Factors Related to the Progression of Clinically Isolated Syndrome to Multiple Sclerosis: A Retrospective Study in Lithuania.

Background and Objectives: Multiple sclerosis (MS) is a demyelinating disease which usually manifests as clinically isolated syndrome (CIS). Approximately 70% of patients with CIS progress to MS. Therefore, there is a pressing need to identify the most accurate predictive factors of CIS developing into MS, some of which could be a clear clinical phenotype of early MS as well as lesions in magnetic resonance imaging (MRI), pathological findings in cerebrospinal fluid (CSF) and evoked potentials (EP) tests. The problem is of outstanding importance since early MS diagnosis and treatment prevents long-term disability. The aim of our study is to analyze the factors that could influence the progression of CIS to MS. Materials and Methods: This study is a retrospective data analysis which included patients with their primary CIS diagnosis between 1st January 2015 and 1st January 2020. The prevalence and predictive value of clinical symptoms, MRI lesions, pathological CSF and EP findings were evaluated in accordance with the final diagnosis and compared between the sexes and age groups. Results: Out of 138 CIS patients, 49 (35.5%) patients progressed to MS. MS patients were more likely to have a diminished sense of vibration and proprioception (χ2 = 9.033, p = 0.003) as well as spinal cord MRI lesions (χ2 = 7.209, p = 0.007) in comparison with the non-MS group. Positive oligoclonal bands (OCBs) in CSF (χ2 = 34.859, p ≤ 0.001) and pathological brainstem auditory evoked potential (BAEP) test findings (χ2 = 10.924, p ≤ 0.001) were more prevalent in the MS group. Diminished sense of vibration and proprioception increased the risk for developing MS by 13 times (p = 0.028), whereas positive OCBs in CSF increased the risk by 100 times (p < 0.001). MS patients that were older than 50 years were more likely to exhibit positive Babinski's reflex (χ2 = 6.993, p = 0.03), decreased muscle strength (χ2 = 13.481, p = 0.001), ataxia (χ2 = 8.135, p = 0.017), and diminished sense of vibration and proprioception (χ2 = 7.918, p = 0.019) in comparison with both younger age groups. Conclusions: Diminished sense of vibration and proprioception, spinal cord MRI lesions, positive OCBs and pathological BAEP test findings were more common among patients that developed MS. Diminished sense of vibration and proprioception along with positive CSF OCBs are predictors of CIS progressing to MS. Older patients that develop MS have more symptoms in general, such as positive Babinski's reflex, decreased muscle strength, ataxia, and diminished sense of vibration and proprioception.

Response inhibition, set shifting, and complex executive function in patients with chronic lower back pain.

OBJECTIVE: The aim of our study was to evaluate how response inhibition, set shifting, and complex executive function (represented by risky decision-making) are altered in chronic lower back pain patients. MATERIALS AND METHODS: A total of 29 patients with chronic lower back pain (CLBP >6 months) aged 49-69 years and 30 healthy volunteers matched for age, gender, and education were enrolled in a case-control study. The study was conducted in the Departments of Neurology and Neurosurgery of Panevezys Regional Hospital, Lithuania. Pain was evaluated by the visual analog scale, Pakula Pain Questionnaire (Lithuanian analog of McGill Pain Questionnaire), and Fibromyalgia Tender Points Examination. A battery of neuropsychological tests used included Stroop Test Victoria version, Trail Making Test parts A and B, and Game of Dice Task (GDT). RESULTS: CLBP patients did not score significantly worse in any examined neuropsychological tests. Response Inhibition correlated inversely with number of tender points in CLBP patients. GDT performance showed no significant difference in net score (number of safe minus risky decisions). Unexpectedly, both groups favored risky decisions. CONCLUSIONS: We found no statistically significant difference in response inhibition, set shifting, or complex executive function between CLBP patients and healthy older adults. Moreover, a risky decision-making pattern found in the Lithuanian population may underscore the importance of cultural context when examining complex executive function. However, further studies are needed to prove this point.

Accuracy, Precision, Sensitivity, and Specificity of Noninvasive ICP Absolute Value Measurements.

An innovative absolute intracranial pressure (ICP) value measurement method has been validated by multicenter comparative clinical studies. The method is based on two-depth transcranial Doppler (TCD) technology and uses intracranial and extracranial segments of the ophthalmic artery as pressure sensors. The ophthalmic artery is used as a natural pair of "scales" that compares ICP with controlled pressure Pe, which is externally applied to the orbit. To balance the scales, ICP = Pe a special two-depth TCD device was used as a pressure balance indicator. The proposed method is the only noninvasive ICP measurement method that does not need patient-specific calibration.

Central retinal artery occlusion or retinal stroke: a neurosonologist's perspective.

In central retinal artery occlusion (CRAO) or retinal stroke, which is usually a vision-threatening condition, timely diagnosis is imperative to improve the chances of retinal preservation and to establish adequate secondary prevention measures. Even though retinal strokes have been traditionally assigned to the field of ophthalmology, while considering reperfusion therapy as the only way to avoid permanent vision loss, we suggest prompt evaluation of CRAO causes (primarily related to cardiovascular risk factors) performed by a well-organized interdisciplinary team (ophthalmologist and neurologist) in a neurovascular center with stroke expertise. Therefore, the most suitable adjunct method for rapidly diagnosing non-arteritic CRAO could be target transorbital ultrasound, performed by an experienced neurologist/neurosonologist in the stroke unit. Consequently, after an ophthalmological assessment, a final decision on thrombolytic therapy could be made. We accept that further research is obviously needed to determine whether transorbital ultrasound could replace ophthalmological investigation in the case of a suspected acute retinal stroke. We assert that retinal stroke requires interdisciplinary treatment in cooperation with neurologists and ophthalmologists, with an additive value for each to achieve the best results for the patient.

Reperfusion Therapies for Acute Ischemic Stroke in COVID-19 Patients: A Nationwide Multi-Center Study.

(1) Background: Acute ischemic stroke (AIS) is a possible complication of the coronavirus disease 2019 (COVID-19). Safety and efficacy data on reperfusion therapies (RT)-intravenous thrombolysis and endovascular treatment (EVT)-in stroke patients with COVID-19 is lacking. (2) Methods: We performed a retrospective nationwide multi-center pair-matched analysis of COVID-19 patients with AIS who underwent RT. We included adult COVID-19 patients with AIS who were treated with RT between 16 March 2020 and 30 June 2021. All subjects were paired with non-infected controls, matched for age, sex, stroke arterial vascular territory, and RT modality. The primary outcome measure was a favorable functional outcome defined by the modified Rankin scale (mRS 0-2). (3) Results: Thirty-one subjects and thirty-one matched controls were included. The median baseline National Institutes of Health Stroke Scale (NIHSS) score was higher in the COVID-19 group (16 vs. 12, p = 0.028). Rates of ischemic changes and symptomatic intracerebral hemorrhages did not differ significantly between the two groups at 24 h after RT. The median NIHSS 24 h after reperfusion remained significantly higher in the COVID-19 group (16 vs. 5, p = 0.003). MRS 0-2 at discharge was significantly less common in COVID-19 patients (22.6% vs. 51.8%, p = 0.018). Three-month mortality was 54.8% in the COVID-19 group versus 12.9% in controls (p = 0.001). (4) Conclusion: Reperfusion therapies on AIS in COVID-19 patients appear to be safe; however, functional outcomes are significantly worse, and 3-month mortality is higher.

Odor Identification and Regional Gray Matter Atrophy in Patients with Alzheimer's Disease, Parkinson's Disease, and the Healthy Elderly: A Cross-Sectional Structural MRI Study.

Multiple associations between impaired olfactory performance and regional cortical and deep gray matter atrophy have been reported in separate studies of patients with Alzheimer's disease (AD), Parkinson's disease (PD), and of the healthy elderly. We aimed to evaluate such possible associations among these populations in a unified manner. Twenty AD, twenty PD patients' and twenty healthy age- and sex-matched controls' odor identification performance was assessed with the Lithuanian adaptation of the Sniffin' Sticks 12 odor identification test, followed by morphometric gray matter analysis by MRI using FreeSurfer. AD patients had significantly lower cognitive performance than both PD patients and the healthy elderly, as evaluated with the Mini-Mental State Examination (MMSE). Odor identification performance was significantly worse in AD and PD patients compared with the healthy elderly; AD patients performed slightly worse than PD patients, but the difference was not statistically significant. Among patients with AD, worse odor identification performance was initially correlated with atrophy of multiple cortical and deep gray matter regions known to be involved in olfactory processing, however, only two measures-decreased thicknesses of the right medial and left lateral orbitofrontal cortices-remained significant after adjustment for possible confounders (age, MMSE score, and global cortical thickness). Among patients with PD and the healthy elderly we found no similar statistically significant correlations. Our findings support the key role of the orbitofrontal cortex in odor identification among patients with AD, and suggest that correlations between impaired odor identification performance and regional gray matter atrophy may be relatively more pronounced in AD rather than in PD.

Ultrasonic Assessment of the Medial Temporal Lobe Tissue Displacements in Alzheimer's Disease.

We aim to estimate brain tissue displacements in the medial temporal lobe (MTL) using backscattered ultrasound radiofrequency (US RF) signals, and to assess the diagnostic ability of brain tissue displacement parameters for the differentiation of patients with Alzheimer's disease (AD) from healthy controls (HC). Standard neuropsychological evaluation and transcranial sonography (TCS) for endogenous brain tissue motion data collection are performed for 20 patients with AD and for 20 age- and sex-matched HC in a prospective manner. Essential modifications of our previous method in US waveform parametrization, raising the confidence of micrometer-range displacement signals in the presence of noise, are done. Four logistic regression models are constructed, and receiver operating characteristic (ROC) curve analyses are applied. All models have cut-offs from 61.0 to 68.5% and separate AD patients from HC with a sensitivity of 89.5% and a specificity of 100%. The area under a ROC curve of predicted probability in all models is excellent (from 95.2 to 95.7%). According to our models, AD patients can be differentiated from HC by a sharper morphology of some individual MTL spatial point displacements (i.e., by spreading the spectrum of displacements to the high-end frequencies with higher variability across spatial points within a region), by lower displacement amplitude differences between adjacent spatial points (i.e., lower strain), and by a higher interaction of these attributes.

Diagnostic Ability of Radiofrequency Ultrasound in Parkinson's Disease Compared to Conventional Transcranial Sonography and Magnetic Resonance Imaging.

We aimed to estimate tissue displacements' parameters in midbrain using ultrasound radiofrequency (RF) signals and to compare diagnostic ability of this RF transcranial sonography (TCS)-based dynamic features of disease affected tissues with conventional TCS (cTCS) and magnetic resonance imaging (MRI) while differentiating patients with Parkinson's disease (PD) from healthy controls (HC). US tissue displacement waveform parametrization by RF TCS for endogenous brain tissue motion, standard neurological examination, cTCS and MRI data collection were performed for 20 PD patients and for 20 age- and sex-matched HC in a prospective manner. Three logistic regression models were constructed, and receiver operating characteristic (ROC) curve analyses were applied. The model constructed of RF TCS-based brain tissue displacement parameters-frequency of high-end spectra peak and root mean square-revealed presumably increased anisotropy in the midbrain and demonstrated rather good diagnostic ability in the PD evaluation, although it was not superior to that of the cTCS or MRI. Future studies are needed in order to establish the true place of RF TCS detected tissue displacement parameters for the evaluation of pathologically affected brain tissue.

Ultrasonography of the Vagus Nerve in the Diagnosis of Parkinson's Disease.

BACKGROUND: It is currently impossible to diagnose Parkinson's disease (PD) in the premotor phase even though at the time of motor symptom onset the number of already degenerated dopaminergic substantia nigra neurons is considerable. Degeneration of the dorsal nucleus of the vagus nerve (VN) has been reported early in the disease course, and it could lead to impaired function of the VN, resulting in certain nonmotor symptoms of PD. Therefore, we raised a hypothesis that the loss of VN neurons could result in a smaller diameter of the VN among PD patients. METHODS: 20 PD patients and 20 age- and gender-matched individuals without any neurodegenerative disease were enrolled in a pilot study. The diameters of the right and left VNs were measured using ultrasonography, their average was calculated, and the narrower VN diameter was noted separately. RESULTS: No difference was found between the PD and control groups neither in the average VN diameter (mean 1.17; 95% confidence interval (CI) 1.10-1.24 vs. 1.13; 1.07-1.18, mm; p=0.353) nor in the narrower VN diameter (mean 1.11; 95% confidence interval (CI) 1.02-1.20 vs. 1.07; 1.02-1.13, mm; p=0.421). The narrower VN diameter and the average VN diameter were not able to distinguish between PD patients and controls (area under curve (AUC) = 0.588, 95% CI = 0.408-0.767, and p=0.344; and AUC = 0.578, 95% CI = 0.396-0.759, and p=0.402). CONCLUSIONS: To conclude, no differences were found in VN diameter between the PD and control groups. Therefore, our data do not support the hypothesis that PD could be associated with a smaller diameter of the VN.

Diagnostic Ability of Structural Transcranial Sonography in Patients with Alzheimer's Disease.

The aim of this study was to assess the diagnostic ability of transcranial sonography (TCS) for the evaluation of the medial temporal lobe (MTL) in Alzheimer's disease (AD). Standard neuropsychological evaluation, TCS and 1.5 T MRI were performed for 20 patients with AD and for 20 age- and sex-matched healthy controls in a prospective manner. Measurements of the size of the third ventricle and heights of the MTL (A) and the choroidal fissure (B) were performed twice on each side by two independent neurosonologists for all participants. On MRI, both conventional and volumetric analyses of the third ventricle and hippocampus were performed. Receiver operating characteristic (ROC) curves analyses were applied. Height of the MTL on TCS had sensitivities of 73.7% (right)/63.2%(left) and specificities of 65% (right)/65-70% (left) Area under a curve (AUC) 75.4-77.2% (right), 60.4-67.8% (left)) for AD. A/B ratio on TCS had sensitivities of 73.7% (right)/57.9% (left) and specificities of 70.0% (right)/55.0% (left) (AUC 73.3% (right), 60.4% (left)) by the experienced neurosonologist, and sensitivities of 78.9% (right and left) and specificities of 60.0% (right)/65.0% (left) (AUC 77.8-80.0%) by the inexperienced neurosonologist for AD. On MRI, linear measurement of the hippocampus and parahippocampal gyrus height had sensitivities of 84.2% (right)/89.5% (left) and specificities of 80.0% (right)/85% (left) (AUC 86.1-92.9%) for AD. Hippocampal volume had sensitivities of 70% (right and left) and specificities of 75% (right)/80% (left) (AUC 77.5-78%) for AD. Atrophy of the right MTL in AD could be detected on TCS with a good diagnostic ability, however MRI performed better on the left.

Quantification of Endogenous Brain Tissue Displacement Imaging by Radiofrequency Ultrasound.

The purpose of this paper is a quantification of displacement parameters used in the imaging of brain tissue endogenous motion using ultrasonic radiofrequency (RF) signals. In a preclinical study, an ultrasonic diagnostic system with RF output was equipped with dedicated signal processing software and subject head-ultrasonic transducer stabilization. This allowed the use of RF scanning frames for the calculation of micrometer-range displacements, excluding sonographer-induced motions. Analysis of quantitative displacement estimates in dynamical phantom experiments showed that displacements of 55 µm down to 2 µm were quantified as confident according to Pearson correlation between signal fragments (minimum p ≤ 0.001). The same algorithm and scanning hardware were used in experiments and clinical imaging which allows translating phantom results to Alzheimer's disease patients and healthy elderly subjects as examples. The confident quantitative displacement waveforms of six in vivo heart-cycle episodes ranged from 8 µm up to 263 µm (Pearson correlation p ≤ 0.01). Displacement time sequences showed promising possibilities to evaluate the morphology of endogenous displacement signals at each point of the scanning plane, while displacement maps-regional distribution of displacement parameters-were essential for tissue characterization.

Graphical and statistical analyses of the oculocardiac reflex during a non-invasive intracranial pressure measurement.

PURPOSE: This study aimed to examine the incidence of the oculocardiac reflex during a non-invasive intracranial pressure measurement when gradual external pressure was applied to the orbital tissues and eye. METHODS: Patients (n = 101) and healthy volunteers (n = 56) aged 20-75 years who underwent a non-invasive intracranial pressure measurement were included in this retrospective oculocardiac reflex analysis. Prespecified thresholds greater than a 10% or 20% decrease in the heart rate from baseline were used to determine the incidence of the oculocardiac reflex. RESULTS: None of the subjects had a greater than 20% decrease in heart rate from baseline. Four subjects had a greater than 10% decrease in heart rate from baseline, representing 0.9% of the total pressure steps. Three of these subjects were healthy volunteers, and one was a glaucoma patient. CONCLUSION: The incidence of the oculocardiac reflex during a non-invasive intracranial pressure measurement procedure was very low and not associated with any clinically relevant effects.

Neurosyphilis manifesting as spinal transverse myelitis.

Spinal myelitis caused by neurosyphilis is an extremely rare disease, and there are only few visual examples of magnetic resonance imaging scans. We present a clinical case of neurosyphilis, which is of great importance concerning diagnostic, differential diagnosis, and tactics of management. A patient complaining of progressive legs weakness, numbness, and shooting-like pain in the legs as well as pelvic dysfunction was admitted to the hospital. Neurological examination revealed spinal cord lesion symptoms: legs weakness, impairment of superficial and deep sensation together with pathological symptoms in the legs. Hernia of intervertebral disc or tumor was suspected, and myelography with computed tomography of the spine was performed. No pathological findings were observed. More precise examination of the patient (a small scar in the genitals and condylomata lata in anal region were noticed) pointed to possible syphilis-induced spinal cord lesion. Serologic syphilis diagnostic tests (Treponema pallidum hemagglutination assay, reagin plasma response, serum enzyme-linked immunosorbent assay) and cerebrospinal fluid tests (general cerebrospinal fluid test and Venereal Disease Research Laboratory test) confirmed the diagnosis of neurosyphilis. Spinal cord lesion determined by magnetic resonance imaging was evaluated as spinal syphilis or syphilis-induced myelitis. Conventional treatment showed a partial effect.

Improved diagnostic value of a TCD-based non-invasive ICP measurement method compared with the sonographic ONSD method for detecting elevated intracranial pressure.

OBJECTIVES: To compare the diagnostic reliability of optic nerve sheath diameter (ONSD) ultrasonography with a transcranial Doppler (TCD)-based absolute intracranial pressure (ICP) value measurement method for detection of elevated ICP in neurological patients. The ONSD method has been only tested previously on neurosurgical patients. METHODS: A prospective clinical study of a non-invasive ICP estimation method based on ONSD correlation with ICP and an absolute ICP value measurement method based on a two-depth TCD technology has recruited 108 neurological patients. Ninety-two of these patients have been enrolled in the final analysis of the diagnostic reliability of ONSD ultrasonography and 85 patients using the absolute ICP value measurement method. All non-invasive ICP measurements were compared with 'Gold Standard' invasive cerebrospinal fluid (CSF) pressure measurements obtained by lumbar puncture. Receiver-operating characteristic (ROC) analysis has been used to investigate the diagnostic value of these two methods. RESULTS: The diagnostic sensitivity, specificity, and the area under the ROC curve (AUC) of the ONSD method for detecting elevated intracranial pressure (ICP >14·7 mmHg) were calculated using a cutoff point of ONSD at 5·0 mm and found to be 37·0%, 58·5%, and 0·57, respectively. The diagnostic sensitivity, specificity, and AUC for the non-invasive absolute ICP measurement method were calculated at the same ICP cutoff point of 14·7 mmHg and were determined to be 68·0%, 84·3%, and 0·87, respectively. CONCLUSIONS: The non-invasive ICP measurement method based on two-depth TCD technology has a better diagnostic reliability on neurological patients than the ONSD method when expressed by the sensitivity and specificity for detecting elevated ICP >14·7 mmHg.