Progressive microstructural alterations in subcortical nuclei in Parkinson's disease: A diffusion magnetic resonance imaging study

ObjectivesTo explore the microstructural alterations in subcortical nuclei in Parkinson's disease (PD) at different stages with diffusion kurtosis imaging (DKI) and tensor imaging and to test the performance of diffusion metrics in identifying PD.Methods108 PD patients (64 patients in early-stage PD group (EPD) and 44 patients in moderate-late-stage PD group (MLPD)) and 64 healthy controls (HC) were included. Tensor and kurtosis metrics in the subcortical nuclei were compared. Partial correlation was used to correlate the diffusion metrics and Unified Parkinson's Disease Rating Scale part-III (UPDRS-III) score. Logistic regression and receiver operating characteristic analysis were applied to test the diagnostic performance of the diffusion metrics.ResultsCompared with HC, both EPD and MLPD patients showed higher fractional anisotropy and axial diffusivity, lower mean kurtosis (MK) and axial kurtosis in substantia nigra, lower MK and radial kurtosis (RK) in globus pallidus (GP) and thalamus (all p < 0.05). Compared with EPD, MLPD patients showed lower MK and RK in GP and thalamus (all p < 0.05). MK and RK in GP and thalamus were negatively correlated with UPDRS-III score (all p < 0.01). The logistic regression model combining kurtosis and tensor metrics showed the best performance in diagnosing PD, EPD, and MLPD (areas under curve were 0.817, 0.769, and 0.914, respectively).ConclusionsPD has progressive microstructural alterations in the subcortical nuclei. DKI is sensitive to detect microstructural alterations in GP and thalamus during PD progression. Combining kurtosis and tensor metrics can achieve a good performance in diagnosing PD.     

Improvement of brain function after surgery in infants with posterior quadrant cortical dysplasia

ObjectiveTo reveal whether neurodevelopmental outcome of infants after epilepsy surgery can be quantitatively assessed by electroencephalography (EEG) functional connectivity analysis.MethodsWe enrolled 13 infants with posterior quadrant dysplasia aged <2 years who were treated using posterior quadrantectomy and 21 age-matched infants. EEG was performed both before and one year after surgery. Developmental quotient (DQ) was assessed both before and 3 years after surgery. The phase lag index (PLI) of three different pairs of electrodes in the nonsurgical hemisphere, i.e., the anterior short distance (ASD), posterior short distance (PSD), and long distance (LD) pairs, were calculated as indices of brain connectivity. The relationship between the PLI and DQ was evaluated.ResultsOverall, 77% infants experienced seizure freedom after surgery. The beta- and gamma- range PLI of PSD pairs increased preoperatively. All these pairs normalized postoperatively. Simple linear regression analysis revealed a significant relationship between the postoperative DQ and the postoperative beta-band PLI of ASD pairs.ConclusionPreoperative abnormal hyper-connectivity was normalized to the control level after surgery. The postoperative hyperconnectivity was associated with long-term neurodevelopmental improvement.SignificancePLI quantifies neurodevelopmental improvements after posterior quadrantectomy.     

Postoperative navigated transcranial magnetic stimulation to predict motor recovery after surgery of tumors in motor eloquent areas

ObjectiveTo know whether motor deficits after tumor surgery are transient is reassuring for the patient and crucial for planning rehabilitation and adjuvant treatment. We analyze the value of postoperative MRI navigated transcranial magnetic stimulation (nTMS) compared to intraoperative MEP monitoring in predicting recovery of motor function.MethodsRetrospective series of nTMS mappings within 14 days after surgery for supratentorial tumors (09/2014–05/2018). All patients with motor deficits of Medical-Research-Council-Grade (MRCS) 0–4- were included.ResultsWe performed nTMS mapping on average 3.8 days after surgery and recorded nTMS MEP in 11 of 13 patients. Motor strength recovered to at least MRCS 4 within one month if postoperative nTMS elicited MEPs (positive predictive value 90.9%). If nTMS did not elicit MEPs, the patient did not recover (negative predictive value 100%). Intraoperative MEP and postoperative nTMS were equally predictive for long-term motor recovery. In cases of intraoperative MEP alteration/signal loss, but a positive postoperative nTMS mapping, 2/3 patients demonstrated a good motor recovery.ConclusionnTMS may predict long-term motor recovery of patients suffering from severe motor deficits directly after resection of tumors located in motor eloquent areas.SignificanceIn cases of intraoperative MEP alterations, postoperative nTMS may clarify the potential for motor recovery.     

Retinal and optic nerve magnetic resonance diffusion-weighted imaging in acute non-arteritic central retinal artery occlusion

ObjectivesDiffusion weighted imaging hyperintensity (DWI-H) has been described in the retina and optic nerve during acute central retinal artery occlusion (CRAO). We aimed to determine whether DWI-H can be accurately identified on standard brain magnetic resonance imaging (MRI) in non-arteritic CRAO patients at two tertiary academic centers.Materials and methodsRetrospective cross-sectional study that included all consecutive adult patients with confirmed acute non-arteritic CRAO and brain MRI performed within 14 days of CRAO. At each center, two neuroradiologists masked to patient clinical data reviewed each MRI for DWI-H in the retina and optic nerve, first independently then together. Statistical analysis for inter-rater reliability and correlation with clinical data was performed.ResultsWe included 204 patients [mean age 67.9±14.6 years; 47.5% females; median time from CRAO to MRI 1 day (IQR 1-4.3); 1.5 T in 127/204 (62.3%) and 3.0 T in 77/204 (37.7%)]. Inter-rater reliability varied between centers (κ = 0.27 vs. κ = 0.65) and was better for retinal DWI-H. Miss and error rates significantly differed between neuroradiologists at each center. After consensus review, DWI-H was identified in 87/204 (42.6%) patients [miss rate 117/204 (57.4%) and error rate 11/87 (12.6%)]. Significantly more patients without DWI-H had good visual acuity at follow-up (p = 0.038).ConclusionsIn this real-world case series, differences in agreement and interpretation accuracy among neuroradiologists limited the role of DWI-H in diagnosing acute CRAO on standard MRI. DWI-H was identified in 42.6% of patients and was more accurately detected in the retina than in the optic nerve. Further studies are needed with standardized novel MRI protocols.     

Correlation between magnetic resonance imaging characteristics and BRAF alteration status in individuals with optic pathway/hypothalamic pilocytic astrocytomas

Background and purposeMost individuals with optic pathway/hypothalamic pilocytic astrocytoma (OPHPA) harbor either the BRAF V600E mutation or KIAA1549-BRAF fusion (K-B). This study aimed to investigate the imaging characteristics of OPHPA in relation to BRAF alteration status.Materials and methodsSeven cases of OPHPA harboring either the BRAF V600E mutation or K-B fusion were included in the study. Preoperative magnetic resonance imaging (MRI) was assessed for degree of T2 hyperintensity on T2-weighted images (T2WI) and the ratio of nonenhancing T2 or fluid-attenuated inversion recovery (FLAIR) hyperintense area to the contrast enhanced area (CE) on gadolinium-enhanced-T1 weighted images (T2/FLAIR-CE mismatch). The T2 signal intensity was normalized to cerebrospinal fluid (T2/CSF) for both the V600E and K-B group and compared. T2/FLAIR-CE mismatch was assessed by calculating the proportion of the tumor volume of nonenhancing high T2 signal intensity to the whole lesion (nonenhancing and enhancing components).ResultsFour and three cases of OPHPA harboring the BRAF V600E mutation and K-B, respectively, were analyzed. The T2/CSF value was higher in the K-B group than in the V600E group. Moreover, the V600E group had a larger T2/FLAIR-CE mismatch than the K-B group.ConclusionsThe BRAF alteration status in individuals with OPHPA was associated with preoperative MRI by focusing on T2 signal intensity and T2/FLAIR-CE mismatch. The BRAF V600E mutation was associated with a lower T2/CSF value and larger T2/FLAIR-CE mismatch, whereas K-B fusion was associated with a higher T2/CSF value and smaller T2/FLAIR-CE mismatch.     

Predictive factors for the development of epilepsy after ischemic stroke

ObjectivesIschemic stroke is one of the most common causes of epilepsy in adults. The incidence of post-stroke epilepsy (PSE) is approximately 7%. Risk factors are higher stroke severity, cortical localization, higher National Institute of Health Stroke Scale (NIHSS) upon admission and acute symptomatic seizures. We analyzed the predictive factors of PSE development in our population.Materials and methodsRetrospective observational cohort of adult patients (age ≥ 18 years) with ischemic stroke assessed between January 2012 and June 2020. Patients with personal history of epilepsy and potentially epileptogenic structural injury other than acute or chronic stroke were excluded. Demographic, clinical and imaging variables were evaluated in a multivariate analysis for independent risk factors associated with PSE.ResultsMedical records of 1586 stroke patients were reviewed, 691 met the inclusion criteria and had at least one year of follow-up. Of them, 428 (61.9%) were males. During follow-up, 6.2% had diagnosis of PSE (42/691) with a higher frequency of: previous ischemic stroke, higher NIHSS upon admission, treatment with rt-PA, higher Fazekas scale grade, cortical involvement, hemorrhagic transformation, acute symptomatic seizures, longer hospitalization and higher modified Rankin Scale (mRS) at discharge compared to the group without PSE. In a multivariate analysis, acute symptomatic seizures (OR=3.22, p: 0.033), cortical involvement (OR=0.274, p < 0.05), Fazekas scale score (OR=0.519, p < 0.05) and mRS at discharge (OR=1.33, p: 0.043) were independent risk factors.ConclusionsThe variables related to higher risk of PSE were similar to those reported in the literature, highlighting the importance of neuroimaging findings, acute symptomatic seizures during hospitalization and neurological deficit at discharge. The data obtained will serve as the basis for construction of predictive models, allowing to individualize PSE probability in our population.     

The ability of magnetic resonance black blood vessel wall imaging to evaluate blunt cerebrovascular injury following acute trauma

Background and purposeBlunt cerebrovascular injury (BCVI) is associated with a significant risk of ischemic stroke when left untreated. Cross-sectional imaging is vital to early BCVI diagnosis and treatment; however, conventional luminal vessel imaging is limited in its ability to evaluate for vessel wall pathology. The purpose of this study is to evaluate the ability of vessel wall magnetic resonance imaging (VWI) to detect and evaluate BCVI in acutely injured trauma patients relative to neck computed tomographic angiography (CTA).Materials and methodsTrauma patients with suspected BCVI on initial neck CTA were prospectively recruited for VWI evaluation. Two neuroradiologists blinded to patient clinical history and CTA findings evaluated each artery independently on VWI and noted the presence and grade of BCVI. These results were subsequently compared to neck CTA findings relative to expert clinical consensus review. Interrater reliability of VWI for detecting BCVI was evaluated using a weighted Cohen κ-statistic.ResultsTen trauma patients (40 cervical arteries) were prospectively evaluated using both CTA and VWI. Out of 18 vascular lesions identified as suspicious for BCVI on CTA, six lesions were determined to represent true BCVI by expert consensus review. There was almost perfect agreement between VWI and expert consensus regarding the presence and grade of BCVI (κ = 0.82). This agreement increased when considering only low grade BCVI. There was only fair agreement between CTA and expert clinical consensus (κ = 0.36). This agreement decreased when considering only low grade BCVI.ConclusionsVWI can potentially accurately identify and evaluate BCVI in acutely injured trauma patients with excellent inter-rater reliability.     

Can we predict intraoperative blood loss in meningioma patients? Application of dynamic susceptibility contrast-enhanced magnetic resonance imaging

PurposeTo evaluate the potential of quantitative dynamic susceptibility contrast (DSC) perfusion MR imaging parameters as imaging biomarkers for predicting intraoperative blood loss in meningioma.MethodsFifty-one non-embolized meningioma patients who had undergone preoperative DSC perfusion MR imaging were retrospectively included. The corrected relative cerebral blood volume (rCBV) and leakage coefficient (K₂) of the entire enhanced tumor were obtained using leakage correction. Tumor volume, location, grade, and other clinical variables, were also analyzed. To investigate the vascularity and vascular permeability of meningiomas, and their correlation with predicting estimated blood loss (EBL) using preoperative DSC perfusion MR imaging, the authors proposed an index reflecting the inherent tendency of meningiomas to bleed after controlling volume (i.e., EBL/cm³). Simple regression was performed to identify predictors of EBL/cm³; subsequently, the relevant variables included in the stepwise multiple linear regression.ResultsOn univariate analysis, EBL/cm³ was correlated with rCBV (r = 0.677; P < 0.001), K₂ (r = 0.294; P = 0.036), and tumor volume (r = –0.312, P = 0.026). EBL/cm³ was not correlated with age (P = 0.873), sex (P = 0.404), tumor location (P = 0.327), or histological grade (P = 0.230). On multiple linear regression, rCBV (β = 0.663 [0.463–0.864], B = 1.293 [0.903–1.684; P < 0.001) and K₂ (β = 0.260 [0.060–0.460], B = 2.277 [0.523–4.031], P = 0.012), were the only independent predictors of EBL/cm³.ConclusionThe rCBV and K₂ derived from DSC perfusion MR imaging in meningiomas may serve as feasible tools for clinicians to predict intraoperative blood loss and facilitate surgical planning.     

Atlas-informed computational processing pipeline for individual targeting of brain areas for therapeutic navigated transcranial magnetic stimulation

ObjectiveNavigated transcranial magnetic stimulation (nTMS) is targeted at different cortical sites for diagnostic, therapeutic, and neuroscientific purposes. Correct identification of the cortical target areas is important for achieving desired effects, but it is challenging when no direct responses arise upon target area stimulation. We aimed at utilizing atlas-based marking of cortical areas for nTMS targeting to present a convenient, rater-independent method for overlaying the individual target sites with brain anatomy.MethodsWe developed a pipeline, which fits a brain atlas to the individual brain and enables visualization of the target areas during the nTMS session. We applied the pipeline to our previous nTMS data, focusing on depression and schizophrenia patients. Furthermore, we included examples of Tourette syndrome and tinnitus therapies, as well as neurosurgical and motor mappings.ResultsIn depression and schizophrenia patients, the visually selected dorsolateral prefrontal cortex (DLPFC) targets were close to the border between atlas areas A9/46 and A8. In the other areas, the atlas-based areas were in agreement with the treatment targets.ConclusionsThe atlas-based target areas agreed well with the cortical targets selected by experts during the treatments.SignificanceOverlaying atlas information over the navigation view is a convenient and useful add-on for improving nTMS targeting.     

Psychological Outcome after Hemorrhagic Stroke is Related to Functional Status

BackgroundTo identify opportunities to improve morbidity after hemorrhagic stroke, it is imperative to understand factors that are related to psychological outcome.Design/MethodsWe prospectively identified patients with non-traumatic hemorrhagic stroke (intracerebral or subarachnoid hemorrhage) between January 2015 and February 2021 who were alive 3-months after discharge and telephonically assessed 1) psychological outcome using the Quality of Life in Neurological Disorders anxiety, depression, emotional and behavioral dyscontrol, fatigue and sleep disturbance inventories and 2) functional outcome using the modified Rankin Scale (mRS) and Barthel Index. We also identified discharge destination for all patients. We then evaluated the relationship between abnormal psychological outcomes (T-score >50) and discharge destination other than home, poor 3-month mRS score defined as 3-5 and poor 3-month Barthel Index defined as <100.Results73 patients were included; 41 (56%) had an abnormal psychological outcome on at least one inventory. There were 41 (56%) patients discharged to a destination other than home, 44 (63%) with poor mRS score and 28 (39%) with poor Barthel Index. Anxiety, depression, emotional and behavioral dyscontrol and sleep disturbance were all associated with a destination other than home, poor mRS score, and poor Barthel Index (all p<0.05). Fatigue was related to poor mRS score and poor Barthel Index (p=0.005 and p=0.006, respectively).ConclusionMultiple psychological outcomes 3-months after hemorrhagic stroke are related to functional status. Interventions to improve psychological outcome and reduce morbidity in patients with poor functional status should be explored by the interdisciplinary team.     

Functional organization of the human primary somatosensory cortex: A stereo-electroencephalography study

ObjectiveThe classical homunculus of the human primary somatosensory cortex (S1) established by Penfield has mainly portrayed the functional organization of convexial cortex, namely Brodmann area (BA) 1. However, little is known about the functions in fissural cortex including BA2 and BA3. We aim at drawing a refined and detailed somatosensory homunculus of the entire S1.MethodsWe recruited 20 patients with drug-resistant focal epilepsy who underwent stereo-electroencephalography for preoperative assessments. Direct electrical stimulation was performed for functional mapping. Montreal Neurological Institute coordinates of the stimulation sites lying in S1 were acquired.ResultsStimulation of 177 sites in S1 yielded 149 positive sites (84%), most of which were located in the sulcal cortex. The spatial distribution of different body-part representations across the S1 surface revealed that the gross medial-to-lateral sequence of body representations within the entire S1 was consistent with the classical “homunculus”. And we identified several unreported body-part representations from the sulcal cortex, such as forehead, deep elbow and wrist joints, and some dorsal body regions.ConclusionsOur results reveal general somatotopical characteristics of the entire S1 cortex and differences with the previous works of Penfield.SignificanceThe classical S1 homunculus was extended by providing further refinement and additional detail.     

High frequency oscillations relate to cognitive improvement after epilepsy surgery in children

ObjectiveTo investigate how high frequency oscillations (HFOs; ripples 80–250 Hz, fast ripples (FRs) 250–500 Hz) and spikes in intra-operative electrocorticography (ioECoG) relate to cognitive outcome after epilepsy surgery in children.MethodsWe retrospectively included 20 children who were seizure free after epilepsy surgery using ioECoG and determined their intelligence quotients (IQ) pre- and two years postoperatively. We analyzed whether the number of HFOs and spikes in pre- and postresection ioECoGs, and their change in the non-resected areas relate to cognitive improvement (with ≥ 5 IQ points increase considered to be clinically relevant (=IQ+ group) and < 5 IQ points as irrelevant (=IQ− group)).ResultsThe IQ+ group showed significantly more FRs in the resected tissue (p = 0.01) and less FRs in the postresection ioECoG (p = 0.045) compared to the IQ− group. Postresection decrease of ripples on spikes was correlated with postoperative cognitive improvement (correlation coefficient = −0.62 with p = 0.01).ConclusionsPostoperative cognitive improvement was related to reduction of pathological HFOs signified by removing FR generating areas with subsequently less residual FRs, and decrease of ripples on spikes in the resection edge of the non-resected area.SignificanceHFOs recorded in ioECoG could play a role as biomarkers in the prediction and understanding of cognitive outcome after epilepsy surgery.     

Bedside neurophysiological tests can identify neonates with stroke leading to cerebral palsy

ObjectiveThe unspecific symptoms of neonatal stroke still challenge its bedside diagnosis. We studied the accuracy of routine electroencephalography (EEG) and simultaneously recorded somatosensory evoked potentials (EEG-SEP) for diagnosis and outcome prediction of neonatal stroke.MethodsWe evaluated EEG and EEG-SEPs from a hospital cohort of 174 near-term neonates with suspected seizures or encephalopathy, 32 of whom were diagnosed with acute ischemic or hemorrhagic stroke in MRI. EEG was scored for background activity and seizures. SEPs were classified as present or absent. Developmental outcome of stroke survivors was evaluated from medical records at 8- to 18-months age.ResultsThe combination of continuous EEG and uni- or bilaterally absent SEP (n = 10) was exclusively seen in neonates with a middle cerebral artery (MCA) stroke (specificity 100%). Moreover, 80% of the neonates with this finding developed with cerebral palsy. Bilaterally present SEPs did not exclude stroke, but predicted favorable neuromotor outcome in stroke survivors (positive predictive value 95%).ConclusionsAbsent SEP combined with continuous EEG background in near-term neonates indicates an MCA stroke and a high risk for cerebral palsy.SignificanceEEG-SEP offers a bedside method for diagnostic screening and a reliable prediction of neuromotor outcome in neonates suspected of having a stroke.     

D-cycloserine normalizes long-term motor plasticity after transcranial magnetic intermittent theta-burst stimulation in major depressive disorder

ObjectivesMajor Depressive Disorder (MDD) is associated with glutamatergic alterations, including the N-methyl-D-aspartate receptor (NMDA-R). The NMDA-R plays an important role in synaptic plasticity, and individuals with MDD have been shown to have impairments in repetitive Transcranial Magnetic Stimulation (rTMS) motor plasticity. Here, we test whether D-cycloserine, a NMDA-R partial agonist, can rescue TMS motor plasticity in MDD.MethodsWe conducted randomized double-blind placebo-controlled crossover studies in healthy (n = 12) and MDD (n = 12) participants. We stimulated motor cortex using TMS intermittent theta burst stimulation (iTBS) with placebo or D-cycloserine (100 mg). Motor evoked potentials (MEPs) were sampled before and after iTBS. Stimulus response curves (SRC) were characterized at baseline, +90 minutes, and the following day.ResultsAcute iTBS MEP facilitation is reduced in MDD and is not rescued by D-cycloserine. After iTBS, SRCs shift to indicate sustained decrease in excitability in healthy participants, yet increased in excitability in MDD participants. D-cycloserine normalized SRC changes from baseline to the following day in MDD participants. In both healthy and MDD participants, D-cycloserine stabilized changes in SRC.ConclusionMDD is associated with alterations in motor plasticity that are rescued and stabilized by NMDA-R agonism.SignificanceAgonism of NMDA receptors rescues iTBS motor plasticity in MDD.     

Neurophysiology of motor skill learning in chronic stroke

ObjectiveMotor learning is relevant in chronic stroke for acquiring compensatory strategies to motor control deficits. However, the neurophysiological mechanisms underlying motor skill acquisition with the paretic upper limb have received little systematic investigation. The aim of this study was to assess the modulation of corticomotor excitability and intracortical inhibition within ipsilesional primary motor cortex (M1) during motor skill learning.MethodsTen people at the chronic stage after stroke and twelve healthy controls trained on a sequential visuomotor isometric wrist extension task. Skill was quantified before, immediately after, 24 hours and 7 days post-training. Transcranial magnetic stimulation was used to examine corticomotor excitability and short- and long-interval intracortical inhibition (SICI and LICI) pre- and post-training.ResultsThe patient group exhibited successful skill acquisition and retention, although absolute skill level was lower compared with controls. In contrast to controls, patients’ ipsilesional corticomotor excitability was not modulated during skill acquisition, which may be attributed to excessive ipsilesional LICI relative to controls. SICI decreased after training for both patient and control groups.ConclusionsOur findings indicate distinct inhibitory networks within M1 that may be relevant for motor learning after stroke.SignificanceThese findings have potential clinical relevance for neurorehabilitation adjuvants aimed at augmenting the recovery of motor function.     

Signal changes in enhanced T1-weighted images related to gadolinium retention: A three-time-point imaging study

Background and PurposeConcern has grown about the finding of gadolinium deposits in the brain after administering gadolinium-based contrast agents (GBCAs). The mechanism is unclear, and related questions remain unanswered, including the stability over time. Therefore, we conducted a three-time-point study to explore T1-weighted (W) signal changes in the dentate nucleus (DN) and globus pallidus (GP), after the first, fifth, and tenth injections of either a macrocyclic agent (gadoterate meglumine) or a linear agent (gadobenate dimeglumine).Materials and methodsFor this retrospective, multicenter, longitudinal study, two groups of 18 (gadoterate meglumine) and 19 (gadobenate dimeglumine) patients were identified. The evolution of the signal over time was analyzed using DN/pons (DN/P) and GP/thalamus (GP/T) ratios.ResultsDN/P and GP/T ratios tended to increase after the fifth administration of gadobenate dimeglumine, following by a downward trend. A trend in a decrease in DN/P and GP/T ratios were found after the fifth and tenth administrations of gadoterate meglumine.ConclusionAfter exposure to gadobenate dimeglumine, the signal intensity (SI) tended to increase after the fifth injection owing to gadolinium accumulation, however, a SI increase was not found after the tenth administration supporting the hypothesis of a slow elimination of the previously retained gadolinium (wash-out effect) from the brain or of a change in form (by dechelation), causing the signal to fade. No increasing SI was found in the DN and GP after exclusive exposure to gadoterate meglumine, thus confirming its stability. We found, instead, a trend for a significative gadolinium elimination over time.     

Training in the practice of noninvasive brain stimulation: Recommendations from an IFCN committee

As the field of noninvasive brain stimulation (NIBS) expands, there is a growing need for comprehensive guidelines on training practitioners in the safe and effective administration of NIBS techniques in their various research and clinical applications. This article provides recommendations on the structure and content of this training. Three different types of practitioners are considered (Technicians, Clinicians, and Scientists), to attempt to cover the range of education and responsibilities of practitioners in NIBS from the laboratory to the clinic. Basic or core competencies and more advanced knowledge and skills are discussed, and recommendations offered regarding didactic and practical curricular components. We encourage individual licensing and governing bodies to implement these guidelines.     

Peripheral nerve imaging in amyotrophic lateral sclerosis

We systematically identified and reviewed 29 studies of peripheral nerve ultrasound or magnetic resonance imaging (MRN) in amyotrophic lateral sclerosis (ALS). The majority of the ultrasound studies reported smaller nerves and nerve roots in ALS compared to healthy controls, but there was a large overlap of the cross-sectional nerve area between ALS and controls. Most of the MRN studies confirmed nerve abnormalities demonstrating slight T2 hyperintensities and, sometimes, mild enlargement of more proximal nerve segments (plexus, roots) in ALS. The size of the proximal nerve segments, i.e. nerve roots, is thus somewhat incongruent between nerve ultrasound and MRN in ALS. Peripheral nerve ultrasound has the potential to differentiate between ALS and multifocal motor neuropathy (MMN) in that patients with MMN have significantly larger nerves. Conversely, there is an overlap of MRN abnormalities in ALS and MMN, restricting the techniques’ utility in the clinical setting. A subgroup of patients with ALS seems to reveal a sonographic nerve pattern suggesting peripheral nerve inflammation. In the future, combined imaging with nerve ultrasound and MRN assessing parameters such as blood flow or textural markers may aid in the understanding of the deep nerve microstructure down to the fascicle level, and thus, in the classification of the nerve state as more degenerative or more inflammatory in ALS. This systematic review provides evidence that nerve imaging abnormalities are common in ALS.     

Differentiating transcranial magnetic stimulation cortical and auditory responses via single pulse and paired pulse protocols: A TMS-EEG study

ObjectiveWe measured the neurophysiological responses of both active and sham transcranial magnetic stimulation (TMS) for both single pulse (SP) and paired pulse (PP; long interval cortical inhibition (LICI)) paradigms using TMS-EEG (electroencephalography).MethodsNineteen healthy subjects received active and sham (coil 90° tilted and touching the scalp) SP and PP TMS over the left dorsolateral prefrontal cortex (DLPFC). We measured excitability through SP TMS and inhibition (i.e., cortical inhibition (CI)) through PP TMS.ResultsCortical excitability indexed by area under the curve (AUC_(25-275ms)) was significantly higher in the active compared to sham stimulation (F(1,18) = 43.737, p < 0.001, η² = 0.708). Moreover, the amplitude of N100-P200 complex was significantly larger (F(1,18) = 9.118, p < 0.01, η² = 0.336) with active stimulation (10.38 ± 9.576 µV) compared to sham (4.295 ± 2.323 µV). Significant interaction effects were also observed between active and sham stimulation for both the SP and PP (i.e., LICI) cortical responses. Finally, only active stimulation (CI = 0.64 ± 0.23, p < 0.001) resulted in significant cortical inhibition.ConclusionThe significant differences between active and sham stimulation in both excitatory and inhibitory neurophysiological responses showed that active stimulation elicits responses from the cortex that are different from the non-specific effects of sham stimulation.SignificanceOur study reaffirms that TMS-EEG represents an effective tool to evaluate cortical neurophysiology with high fidelity.