Evidence for Shared Neural Information Between Muscle Synergies and Corticospinal Efficacy

Stroke survivors often exhibit gait dysfunction which compromises self-efficacy and quality of life. Muscle Synergy Analysis (MSA), derived from electromyography (EMG), has been argued as a method to quantify the complexity of descending motor commands and serve as a direct correlate of neural function. However, controversy remains regarding this interpretation, specifically attribution of MSA as a neuromarker. Here we sought to determine the relationship between MSA and accepted neurophysiological parameters of motor efficacy in healthy controls, high (HFH) and low (LFH) functioning stroke survivors. Surface EMG was collected from twenty-four participants while walking at their self-selected speed. Concurrently, transcranial magnetic stimulation (TMS) was administered, during walking, to elicit motor evoked potentials (MEPs) in the plantarflexor muscles during the pre-swing phase of gait. MSA was able to differentiate control and LFH individuals. Conversely, motor neurophysiological parameters including soleus MEP area, revealed that MEP latency differentiated control and HFH individuals. Significant correlations were revealed between MSA and motor neurophysiological parameters adding evidence to our understanding of MSA as a correlate of neural function and highlighting the utility of combining MSA with other relevant outcomes to aid interpretation of this analysis technique.

Approach to the Patient with Gait Disturbance

The assessment of patients presenting with disorders of gait can be a daunting task for neurologists given the broad potential localization and differential diagnosis. However, gait disorders are extremely common in outpatient neurology, and all neurologists should be comfortable with the assessment, triage, and management of patients presenting with difficulty walking. Here, we aim to present a manageable framework for neurologists to approach the assessment of patients presenting with gait dysfunction. We suggest a chief complaint-based phenomenological characterization of gait, using components of the neurological history and examination to guide testing and treatment. We present the framework to mirror the outpatient visit with the patient, highlighting (1) important features of the gait history, including the most common gait-related chief complaints and common secondary (medical) causes of gait dysfunction; (2) gait physiology and a systematic approach to the gait examination allowing appropriate characterization of gait phenomenology; (3) an algorithmic approach to ancillary testing for patients with gait dysfunction based on historical and examination features; and (4) definitive and supportive therapies for the management of patients presenting with common neurological disorders of gait.

P.213 Long-Term Improvement Of Gait And Cognition After Primary Endoscopic Third Ventriculostomy (ETV) In Adult Obstructive Hydrocephalus

Background: Adults with obstructive hydrocephalus often present with cognitive and/or gait dysfunction in addition to symptoms of raised ICP. We previously reported improvement of cognitive and gait function 3 months following primary adult ETV. This abstract presents long-term results in this group. Methods: Obstructive hydrocephalus was identified based on tri-ventriculomegaly on CT and/or MRI. Gait velocity (10 m timed gait) and cognitive function (Montreal Cognitive Assessment [MoCA]) were measured at two timepoints: pre-ETV and ≥9 months post-ETV. Results: Sixteen adults underwent primary ETV and completed a long-term assessment. Mean age was 60 years and 10 (63%) were male. Etiology: 10 (62.5%) congenital and 6 (37.5%) acquired. Mean long-term follow-up time for cognitive and gait assessments was 14.4 and 13.7 months, respectively. The long-term MoCA within patient median change was +2 points (n= 15; p = 0.007). Group medians were 23/30 (pre-ETV) and 26/30 (post-ETV). The long-term gait velocity within patient median change was +0.4 m/s (n= 12; p < 0.001). Group medians were 0.7 m/s (pre-ETV) and 1.3 m/s (post-ETV). Conclusions: ETV in adults with obstructive hydrocephalus results in long-term improvement of cognition and gait velocity when assessed ≥9 months post-ETV. Larger cohorts will determine the generalizability of these results. Hydrocephalus Association supported project.

Parkinsonian gait effects with DBS are associated with pallido-peduncular axis activation

Background: Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) often shows variable outcomes on treating gait dysfunction in Parkinson's disease (PD). Such variability may stem from which specific neuronal pathways are modulated by DBS and the extent to which those pathways are modulated relative to one another. Objective: Leveraging ultra-high-field (7T) imaging data and subject-specific computational models, this study investigated how activation of seven distinct pathways in and around STN, including the pallidopeduncular and pedunculopallidal pathways, affect step length at clinically-optimized STN-DBS settings. Methods: Personalized computational models were developed for 10 subjects with a clinical diagnosis of PD and with bilateral STN-DBS implants. Results: The subject-specific pathway activation models showed a significant positive association between activation of the pedunculopallidal pathway and increased step length, and negative association on step length with pallidopeduncular pathway and hyperdirect pathway activation. Conclusions: The STN region includes multiple pathways, including fibers of passage to and from the mesencephalic locomotor area. Future clinical optimization of STN-DBS should consider these fibers of passage in the context of treating parkinsonian gait.

Substantia nigra degradation results in widespread changes in medial zona incerta afferent and efferent connectomics

Parkinson disease (PD) is a complex disease affecting many facets of movement, especially gait abnormalities such as shuffling and freezing of gait. The nigrostriatal pathways of the basal ganglia are traditionally targeted by existing therapies; however, other pathways may be more relevant to gait, such as the pedunculopontine nucleus and the zona incerta (ZI). The A13 nucleus may be such a target as it has emerged as an area of interest in dopamine motor function. Yet, this area remains understudied compared to other dopamine nuclei, especially in animal models of PD. In 6-OHDA mice, we found a reduction in locomotion in the open field and gait dysfunction during treadmill tests. Medial ZI dopamine cells, containing the A13 nucleus, were preserved following 6-OHDA, in contrast to a marked reduction in substantia nigra pars compacta (SNc) neurons. There was extensive remodelling of the A13 afferent and efferent connectome following nigrostriatal lesions. Afferent input patterns displayed a marked reduction in cross-correlation across brain regions in 6-OHDA mice, while efferent projections showed an increase. In a human PD patient with advanced gait dysfunction we found that the A13 nucleus was preserved, suggesting that remodelling could also occur in humans. This work points to the A13 region as a potential therapeutic target in PD.

Leriche Syndrome Misdiagnosed as Complex Regional Pain Syndrome in a Patient with Neuropathic Pain Caused by a Chip Fracture: A Case Report

Introduction: Leriche syndrome is an aortoiliac occlusive disease caused by atherosclerotic occlusion. We report a case of Leriche syndrome with a fracture that was suspected as complex regional pain syndrome (CRPS), as the post-traumatic pain gradually worsened in the form of excruciating neuropathic pain. Case Report: A 52-year-old woman with a history of hypertension was referred to the Department of Pain Medicine from a local orthopedic clinic because of suspected CRPS for excruciating neuropathic pain for one month. She complained of gait dysfunction and severe pain in the right foot following an incident of trauma with the right first toe. The average pain intensity assessed using the visual analog scale (VAS) was 90 (0: no pain, 100: the worst pain imaginable), and the neuropathic pain was evident as a score of 6/10 on Douleur neuropathique 4. Allodynia, hyperalgesia, blue discoloration of the skin, asymmetric temperature change (1.38 °C), and edematous soft tissue changes were observed. Ultrasonography showed a chip fracture in the first distal phalanx of the right first toe. The diagnosis was most probably CRPS type I according to the Budapest research criteria for CRPS. However, multiple pain management techniques were insufficient in controlling the symptoms. A month and a half later, an ankle-brachial index score of less than 0.4 suggested severe peripheral artery disease. Computed tomography angiography showed total occlusion between the infrarenal abdominal aorta and the bilateral common iliac arteries. Therefore, she underwent aortic-bifemoral bypass surgery with a diagnosis of Leriche syndrome. Three months after the surgery, the average pain intensity was graded as 10 on the VAS (0–100), the color of the skin of the right first toe improved and no gait dysfunction was observed. Conclusion: A chip fracture in a region with insufficient blood flow could manifest as excruciating neuropathic pain in Leriche syndrome.

Successful Application of an Insole with a Metatarsal Inhibition Bar and Deep Heel Cup for Improving Gait Dysfunction in a Patient with Poor Coordination with Disrupted Corticoreticular Tracts: A Case Report

We report the successful management of gait dysfunction in a patient with coordination problems using an insole with a metatarsal inhibition bar (MIB) and a deep heel cup. Furthermore, we investigated the state of the neural tracts via diffusion tensor tractography (DTT). A 23-month-old boy with gait dysfunction presented with toe walking with a wide base and decreased hip flexion. Motor weakness or spasticity was not observed. Conventional brain magnetic resonance imaging did not reveal any abnormal findings, but DTT revealed disrupted bilateral corticoreticulospinal tracts (CRTs). No abnormalities were observed in the corticospinal tract or the medial lemniscus. We applied a custom-made insole with an MIB and a deep heel cup. Immediately after application, the patient’s gait pattern stabilized significantly and was nearly normalized. Our therapeutic experience indicates that the application of an insole with an MIB and deep heel cups could be beneficial for patients with coordination problems and gait dysfunction. Our DTT results showed that CRTs could be the causative brain pathology for gait dysfunction in patients with coordination problems.