitability is associated with hand function, underlining the importance of parallel recovery of the sensory and motor systems for normal hand dexterity.
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