Deep Brain Stimulation Improves Parkinson's Disease-Associated Pain by Decreasing Spinal Nociception.

Dopamine exerts antinociceptive effects on pain in PD at cortical and spinal levels, whereas only cortical effects have been described for DBS, so far. By assessing the nociceptive flexion reflex (NFR) threshold at medication on, and DBS ON and OFF in two patients, we showed that DBS additionally decreases spinal nociception.

Evaluation of the Rotational Stability of Directional Deep Brain Stimulation Leads: A Case Series and Systematic Review.

BACKGROUND: The rotational stability of directional deep brain stimulation leads is a major prerequisite for sustained clinical effects. Data on directional lead stability are limited and controversial. METHODS: We aimed to evaluate the long-term rotational stability of directional leads and define confounding factors in our own population and the current literature. We retrospectively evaluated the orientation of directional leads in patients with available postoperative computed tomography (CT; T1; day of surgery) and an additional postoperative image (T2; CT or rotational fluoroscopy) performed more than 7 days after the initial scan. The potential impact of intracranial air was assessed. We also reviewed the literature to define factors impacting stability. RESULTS: Thirty-six leads were evaluated. The mean follow-up between T1 and T2 was 413.3 (7-1,171) days. The difference in rotation between T1 and T2 was 2.444 ± 2.554 degrees (range: 0-9.0 degrees). The volume of intracranial air did not impact the rotation. The literature search identified one factor impacting the stability of directional leads, which is the amount of twist applied at implantation. CONCLUSION: Directional leads for deep brain stimulation show stable long-term orientation after implantation. Based on our literature review, large amounts of twist during implantation can lead to delayed rotation and should thus be avoided.

Development and Validation of the Dystonia-Pain Classification System: A Multicenter Study.

BACKGROUND: Dystonia is associated with disabling nonmotor symptoms like chronic pain (CP), which is prevalent in dystonia and significantly impacts the quality of life (QoL). There is no validated tool for assessing CP in dystonia, which substantially hampers pain management. OBJECTIVE: The aim was to develop a CP classification and scoring system for dystonia. METHODS: A multidisciplinary group was established to develop the Dystonia-Pain Classification System (Dystonia-PCS). The classification of CP as related or unrelated to dystonia was followed by the assessment of pain severity score, encompassing pain intensity, frequency, and impact on daily living. Then, consecutive patients with inherited/idiopathic dystonia of different spatial distribution were recruited in a cross-sectional multicenter validation study. Dystonia-PCS was compared to validated pain, mood, QoL, and dystonia scales (Brief Pain Inventory, Douleur Neuropathique-4 questionnaire, European QoL-5 Dimensions-3 Level Version, and Burke-Fahn-Marsden Dystonia Rating Scale). RESULTS: CP was present in 81 of 123 recruited patients, being directly related to dystonia in 82.7%, aggravated by dystonia in 8.8%, and nonrelated to dystonia in 7.5%. Dystonia-PCS had excellent intra-rater (Intraclass Correlation Coefficient - ICC: 0.941) and inter-rater (ICC: 0.867) reliability. In addition, pain severity score correlated with European QoL-5 Dimensions-3 Level Version's pain subscore (r = 0.635, P < 0.001) and the Brief Pain Inventory's severity and interference scores (r = 0.553, P < 0.001 and r = 0.609, P < 0.001, respectively). CONCLUSIONS: Dystonia-PCS is a reliable tool to categorize and quantify CP impact in dystonia and will help improve clinical trial design and management of CP in patients affected by this disorder. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Central Retinal Artery Occlusion: Current Practice, Awareness and Prehospital Delays in Switzerland.

Background and Purpose: Central retinal artery occlusion (CRAO) often leads to permanent monocular blindness. Hence, early recognition and rapid re-perfusion is of paramount importance. This study aims to describe prehospital pathways in CRAO compared to stroke and study the knowledge about CRAO. Methods: (1) Description of baseline characteristics, prehospital pathways/delays, and acute treatment (thrombolysis/thrombectomy vs. standard of care) of patients with CRAO and ischemic stroke registered in the Swiss Stroke Registry. (2) Online survey about CRAO knowledge amongst population, general practitioners (GPs) and ophthalmologists in Eastern Switzerland. Results: Three hundred and ninety seven CRAO and 32,816 ischemic stroke cases were registered from 2014 until 2019 in 20 Stroke Centers/Units in Switzerland. In CRAO, 25.6% arrived at the hospital within 4 h of symptom onset and had a lower rate of emergency referrals. Hence, the symptom-to-door time was significantly longer in CRAO compared to stroke (852 min. vs. 300 min). The thrombolysis/thrombectomy rate was 13.2% in CRAO and 30.9% in stroke. 28.6% of the surveyed population recognized CRAO-symptoms, 55.4% of which would present directly to the emergency department in contrast to 90.0% with stroke symptoms. Almost 100% of the ophthalmologist and general practitioners recognized CRAO as a medical emergency and 1/3 of them considered IV thrombolysis a potentially beneficial therapy. Conclusions: CRAO awareness of the general population and physician awareness about the treatment options as well as the non-standardized prehospital organization, seems to be the main reason for the prehospital delays and impedes treating CRAO patients. Educational efforts should be undertaken to improve awareness about CRAO.

Parkinson's Disease and Deep Brain Stimulation Have an Impact on My Life: A Multimodal Study on the Experiences of Patients and Family Caregivers.

Parkinson's disease (PD) has a large impact on patients' physical and mental health, which also greatly affects their family caregivers. Deep brain stimulation (DBS) has emerged as an effective treatment for PD, but different authors have expressed their concerns about the potential impact of DBS on personality and identity. Our study aims at better understanding how patients and family caregivers experience life with PD and DBS, the impact of both on their personal and social lives, and their perception of the changes that have occurred as a result of the disease and the treatment. Our study applies a multimodal approach by means of narrative semi-structured interviews and drawings. Seven principal themes have been identified: "everyone's Parkinson's is different", "changing as a person during the disease", "going through Parkinson's together", "DBS improved my life", "I am treated with DBS but I have Parkinson's still", "DBS is not perfect", and "being different after DBS". PD is perceived as an unpredictable and heterogeneous disease that changes from person to person, as does the effect of DBS. While DBS side-effects may have an impact on patients' personality, behavior, and self-perception, PD symptoms and drug side-effects also have a great impact on these aspects.

Facilitatory rTMS over the Supplementary Motor Cortex Impedes Gait Performance in Parkinson Patients with Freezing of Gait.

Freezing of gait (FOG) in Parkinson's disease (PD) occurs frequently in situations with high environmental complexity. The supplementary motor cortex (SMC) is regarded as a major network node that exerts cortical input for motor control in these situations. We aimed at assessing the impact of single-session (excitatory) intermittent theta burst stimulation (iTBS) of the SMC on established walking during FOG provoking situations such as passing through narrow spaces and turning for directional changes. Twelve PD patients with FOG underwent two visits in the off-medication state with either iTBS or sham stimulation. At each visit, spatiotemporal gait parameters were measured during walking without obstacles and in FOG-provoking situations before and after stimulation. When patients passed through narrow spaces, decreased stride time along with increased stride length and walking speed (i.e., improved gait) was observed after both sham stimulation and iTBS. These effects, particularly on stride time, were attenuated by real iTBS. During turning, iTBS resulted in decreased stride time along with unchanged stride length, a constellation compatible with increased stepping frequency. The observed iTBS effects are regarded as relative gait deterioration. We conclude that iTBS over the SMC increases stepping frequency in PD patients with FOG, particularly in FOG provoking situations.

Dual-Task Treadmill Training for the Prevention of Falls in Parkinson's Disease: Rationale and Study Design.

Various factors, such as fear of falling, postural instability, and altered executive function, contribute to the high risk of falling in Parkinson's disease (PD). Dual-task training is an established method to reduce this risk. Motor-perceptual task combinations typically require a patient to walk while simultaneously engaging in a perceptual task. Motor-executive dual-tasking (DT) combines locomotion with executive function tasks. One augmented reality treadmill training (AR-TT) study revealed promising results of a perceptual dual-task training with a markedly reduced frequency of falls especially in patients with PD. We here propose to compare the effects of two types of concurrent tasks, perceptual and executive, on high-intensity TT). Patients will be trained with TT alone, in combination with an augmented reality perceptual DT (AR-TT) or with an executive DT (Random Number Generation; RNG-TT). The results are expected to inform research on therapeutic strategies for the training of balance in PD.

Do directional deep brain stimulation leads rotate after implantation?

BACKGROUND: The two middle contacts of directional leads (d-leads) for deep brain stimulation are split into three segments, allowing current steering toward desired axial directions. To facilitate programming, their final orientation needs to be reliably determined. However, it is currently unclear whether d-leads rotate after implantation. Our objective was to assess the degree of d-lead rotation after implantation. METHODS: We retrospectively analyzed d-lead orientation on intraoperative X-rays, postoperative CT scans (latencies to surgery: 108-189 min postoperatively), and rotational fluoroscopies (4-9 days postoperatively) for a consecutive series of 32 implanted d-leads. For five d-leads, a CT scan with a mean follow-up of 57 days (range 28-182) was available. All d-leads were implanted with the marker facing anterior and the intention to hit an "iron sight" (ISi) on the X-ray, indicating anterior orientation (i.e., 0° ± 6°). RESULTS: In nine d-leads, an ISi was visible on the final X-ray; median orientation was 1.5° (range 0.5-6.0°) at the first follow-up CT, confirming anterior orientation. In d-leads without ISi or where ISi was not evaluable, the median rotation was 15.5° (9.5-35.0°) and 26.5° (5.5-62.0°), respectively. The orientation of the initial CT was comparable with the orientation determined by the postoperative rotational fluoroscopy and second CT in all d-lead groups. CONCLUSION: D-lead orientation does not change within the first week after implantation. We provide first indications that d-lead orientation remains stable for several weeks after surgery. Determination of lead orientation using marker-based X-ray alone seems too imprecise; adding the ISi method can increase determination of intraoperative orientation.

The Parkinson disease pain classification system: results from an international mechanism-based classification approach.

ABSTRACT: Pain is a common nonmotor symptom in patients with Parkinson disease (PD) but the correct diagnosis of the respective cause remains difficult because suitable tools are lacking, so far. We developed a framework to differentiate PD- from non-PD-related pain and classify PD-related pain into 3 groups based on validated mechanistic pain descriptors (nociceptive, neuropathic, or nociplastic), which encompass all the previously described PD pain types. Severity of PD-related pain syndromes was scored by ratings of intensity, frequency, and interference with daily living activities. The PD-Pain Classification System (PD-PCS) was compared with classic pain measures (ie, brief pain inventory and McGill pain questionnaire [MPQ], PDQ-8 quality of life score, MDS-UPDRS scores, and nonmotor symptoms). 159 nondemented PD patients (disease duration 10.2 ± 7.6 years) and 37 healthy controls were recruited in 4 centers. PD-related pain was present in 122 patients (77%), with 24 (15%) suffering one or more syndromes at the same time. PD-related nociceptive, neuropathic, or nociplastic pain was diagnosed in 87 (55%), 25 (16%), or 35 (22%), respectively. Pain unrelated to PD was present in 35 (22%) patients. Overall, PD-PCS severity score significantly correlated with pain's Brief Pain Inventory and MPQ ratings, presence of dyskinesia and motor fluctuations, PDQ-8 scores, depression, and anxiety measures. Moderate intrarater and interrater reliability was observed. The PD-PCS is a valid and reliable tool for differentiating PD-related pain from PD-unrelated pain. It detects and scores mechanistic pain subtypes in a pragmatic and treatment-oriented approach, unifying previous classifications of PD-pain.

Evaluation of Automatic Segmentation of Thalamic Nuclei through Clinical Effects Using Directional Deep Brain Stimulation Leads: A Technical Note.

Automatic anatomical segmentation of patients' anatomical structures and modeling of the volume of tissue activated (VTA) can potentially facilitate trajectory planning and post-operative programming in deep brain stimulation (DBS). We demonstrate an approach to evaluate the accuracy of such software for the ventral intermediate nucleus (VIM) using directional leads. In an essential tremor patient with asymmetrical brain anatomy, lead placement was adjusted according to the suggested segmentation made by the software (Brainlab). Postoperatively, we used directionality to assess lead placement using side effect testing (internal capsule and sensory thalamus). Clinical effects were then compared to the patient-specific visualization and VTA simulation in the GUIDE™ XT software (Boston Scientific). The patient's asymmetrical anatomy was correctly recognized by the software and matched the clinical results. VTA models matched best for dysarthria (6 out of 6 cases) and sensory hand side effects (5/6), but least for facial side effects (1/6). Best concordance was observed for the modeled current anterior and back spread of the VTA, worst for the current side spread. Automatic anatomical segmentation and VTA models can be valuable tools for DBS planning and programming. Directional DBS leads allow detailed postoperative assessment of the concordance of such image-based simulation and visualization with clinical effects.

Altered activation and connectivity of the supplementary motor cortex at motor initiation in Parkinson's disease patients with freezing.

OBJECTIVE: Motor initiation failure is a key feature of freezing of gait (FOG) due to Parkinson's disease (PD). The supplementary motor cortex (SMC) plays a central role in its pathophysiology. We aimed at investigating SMC activation, connectivity and plasticity with regard to motor initiation in FOG. METHODS: Twelve patients with FOG and eleven without FOG underwent a multimodal electrophysiological evaluation of SMC functioning including the Bereitschaftspotential and movement-related desynchronisation of cortical beta oscillations. SMC plasticity was modulated by intermittent theta burst stimulation (iTBS) and its impact on gait initiation was assessed by a three-dimensional gait analysis. RESULTS: Prior to volitional movements the Bereitschaftspotential was smaller and beta power was less strongly attenuated over the SMC in patients with FOG compared to those without. Pre-motor coherence between the SMC and the primary motor cortex in the beta frequency range was also stronger in patients with FOG. iTBS resulted in a relative deterioration of gait initiation. CONCLUSIONS: Reduced activation of the SMC along with increased SMC connectivity in the beta frequency range hinder a flexible shift of the motor set as it is required for gait initiation. SIGNIFICANCE: Altered SMC functioning plays an important role for motor initiation failure in PD-related FOG.

Decreased grey matter in the postural control network is associated with lateral flexion of the trunk in Parkinson's disease.

BACKGROUND: Disruption of central networks, particularly of those responsible for integrating multimodal afferents in a spatial reference frame, were proposed in the pathophysiology of lateral trunk flexion in Parkinson's disease (PD). Knowledge about the underlying neuroanatomical structures is limited. OBJECTIVE: To investigate if decreased focal grey matter (GM) is associated with trunk flexion to the side and if the revealed GM clusters correlate with a disturbed perception of verticality in PD. METHODS: 37 PD patients with and without lateral trunk flexion were recruited. Standardized photos were taken from each patient and trunk orientation was measured by a blinded rater. Voxel-based morphometry (VBM) was used to detect associated clusters of decreased GM. The subjective visual vertical (SVV) was assessed as a marker for perception of verticality and SVV estimates were correlated with GM clusters. RESULTS: VBM revealed clusters of decreased GM in the right posterior parietal cortex and in the right thalamus were associated with lateral trunk flexion. The SVV correlated with the extent of trunk flexion, and the side of the SVV tilt correlated with the side of trunk flexion. GM values from the thalamus correlated with the SVV estimates. CONCLUSIONS: We report an association between neurodegenerative changes within the posterior parietal cortex and the thalamus and lateral trunk flexion in PD. These brain structures are part of a network proposed to be engaged in postural control and spatial self-perception. Disturbed perception of verticality points to a shifted egocentric spatial reference as an important pathophysiological feature.

Temporal discrimination is altered in patients with isolated asymmetric and jerky upper limb tremor.

BACKGROUND: Unilateral or very asymmetric upper limb tremors with a jerky appearance are poorly investigated. Their clinical classification is an unsolved problem because their classification as essential tremor versus dystonic tremor is uncertain. To avoid misclassification as essential tremor or premature classification as dystonic tremor, the term indeterminate tremor was suggested. OBJECTIVES: The aim of this study was to characterize this tremor subgroup electrophysiologically and evaluate whether diagnostically meaningful electrophysiological differences exist compared to patients with essential tremor and dystonic tremor. METHODS: We enrolled 29 healthy subjects and 64 patients with tremor: 26 with dystonic tremor, 23 with essential tremor, and 15 patients with upper limb tremor resembling essential tremor but was unusually asymmetric and jerky (indeterminate tremor). We investigated the somatosensory temporal discrimination threshold, the short-interval intracortical inhibition, and the cortical plasticity by paired associative stimulation. RESULTS: Somatosensory temporal discrimination threshold was significantly increased in patients with dystonic tremor and indeterminate tremor, but it was normal in the essential tremor patients and healthy controls. Significant differences in short-interval intracortical inhibition and paired associative stimulation were not found among the three patient groups and controls. CONCLUSION: These results indicate that indeterminate tremor, as defined in this study, shares electrophysiological similarities with dystonic tremor rather than essential tremor. Therefore, we propose that indeterminate tremor should be considered as a separate clinical entity from essential tremor and that it might be dystonic in nature. Somatosensory temporal discrimination appears to be a useful tool in tremor classification. © 2019 International Parkinson and Movement Disorder Society.

Development and Validation of a Prognostic Model of Swallowing Recovery and Enteral Tube Feeding After Ischemic Stroke.

Importance: Predicting the duration of poststroke dysphagia is important to guide therapeutic decisions. Guidelines recommend nasogastric tube (NGT) feeding if swallowing impairment persists for 7 days or longer and percutaneous endoscopic gastrostomy (PEG) placement if dysphagia does not recover within 30 days, but, to our knowledge, a systematic prediction method does not exist. Objective: To develop and validate a prognostic model predicting swallowing recovery and the need for enteral tube feeding. Design, Setting, and Participants: We enrolled participants with consecutive admissions for acute ischemic stroke and initially severe dysphagia in a prospective single-center derivation (2011-2014) and a multicenter validation (July 2015-March 2018) cohort study in 5 tertiary stroke referral centers in Switzerland. Exposures: Severely impaired oral intake at admission (Functional Oral Intake Scale score <5). Main Outcomes and Measures: Recovery of oral intake (primary end point, Functional Oral Intake Scale ≥5) or return to prestroke diet (secondary end point) measured 7 (indication for NGT feeding) and 30 (indication for PEG feeding) days after stroke. Results: In total, 279 participants (131 women [47.0%]; median age, 77 years [interquartile range, 67-84 years]) were enrolled (153 [54.8%] in the derivation study; 126 [45.2%] in the validation cohort). Overall, 64% (95% CI, 59-71) participants failed to recover functional oral intake within 7 days and 30% (95% CI, 24-37) within 30 days. Prolonged swallowing recovery was independently associated with poor outcomes after stroke. The final prognostic model, the Predictive Swallowing Score, included 5 variables: age, stroke severity on admission, lesion location, initial risk of aspiration, and initial impairment of oral intake. Predictive Swallowing Score prediction estimates ranged from 5% (score, 0) to 96% (score, 10) for a persistent impairment of oral intake on day 7 and from 2% to 62% on day 30. Model performance in the validation cohort showed a discrimination (C statistic) of 0.84 (95% CI, 0.76-0.91; P < .001) for predicting the recovery of oral intake on day 7 and 0.77 (95% CI, 0.67-0.87; P < .001) on day 30, and a discrimination for a return to prestroke diet of 0.94 (day 7; 95% CI, 0.87-1.00; P < .001) and 0.71 (day 30; 95% CI, 0.61-0.82; P < .001). Calibration plots showed high agreement between the predicted and observed outcomes. Conclusions and Relevance: The Predictive Swallowing Score, available as a smartphone application, is an easily applied prognostic instrument that reliably predicts swallowing recovery. It will support decision making for NGT or PEG insertion after ischemic stroke and is a step toward personalized medicine.

Sensory trick efficacy in cervical dystonia is linked to processing of neck proprioception.

BACKGROUND: Muscle vibration activates muscle spindles and when applied over posterior neck muscles during stance modulates global body orientation. This is characterised by a tonic forward sway response that is reportedly diminished or absent in patients with idiopathic cervical dystonia. OBJECTIVE: To investigating the impact of the sensory trick on vibration-induced postural responses. METHODS: 20 patients with idiopathic cervical dystonia and a sensory trick, 15 patients without a trick, and 16 healthy controls were recruited. Neck muscle vibration was applied bilaterally over the upper trapezius under three different conditions: 1) Quiet standing; 2) standing while performing the trick (or trick-like movement in non-responders); 3) standing while elevating the flexed arm without touching any part of the body. Centre of pressure position and whole-body orientation in the sagittal plane were analysed. RESULTS: Patients with a sensory trick responded similarly to healthy controls: neck muscle vibration led to an initial forward sway of the body that slowly increased during the prolonged vibration for all three conditions. This response was mainly mediated by ankle flexion. In patients without a trick, the initial sagittal sway was significantly reduced in all three conditions and the later slow increase was absent. Performance of the trick did not have an effect on any aspect of the response in either cervical dystonia group. CONCLUSIONS: The whole-body response to neck vibration in cervical dystonia differs depending on the effectiveness of the sensory trick to alleviate the dystonic neck posture. Variable pathophysiology of proprioceptive processing may be the common factor.

Parkinsonian signs in patients with cervical dystonia treated with pallidal deep brain stimulation.

Pallidal deep brain stimulation is an established treatment in patients with dystonia. However, evidence from case series or uncontrolled studies suggests that it may lead in some patients to specific parkinsonian symptoms such as freezing of gait, micrographia, and bradykinesia. We investigated parkinsonian signs using the Movement Disorder Society Unified Parkinson's Disease Rating Scale motor score by means of observer-blinded video ratings in a group of 29 patients treated with pallidal stimulation and a non-surgical control group of 22 patients, both with predominant cervical dystonia. Additional assessments included MRI-based models of volume of neural tissue activated to investigate areas of stimulation related to dystonic symptom control and those likely to induce parkinsonian signs as well as an EMG analysis to investigate functional vicinity of stimulation fields to the pyramidal tract. Compared with controls, stimulated patients had significantly higher motor scores (median, 25th-75th percentile: 14.0, 8.0-19.5 versus 3.0, 2.0-8.0; P < 0.0001), as well as bradykinesia (8.0, 6.0-14.0 versus 2.0, 0.0-3.0; P < 0.0001) and axial motor subscores (2.0, 1.0-4.0 versus 0.0, 0.0-1.0; P = 0.0002), while rigidity and tremor subscores were not different between groups. Parkinsonian signs were partially reversible upon switching stimulation off for a median of 90 min in a subset of 19 patients tolerating this condition. Furthermore, the stimulation group reported more features of freezing of gait on a questionnaire basis. Quality of life was better in stimulated patients compared with control patients, but parkinsonian signs were negatively associated with quality of life. In the descriptive imaging analysis maximum efficacy for dystonia improvement projected to the posteroventrolateral internal pallidum with overlapping clusters driving severity of bradykinesia and axial motor symptoms. The severities of parkinsonian signs were not correlated with functional vicinity to the pyramidal tract as assessed by EMG. In conclusion, parkinsonian signs, particularly bradykinesia and axial motor signs, due to pallidal stimulation in dystonic patients are frequent and negatively impact on motor functioning and quality of life. Therefore, patients with pallidal stimulation should be monitored closely for such signs both in clinical routine and future clinical trials. Spread of current outside the internal pallidum is an unlikely explanation for this phenomenon, which seems to be caused by stimulation of neural elements within the stimulation target volume.

Endophenotyping in idiopathic adult onset cervical dystonia.

OBJECTIVE: Idiopathic adult onset cervical dystonia (IAOCD) is considered to be a partially penetrant autosomal dominant genetic condition. Dystonia may result from genetic and environmental factors. In this view, part of the physiology should be an endophenotype stemming from the genetic background. We assessed the most discriminative test to separate patients with IAOCD and healthy controls for further endophenotyping in non-affected 1st degree relatives. METHODS: We included patients with IAOCD, their 1st degree relatives and healthy controls. Tests performed: (1) Sensory temporal discrimination (visual, tactile, visuo-tactile), (2) Paired pulse paradigms using transcranial magnetic stimulation (TMS), (3) Mental rotation paradigms. RESULTS: 45 patients with IAOCD, 23 healthy controls and 14 non-affected 1st degree relatives were recruited. Visuo-tactile temporal discrimination separated best between controls and patients as well as between controls and 1st degree relatives. 36% of the latter had an abnormal visuo-tactile temporal discrimination. No difference between patients and healthy controls was found for the other paradigms. CONCLUSIONS: Visuo-tactile temporal discrimination separates controls from patients with IAOCD and its 1st degree relatives. 36% of the latter had abnormal visuo-tactile thresholds supporting the role of visuo-tactile temporal discrimination as an endophenotype for IAOCD. SIGNIFICANCE: Even though the study was of exploratory design, our findings expand the understanding of endophenotypes in IAOCD.

Diverging lesion and connectivity patterns influence early and late swallowing recovery after hemispheric stroke.

Knowledge about the recovery of oral intake after hemispheric stroke is important to guide therapeutic decisions, including the administration of enteral tube feeding and the choice of the appropriate feeding route. They aimed to determine the localization and connectivity of lesions in impaired recovery versus recovered swallowing after initially dysphagic stroke. Sixty-two acute ischemic hemispheric stroke patients with impaired oral intake were included in a prospective observational cohort study. Voxel-based lesion-symptom mapping and probabilistic tractography were used to determine the association of lesion location and connectivity with impaired recovery of oral intake ≥7 days (indication for early tube feeding) and ≥4 weeks (indication for percutaneous endoscopic gastrostomy feeding) after stroke. Two distinct patterns influencing recovery of swallowing were recognized. Firstly, impaired recovery of oral intake after ≥7 days was significantly associated with lesions of the superior corona radiata (65% of statistical map, P < 0.05). The affected fibers were connected with the thalamus, primary motor, and supplemental motor areas and the basal ganglia. Secondly, impaired recovery of oral intake after ≥4 weeks significantly correlated with lesions of the anterior insula (54% of statistical map, P < 0.05), which was connected to adjacent operculo-insular areas of deglutition. These findings indicate that early swallowing recovery is influenced by white matter lesions disrupting thalamic and corticobulbar projection fibers. Late recovery is determined by specific cortical lesions affecting association fibers. This knowledge may help clinicians to identify patients at risk of prolonged swallowing problems that would benefit from enteral tube feeding. Hum Brain Mapp 38:2165-2176, 2017. © 2017 Wiley Periodicals, Inc.