Using normative modeling and machine learning for detecting mild traumatic brain injury from magnetoencephalography data.

New biomarkers are urgently needed for many brain disorders; for example, the diagnosis of mild traumatic brain injury (mTBI) is challenging as the clinical symptoms are diverse and nonspecific. EEG and MEG studies have demonstrated several population-level indicators of mTBI that could serve as objective markers of brain injury. However, deriving clinically useful biomarkers for mTBI and other brain disorders from EEG/MEG signals is hampered by the large inter-individual variability even across healthy people. Here, we used a multivariate machine-learning approach to detect mTBI from resting-state MEG measurements. To address the heterogeneity of the condition, we employed a normative modeling approach and modeled MEG signal features of individual mTBI patients as deviations with respect to the normal variation. To this end, a normative dataset comprising 621 healthy participants was used to determine the variation in power spectra across the cortex. In addition, we constructed normative datasets based on age-matched subsets of the full normative data. To discriminate patients from healthy control subjects, we trained support-vector-machine classifiers on the quantitative deviation maps for 25 mTBI patients and 20 controls not included in the normative dataset. The best performing classifier made use of the full normative data across the entire age and frequency ranges. This classifier was able to distinguish patients from controls with an accuracy of 79%. Inspection of the trained model revealed that low-frequency activity in the theta frequency band (4-8 Hz) is a significant indicator of mTBI, consistent with earlier studies. The results demonstrate the feasibility of using normative modeling of MEG data combined with machine learning to advance diagnosis of mTBI and identify patients that would benefit from treatment and rehabilitation. The current approach could be applied to a wide range of brain disorders, thus providing a basis for deriving MEG/EEG-based biomarkers.

Somatotopic disruption of the functional connectivity of the primary sensorimotor cortex in complex regional pain syndrome type 1.

In complex regional pain syndrome (CRPS), the representation area of the affected limb in the primary sensorimotor cortex (SM1) reacts abnormally during sensory stimulation and motor actions. We recorded 3T functional magnetic resonance imaging resting-state data from 17 upper-limb CRPS type 1 patients and 19 healthy control subjects to identify alterations of patients' SM1 function during spontaneous pain and to find out how the spatial distribution of these alterations were related to peripheral symptoms. Seed-based correlations and independent component analyses indicated that patients' upper-limb SM1 representation areas display (i) reduced interhemispheric connectivity, associated with the combined effect of intensity and spatial extent of limb pain, (ii) increased connectivity with the right anterior insula that positively correlated with the duration of CRPS, (iii) increased connectivity with periaqueductal gray matter, and (iv) disengagement from the other parts of the SM1 network. These findings, now reported for the first time in CRPS, parallel the alterations found in patients suffering from other chronic pain conditions or from limb denervation; they also agree with findings in healthy persons who are exposed to experimental pain or have used their limbs asymmetrically. Our results suggest that CRPS is associated with a sustained and somatotopically specific alteration of SM1 function, that has correspondence to the spatial distribution of the peripheral manifestations and to the duration of the syndrome.

Reproducibility of Rolandic beta rhythm modulation in MEG and EEG.

The Rolandic beta rhythm, at ∼20 Hz, is generated in the somatosensory and motor cortices and is modulated by motor activity and sensory stimuli, causing a short lasting suppression that is followed by a rebound of the beta rhythm. The rebound reflects inhibitory changes in the primary sensorimotor (SMI) cortex, and thus it has been used as a biomarker to follow the recovery of patients with acute stroke. The longitudinal stability of beta rhythm modulation is a prerequisite for its use in long-term follow-ups. We quantified the reproducibility of beta rhythm modulation in healthy subjects in a 1-year-longitudinal study both for MEG and EEG at T0, 1 month (T1-month, n = 8) and 1 year (T1-year, n = 19). The beta rhythm (13-25 Hz) was modulated by fixed tactile and proprioceptive stimulations of the index fingers. The relative peak strengths of beta suppression and rebound did not differ significantly between the sessions, and intersession reproducibility was good or excellent according to intraclass correlation-coefficient values (0.70-0.96) both in MEG and EEG. Our results indicate that the beta rhythm modulation to tactile and proprioceptive stimulation is well reproducible within 1 year. These results support the use of beta modulation as a biomarker in long-term follow-up studies, e.g., to quantify the functional state of the SMI cortex during rehabilitation and drug interventions in various neurological impairments.NEW & NOTEWORTHY The present study demonstrates that beta rhythm modulation is highly reproducible in a group of healthy subjects within a year. Hence, it can be reliably used as a biomarker in longitudinal follow-up studies in different neurological patient groups to reflect changes in the functional state of the sensorimotor cortex.

Early clinical features of new-onset refractory status epilepticus (NORSE) in adults.

BACKGROUND: The aim of this study was to identify early clinical features of patients with new-onset refractory status epilepticus (NORSE) that could direct the treatment in the first days of hospitalisation. METHODS: A retrospective cohort study of adult NORSE patients treated in the intensive care units of Helsinki University Hospital 2007-2018. RESULTS: We found 19 adult NORSE patients who divided into three subgroups on the basis of their clinical features: viral encephalitis (n = 5, 26%), febrile infection-related epilepsy syndrome (FIRES) (n = 6, 32%) and afebrile NORSE (n = 8, 42%). FIRES and afebrile NORSE patients remained without confirmed etiology, but retrospectively two paraneoplastic and two neurodegenerative causes were suspected in the afebrile NORSE group. Viral encephalitis patients were median 64 years old (IQR 55-64), and four (80%) had prodromal fever and abnormal findings in the first brain imaging. FIRES patients were median 21 years old (IQR 19-24), all febrile and had normal brain imaging at onset. In the afebrile NORSE group, median age was 67 (IQR 59-71) and 50% had prodromal cognitive or psychiatric symptoms. FIRES patients differed from other NORSE patients by younger age (p = 0.001), respiratory prodromal symptoms (p = 0.004), normal brain MRI (p = 0.044) and lack of comorbidities (p = 0.011). They needed more antiseizure medications (p = 0.001) and anesthetics (p = 0.002), had a longer hospital stay (p = 0.017) and more complications (p < 0.001). CONCLUSIONS: Among febrile NORSE patients, FIRES group was distinctive due to patients' young age, prodromal respiratory symptoms and normal first brain imaging. These features should be confirmed by subsequent studies as basis for selecting patients for early intensive immunotherapy.

Is infarct core growth linear? Infarct volume estimation by computed tomography perfusion imaging.

OBJECTIVES: Current guidelines for recanalization treatment are based on the time elapsed between symptom onset and treatment and visualization of existing penumbra in computed tomography perfusion (CTP) imaging. The time window for treatment options relies on linear growth of infarction although individual infarct growth rate may vary. We aimed to test how accurately the estimated follow-up infarct volume (eFIV) can be approximated by using a linear growth model based on CTP baseline imaging. If eFIV did not fall within the margins of +/- 19% of the follow-up infarct volume (FIV) measured at 24 h from non-enhanced computed tomography images, the results would imply that the infarct growth is not linear. MATERIALS AND METHODS: All consecutive endovascularly treated (EVT) patients from 11/2015 to 9/2019 at the Helsinki University Hospital with large vessel occlusion (LVO), CTP imaging, and known time of symptom onset were included. Infarct growth rate was assumed to be linear and calculated by dividing the ischemic core volume (CTPcore ) by the time from symptom onset to baseline imaging. eFIV was calculated by multiplying the infarct growth rate with the time from baseline imaging to recanalization or in case of futile recanalization to follow-up imaging at 24 h, limited to the penumbra. Collateral flow was estimated by calculating hypoperfusion intensity ratio (HIR). RESULTS: Of 5234 patients, 48 had LVO, EVT, CTP imaging, and known time of symptom onset. In 40/48 patients (87%), infarct growth was not linear. HIR did not differ between patients with linear and nonlinear growth (p > .05). As expected, in over half of the patients with successful recanalization eFIV exceeded FIV. CONCLUSIONS: Infarct growth was not linear in most patients and thus time elapsed from symptom onset and CTPcore appear to be insufficient parameters for clinical decision-making in EVT candidates.

Comparing MEG and EEG in detecting the ~20-Hz rhythm modulation to tactile and proprioceptive stimulation.

Modulation of the ~20-Hz brain rhythm has been used to evaluate the functional state of the sensorimotor cortex both in healthy subjects and patients, such as stroke patients. The ~20-Hz brain rhythm can be detected by both magnetoencephalography (MEG) and electroencephalography (EEG), but the comparability of these methods has not been evaluated. Here, we compare these two methods in the evaluating of ~20-Hz activity modulation to somatosensory stimuli. Rhythmic ~20-Hz activity during separate tactile and proprioceptive stimulation of the right and left index finger was recorded simultaneously with MEG and EEG in twenty-four healthy participants. Both tactile and proprioceptive stimulus produced a clear suppression at 300-350 â€‹ms followed by a subsequent rebound at 700-900 â€‹ms after stimulus onset, detected at similar latencies both with MEG and EEG. The relative amplitudes of suppression and rebound correlated strongly between MEG and EEG recordings. However, the relative strength of suppression and rebound in the contralateral hemisphere (with respect to the stimulated hand) was significantly stronger in MEG than in EEG recordings. Our results indicate that MEG recordings produced signals with higher signal-to-noise ratio than EEG, favoring MEG as an optimal tool for studies evaluating sensorimotor cortical functions. However, the strong correlation between MEG and EEG results encourages the use of EEG when translating studies to clinical practice. The clear advantage of EEG is the availability of the method in hospitals and bed-side measurements at the acute phase.

Reproducibility of corticokinematic coherence.

Corticokinematic coherence (CKC) between limb kinematics and magnetoencephalographic (MEG) signals reflects cortical processing of proprioceptive afference. However, it is unclear whether strength of CKC is reproducible across measurement sessions. We thus examined reproducibility of CKC in a follow-up study. Thirteen healthy right-handed volunteers (7 females, 21.7 ±â€¯4.3 yrs) were measured using MEG in two separate sessions 12.6 ±â€¯1.3 months apart. The participant was seated and relaxed while his/her dominant or non-dominant index finger was continuously moved at 3 Hz (4 min for each hand) using a pneumatic movement actuator. Finger kinematics were recorded with a 3-axis accelerometer. Coherence was computed between finger acceleration and MEG signals. CKC strength was defined as the peak coherence value at 3 Hz form a single sensor among 40 pre-selected Rolandic gradiometers contralateral to the movement. Pneumatic movement actuator provided stable proprioceptive stimuli and significant CKC responses peaking at the contralateral Rolandic sensors. In the group level, CKC strength did not differ between the sessions in dominant (Day-1 0.40 ±â€¯0.19 vs. Day-2 0.41 ±â€¯0.17) or non-dominant (0.35 ±â€¯0.16 vs. 0.36 ±â€¯0.17) hand, nor between the hands. Intraclass-correlation coefficient (ICC) values indicated excellent inter-session reproducibility for CKC strength for both dominant (0.86) and non-dominant (0.97) hand. However, some participants showed pronounced inter-session variability in CKC strength, but only for the dominant hand. CKC is a promising tool to study proprioception in long-term longitudinal studies in the group level to follow, e.g., integrity of cortical proprioceptive processing with motor functions after stroke.

Theta-Band Oscillations as an Indicator of Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) patients continue to pose a diagnostic challenge due to their diverse symptoms without trauma-specific changes in structural imaging. We addressed here the possible early changes in spontaneous oscillatory brain activity after mTBI, and their feasibility as an indicator of injury in clinical evaluation. We recorded resting-state magnetoencephalography (MEG) data in both eyes-open and eyes-closed conditions from 26 patients (11 females and 15 males, aged 20-59) with mTBI 6 days-6 months after the injury, and compared their spontaneous oscillatory activity to corresponding data from 139 healthy controls. Twelve of the patients underwent a follow-up measurement at 6 months. Ten of all patients were without structural lesions in MRI. At single-subject level, aberrant 4-7 Hz (theta) band activity exceeding the + 2 SD limit of the healthy subjects was visible in 7 out of 26 patients; three out of the seven patients with abnormal theta activity were without any detectable lesions in MRI. Of the patients that participated in the follow-up measurements, five showed abnormal theta activity in the first recording, but only two in the second measurement. Our results suggest that aberrant theta-band oscillatory activity can provide an early objective sign of brain dysfunction after mTBI. In 3/7 patients, the slow-wave activity was transient and visible only in the first recording, urging prompt timing for the measurements in clinical settings.

Recovery of the 20 Hz Rebound to Tactile and Proprioceptive Stimulation after Stroke.

Sensorimotor integration is closely linked to changes in motor-cortical excitability, observable in the modulation of the 20 Hz rhythm. After somatosensory stimulation, the rhythm transiently increases as a rebound that reflects motor-cortex inhibition. Stroke-induced alterations in afferent input likely affect motor-cortex excitability and motor recovery. To study the role of somatosensory afferents in motor-cortex excitability after stroke, we employed magnetoencephalographic recordings (MEG) at 1-7 days, one month, and 12 months in 23 patients with stroke in the middle cerebral artery territory and 22 healthy controls. The modulation of the 20 Hz motor-cortical rhythm was evaluated to two different somatosensory stimuli, tactile stimulation, and passive movement of the index fingers. The rebound strengths to both stimuli were diminished in the acute phase compared to the controls and increased significantly during the first month after stroke. However, only the rebound amplitudes to tactile stimuli fully recovered within the follow-up period. The rebound strengths in the affected hemisphere to both stimuli correlated strongly with the clinical scores across the follow-up. The results show that changes in the 20 Hz rebound to both stimuli behave similarly and occur predominantly during the first month. The 20 Hz rebound is a potential marker for predicting motor recovery after stroke.

Headache as symptom of intracranial hemorrhage.

The most important signs of danger of a headache patient include exceptionally intense or acute headache, transient loss or progressive impairment of consciousness, and neurological deficit symptoms. These patients are referred to an urgent assessment by a physician. Computed tomography scanning of the head is carried out in the case of suspected hemorrhage of a headache patient. Routine diagnosis employing cerebrospinal fluid analysis can be abandoned when excluding subarachnoid hemorrhage in a patient with headache symptoms, if blood is with certainty not observed in the CT scan of the head and no more than six hours have passed after the onset of the symptom. If subarachnoid hemorrhage is detected, cerebral CT angiography will be performed at the same time and a neurosurgeon consulted about the need of operative treatment.

Cortical Excitability Measured with nTMS and MEG during Stroke Recovery.

OBJECTIVE: Stroke alters cortical excitability both in the lesioned and in the nonlesioned hemisphere. Stroke recovery has been studied using transcranial magnetic stimulation (TMS). Spontaneous brain oscillations and somatosensory evoked fields (SEFs) measured by magnetoencephalography (MEG) are modified in stroke patients during recovery. METHODS: We recorded SEFs and spontaneous MEG activity and motor threshold (MT) short intracortical inhibition (SICI) and intracortical facilitation (ICF) with navigated TMS (nTMS) at one and three months after first-ever hemispheric ischemic strokes. Changes of MEG and nTMS parameters attributed to gamma-aminobutyrate and glutamate transmission were compared. RESULTS: ICF correlated with the strength and extent of SEF source areas depicted by MEG at three months. The nTMS MT and event-related desynchronization (ERD) of beta-band MEG activity and SICI and the beta-band MEG event-related synchronization (ERS) were correlated, but less strongly. CONCLUSIONS: This first report using sequential nTMS and MEG in stroke recovery found intra- and interhemispheric correlations of nTMS and MEG estimates of cortical excitability. ICF and SEF parameters, MT and the ERD of the lesioned hemisphere, and SICI and ERS of the nonlesioned hemisphere were correlated. Covarying excitability in the lesioned and nonlesioned hemispheres emphasizes the importance of the hemispheric balance of the excitability of the sensorimotor system.

Symptomatic intracranial hemorrhage after stroke thrombolysis: comparison of prediction scores.

BACKGROUND AND PURPOSE: Several prognostic scores have been developed to predict the risk of symptomatic intracranial hemorrhage (sICH) after ischemic stroke thrombolysis. We compared the performance of these scores in a multicenter cohort. METHODS: We merged prospectively collected data of patients with consecutive ischemic stroke who received intravenous thrombolysis in 7 stroke centers. We identified and evaluated 6 scores that can provide an estimate of the risk of sICH in hyperacute settings: MSS (Multicenter Stroke Survey); HAT (Hemorrhage After Thrombolysis); SEDAN (blood sugar, early infarct signs, [hyper]dense cerebral artery sign, age, NIH Stroke Scale); GRASPS (glucose at presentation, race [Asian], age, sex [male], systolic blood pressure at presentation, and severity of stroke at presentation [NIH Stroke Scale]); SITS (Safe Implementation of Thrombolysis in Stroke); and SPAN (stroke prognostication using age and NIH Stroke Scale)-100 positive index. We included only patients with available variables for all scores. We calculated the area under the receiver operating characteristic curve (AUC-ROC) and also performed logistic regression and the Hosmer-Lemeshow test. RESULTS: The final cohort comprised 3012 eligible patients, of whom 221 (7.3%) had sICH per National Institute of Neurological Disorders and Stroke, 141 (4.7%) per European Cooperative Acute Stroke Study II, and 86 (2.9%) per Safe Implementation of Thrombolysis in Stroke criteria. The performance of the scores assessed with AUC-ROC for predicting European Cooperative Acute Stroke Study II sICH was: MSS, 0.63 (95% confidence interval, 0.58-0.68); HAT, 0.65 (0.60-0.70); SEDAN, 0.70 (0.66-0.73); GRASPS, 0.67 (0.62-0.72); SITS, 0.64 (0.59-0.69); and SPAN-100 positive index, 0.56 (0.50-0.61). SEDAN had significantly higher AUC-ROC values compared with all other scores, except for GRASPS where the difference was nonsignificant. SPAN-100 performed significantly worse compared with other scores. The discriminative ranking of the scores was the same for the National Institute of Neurological Disorders and Stroke, and Safe Implementation of Thrombolysis in Stroke definitions, with SEDAN performing best, GRASPS second, and SPAN-100 worst. CONCLUSIONS: SPAN-100 had the worst predictive power, and SEDAN constantly the highest predictive power. However, none of the scores had better than moderate performance.

[Imaging of brain changes in chronic pain]. / Krooniseen kipuun liittyvien aivomuutosten kuvantaminen.

Modern methods of brain imaging have enabled objective measurements of functional and structural brain changes associated with chronic pain conditions. According to recent investigations, chronic pain is not only associated with abnormally strong or prolonged activity of regions processing acute pain, but also with activation of brain networks that are characteristic for each pain state, changes in cortical remodeling, as well as local reduction of grey matter in several regions of the brain. Brain changes associated with chronic pain facilitate the understanding of mechanisms of various chronic pain conditions.

Simulation-based feasibility study of monitoring of intracerebral hemorrhages and detection of secondary hemorrhages using electrical impedance tomography.

Purpose: We present a simulation-based feasibility study of electrical impedance tomography (EIT) for continuous bedside monitoring of intracerebral hemorrhages (ICH) and detection of secondary hemorrhages. Approach: We simulated EIT measurements for six different hemorrhage sizes at two different hemorrhage locations using an anatomically detailed computational head model. Using this dataset, we test the ICH monitoring and detection performance of our tailor-made, patient-specific stroke-monitoring algorithm that utilizes a novel combination of nonlinear region-of-interest difference imaging, parallel level sets regularization and a prior-conditioned least squares algorithm. We compare the results of our algorithm to the results of two reference algorithms, a total variation regularized absolute imaging algorithm and a linear difference imaging algorithm. Results: The tailor-made stroke-monitoring algorithm is capable of indicating smaller changes in the simulated hemorrhages than either of the reference algorithms, indicating better monitoring and detection performance. Conclusions: Our simulation results from the anatomically detailed head model indicate that EIT equipped with a patient-specific stroke-monitoring algorithm is a promising technology for the unmet clinical need of having a technology for continuous bedside monitoring of brain status of acute stroke patients.

Symptomatic intracranial hemorrhage after stroke thrombolysis: the SEDAN score.

OBJECTIVE: A study was undertaken to develop a score for assessing risk for symptomatic intracranial hemorrhage (sICH) in ischemic stroke patients treated with intravenous (IV) thrombolysis. METHODS: The derivation cohort comprised 974 ischemic stroke patients treated (1995-2008) with IV thrombolysis at the Helsinki University Central Hospital. The predictive value of parameters associated with sICH (European Cooperative Acute Stroke Study II) was evaluated, and we developed our score according to the magnitude of logistic regression coefficients. We calculated absolute risks and likelihood ratios of sICH per increasing score points. The score was validated in 828 patients from 3 Swiss cohorts (Lausanne, Basel, and Geneva). Performance of the score was tested with area under a receiver operating characteristic curve (AUC-ROC). RESULTS: Our SEDAN score (0 to 6 points) comprises baseline blood Sugar (glucose; 8.1-12.0 mmol/l [145-216 mg/dl] = 1; >12.0 mmol/l [>216 mg/dl] = 2), Early infarct signs (yes = 1) and (hyper)Dense cerebral artery sign (yes = 1) on admission computed tomography scan, Age (>75 years = 1), and NIH Stroke Scale on admission (≥10 = 1). Absolute risk for sICH in the derivation cohort was: 1.4%, 2.9%, 8.5%, 12.2%, 21.7%, and 33.3% for 0, 1, 2, 3, 4, and 5 score points, respectively. In the validation cohort, absolute risks were similar (1.0%, 3.5%, 5.1%, 9.2%, 16.9%, and 27.8%, respectively). AUC-ROC was 0.77 (0.71-0.83; p < 0.001). INTERPRETATION: Our SEDAN score reliably assessed risk for sICH in IV thrombolysis-treated patients with anterior- and posterior circulation ischemic stroke, and it can support clinical decision making in high-risk patients. External validation of the score supports its generalization.

Aberrant temporal and spatial brain activity during rest in patients with chronic pain.

In the absence of external stimuli, human hemodynamic brain activity displays slow intrinsic variations. To find out whether such fluctuations would be altered by persistent pain, we asked 10 patients with unrelenting chronic pain of different etiologies and 10 sex- and age-matched control subjects to rest with eyes open during 3-T functional MRI. Independent component analysis was used to identify functionally coupled brain networks. Time courses of an independent component comprising the insular cortices of both hemispheres showed stronger spectral power at 0.12 to 0.25 Hz in patients than in control subjects, with the largest difference at 0.16 Hz. A similar but weaker effect was seen in the anterior cingulate cortex, whereas activity of the precuneus and early visual cortex, used as a control site, did not differ between the groups. In the patient group, seed point-based correlation analysis revealed altered spatial connectivity between insulae and anterior cingulate cortex. The results imply both temporally and spatially aberrant activity of the affective pain-processing areas in patients suffering from chronic pain. The accentuated 0.12- to 0.25-Hz fluctuations in the patient group might be related to altered activity of the autonomic nervous system.

Association of admission plasma glucose level and cerebral computed tomographic perfusion deficit volumes.

INTRODUCTION: Hyperglycemia in acute ischemic stroke (AIS) is frequent and associated with worse outcome. Yet, strict glycemic control in AIS patients has failed to yield beneficial outcome. So far, the underlying pathophysiological mechanisms of admission hyperglycemia in AIS have remained not fully understood. We aimed to evaluate the yet equivocal association of hyperglycemia with computed tomographic perfusion (CTP) deficit volumes. PATIENTS AND METHODS: We included 832 consecutive AIS and transient ischemic attack (TIA) patients who underwent CTP as a part of screening for recanalization treatment (stroke code) between 3/2018 and 10/2020, from the prospective cohort of Helsinki Stroke Quality Registry. Associations of admission glucose level (AGL) and CTP deficit volumes, namely ischemic core, defined as relative cerebral blood flow <30%, and hypoperfusion lesions Time-to-maximum (Tmax) >6 s and Tmax >10s, as determined with RAPID® software, were analyzed with a linear regression model adjusted for age, sex, C-reactive protein, and time from symptom onset to imaging. RESULTS: AGL median was 6.8 mmol/L (interquartile range 5.9-8.0 mmol/L), and 222 (27%) patients were hyperglycemic (glucose >7.8 mmol/L) on admission. In non-diabetic patients (643 [77%]), AGL was significantly associated with volume of Tmax. >6 s (regression coefficient [RC] 4.8, 95% confidence interval [CI] 0.49-9.1), of Tmax >10s (RC 4.6, 95% CI 1.2-8.1), and of ischemic core (RC 2.6, 95% CI 0.64-4.6). No significant associations were shown in diabetic patients. CONCLUSION: Admission hyperglycemia appears to be associated with both larger volume of hypoperfusion lesions and of ischemic core in non-diabetic stroke code patients with AIS and TIA.

Comparative analysis of core and perfusion lesion volumes between commercially available computed tomography perfusion software.

Introduction: Computed tomography perfusion (CTP) imaging has become an important tool in evaluating acute recanalization treatment candidates. Large clinical trials have successfully used RAPID automated imaging analysis software for quantifying ischemic core and penumbra, yet other commercially available software vendors are also on the market. We evaluated the possible difference in ischemic core and perfusion lesion volumes and the agreement rate of target mismatch between OLEA, MIStar, and Syngo.Via versus RAPID software in acute recanalization treatment candidates. Patients and methods: All consecutive stroke-code patients with baseline CTP RAPID imaging at Helsinki University Hospital during 8/2018-9/2021 were included. Ischemic core was defined as cerebral blood flow <30% than the contralateral hemisphere and within the area of delay time (DT) >3s with MIStar. Perfusion lesion volume was defined as DT > 3 s (MIStar) and Tmax > 6 s with all other software. A perfusion mismatch ratio of ⩾1.8, a perfusion lesion volume of ⩾15 mL, and ischemic core <70 mL was defined as target mismatch. The mean pairwise differences of the core and perfusion lesion volumes between software were calculated using the Bland-Altman method and the agreement of target mismatch between software using the Pearson correlation. Results: A total of 1606 patients had RAPID perfusion maps, 1222 of which had MIStar, 596 patients had OLEA, and 349 patients had Syngo.Via perfusion maps available. Each software was compared with simultaneously analyzed RAPID software. MIStar showed the smallest core difference compared with RAPID (-2 mL, confidence interval (CI) from -26 to 22), followed by OLEA (2 mL, CI from -33 to 38). Perfusion lesion volume differed least with MIStar (4 mL, CI from -62 to 71) in comparison with RAPID, followed by Syngo.Via (6 mL, CI from -94 to 106). MIStar had the best agreement rate with target mismatch of RAPID followed by OLEA and Syngo.Via. Discussion and conclusion: Comparison of RAPID with three other automated imaging analysis software showed variance in ischemic core and perfusion lesion volumes and in target mismatch.

Activation in parietal operculum parallels motor recovery in stroke.

Motor recovery after stroke requires continuous interaction of motor and somatosensory systems. Integration of somatosensory feedback with motor programs is needed for the automatic adjustment of the speed, range, and strength of the movement. We recorded somatosensory evoked fields (SEFs) to tactile finger stimulation with whole-scalp magnetoencephalography in 23 acute stroke patients at 1 week, 1 month, and 3 months after stroke to investigate how deficits in the somatosensory cortical network affect motor recovery. SEFs were generated in the contralateral primary somatosensory cortex (SI) and in the bilateral parietal opercula (PO) in controls and patients. In the patients, SI amplitude or latency did not correlate with any of the functional outcome measures used. In contrast, the contralateral PO (cPO) amplitude to the affected hand stimuli correlated significantly with hand function in the acute phase and during recovery; the weaker the PO activation, the clumsier the hand was. At 1 and 3 months, enhancement of the cPO activation paralleled the improvement of the hand function. Whole-scalp magnetoencephalography measurements revealed that dysfunction of somatosensory cortical areas distant from the ischemic lesion may affect the motor recovery. Activation strength of the PO paralleled motor recovery after stroke, suggesting that the PO area is an important hub in mediating modulatory afferent input to motor cortex.

Probing modifications of cortical excitability during stroke recovery with navigated transcranial magnetic stimulation.

OBJECTIVE: To follow cortical excitability changes during recovery from stroke with navigated transcranial magnetic stimulation (nTMS), in particular, to characterize changes of short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF), to correlate them with recovery of upper extremity function, and to detect possible shifts of cortical hand representations. METHODS: Single and paired pulse nTMS were delivered to the hemisphere with infarction and to the hemisphere without infarction in 14 first-ever stroke patients at 1 (T1) and 3 months (T2) after stroke. Electromyographic responses to nTMS stimulation were recorded from the first dorsal interosseus muscles. nTMS was used to ensure an accurate coil repositioning in repeated measurements. Hand function recovery was clinically evaluated using the Action Research Arm Test (ARAT) and 9-hole peg test (9-HPT). RESULTS: SICI and ICF were modulated in both hemispheres during recovery. Inhibition in the hemisphere without infarction correlated significantly with the affected hand performance at T2; stronger disinhibition (poor inhibition) was associated with worse hand performance. Location of hand muscle representations was shifted in 3 well-recovered patients out of 14 patients at T2. CONCLUSIONS: In line with earlier studies, disinhibition in the hemisphere without infarction may be related to poor recovery of the affected hand. Usage of the affected hand during stroke recovery seems to influence these cortical excitability changes. nTMS is a valuable tool for tracking muscle cortical representation changes during brain reorganization.