Systematic review of cases of acute myelitis in individuals with COVID-19.

BACKGROUND AND PURPOSE: An incremental number of cases of acute transverse myelitis (ATM) in individuals with ongoing or recent coronavirus disease 2019 (COVID-19) have been reported. METHODS: A systematic review was performed of cases of ATM described in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by screening both articles published and in preprint. RESULTS: Twenty cases were identified. There was a slight male predominance (60.0%) and the median age was 56 years. Neurological symptoms first manifested after a mean of 10.3 days from the first onset of classical, mostly respiratory symptoms of COVID-19. Overall, COVID-19 severity was relatively mild. Polymerase chain reaction of cerebrospinal fluid for SARS-CoV-2 was negative in all 14 cases examined. Cerebrospinal fluid findings reflected an inflammatory process in most instances (77.8%). Aquaporin-4 and myelin oligodendrocyte protein antibodies in serum (tested in 10 and nine cases, respectively) were negative. On magnetic resonance imaging, the spinal cord lesions spanned a mean of 9.8 vertebral segments, necrotic-hemorrhagic transformation was present in three cases and two individuals had additional acute motor axonal neuropathy. More than half of the patients received a second immunotherapy regimen. Over a limited follow-up period of several weeks, 90% of individuals recovered either partially or near fully. CONCLUSION: Although causality cannot readily be inferred, it is possible that cases of ATM occur para- or post-infectiously in COVID-19. All identified reports are anecdotal and case descriptions are heterogeneous. Whether the condition and the observed radiological characteristics are specific to SARS-CoV-2 infection needs to be clarified.

Connectivity Analysis during Rubber Hand Illusion-A Pilot TMS-EEG Study in a Patient with SCI.

Background: Bodily self-perception is an important concept for several neurological disorders, including spinal cord injury (SCI). Changing one's bodily self-perception, e.g., via rubber hand illusion (RHI), induces alterations of bottom-up and top-down pathways and with this the connectivity between involved brain areas. We aim to examine whether (1) this process can be manipulated by changing cortical excitability, (2) connectivity between relevant brain areas differ when the RHI cannot be evoked, and (3) how this projection differs in a patient with SCI. Method: We applied RHI and facilitatory theta burst stimulation (TBS) on the right primary somatosensory cortex (S1) of 18 healthy participants and one patient with incomplete, cervical SCI. During RHI, we recorded high-density electroencephalography (HD-EEG) and extracted directed and nondirected connectivity measures. Results: There is no difference in connectivity between sham and real TBS or in the effectivity of RHI. We observed a higher laterality in the patient, i.e., higher connectivity of the right and lower of the left hemisphere. Besides this, connectivity patterns do not differ between healthy participants and the patient. Conclusion: This connectivity pattern might represent a neuroplastic response in the attempt to overcome the functional impairment of the patient resulting in a similar overall connectivity pattern to the healthy participants, yet with a higher sensitivity towards RHI and a higher laterality. The cortico-cortical communication was not altered depending on whether the illusion was provoked or not; hence, the perceptory illusion could not be observed in the EEG analysis.

Actigraphy in brain-injured patients - A valid measurement for assessing circadian rhythms?

BACKGROUND: Actigraphy has received increasing attention in classifying rest-activity cycles. However, in patients with disorders of consciousness (DOC), actigraphy data may be considerably confounded by passive movements, such as nursing activities and therapies. Consequently, this study verified whether circadian rhythmicity is (still) visible in actigraphy data from patients with DOC after correcting for passive movements. METHODS: Wrist actigraphy was recorded over 7-8 consecutive days in patients with DOC (diagnosed with unresponsive wakefulness syndrome [UWS; n = 19] and [exit] minimally conscious state [MCS/EMCS; n = 11]). The presence and actions of clinical and research staff as well as visitors were indicated using a tablet in the patient's room. Following removal and interpolation of passive movements, non-parametric rank-based tests were computed to identify differences between circadian parameters of uncorrected and corrected actigraphy data. RESULTS: Uncorrected actigraphy data overestimated the interdaily stability and intradaily variability of patients' activity and underestimated the deviation from a circadian 24-h rhythm. Only 5/30 (17%) patients deviated more than 1 h from 24 h in the uncorrected data, whereas this was the case for 17/30 (57%) patients in the corrected data. When contrasting diagnoses based on the corrected dataset, stronger circadian rhythms and higher activity levels were observed in MCS/EMCS as compared to UWS patients. Day-to-night differences in activity were evident for both patient groups. CONCLUSION: Our findings indicate that uncorrected actigraphy data overestimates the circadian rhythmicity of patients' activity, as nursing activities, therapies, and visits by relatives follow a circadian pattern itself. Therefore, we suggest correcting actigraphy data from patients with reduced mobility.

Influence of sports on cortical excitability in patients with spinal cord injury: a TMS study.

Background: Patients with spinal cord injury (SCI) show abnormal cortical excitability that might be caused by deafferentation. We hypothesize a reduced short-interval intracortical inhibition preceding movement in patients with SCI compared with healthy participants. In addition, we expect that neuroplasticity induced by different types of sports can modulate intracortical inhibition during movement preparation in patients with SCI. Methods: We used a reaction test and paired-pulse transcranial magnetic stimulation to record cortical excitability, assessed by measuring amplitudes of motor-evoked potentials in preparation of movement. The participants were grouped as patients with SCI practicing wheelchair dancing (n = 7), other sports (n = 6), no sports (n = 9), and healthy controls (n = 24). Results: There were neither significant differences between healthy participants and the patients nor between the different patient groups. A non-significant trend (p = .238), showed that patients engaged in sports have a stronger increase in cortical excitability compared with patients of the non-sportive group, while the patients in the other sports group expressed the highest increase in cortical excitability. Conclusion: The small sample sizes limit the statistical power of the study, but the trending effect warrants further investigation of different sports on the neuroplasticity in patients with SCI. It is not clear how neuroplastic changes impact the sensorimotor output of the affected extremities in a patient. This needs to be followed up in further studies with a greater sample size.

Visuomotor integration in early Alzheimer's disease: A TMS study.

BACKGROUND AND PURPOSE: Cortical visuomotor integration is altered in Alzheimer's disease (AD), even at an early stage of the disease. The aim of this study was to assess the connections between the primary visual (V1) and motor (M1) areas in patients with early AD using a paired-pulse, twin-coil transcranial magnetic stimulation (TMS) technique. METHODS: Visuomotor connections (VMCs) were assessed in 13 subjects with probable AD and 16 healthy control subjects. A conditioning stimulus over the V1 phosphene hotspot was followed at interstimulus intervals (ISIs) of 18 and 40 ms by a test stimulus over M1, to elicit motor evoked potentials (MEPs) in the contralateral first dorsal interosseous muscle. RESULTS: Significant effects due to VMCs, consisting of enhanced MEP suppression at ISI of 18 and 40 ms, were observed in the AD patients. Patients with AD showed an excessive inhibitory response of the right M1 to inputs travelling from V1 at given ISIs. CONCLUSIONS: This study provides neurophysiological evidence of altered functional connectivity between visual and motor areas in AD.

Spontaneous spinal cord infarction in Austria: a two-center comparative study.

Background: Spinal cord infarction (SCI) is a neurological emergency associated with high rates of persistent neurological deficits. Knowledge about this rare but potentially treatable condition needs to be expanded. Objective: To describe the characteristics of spontaneous SCI in a large retrospective series of patients treated at two tertiary care centers in Austria. Methods: We performed a descriptive and comparative analysis of spontaneous SCI treated at the University Hospitals of Salzburg and Graz between the years 2000 and 2020. The analysis included pre- and in-hospital procedures, clinical presentation, etiology, diagnostic certainty, reperfusion therapy, and functional outcome at discharge. Results: We identified 88 cases, 61% were ascertained in the second half of the study period. The median age was 65.5 years [interquartile range (IQR) = 56-74], 51.1% were women. Anterior spinal artery infarction was the predominant syndrome (82.9%). Demographics, vascular comorbidities, and clinical presentation did not differ between the centers. The most frequent etiology and level of diagnostic certainty were distinct, with atherosclerosis (50%) and definite SCI (42%), and unknown (52.5%) and probable SCI (60%) as front runners in Salzburg and Graz, respectively. Patients arrived after a median of 258.5 min (IQR = 110-528) at the emergency room. The first magnetic resonance imaging (MRI) of the spinal cord was performed after a median of 148 min (IQR = 90-312) from admission and was diagnostic for SCI in 45%. Two patients received intravenous thrombolysis (2.2%). The outcome was poor in 37/77 (48%). Conclusion: Demographics, clinical syndromes, and quality benchmarks for spontaneous SCI were consistent at two Austrian tertiary care centers. Our findings provide the foundation for establishing standards for pre- and in-hospital care to improve outcomes.

Narrative Review: Quantitative EEG in Disorders of Consciousness.

In this narrative review, we focus on the role of quantitative EEG technology in the diagnosis and prognosis of patients with unresponsive wakefulness syndrome and minimally conscious state. This paper is divided into two main parts, i.e., diagnosis and prognosis, each consisting of three subsections, namely, (i) resting-state EEG, including spectral power, functional connectivity, dynamic functional connectivity, graph theory, microstates and nonlinear measurements, (ii) sleep patterns, including rapid eye movement (REM) sleep, slow-wave sleep and sleep spindles and (iii) evoked potentials, including the P300, mismatch negativity, the N100, the N400 late positive component and others. Finally, we summarize our findings and conclude that QEEG is a useful tool when it comes to defining the diagnosis and prognosis of DOC patients.

Cholinergic neurotransmission and olfactory function in obstructive sleep apnea syndrome: a TMS study.

BACKGROUND/OBJECTIVE: Odor identification and discrimination are reduced in subjects with obstructive sleep apnea syndrome (OSAS), but the pathophysiology of the olfactory dysfunction in OSAS is still poorly understood. Experimental evidence suggests that olfactory impairment could be related to central cholinergic dysfunction. Short latency afferent inhibition (SAI) is a paired-pulse transcranial magnetic stimulation (TMS) protocol that gives the opportunity to test an inhibitory cholinergic circuit in the human cerebral motor cortex. The objective of the study was to assess the cholinergic function, as measured by SAI, in OSAS patients with olfactory impairment. METHODS: We applied SAI technique in 20 patients with OSAS and in 20 healthy control subjects; SAI values were correlated with the Sniffin' Sticks olfactory test results. RESULTS: SAI was reduced in OSAS patients when compared with control subjects. We also found a strong negative correlation between olfactory parameters and SAI. CONCLUSIONS: These findings suggest that cholinergic dysfunction is a robust determinant of hyposmia also in OSAS patients. Reduced SAI values and presence of olfactory impairment might indicate an increased risk of cognitive decline in patients with OSAS.

Delayed Hospital Presentation and Neuroimaging in Non-surgical Spinal Cord Infarction.

BACKGROUND: Lack of timely recognition and neuroimaging may be a barrier to reperfusion efforts in acute spinal cord infarction. METHODS: We performed a retrospective study of patients diagnosed with acute non-surgical spinal cord infarction at our tertiary academic center from 2001 to 2015. We studied parameters associated with time from symptom onset to initial hospital presentation and magnetic resonance imaging (MRI) of the spinal cord. RESULTS: We identified 39 patients among whom anterior spinal artery syndrome was the most frequent presentation (87.2%) and atherosclerosis the most common etiology (56.4%). Nearly, half of the patients presented to the emergency department on the same day of symptom onset (48.7%) but only nine (23.1%) within the first 6 h. Average time from symptom onset to spinal cord MRI was 3.2 days. We could not identify clinical, radiological, or outcome patterns associated with early vs. delayed presentation and imaging. DISCUSSION: Our study found a time lag from symptom onset to hospital presentation and spinal cord MRI in patients with acute spinal cord infarction. These findings point at low clinical suspicion of spinal cord syndromes and limited recognition as a potentially treatable medical emergency.

Cortical afferent inhibition reflects cognitive impairment in obstructive sleep apnea syndrome: a TMS study.

OBJECTIVES: Patients with obstructive sleep apnea syndrome (OSAS) show neurocognitive impairment, but the exact mechanisms that cause cognitive dysfunctions remain unknown. The cholinergic system is known to play a key role in all attentional processes and cognitive functions. A transcranial magnetic stimulation (TMS) protocol may give direct information about the function of some cholinergic circuits in the human brain; this technique relies on short latency afferent inhibition (SAI) of the motor cortex. The objective of this exploratory study was to test the hypothesis that impaired cognitive performances in OSAS patients are associated with a dysfunction of the cholinergic system, as assessed by SAI. METHODS: We applied SAI technique in a group of 13 patients with OSAS and compared the data with those from a group of 13 age-matched healthy subjects. All the patients underwent a sleep study, an extensive neuropsychological evaluation, and TMS examination. RESULTS: Mean SAI was significantly reduced in our OSAS patients when compared with controls. The neuropsychological evaluation showed impairments in most cognitive areas in the OSAS patients. SAI values were strongly correlated with the neuropsychological test scores. CONCLUSIONS: These findings suggest that the cognitive deficits in OSAS may be, at least in part, secondary to alterations in cholinergic neurotransmission, presumably caused by nocturnal hypoxemia. TMS studies may shed light on the pathophysiological mechanisms of the cognitive disturbances in OSAS patients.

Enhancing sleep quality and memory in insomnia using instrumental sensorimotor rhythm conditioning.

EEG recordings over the sensorimotor cortex show a prominent oscillatory pattern in a frequency range between 12 and 15 Hz (sensorimotor rhythm, SMR) under quiet but alert wakefulness. This frequency range is also abundant during sleep, and overlaps with the sleep spindle frequency band. In the present pilot study we tested whether instrumental conditioning of SMR during wakefulness can enhance sleep and cognitive performance in insomnia. Twenty-four subjects with clinical symptoms of primary insomnia were tested in a counterbalanced within-subjects-design. Each patient participated in a SMR- as well as a sham-conditioning training block. Polysomnographic sleep recordings were scheduled before and after the training blocks. Results indicate a significant increase of 12-15 Hz activity over the course of ten SMR training sessions. Concomitantly, the number of awakenings decreased and slow-wave sleep as well as subjective sleep quality increased. Interestingly, SMR-training enhancement was also found to be associated with overnight memory consolidation and sleep spindle changes indicating a beneficial cognitive effect of the SMR training protocol for SMR "responders" (16 out of 24 participants). Although results are promising it has to be concluded that current results are of a preliminary nature and await further proof before SMR-training can be promoted as a non-pharmacological approach for improving sleep quality and memory performance.

Usability and potential of geostatistics for spatial discrimination of multiple sclerosis lesion patterns.

BACKGROUND AND PURPOSE: In multiple sclerosis (MS) the individual disease courses are very heterogeneous among patients and biomarkers for setting the diagnosis and the estimation of the prognosis for individual patients would be very helpful. For this purpose, we are developing a multidisciplinary method and workflow for the quantitative, spatial, and spatiotemporal analysis and characterization of MS lesion patterns from MRI with geostatistics. METHODS: We worked on a small data set involving three synthetic and three real-world MS lesion patterns, covering a wide range of possible MS lesion configurations. After brain normalization, MS lesions were extracted and the resulting binary 3-dimensional models of MS lesion patterns were subject to geostatistical indicator variography in three orthogonal directions. RESULTS: By applying geostatistical indicator variography, we were able to describe the 3-dimensional spatial structure of MS lesion patterns in a standardized manner. Fitting a model function to the empirical variograms, spatial characteristics of the MS lesion patterns could be expressed and quantified by two parameters. An orthogonal plot of these parameters enabled a well-arranged comparison of the involved MS lesion patterns. CONCLUSIONS: This method in development is a promising candidate to complement standard image-based statistics by incorporating spatial quantification. The work flow is generic and not limited to analyzing MS lesion patterns. It can be completely automated for the screening of radiological archives.

Modulation of motor cortex excitability by different levels of whole-hand afferent electrical stimulation.

OBJECTIVE: In a previous transcranial magnetic stimulation (TMS) study we demonstrated that suprathreshold mesh-glove (MG) whole-hand stimulation elicits lasting changes in motor cortical excitability. Currently, there is no consensus with regard to the optimal parameters for the induction of sensorimotor cortical plasticity using peripheral electrical stimulation. Thus, in the present study we explore the modulatory effects of MG stimulation at different stimulus intensities and different frequencies in order to identify an optimal stimulation protocol. METHODS: MG stimulation was performed on 12 healthy subjects in separate sessions at different stimulation levels: sub-sensory at 50 Hz, sensory at 50 Hz and motor at 2 Hz. To verify if stimulation at lower frequencies is less effective, an additional experiment at sensory level with 2 Hz was performed. TMS was used to assess motor threshold (MT), motor evoked potentials (MEPs) recruitment curve (RC), short latency intracortical inhibition (SICI) and intracortical facilitation (ICF) to paired-pulse TMS at baseline (T0), immediately after (T1) and 1h (T2) after 30 min of MG stimulation. F-wave studies were performed to assess spinal motoneuron excitability. RESULTS: MG stimulation at sub-sensory/50 Hz and sensory/2 Hz level determines no significant cortical excitability changes; at sensory/50 Hz level and at motor/2 Hz level we found decreased MT, increased MEP RC as well as reduced SICI and increased ICF at T1 and T2. CONCLUSIONS: MG stimulation at sensory/50 Hz and motor/2 Hz level induces similar long-lasting modulatory effects on motor cortical excitability. Both the strength of the corticospinal projections and the intracortical networks are influenced to the same extend. SIGNIFICANCE: The study provides further evidence that stimulation intensity and frequency can independently modulate motor cortical plasticity. The selection of optimal stimulation parameters has potentially important implications for the neurorehabilitation of patients after brain damage (e.g. stroke, traumatic brain injury) with hand motor deficits.

Current endovascular treatment of acute stroke and future aspects.

Acute ischemic stroke remains a condition of high morbidity and mortality. Until now, the only established therapy has been intravenous (IV) tissue-type plasminogen activator (tPA). Only 3-10% of patients with acute ischemic stroke receive this treatment. On the basis of data from part 3 of the European Collaborative Acute Stroke Study (ECASS III), the time window for beneficial treatment of ischemic stroke with IV tPA has been extended from 3 to 4.5h after the onset of stroke symptoms. Beyond that window of opportunity, and additionally to IV treatment, interventional stroke therapy has assumed an important role for the treatment of acute ischemic stroke. Currently, new promising pharmacological and mechanical treatment options are being established as routine procedures to achieve a further improved outcome for stroke patients.