Thoracic outlet decompression surgery for Gilliatt-Sumner hand as a presentation of neurogenic thoracic outlet syndrome.

BACKGROUND: Chronic compression of the inferior trunk of the brachial plexus can result in severe pain and progressive atrophy and weakness of the musculature of the forearm and hand, known as Gilliatt-Sumner hand (GSH). The objective of treatment for these patients is to stop further atrophy and pain. Restoration of motor function has been thought to be seldom achieved. The aim of the present contemporary case series was to describe the diagnosis, treatment, and outcomes of surgery for GSH. METHODS: All patients referred between January 2017 and May 2021 with visible signs of a GSH were included. Visible GSH signs were defined as muscle atrophy of the abductor digiti minimi, abductor pollicis brevis, and/or interosseous musculature. All the patients had undergone additional electrodiagnostic (ED) assessments and high-resolution ultrasound (HRUS) studies. All the patients with a diagnosis of GSH had undergone thoracic outlet decompression (TOD) surgery using a transaxillary or supraclavicular approach. The outcomes were measured using the thoracic outlet syndrome disability scale, cervical brachial symptom questionnaire, and disability of the arm, shoulder, and hand scale scores and patient-reported outcomes of motor function, measured using a numerical rating scale (NRS). The standardized elevated arm stress test (sEAST) was used to assess the patients' motor function before and after TOD surgery. RESULTS: A total of 20 patients had been referred to our center with visible signs of a GSH. The clinical examination showed atrophy of the abductor digiti minimi, abductor pollicis brevis, and interosseous musculature in all 20 patients. The ED assessments showed plexopathy of the lower brachial plexus in all the patients. HRUS showed an indented inferior trunk of the brachial plexus (so-called wedge-sickle sign) in 18 patients (90%). Of the 20 patients, 17 had undergone TOD surgery (15 transaxillary TOD and 2 supraclavicular TOD). Three patients had refrained from surgery. The median follow-up interval was 15.0 months (interquartile range, 14.0 months). The thoracic outlet syndrome disability scale score had improved significantly (preoperatively: mean, 6.31; 95% confidence interval [CI], 5.49-7.13; postoperatively: mean, 4.25; 95% CI, 2.80-5.70; P = .026). The same improvement was seen for the cervical brachial symptom questionnaire scores (preoperatively: mean, 77.75; 95% CI, 66.63-88.87; postoperatively: mean, 42.65; 95% CI, 24.77-60.77; P = .001) and disability of the arm, shoulder, and hand scale scores (preoperatively: mean, 59.13; 95% CI, 51.49-66.77; postoperatively: mean, 40.96; 95% CI, 24.41-57.51; P = .032). The NRS score for muscle weakness and sEAST score showed no statistically significant differences before and after TOD for the whole group (mean preoperative NRS score for muscle weakness, 6.22; 95% CI, 4.31-8.14; mean postoperative NRS score for muscle weakness, 5.11; 95% CI, 3.25-6.97; P = .269). However, four patients (23.52%) had reported a ≥50% decrease in the NRS score for muscle weakness and a minimum increase of 20% in the total and average force using the sEAST. The NRS for numbness showed a statistically significant decrease for the whole group (preoperatively: mean, 5.67; 95% CI, 4.18-7.16; postoperatively: mean, 3.33; 95% CI, 1.37-5.29; P = .029). CONCLUSIONS: A combination of physical examination, ED assessments, and HRUS studies can differentiate GSH in the differential diagnosis. HRUS appears to have an advantage over ED studies in confirming GSH by visualization of compression of the brachial plexus. TOD surgery will stop the progressive muscle atrophy and significantly reduce neurogenic thoracic outlet syndrome complaints, and, in some patients, motor function will recover.

Reliability and validity of the standardized elevated arm stress test in the diagnosis of neurogenic thoracic outlet syndrome.

OBJECTIVE: We developed a standardized elevated arm stress test (sEAST) meter to standardize patients' posture and measure additional grip and fatigue parameters. In the present prospective cohort study, we aimed to determine the reliability and validity of the sEAST in the diagnosis of neurogenic thoracic outlet syndrome (NTOS). METHODS: Patients evaluated for NTOS between October 2018 and February 2020 were included and performed the sEAST. The patients were classified into a proven NTOS group or a symptomatic control group using the reporting standards for NTOS and the outcome of thoracic outlet decompression surgery. Healthy persons were recruited as an asymptomatic control group. The test-retest reliability, area under the receiver operating characteristic curve, and positive and negative predictive values were calculated for each sEAST parameter. RESULTS: A total of 426 patients with suspected NTOS and 147 healthy controls had performed the sEAST. The validity analysis was performed with data from 111 patients with proven NTOS, 94 symptomatic controls, and 147 asymptomatic controls. The reporting standards were inconclusive for 116 patients; 77 patients had been excluded because thoracic outlet decompression surgery had not been performed or was unsuccessful, and 28 because they had arterial or venous thoracic outlet syndrome. The area under the receiver operating characteristic curve for the proven NTOS group compared with the asymptomatic control and symptomatic control groups ranged from 0.59 to 0.77 and 0.54 to 0.63, respectively. The positive predictive value ranged from 46% to 65% and the negative predictive value from 51% to 66%. The test-retest reliability analysis for 80 patients with multiple sEAST measurements showed moderate to good (0.52-0.87) intraclass correlation coefficient values for the duration and grip strength parameters. However, the grip fatigue parameters demonstrated poor (0.46-0.16) intraclass correlation coefficient values. CONCLUSIONS: The sEAST showed good test-retest reliability for the duration and grip strength parameters. However, the discriminative value of all sEAST parameters was low for NTOS diagnostics. The good test-retest reliability of the sEAST parameters indicates that they could be valuable outcome measures for comparison in a diagnostic care pathway.

Reliability and validity of the elevated arm stress test in the diagnosis of neurogenic thoracic outlet syndrome.

OBJECTIVES: The objective of this retrospective analysis of prospectively collected data was to assess the test-retest reliability and validity of the elevated arm stress test (EAST) as measured by the duration in a cohort of patients with suspected neurogenic thoracic outlet syndrome (NTOS). METHODS: Patients evaluated for NTOS between January 2017 and September 2018 were identified. Test-retest reliability by the intraclass correlation coefficient was determined for duration of the EAST. For the validity analysis, patients were classified in a proven NTOS group or a symptomatic control group without NTOS using the Society for Vascular Surgery reporting standards and the outcome of thoracic outlet decompression surgery. A receiver operating characteristic curve was made for the duration of EAST. The area under the curve, and positive and negative predictive values were calculated for the EAST. RESULTS: In total, 428 patients with suspected NTOS were retrospectively analyzed. Of these patients, 61 were excluded because no EAST data was available. Another 101 patients were excluded because of inconclusive reporting standards, arterial or venous TOS, or because thoracic outlet decompression surgery was not performed or had a negative result. The validity analysis in the remaining 266 patients showed an area under the curve for the duration of the EAST of 0.62 (95% confidence interval, 0.55-0.69). The positive predictive value of the duration ranged between 65% and 66%, and the negative predictive value between 53% and 58%. For the test-retest reliability analysis, 118 patients were excluded because they performed only one measurement in a 100-day time period. Analysis in the remaining 148 patients showed an intraclass correlation coefficient value of 0.65 (95% confidence interval, 0.55-0.74) for duration. CONCLUSIONS: The EAST measured by the duration showed a moderate test-retest reliability, but the discriminative value was low in the diagnosis of NTOS. The outcome of the EAST measured by the duration should be used with caution.

Redo surgery for neurogenic thoracic outlet syndrome is useful.

OBJECTIVES: Surgery for neurogenic thoracic outlet syndrome (NTOS) has shown good outcome in numerous case series. However, 5% to 30% of patients will have persistent or recurrent symptoms, caused by incomplete first rib resection, reattachment of residual scalene muscle, fibrous scarring around the brachial plexus, or a wrong NTOS diagnosis. In patients with a sound diagnosis of recurrent or persisting NTOS, not responding to conservative measures, a secondary procedure can be considered. We report the results of redo thoracic outlet decompression surgery through the supraclavicular approach (SC-REDO-TOD) for persistent or recurrent NTOS. METHODS: A retrospective review of a prospective database was performed. Every patient referred from September 2016 until January 2020 was eligible for inclusion. In an SC-REDO-TOD, we perform complete (cartilage-cartilage) resection of the first rib, any bony and fibrous anomalies, complete anterior and middle scalenectomy, and complete neurolysis of the brachial plexus (complete anatomical decompression of the brachial plexus). Clinical outcomes were assessed by questionnaires including the Disability of Arm, Shoulder and Hand (DASH), Cervico-Brachial Symptoms Questionnaire (CBSQ), and TOS (thoracic outlet syndrome) Disability scale. RESULTS: In total, 45 patients had a SC-REDO-TOD. The median duration of hospital admission after SC-REDO-TOD was 1.41 days (interquartile range, 1.00 day). In total, 30 (66.66%) of 45 patients had recurrent NTOS, and 15 (33.33%) of 45 patients had persisting NTOS. Postoperative complications were seen in eight patients (18.18%). One patient had postoperative complications with permanent impairment (Horner syndrome). Seven patients had postoperative complications with full recovery (three patients had a chylous leakage that was treated with a median-chain triglycerides diet for 6 weeks, three patients had transient phrenic nerve palsy with full recovery <6 weeks, and one patient had a discrete Horner syndrome that resolved in 6 weeks). The median time of follow-up was 19.50 months (interquartile range, 14.00 months) and the response rate to the questionnaires was 91.11% at 6 months and 64.44% at 12 months. We found a positive and statistically significant difference for DASH score, CBSQ score, and TOS Disability Scale score comparing scores for all patients. (DASH score: P < .001; CBSQ score: P < .001; TOS Disability Scale: P < .001). Patients with first rib remnants showed a significant better response (lower DASH, CBSQ and TOS Disability Scale scores) compared with patients without first rib remnants (DASH score: P = .004; CBSQ score: P ≤ .014; TOS Disability Scale: P = .009). CONCLUSIONS: SC-REDO-TOD after a previous NTOS surgery shows good results with a low risk of permanent impairment. Patients with NTOS with first rib remnants after primary surgery seem to benefit the most from SC-REDO-TOD surgery.

Surgery Versus Continued Conservative Treatment for Neurogenic Thoracic Outlet Syndrome: the First Randomised Clinical Trial (STOPNTOS Trial).

OBJECTIVE: Neurogenic thoracic outlet syndrome (NTOS) is one of the most controversial clinical entities in medicine. Several major case series have shown promising results of surgery; however, solid scientific evidence is lacking. The aim of this trial was to objectify the effect of thoracic outlet decompression (TOD). METHODS: A single centre (high volume, tertiary TOS centre), non-blinded, randomised controlled trial was conducted with parallel group design. Patients with a diagnosis of NTOS refractory to conservative therapy were randomised to one of two intervention arms, receiving either a transaxillary thoracic outlet decompression (TA-TOD) or continued conservative treatment. After three months, the conservative treated group was also offered a TA-TOD. The primary outcome was change in Disability of the Arm, Shoulder and Hand (DASH) questionnaire score. Secondary outcomes were changes in Cervical Brachial Symptoms Questionnaire (CBSQ), TOS disability scale, and quality of life scores. Outcomes were assessed at baseline, three, six, and 12 months after inclusion. RESULTS: Fifty patients were enrolled in this trial: 25 in the TA-TOD group and 25 in the continued conservative treatment group. Follow up was completed in 24 and 22 patients, respectively. At three months, there was a statistically significant difference in DASH scores (TA-TOD: mean 45.15, 95% confidence interval [CI] 38.08 - 52.21; conservative treatment: mean 64.92, 95% CI 57.54 - 72.30; p < .001). All patients in the conservative treatment group applied for surgery three months after randomisation. After surgery of the conservative treatment group, there was no statistically significant difference between the groups for all primary and secondary outcome measures. CONCLUSIONS: TA-TOD for NTOS is effective in patients who do not respond to conservative treatment. Trial register number: NL63986.100.17.

Duplex Ultrasound Studies Are Neither Necessary or Sufficient for the Diagnosis of Neurogenic Thoracic Outlet Syndrome.

BACKGROUND: Duplex ultrasound (DU) is used in the diagnosis of neurogenic thoracic outlet syndrome (NTOS) to measure compression of the subclavian artery (SCA) which is thought to strengthen the NTOS diagnosis. However, the value of DU in NTOS remains unclear. METHODS: A retrospective review of a prospectively acquired database from the TOS center of the Catharina Hospital Eindhoven was performed of patients referred between January 2017 and December 2019. Only "proven NTOS" patients, defined as a successful response to thoracic outlet decompression (TOD) surgery based on patient-reported outcomes (NRS pain scale, CBSQ and DASH score) were included to exclude wrongfully diagnosed NTOS patient. The presence of vascular symptoms (defined as discoloration, edema or temperature changes of the hand or fingers), results of provocative maneuvers, and outcome of DU was used for analysis. To assess the link between vascular symptoms and compression on DU, a chi-squared test was performed. Further, we looked for a correlation between vascular symptoms, compression on DU and clinical outcome using a repeated measures analysis of variance (ANOVA). RESULTS: Vascular symptoms were seen in 49 of 133 patients (36.8%). In total, 51 of 133 patients (38.3%) had at least 50% variation in SCA peak systolic velocity (PSV) during DU at the level of SCA stenosis. SCA occlusion was seen in 11 patients (8.3%) during provocative maneuvers. The presence of clinical "arterial symptoms" was not significantly correlated with vascular laboratory findings, neither for alterations in PSV during DU (P = 0.245) nor for positional SCA occlusion (P = 0.540). No statistically significant correlations between the degree of SCA stenosis and postoperative outcomes, as measured with the DASH, CBSQ, or NRS scale for pain were found (P = 0.787). CONCLUSIONS: The role of DU in the work-up of NTOS in patients with vascular complaints is questionable. Changes in flow velocities are seen in NTOS patients and do not correlate with "vascular symptoms" or clinical outcome.

Feasibility and Outcomes of a Multidisciplinary Care Pathway for Neurogenic Thoracic Outlet Syndrome: A Prospective Observational Cohort Study.

OBJECTIVE: The North American Society for Vascular Surgery (SVS) reporting standards for neurogenic thoracic outlet syndrome (NTOS) were published in 2016 to produce consistency in the diagnosis and treatment of NTOS, but outcomes resulting from following these standards are not yet available. The results of a standardised multidisciplinary care pathway for NTOS based on the North American SVS reporting standards for NTOS are reported. METHODS: Patients referred between August 2016 and December 2019 with suspected NTOS were evaluated in this single center prospective cohort study. Diagnosis and treatment were performed according to a care pathway based on the North American SVS reporting standards. The outcome of surgically treated patients was determined by the Derkash score, thoracic outlet syndrome disability scale (TDS), Cervical Brachial Score Questionnaire (CBSQ), Disability of the Arm Shoulder and Hands Dutch language version (DASH-DLV) and Short Form-12 (SF-12) at three, six, 12, and 24 months. RESULTS: Of 856 referred patients, 476 (55.6%) patients were diagnosed with NTOS. Dedicated physiotherapy was successful in 186 patients (39.1%). Surgical treatment was performed in 290 (60.9%) patients of whom 274 were included in the follow up. At a mean follow up of 16.9 ± 9.2 months, significant improvement (p < .001) in TDS, CBSQ, DASH-DLV, and SF-12 scores was seen in the surgical group between baseline and all follow up intervals. Derkash outcome after surgical intervention was excellent in 83 (30.3%), good in 114 (41.6%), fair in 43 (15.7%), and poor in 34 (12.4%) of the patients. Complications occurred in 16 (5.8%) patients, and 32 (10.4%) patients experienced recurrent or persistent NTOS complaints. CONCLUSION: A multidisciplinary care pathway based on the North American SVS reporting standards for NTOS helped to confirm the diagnosis in 56% of patients referred, and guided the selection of patients who might benefit from thoracic outlet decompression surgery after unsuccessful dedicated physiotherapy. Intermediate follow up showed good outcomes in the majority of surgically treated patients.

Same Admission Hybrid Treatment of Primary Upper Extremity Deep Venous Thrombosis with Thrombolysis, Transaxillary Thoracic Outlet Decompression, and Immediate Endovascular Evaluation.

BACKGROUND: Multiple algorithms exist for treating acute primary upper extremity deep venous thrombosis (pUEDVT) caused by venous thoracic outlet syndrome (VTOS). In this case series, we present the results of our dedicated same admission treatment algorithm. METHODS: All patients between January 2015 and December 2019 with an established acute upper extremity deep venous thrombosis (symptoms <14 days) caused by VTOS were treated according to an algorithm consisting of same admission thrombolysis, transaxillary thoracic outlet decompression (TA-TOD) with extensive venolysis, and venography. If a residual stenosis of the subclavian vein was identified on venography, including by means of low-pressure diagnostic balloon inflation, correction by percutaneous transluminal angioplasty (PTA) was performed. The thoracic outlet syndrome disability scale, the Dutch language version of the disabilities of the arm, shoulder, and hand, and the VEINES-quality of life (VEINES-QOL/VEINES-symptoms) questionnaires were collected during follow-up. RESULTS: In total, 10 patients were treated for acute pUEDVT. After successful thrombolysis (100%) and TA-TOD, immediate venography showed residual stenosis of the subclavian vein in 8 of 10 patients (80%). Low-pressure dilatation of a balloon suited to the geometry of the axillosubclavian vein showed significant tapering in all cases (10/10) after which a formal venous PTA was performed. No stents were used. Mean time to discharge was 6.4 days. All patients were free of symptoms at a mean follow-up period of 34.4 months. Eight of the 10 patients completed follow-up questionnaires and reported a mean thoracic outlet syndrome disability scale of 0.6, mean disabilities of the arm, shoulder, and hand score of 4.2, and a median VEINES-Symptoms of 55.23 (IQR, 12.13), and VEINES-QOL of 55.29 (IQR, 15.42). CONCLUSIONS: A same admission treatment algorithm for acute pUEDVT in patients with VTOS including thrombolysis, TA-TOD with extensive venolysis, and immediate venography with PTA is effective with promising intermediate results.

Intact working memory in non-manifesting LRRK2 carriers--an fMRI study.

Cognitive impairments are prevalent in patients with Parkinson's disease. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of genetic Parkinsonism. Non-manifesting carriers of the G2019S mutation in the LRRK2 gene were found to have lower executive functions as measured by the Stroop task. This exploratory study aimed to assess whether the cognitive impairment in non-manifesting carriers is specific for executive functions or includes other cognitive domains such as working memory. We recruited 77 non-manifesting first-degree relatives of Parkinson's disease patients (38 carriers). A block-design fMRI N-back task, with 0-back, 2-back and 3-back conditions, was used in order to assess working memory. Participants were well matched on the Montreal Cognitive Assessment, University of Pennsylvania Smell Identification Test, Unified Parkinson's Disease Rating Scale part III, digit span, age, gender and Beck Depression Inventory. The task achieved the overall expected effect in both groups with longer reaction times and lower accuracy rates with increasing task demands. However, no whole-brain or region-of-interest between-groups differences were found on any of the task conditions. These results indicate that non-manifesting carriers of the G2019S mutation in the LRRK2 gene have a specific cognitive profile with executive functions, as assessed by the Stroop task, demonstrating significant impairment but with working memory, as assessed with the N-back task, remaining relatively intact. These finding shed light on the pre-motor cognitive changes in this unique 'at risk' population and should enable more focused cognitive assessments of these cohorts.

A voxel-based morphometry and diffusion tensor imaging analysis of asymptomatic Parkinson's disease-related G2019S LRRK2 mutation carriers.

BACKGROUND: Patients with Parkinson's disease have reduced gray matter volume and fractional anisotropy in both cortical and sub-cortical structures, yet changes in the pre-motor phase of the disease are unknown. METHODS: A comprehensive imaging study using voxel-based morphometry and diffusion tensor imaging tract-based spatial statistics analysis was performed on 64 Ashkenazi Jewish asymptomatic first degree relatives of patients with Parkinson's disease (30 mutation carriers), who carry the G2019S mutation in the leucine-rich repeat kinase 2 (LRRK2) gene. RESULTS: No between-group differences in gray matter volume could be noted in either whole-brain or volume-of-interest analysis. Diffusion tensor imaging analysis did not identify group differences in white matter areas, and volume-of-interest analysis identified no differences in diffusivity parameters in Parkinson's disease-related structures. CONCLUSIONS: G2019S carriers do not manifest changes in gray matter volume or diffusivity parameters in Parkinson's disease-related structures prior to the appearance of motor symptoms.

Trans-axillary thoracic outlet decompression.

Thoracic outlet syndrome (TOS) is a group of conditions thought to be caused by the compression of neurovascular structures going to the upper extremity. TOS is a difficult disease to diagnose, and surgical treatment remains challenging. Many different surgical techniques for the treatment of TOS have been described in the literature and many reasonable to good outcomes have been reported, which makes it hard for surgeons to determine which techniques should be used. Our aim was to describe the rationale, techniques, and outcomes associated with the surgical treatment of TOS. Most patients in our center are treated primarily through a trans-axillary approach. We will elaborate on the technical details of performing trans-axillary thoracic outlet decompression. The essential steps during surgery are illustrated with videos. We focused on the idea behind performing a trans-axillary thoracic outlet decompression in primary cases. Institutional data on the outcomes of this surgical approach are described briefly.

Weight-specific anticipatory coding of grip force in human dorsal premotor cortex.

The dorsal premotor cortex (PMd) uses prior sensory information for motor preparation. Here, we used a conditioning-and-map approach in 11 healthy male humans (mean age 27 years) to further clarify the role of PMd in anticipatory motor control. We transiently disrupted neuronal processing in PMd, using either continuous theta burst stimulation (cTBS) at 80% (inhibitory cTBS) or 30% (sham cTBS) of active motor threshold. The conditioning effects of cTBS on preparatory brain activity were assessed with functional MRI, while participants lifted a light or heavy weight in response to a go-cue (S2). An additional pre-cue (S1) correctly predicted the weight in 75% of the trials. Participants were asked to use this prior information to prepare for the lift. In the sham condition, grip force showed a consistent undershoot, if the S1 incorrectly prompted the preparation of a light lift. Likewise, an S1 that falsely announced a heavy weight produced a consistent overshoot in grip force. In trials with incorrect S1, preparatory activity in left PMd during the S1-S2 delay period predicted grip force undershoot but not overshoot. Real cTBS selectively abolished this undershoot in grip force. Furthermore, preparatory S1-S2 activity in left PMd no longer predicted the individual undershoot after real cTBS. Our results provide converging evidence for a causal involvement of PMd in anticipatory downscaling but not upscaling of grip force, suggesting an inhibitory role of PMd in anticipatory grip force control during object lifting.

Compensatory activity in the extrastriate body area of Parkinson's disease patients.

Compensatory mechanisms are a crucial component of the cerebral changes triggered by neurodegenerative disorders. Identifying such compensatory mechanisms requires at least two complementary approaches: localizing candidate areas using functional imaging, and showing that interference with these areas has behavioral consequences. Building on recent imaging evidence, we use this approach to test whether a visual region in the human occipito-temporal cortex-the extrastriate body area-compensates for altered dorsal premotor activity in Parkinson's disease (PD) during motor-related processes. We separately inhibited the extrastriate body area and dorsal premotor cortex in 11 PD patients and 12 healthy subjects, using continuous theta burst stimulation. Our goal was to test whether these areas are involved in motor compensatory processes. We used motor imagery to isolate a fundamental element of motor planning, namely subjects' ability to incorporate the current state of their body into a motor plan (mental hand rotation). We quantified this ability through a posture congruency effect (i.e., the improvement in subjects' performance when their current body posture is congruent to the imagined movement). Following inhibition of the right extrastriate body area, the posture congruency effect was lost in PD patients, but not in healthy subjects. In contrast, inhibition of the left dorsal premotor cortex reduced the posture congruency effect in healthy subjects, but not in PD patients. These findings suggest that the right extrastriate body area plays a compensatory role in PD by supporting a function that is no longer performed by the dorsal premotor cortex.

Cerebral pathological and compensatory mechanisms in the premotor phase of leucine-rich repeat kinase 2 parkinsonism.

Compensatory cerebral mechanisms can delay motor symptom onset in Parkinson's disease. We aim to characterize these compensatory mechanisms and early disease-related changes by quantifying movement-related cerebral function in subjects at significantly increased risk of developing Parkinson's disease, namely carriers of a leucine-rich repeat kinase 2-G2019S mutation associated with dominantly inherited parkinsonism. Functional magnetic resonance imaging was used to examine cerebral activity evoked during internal selection of motor representations, a core motor deficit in clinically overt Parkinson's disease. Thirty-nine healthy first-degree relatives of Ashkenazi Jewish patients with Parkinson's disease, who carry the leucine-rich repeat kinase 2-G2019S mutation, participated in this study. Twenty-one carriers of the leucine-rich repeat kinase 2-G2019S mutation and 18 non-carriers of this mutation were engaged in a motor imagery task (laterality judgements of left or right hands) known to be sensitive to motor control parameters. Behavioural performance of both groups was matched. Mutation carriers and non-carriers were equally sensitive to the extent and biomechanical constraints of the imagined movements in relation to the current posture of the participants' hands. Cerebral activity differed between groups, such that leucine-rich repeat kinase 2-G2019S carriers had reduced imagery-related activity in the right caudate nucleus and increased activity in the right dorsal premotor cortex. More severe striatal impairment was associated with stronger effective connectivity between the right dorsal premotor cortex and the right extrastriate body area. These findings suggest that altered movement-related activity in the caudate nuclei of leucine-rich repeat kinase 2-G2019S carriers might remain behaviourally latent by virtue of cortical compensatory mechanisms involving long-range connectivity between the dorsal premotor cortex and posterior sensory regions. These functional cerebral changes open the possibility to use a prospective study to test their relevance as early markers of Parkinson's disease.

Surgical approaches for thoracic outlet decompression in the treatment of thoracic outlet syndrome.

Thoracic outlet syndrome (TOS) is a controversial and uncommon syndrome. Three different diagnoses can be made based on the compressed structure: arterial TOS, venous TOS, and neurogenic TOS. Diagnosing TOS, especially neurogenic TOS, remains difficult since a single diagnostic tool does not exist. Although this resulted in a lot of confusion, standardization of care and outcome improved daily care practice measures in the last decade. Current treatment algorithms consist of both conservative and surgical treatment approaches, which should be chosen depending on the type of TOS and extend of the complaints. Surgical treatment of TOS is performed via thoracic outlet decompression (TOD). TOD surgery includes complete resection of the first rib (cartilage to cartilage), transection of the scalene muscles and complete neurolysis/venolysis or arteriolysis. Four different approaches can be chosen for TOD surgery: the transaxillary (TA), supraclavicular (SC), paraclavicular (PC), and infraclavicular (IC) approach. The TA, SC, and PC approach can be used for every form of TOS. However, the PC approach is mostly used for treating venous TOS. The IC approach has no role in treating neurogenic or arterial TOS and is only used for venous TOS. Every approach has its own benefits and limitations and literature does not agree on what approach is best. Therefore, the used surgical approach for TOD should be based on the surgeon's preference and experience. The aim of this review is to present an overview of the diagnostic pathway and provide an in-depth description of the surgical approach in each form of TOS.

General Overview and Diagnostic (Imaging) Techniques for Neurogenic Thoracic Outlet Syndrome.

Thoracic outlet syndrome is an uncommon and controversial syndrome. Three different diagnoses can be made based on the compressed structure, arterial TOS, venous TOS, and neurogenic TOS, though combinations do exist as well. Diagnosing NTOS is difficult since no specific objective diagnostic modalities exist. This has resulted in a lot of controversy in recent decades. NTOS remains a clinical diagnosis and is mostly diagnosed based on the exclusion of an extensive list of differential diagnoses. To guide the diagnosis and treatment of TOS, a group of experts published the reporting standards for TOS in 2016. However, a consensus was not reached regarding a blueprint for a daily care pathway in this document. Therefore, we constructed a care pathway based on the reporting standards for both the diagnosis and treatment of NTOS patients. This care pathway includes a multidisciplinary approach in which different diagnostic tests and additional imaging techniques are combined to diagnose NTOS or guide patients in their treatment for differential diagnoses. The aim of the present work is to discuss and explain the diagnostic part of this care pathway.

The human dorsal premotor cortex facilitates the excitability of ipsilateral primary motor cortex via a short latency cortico-cortical route.

In non-human primates, invasive tracing and electrostimulation studies have identified strong ipsilateral cortico-cortical connections between dorsal premotor- (PMd) and the primary motor cortex (M1(HAND) ). Here, we applied dual-site transcranial magnetic stimulation (dsTMS) to left PMd and M1(HAND) through specifically designed minicoils to selectively probe ipsilateral PMd-to-M1(HAND) connectivity in humans. A suprathreshold test stimulus (TS) was applied to M1(HAND) producing a motor evoked potential (MEP) of about 0.5 mV in the relaxed right first dorsal interosseus muscle (FDI). A subthreshold conditioning stimulus (CS) was given to PMd 2.0-5.2 ms after the TS at intensities of 50-, 70-, or 90% of TS. The CS to PMd facilitated the MEP evoked by TS over M1(HAND) at interstimulus intervals (ISI) of 2.4 or 2.8 ms. There was a second facilitatory peak at ISI of 4.4 ms. PMd-to-M1(HAND) facilitation did not change as a function of CS intensity. Even at higher intensities, the CS alone failed to elicit a MEP or a cortical silent period in the pre-activated FDI, excluding a direct spread of excitation from PMd to M1(HAND). No MEP facilitation was present while CS was applied rostrally over lateral prefrontal cortex. Together our results indicate that our dsTMS paradigm probes a short-latency facilitatory PMd-to-M1(HAND) pathway. The temporal pattern of MEP facilitation suggests a PMd-to-M1(HAND) route that targets intracortical M1(HAND) circuits involved in the generation of indirect corticospinal volleys. This paradigm opens up new possibilities to study context-dependent intrahemispheric PMd-to-M1(HAND) interactions in the intact human brain.

Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis.

OBJECTIVE: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD. METHODS: We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel-Haenszel procedure was used to estimate odds ratios. RESULTS: Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 × 10(-6) for ALS and p = 4.3 × 10(-5) for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD. INTERPRETATION: The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD.