A "Post-mortem" of COVID-19-associated stroke: a case-control study.

OBJECTIVES: To assess whether COVID-19 could be a concurrent factor in the genesis and/or worsening of stroke and to provide data on COVID-19 -associated stroke patients during the first pandemic wave and comparative data on COVID-19 negative stroke patients in the same period. MATERIALS AND METHODS: This is a retrospective, observational, case-control, single centre study, carried out in a General Hospital in northern Italy. Sixty-three consecutive stroke patients were included, COVID-19-associated stroke was classified as cases and non COVID-19-associated stroke as controls. RESULTS: A total of 19/63 (28.8%) had a COVID-19-associated stroke, 11 /63 (17.5%) were haemorrhagic and 52/63 (82.5%) ischaemic. COVID-19-associated strokes were more severe (p-value 0.019) and had a higher risk of severe disability and/or death (OR 3.79, CI 95%: 1.21-11.93, p-value 0.19). The COVID-19-associated stroke patients with onset during hospitalization for COVID-19 had a more severe stroke than patients with COVID-19 onset during hospitalization for stroke (p-value 0.019). CONCLUSION: Although no relationship was observed between the stroke aetiology and COVID-19, intriguingly, COVID-associated stroke turned out to be more severe and disabling. Hopefully, further studies will provide more data and help in the management of this emerging population.

Prevalence of temporomandibular disorder pain, jaw noises and oral behaviours in an adult Italian population sample.

To evaluate the prevalence of temporomandibular disorder pain (TMD-pain), temporomandibular joint (TMJ) noises, oral behaviours in an Italian adult population sample, their possible association with gender, oral behaviours, self-reported facial trauma and orthodontic treatment. Subjects older than 18 years were recruited from general population in public spaces during their daily life. A specific questionnaire was developed to collect data on TMD-pain, TMJ noises, oral behaviours, orthodontic treatment and facial trauma. A total of 4299 subjects were included in the study. The most common symptom in the sample was TMJ clicking (30.7%), followed by TMD-pain (16.3%) and TMJ crepitus (10.3%). Oral behaviours were reported in 29% of the sample; 43.6% of the sample reported a previous or ongoing orthodontic treatment. TMD-pain and TMJ clicking were significantly associated to gender, oral behaviours and a positive history of previous facial trauma. Crepitus was significantly associated to oral behaviours, facial trauma and higher age. Ongoing orthodontic treatment was significantly associated to TMD-pain and TMJ sounds. In a general Italian adult population sample, TMD-pain is associated to female gender and is less prevalent than TMJ clicking. TMDs are associated to trauma and oral behaviours.

Cortical ischemic lesion burden measured by DIR is related to carotid artery disease severity.

BACKGROUND: Over time, exposure to cerebrovascular risk factors and carotid artery disease may cause multiple asymptomatic brain cortical and subcortical microinfarcts, which are commonly found at brain autopsy. So far, lack of convenient neuroimaging tools limited the investigation of grey matter ischemic damage in vivo. We applied the Double Inversion Recovery (DIR) sequence to explore the impact of carotid artery disease on intracortical ischemic lesion load in vivo, taking into account the impact of demographic characteristics and vascular risk factors. METHODS: DIR was acquired in 62 patients with common cerebrovascular risk factors stratified in three groups according to carotid artery disease severity. Intracortical lesions scored on DIR (DIRlns) were classified by vascular territory, lobe and hemisphere. White matter hyperintensities (WMHs) volume was also quantified on Fluid Attenuated Inversion Recovery sequence (FLAIR). RESULTS: Among demographic characteristics and cerebrovascular risk variables explored, General Linear Model indicated that age and carotid artery disease were significantly associated to DIRlns. After correcting for age, DIRlns load was found to be significantly dependent on carotid artery stenosis severity (F(2, 58) = 5.56, p = 0.006). A linear positive correlation between DIRlns and WMHs was found after correcting for age (p = 0.003). CONCLUSIONS: Carotid disease severity is associated with DIRlns accrual. Microembolism and impaired cerebral hemodynamics may act as physiopathological mechanisms underlying cortical ischemic damage. The role of other factors, such as small vessel disease and the possible interaction with carotid disease, remains to be further explored.

Short-term Effects of a First-Line Treatment Including Counseling and Self-Management Strategies on Chronic TMD Muscle Pain and Awake Bruxism in Women.

AIMS: To evaluate the short-term effects of a standardized first-line noninvasive approach (FL-A) including counseling and self-management strategies on pain, masticatory muscle tenderness, and awake bruxism in women with chronic temporomandibular disorder myalgia (mTMD) and to test whether patients' trait anxiety predicted their response to treatment. METHODS: FL-A was administered to 14 women with chronic mTMD (mean age ± SD = 33.8 ± 11.1 years; 8 with Graded Chronic Pain Scale [GCPS] grade I and 6 with grade II). Its effects on facial pain, masticatory muscle tenderness, and spontaneous awake bruxism episodes were evaluated using questionnaires, surface electromyography, and quantitative sensory testing. General linear models were used to test FL-A efficacy after 1 (T1) and 2 (T2) months. RESULTS: FL-A reduced pain (from baseline [T0] to T2, P = .010), the frequency of awake bruxism episodes (T0 to T1, P = .024), and their intensity by about 30% (T0 to T1, P < .001). Pressure pain thresholds at the masticatory muscle locations increased significantly from T0 to T2 (P < .001). Patients' trait anxiety decreased significantly from T0 to T2 (P = .030). Trait anxiety measured at baseline was not correlated with relative changes in pain (T0 to T2, P = .248). CONCLUSION: In the short term, FL-A reduces facial pain, masticatory muscle tenderness, and awake bruxism in women with chronic mTMD with low disability. A conservative management strategy should be prioritized for the initial management of these patients.

Multiple Sclerosis Treatment in the COVID-19 Era: A Risk-Benefit Approach.

The COVID-19 pandemic poses an ongoing global challenge, and several risk factors make people with multiple sclerosis (pwMS) particularly susceptible to running a severe disease course. Although the literature does report numerous articles on the risk factors for severe COVID-19 and vaccination response in pwMS, there is a scarcity of reviews integrating both these aspects into strategies aimed at minimizing risks. The aim of this review is to describe the risk of vulnerable pwMS exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the issues related to the SARS-CoV-2 vaccine and to evidence possible future strategies in the clinical management of pwMS. The authors searched for papers on severe COVID-19 risk factors, SARS-CoV-2 vaccination and people with multiple sclerosis in support of this narrative literature review. We propose a multilevel strategy aimed at: the evaluation of risk factors for severe COVID-19 in people with multiple sclerosis, identifying the most appropriate vaccination schedule that is safe for people on disease-modifying drugs (DMDs) and a strict follow-up of high-risk people with multiple sclerosis to allow for the prompt administration of monoclonal antibodies to manage COVID-19 risks in this patient population.

The Impact of Highly Effective Treatment in Pediatric-Onset Multiple Sclerosis: A Case Series.

INTRODUCTION: Pediatric-onset multiple sclerosis (POMS) is characterized by high inflammatory disease activity. Our aim was to describe the treatment sequencing and report the impact highly effective disease-modifying treatment (HET) had on disease activity. MATERIALS AND METHODS: Five consecutive patients with POMS were administered HET following lower efficacy drug or as initial therapy. Data on treatment sequencing, relapses and MRIs were collected during the follow-up. RESULTS: Our patients had an average age of 13.8 years (range 9-17) at diagnosis and 13.4 years (range 9-16) at disease onset, and 2/5 (40%) POMS were female. The pre-treatment average annualized relapse rate was 1.6 (range 0.8-2.8), and the average follow-up length was 5 years (range 3-7). A total of 2/5 (40%) patients were stable on HET at initial therapy, and 3/5 (60%) required an escalation to more aggressive treatment, even if two of them had been put on HET as initial treatment. Four out of five patients (80%) had No Evidence of Disease Activity-3 status (NEDA-3) at an average follow-up of 3 years (range 2-5). CONCLUSION: It has been observed that in a recent time period all the cases had prompt diagnosis, early HET or escalation to HET with a good outcome in 80% of the cases.

Jaw muscle activity patterns in women with chronic TMD myalgia during standardized clenching and chewing tasks.

Objective: To examine jaw muscle activity of women with chronic temporomandibular myalgia (mTMD). It was hypothesized that mTMD patients had a different masticatory muscle activity, increased work during isometric clenching, and a reduced chewing frequency as compared to TMD-free subjects.Methods: The electromyographic (EMG) activity of temporalis anterior (TA) and masseter (MM) of 27 women with mTMD and 18 TMD-free women was recorded during clenching tasks and while chewing. EMG indices comparing the activity of paired jaw muscles were computed.Results: Women with TMD myalgia had greater muscular work than controls (p = 0.025). The activity of TA and MM were similar between right and left sides in both groups. mTMD patients had a greater activity of MM than TA (p = 0.028). No between-groups differences were found in chewing rate.Conclusion: Women with mTMD showed an abnormal recruitment of the jaw-closing muscles during functional tasks, which may predispose to further tissue injury.

Anodal transcranial direct current stimulation enhances procedural consolidation.

The primary motor cortex (M1) area recruitment enlarges while learning a finger tapping sequence. Also M1 excitability increases during procedural consolidation. Our aim was to investigate whether increasing M1 excitability by anodal transcranial DC stimulation (AtDCS) when procedural consolidation occurs was able to induce an early consolidation improvement. Forty-seven right-handed healthy participants were trained in a nine-element serial finger tapping task (SFTT) executed with the left hand. Random series blocks were interspersed with training series blocks. Anodal or sham tDCS was administered over the right M1 after the end of the training session. After stimulation, the motor skills of both trained and a new untrained sequential series blocks were tested again. For each block, performance was estimated as the median execution time of correct series. Early consolidation of the trained series, assessed by the performance difference between the first block after and the last block before stimulation normalized by the random, was enhanced by anodal and not by sham tDCS. Stimulation did not affect random series execution. No stimulation effect was found on the on-line learning of the trained and new untrained series. Our results suggest that AtDCS applied on M1 soon after training improves early consolidation of procedural learning. Our data highlight the importance of neuromodulation procedures for understanding learning processes and support their use in the motor rehabilitation setting, focusing on the timing of the application.

Oxidative Stress Related to Iron Metabolism in Relapsing Remitting Multiple Sclerosis Patients With Low Disability.

Oxidative status may play a role in chronic inflammation and neurodegeneration which are considered critical etiopathogenetic factors in Multiple Sclerosis (MS), both in the early phase of the disease and in the progressive one. The aim of this study is to explore oxidative status related to iron metabolism in peripheral blood of stable Relapsing-Remitting MS with low disability. We studied 60 Relapsing-Remitting MS patients (age 37.2 ± 9.06, EDSS median 1.0), and 40 healthy controls (age 40.3 ± 10.86). We measured total hydroperoxides (dROMs test) and Total Antioxidant Status (TAS), along with the iron metabolism biomarkers: Iron (Fe), ferritin (Ferr), transferrin (Tf), transferrin saturation (Tfsat), and ceruloplasmin (Cp) panel biomarkers [concentration (iCp) and enzymatic activity (eCp), copper (Cu), ceruloplasmin specific activity (eCp:iCp), copper to ceruloplasmin ratio (Cu:Cp), non-ceruloplasmin copper (nCp-Cu)]. We computed also the Cp:Tf ratio as an index of oxidative stress related to iron metabolism. We found lower TAS levels in MS patients than in healthy controls (CTRL) and normal reference level and higher dROMs and Cp:Tf ratio in MS than in healthy controls. Cp and Cu were higher in MS while biomarkers of iron metabolism were not different between patients and controls. Both in controls and MS, dROMs correlated with iCp (CTRL r = 0.821, p < 0.001; MS r = 0.775 p < 0.001) and eCp (CTRL r = 0.734, p < 0.001; MS r = 0.820 p < 0.001). Moreover, only in MS group iCp correlated negatively with Tfsat (r = -0.257, p = 0.047). Dividing MS patients in "untreated" group and "treated" group, we found a significant difference in Fe values [F(2, 97) = 10.136, p < 0.001]; in particular "MS untreated" showed higher mean values (mean = 114.5, SD = 39.37 µg/dL) than CTRL (mean 78.6, SD = 27.55 µg/dL p = 0.001) and "MS treated" (mean = 72.4, SD = 38.08 µg/dL; p < 0.001). Moreover, "MS untreated" showed significantly higher values of Cp:Tf (mean = 10.19, SD = 1.77∗10-2; p = 0.015), than CTRL (mean = 9.03, SD = 1.46 ∗10-2). These results suggest that chronic oxidative stress is relevant also in the remitting phase of the disease in patients with low disability and short disease duration. Therefore, treatment with antioxidants may be beneficial also in the early stage of the disease to preserve neuronal reserve.

Assessment of the Incremental Diagnostic Value of Florbetapir F 18 Imaging in Patients With Cognitive Impairment: The Incremental Diagnostic Value of Amyloid PET With [18F]-Florbetapir (INDIA-FBP) Study.

IMPORTANCE: Cerebral amyloidosis is a key abnormality in Alzheimer disease (AD) and can be detected in vivo with positron emission tomography (PET) ligands. Although amyloid PET has clearly demonstrated analytical validity, its clinical utility is debated. OBJECTIVE: To evaluate the incremental diagnostic value of amyloid PET with florbetapir F 18 in addition to the routine clinical diagnostic assessment of patients evaluated for cognitive impairment. DESIGN, SETTING, AND PARTICIPANTS: The Incremental Diagnostic Value of Amyloid PET With [18F]-Florbetapir (INDIA-FBP) Study is a multicenter study involving 18 AD evaluation units from eastern Lombardy, Northern Italy, 228 consecutive adults with cognitive impairment were evaluated for AD and other causes of cognitive decline, with a prescan diagnostic confidence of AD between 15% and 85%. Participants underwent routine clinical and instrumental diagnostic assessment. A prescan diagnosis was made, diagnostic confidence was estimated, and drug treatment was provided. At the time of this workup, an amyloid PET/computed tomographic scan was performed, and the result was communicated to physicians after workup completion. Physicians were asked to review the diagnosis, diagnostic confidence, and treatment after the scan. The study was conducted from August 5, 2013, to December 31, 2014. MAIN OUTCOMES AND MEASURES: Primary outcomes were prescan to postscan changes of diagnosis, diagnostic confidence, and treatment. RESULTS: Of the 228 participants, 107 (46%) were male; mean (SD) age was 70.5 (7) years. Diagnostic change occurred in 46 patients (79%) having both a previous diagnosis of AD and an amyloid-negative scan (P < .001) and in 16 (53%) of those with non-AD diagnoses and an amyloid-positive scan (P < .001). Diagnostic confidence in AD diagnosis increased by 15.2% in amyloid-positive (P < .001; effect size Cohen d = 1.04) and decreased by 29.9% in amyloid-negative (P < .001; d = -1.19) scans. Acetylcholinesterase inhibitors and memantine hydrochloride were introduced in 61 (65.6%) patients with positive scan results who had not previously received those drugs, and the use of the drugs was discontinued in 6 (33.3%) patients with negative scan results who were receiving those drugs (P < .001). CONCLUSIONS AND RELEVANCE: Amyloid PET in addition to routine assessment in patients with cognitive impairment has a significant effect on diagnosis, diagnostic confidence, and drug treatment. The effect on health outcomes, such as morbidity and mortality, remains to be assessed.

Lumbosacral multiradiculopathy responsive to antibiotic therapy: description of four patients with lumbar spondylosis and a superimposed Lyme disease.

Lyme disease is a diffuse zoonosis caused by spirochaetes of the Borrelia burgdorferi species complex. Neurological manifestations of the disease, involving central or peripheral nervous system, are common. This study describes four consecutive patients with an MRI-proven lumbosacral spondylosis, who complained of progressive worsening of symptoms in the last months in which serological evaluation suggested a superimposed B. Burgdorferi infection. Four patients, all from the Lazio region, were admitted to the Department of Neurology. Extensive laboratory studies and clinical, anamnestic and neurophysiological evaluation were performed in all cases. In all cases, anamnesis revealed a previous diagnosis of lumbosacral foraminal stenosis. Clinical and neurophysiological findings were consistent with a lumbosacral multiradiculopathy. Considering serological evaluation suggestive of a superimposed B. burgdorferi infection a proper antibiotic therapy was started. All cases showed a marked improvement of symptoms. Clinicians should be aware that in all cases of lumbosacral multiradiculopathy, even if a mechanical cause is documented, B. burgdorferi may be a simply treatable condition.

Social impairment of individuals suffering from different types of chronic orofacial pain.

BACKGROUND: The daily life of patients suffering from orofacial pain is considerably impaired as compared to healthy subjects. The aim of this study was to investigate the influence of different categories of orofacial pain on the habitual life of adult individuals. METHODS: Seven hundred eighty-one individuals with orofacial pain were recruited from an initial sample of 1,058 patients. All the individuals were allocated to groups according to their diagnosis: myofascial pain (group A, 676 subjects, 525 females and 151 males; mean age ± SD = 35.2 ± 12.6), migraine (group B, 39 subjects, 29 females and 10 males; mean age ± SD 36.0 ± 10.7), and both myofascial pain and migraine (group C, 66 subjects, 56 females and 10 males, mean age ± SD = 35.6 ± 10.8). Characteristic pain intensity (CPI), disability days (DD), disability score (DS), and graded chronic pain intensity (GCPS) were calculated according to Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) axis II. Depression and somatization (nonspecific physical symptoms) scores were also calculated. RESULTS: A significant association between groups and GCPS categories was found (p < 0.0001). Post hoc tests showed a significant difference between groups A and B and between A and C, but not between B and C. In group A, the most frequent GCPS score was grade II. The most frequent GCPS score in groups B and C was grade III, indicating a moderate limiting impairment. This score was more frequent in group B (41%) than in the other groups (group A = 20.6%, group C = 34.8%). GCPS grade IV was more frequent in group C (19.7%) than in the other groups. Group C had significantly higher scores for nonspecific physical symptoms than group A (p < 0.05). CONCLUSIONS: Myofascial pain and migraine sensibly affect the common daily life of adult individuals. The comorbidity of both conditions determines a major impairment.

Diffusion-weighted lesions after carotid artery stenting are associated with cognitive impairment.

The effect of carotid artery stenting (CAS) on cognitive function is still debated. Cerebral microembolism, detectable by post-procedural diffusion-weighted imaging (DWI) lesions, has been suggested to predispose to cognitive decline. Our study aimed at evaluating the effect of CAS on cognitive profile focusing on the potential role of cerebral microembolic lesions, taking into consideration the impact of factors potentially influencing cognitive status (demographic features, vascular risk profile, neuropsychological evaluation at baseline and magnetic resonance (MR) markers of brain structural damage). Thirty-seven patients with severe carotid artery stenosis were enrolled. Neurological assessment, neuropsychological evaluation and brain MR were performed the day before CAS (E0). Brain MR with DWI was repeated the day after CAS (E1), while neuropsychological evaluation was done after a 14-month median period (E2). Volumes of both white matter hyperintensities and whole brain were estimated at E0 on axial MR FLAIR and T1w-SE sequences, respectively. Unadjusted ANOVA analysis showed a significant CAS*DWI interaction for MMSE (F=7.154(32), p=.012). After adjusting for factors potentially influencing cognitive status CAS*DWI interaction was confirmed for MMSE (F=7.092(13), p=.020). Patients with DWI lesions showed a mean E2-E0 MMSE reduction of -3.1, while group without DWI lesions showed a mean E2-E0 MMSE of +1.1. Our study showed that peri-procedural brain microembolic load impacts negatively on cognitive functions, independently from the influence of patients-related variables.

Evaluation of the short-term effectiveness of education versus an occlusal splint for the treatment of myofascial pain of the jaw muscles.

BACKGROUND: The authors conducted a clinical trial to compare the effectiveness of an education program with that of an occlusal splint in treating myofascial pain of the jaw muscles across a short period. METHOD: The authors assigned 44 patients randomly to two treatment groups; 41 patients completed the study. The first group (four male, 19 female; mean [standard deviation {SD}] age, 31.4 [14.0] years) received information regarding the nature of temporomandibular disorder (TMD) and self-care measures, whereas the second group (five male, 13 female; mean [SD] age, 31.1 [8.8] years) received an occlusal splint. One of the authors evaluated each patient every three weeks during a three-month treatment period. Treatment outcomes included pain-free maximal mouth opening, spontaneous muscle pain, pain during chewing and headache. RESULTS: After three months, changes in spontaneous muscle pain differed significantly between the education and occlusal splint groups (P = .034; effect size = 0.33). Changes in pain-free maximal mouth opening did not differ significantly between groups (P = .528; effect size = 0.20). Changes of headache and pain on chewing did not differ significantly between groups (P ≥ .550, effect size ≤ 0.10). CONCLUSIONS: During a short period, education was slightly more effective than an occlusal splint delivered without education in reducing spontaneous muscle pain in patients with TMD. Pain-free mouth opening, headache and pain during chewing were not significantly different between the two treatments.

Transcranial magnetic stimulation studies in Alzheimer's disease.

Although motor deficits affect patients with Alzheimer's disease (AD) only at later stages, recent studies demonstrated that primary motor cortex is precociously affected by neuronal degeneration. It is conceivable that neuronal loss is compensated by reorganization of the neural circuitries, thereby maintaining motor performances in daily living. Effectively several transcranial magnetic stimulation (TMS) studies have demonstrated that cortical excitability is enhanced in AD and primary motor cortex presents functional reorganization. Although the best hypothesis for the pathogenesis of AD remains the degeneration of cholinergic neurons in specific regions of the basal forebrain, the application of specific TMS protocols pointed out a role of other neurotransmitters. The present paper provides a perspective of the TMS techniques used to study neurophysiological aspects of AD showing also that, based on different patterns of cortical excitability, TMS may be useful in discriminating between physiological and pathological brain aging at least at the group level. Moreover repetitive TMS might become useful in the rehabilitation of AD patients. Finally integrated approaches utilizing TMS together with others neuro-physiological techniques, such as high-density EEG, and structural and functional imaging as well as biological markers are proposed as promising tool for large-scale, low-cost, and noninvasive evaluation of at-risk populations.