SARS-CoV-2 pathophysiology and assessment of coronaviruses in CNS diseases with a focus on therapeutic targets.

The novel Coronavirus disease of 2019 (nCOV-19) is a viral outbreak noted first in Wuhan, China. This disease is caused by Severe Acute Respiratory Syndrome (SARS) Coronavirus (CoV)-2. In the past, other members of the coronavirus family, such as SARS and Middle East Respiratory Syndrome (MERS), have made an impact in China and the Arabian peninsula respectively. Both SARS and COVID-19 share similar symptoms such as fever, cough, and difficulty in breathing that can become fatal in later stages. However, SARS and MERS infections were epidemic diseases constrained to limited regions. By March 2020 the SARS-CoV-2 had spread across the globe and on March 11th, 2020 the World Health Organization (WHO) declared COVID-19 as pandemic disease. In severe SARS-CoV-2 infection, many patients succumbed to pneumonia. Higher rates of deaths were seen in older patients who had co-morbidities such as diabetes mellitus, hypertension, cardiovascular disease (CVD), and dementia. In this review paper, we discuss the effect of SARS-CoV-2 on CNS diseases, such as Alzheimer's-like dementia, and diabetes mellitus. We also focus on the virus genome, pathophysiology, theranostics, and autophagy mechanisms. We will assess the multiorgan failure reported in advanced stages of SARS-CoV-2 infection. Our paper will provide mechanistic clues and therapeutic targets for physicians and investigators to combat COVID-19.

Orthotic management of instability of the knee related to neuromuscular and central nervous system disorders: qualitative interview study of patient perspectives.

OBJECTIVES: Adults with knee instability related to neuromuscular disorders or central nervous conditions often experience mobility problems and rely on orthoses to improve function and mobility. Patient views of device effectiveness and acceptability are underexplored. Our study aimed to elicit device users' perspectives regarding fitting, acceptability, effectiveness and use of orthoses, and identify important treatment outcomes. DESIGN: Qualitative descriptive study using in-depth semistructured interviews. Interview transcriptions were coded and thematically analysed, using 'Framework'. SETTING AND PARTICIPANTS: A purposive sample of 24 adult users of orthotic devices. Nineteen patients were recruited across three National Health Service sites, and five people through charities/patient support groups in England. Half of the participants had been diagnosed with poliomyelitis, and the remainder with multiple sclerosis, Charcot-Marie-Tooth disease, spinal injury or spina bifida, and stroke. The median age of participants was 64.5 years (range 36-80 years). RESULTS: Patients' medical condition impacted significantly on daily life. Participants relied on orthotic devices to enable engagement in daily activities. Patient goals for mobility were linked to individual circumstances. Desired treatment outcomes included reduction in pain, trips and falls, with improved balance and stability. Effectiveness, reliability, comfort and durability were the most valued features of orthoses and associated with reported use. Obtaining suitable footwear alongside orthotic devices was a significant concern. Time pressures during device fitting were viewed negatively. CONCLUSIONS: Orthotic devices for knee instability play a crucial role in promoting, maintaining and enhancing physical and psychological health and well-being, enabling patients to work, engage in family life and enjoy social activities. Future research should consider how best to measure the impact of orthotic devices on patient quality of life and daily functioning outside the clinic setting, as well as device use and any adverse effects. TRIAL REGISTRATION NUMBER: This qualitative study was retrospectively registered as Current Controlled Trials ISRCTN65240228.

The pediatric version of the eating assessment tool-10 has discriminant ability to detect aspiration in children with neurological impairments.

BACKGROUND: The aim of this study was to determine the ability of the Pediatric version of the Eating Assessment Tool-10 (PEDI-EAT-10) to detect aspiration in children with neurological impairments. METHODS: Two hundred and fifty-four children were included. Swallowing function was imaged with videofluoroscopic swallowing study (VFSS). The penetration and aspiration scale (PAS) was used to determine the penetration and aspiration severity. Parents completed the PEDI-EAT-10, which is a 10 item, reliable, and valid dysphagia symptom specific outcome instrument. KEY RESULTS: The mean age of children was 59.91 ± 55.33 months (min = 18, max = 315), of which 52.8% were male. The mean PEDI-EAT-10 of children with airway aspiration (PAS > 5) was 22.32 ± 10.73 (min = 0, max = 40) and the mean PEDI-EAT-10 of children who did not have aspiration (PAS < 6) was 12.35 ± 8.64 (min = 0, max = 40). A linear correlation was found between PEDI-EAT-10 and PAS scores of children (r = 0.41, P < 0.001). The sensitivity of a PEDI-EAT-10 score greater than 12 in predicting aspiration was 77% and the specificity was 54%. A PEDI-EAT-10 score greater than 12 has a positive predictive value of 69% and a negative predictive value of 64%. CONCLUSIONS AND INFERENCES: The PEDI-EAT-10 could be used to detect unsafe airway issues to identify and refer children for further instrumental swallowing evaluation.

Orthotic management of instability of the knee related to neuromuscular and central nervous system disorders: systematic review, qualitative study, survey and costing analysis.

BACKGROUND: Patients who have knee instability that is associated with neuromuscular disease (NMD) and central nervous system (CNS) conditions can be treated using orthoses, such as knee-ankle-foot orthoses (KAFOs). OBJECTIVES: To assess existing evidence on the effectiveness of orthoses; patient perspectives; types of orthotic devices prescribed in the UK NHS; and associated costs. METHODS: Qualitative study of views of orthoses users - a qualitative in-depth interview study was undertaken. Data were analysed for thematic content. A coding scheme was developed and an inductive approach was used to identify themes. Systematic review - 18 databases were searched up to November 2014: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, Cumulative Index to Nursing and Allied Health, EMBASE, PASCAL, Scopus, Science Citation Index, BIOSIS Previews, Physiotherapy Evidence Database, Recal Legacy, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Health Technology Assessment database, Cochrane Central Register of Controlled Trials, Conference Proceedings Citation Index: Science, Health Management Consortium, ClinicalTrials.gov, International Clinical Trials Registry Platform and National Technical Information Service. Studies of adults using an orthosis for instability of the knee related to NMD or a CNS disorder were included. Data were extracted and quality was assessed by two researchers. Narrative synthesis was undertaken. Survey and costing analysis - a web survey of orthotists, physiotherapists and rehabilitation medicine physicians was undertaken. Telephone interviews with orthotists informed a costing analysis. RESULTS: Qualitative study - a total of 24 people participated. Potential for engagement in daily activities was of vital importance to patients; the extent to which their device enabled this was the yardstick by which it was measured. Patients' prime desired outcome was a reduction in pain, falls or trips, with improved balance and stability. Effectiveness, reliability, comfort and durability were the most valued features of orthoses. Many expressed frustration with perceived deficiencies in service provision relating to appointment and administrative systems and referral pathways. Systematic review - a total of 21 studies (478 participants) were included of people who had post-polio syndrome, inclusion body myositis, were post stroke or had spinal cord injury. The studies evaluated KAFOs (mainly carbon fibre), stance control KAFO and hip KAFOs. All of the studies were at risk of bias and, in general, were poorly reported. Survey and costing analysis - in total, 238 health-care professionals responded. A range of orthoses is prescribed for knee instability that is related to NMD or CNS conditions, approximately half being custom-made. At least 50% of respondents thought that comfort and confidence in mobility were extremely important treatment outcomes. The cost of individual KAFOs was highly variable, ranging from £73 to £3553. CONCLUSIONS: Various types of orthoses are used in the NHS to manage patients with NMD/CNS conditions and knee instability, both custom-made and prefabricated, of variable cost. Evidence on the effectiveness of the orthoses is limited, especially in relation to the outcomes that are important to orthoses users. LIMITATIONS: The population included was broad, limiting any in-depth consideration of specific conditions. The response rate to the survey was low, and the costing analysis was based on some assumptions that may not reflect the true costs of providing KAFOs. FUTURE WORK: Future work should include high-quality research on the effectiveness and cost-effectiveness of orthoses; development of a core set of outcome measures; further exploration of the views and experiences of patients; and the best models of service delivery. STUDY REGISTRATION: This study is registered as PROSPERO CRD42014010180. The qualitative study is registered as Current Controlled Trials ISRCTN65240228. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Ten Years Experiences With Preoperative Evaluation Clinic for Day Admission Cardiac and Major Vascular Surgical Patients: Model for "Perioperative Anesthesia and Surgical Home".

Admission on the day of surgery for elective cardiac and noncardiac surgery is the prevalent practice in North America and Canada. This approach realizes medical, psychological and logistical benefits, and its success is predicated on an effective outpatient preoperative evaluation. The establishment of a highly functional preoperative clinic with a comprehensive set up and efficient logistical pathways is invaluable. This notion in recent years has included the entire perioperative period, and the concept of a perioperative anesthesia/surgical home (PASH) is gaining popularity. The anesthesiologists as perioperative physicians can organize and lead the entire process from the preoperative evaluation, through the hosptial discharge. The functions of the PASH include preoperative optimization of medical conditions and psychological preparation of the patients and their support system; the care in the operating room and intensive care unit; pain management; respiratory therapy; cardiac rehabilitation; and specialized nutrition. Along with oversight of the medical issues, the preoperative visit is an opportune time for counseling, clarification of expectations and discussion of research, as well as for utilization of various informatics systems to consolidate the pertinent information and distribute it to relevant health care providers. We review the scientific foundation and practical applications of a preoperative visit and share our experience with the development of the preoperative evaluation clinic, designed specifically for cardiac and major vascular patients scheduled for day admission surgery. The ultimate goal of preoperative evaluation clinic is to ensure a safe, efficient, and cost-effective perioperative care for patients undergoing a complex type of surgery.

Cognitive outcome after spinal anesthesia and surgery during infancy.

BACKGROUND: Observational studies on pediatric anesthesia neurotoxicity have been unable to distinguish long-term effects of general anesthesia (GA) from factors associated with the need for surgery. A recent study on elementary school children who had received a single GA during the first year of life demonstrated an association in otherwise healthy children between the duration of anesthesia and diminished test scores and also revealed a subgroup of children with "very poor academic achievement" (VPAA), scoring below the fifth percentile on standardized testing. Analysis of postoperative cognitive function in a similar cohort of children anesthetized with an alternative to GA may help to begin to separate the effects of anesthesia from other confounders. METHODS: We used a novel methodology to construct a combined medical and educational database to search for these effects in a similar cohort of children receiving spinal anesthesia (SA) for the same procedures. We compared former patients with a control population of students matched by grade, gender, year of testing, and socioeconomic status. RESULTS: Vermont Department of Education records were analyzed for 265 students who had a single exposure to SA during infancy for circumcision, pyloromyotomy, or inguinal hernia repair. Exposure to SA and surgery had no significant effect on the odds of children having VPAA. (mathematics: P = 0.18; odds ratio 1.50, confidence interval (CI), 0.83-2.68; reading: P = 0.55; odds ratio = 1.19, CI, 0.67-2.1). There was no relationship between duration of exposure to SA and surgery and performance on mathematics (P = 0.73) or reading (P = 0.57) standardized testing. There was a small but statistically significant decrease in reading and math scores in the exposed group (mathematics: P = 0.03; reading: P = 0.02). CONCLUSIONS: We found no link between duration of surgery with infant SA and scores on academic achievement testing in elementary school. We also found no relationship between infant SA and surgery with VPAA on elementary school testing, although the CIs were wide.

Psychoneuroimmunology and related mechanisms in understanding health disparities in vulnerable populations.

The nervous system as well as the endocrine system maintain extensive communication with the immune system through the influence of hormones and neurotransmitters and also by way of the hardwiring of sympathetic and parasympathetic nerves to the lymphoid organs. There is now convincing evidence that the communication between these three body systems is bidirectional. This chapter will provide a succinct review of how neuroendocrine and immune functions are affected in factors that impact vulnerability, such as aging, acute infection, and central nervous system injury. Given that the relevant literature on these topics is vast, the presentation in this chapter will serve to highlight primary references that reflect state of the science in these systems of focus.

Decision analysis: an aid to the diagnosis of Whipple's disease.

BACKGROUND: Diagnosis of Whipple's disease, a rare systemic infection affecting predominantly the small bowel, is based on the identification of the bacterium Tropheryma whipplei. AIMS: To make explicit diagnostic uncertainties in Whipple's disease through a decision analysis, considering two different clinical scenarios at presentation. METHODS: Using appropriate software, a decision tree estimated the consequences after testing different strategies for diagnosis of Whipple's disease. Probabilities and outcomes to determine the optimum expected value were based on MEDLINE search. RESULTS: In patients with clinically-predominant intestinal involvement, diagnostic strategies considering intestinal biopsy for histology (including appropriate staining) and the polymerase chain reaction testing for bacterial DNA were similarly effective. In case of failure of one procedure, the best sequential choice was a polymerase chain reaction analysis after a negative histology. Of the five strategies tested for cases with predominant focal neurological involvement, the stereotaxis cerebral biopsy evidenced the highest expected value. However, using quality-adjusted life-years considering the morbidity of methods, intestinal biopsy for PCR determination was the best choice. CONCLUSIONS: In patients with Whipple's disease having predominant digestive involvement, intestinal biopsies for histology should be indicated first and, if negative, a bacterial polymerase chain reaction determination should be the next option. Although the molecular polymerase chain reaction assessment of cerebral biopsies has the highest diagnostic yield in neurological Whipple's disease, its associated morbidity means that analyses of intestinal samples are more appropriate.

Secondary conditions in a community-based sample of women with physical disabilities over a 1-year period.

OBJECTIVE: To examine prevalence and predictors of secondary conditions in women with physical disabilities. DESIGN: Cross-sectional. SETTING: Women were recruited through private and public health clinics and various community organizations. PARTICIPANTS: A sample of 443 predominantly ethnic minority women with physical disabilities. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Health Conditions Checklist interference score. RESULTS: Aggregated data over a 1-year period showed that nearly the entire sample reported interference from pain (94.5%) and fatigue (93.7%) and that at least three quarters of the sample reported problems with spasticity (85.4%), weakness (81.8%), sleep problems (80.2%), vision impairment (77.9%), and circulatory problems (77.9%). Obesity was substantially more prevalent in this sample (47.6%) than in the general population of women (34.0%). The mean number of secondary conditions per woman +/- standard deviation was 14.6+/-6.2 (range, 1-42), with 75% of the sample endorsing 10 or more conditions. On average, women reported experiencing 5.7+/-4.03 (range, 0-20) conditions that they rated as significant or chronic. A third (33.4%) of the variance in interference scores was accounted for in the regression analysis, with significant variance accounted for by race, disability type (women with joint and connective tissue disorders and women with postpolio reported the highest overall interference scores), greater functional limitations, and lower levels of general mental health. CONCLUSIONS: Secondary conditions in women with physical disabilities are substantially more problematic than reported previously in the literature. Further research is needed to determine health disparities of women with and without disabilities. Measurement issues and the clinical relevance of these findings are discussed.

[Assessment of neuropathic pain]. / Utredning av nevropatisk smerte.

Neuropathic pain is underdiagnosed and, in consequence, not properly treated. Neuropathic pain is defined as pain initiated or caused by a primary lesion or dysfunction in the nervous system. The term dysfunction is not clearly defined and is suggested not used. The prevalence of neuropathic pain is unknown, but a few detailed studies show that neuropathic pain is more common than previously assumed. Some common causes of neuropathic pain are entrapment/injuries to peripheral nerves, painful neuropathies, infections in the nervous system (i.e. postherpetic neuralgia), spinal cord injuries, multiple sclerosis and cerebral infarcts. Evaluation of neuropathic pain is performed on the basis of a thorough clinical examination which includes detailed questioning of different types of pain. Both spontaneous (ongoing and paroxysmal) as well as evoked pain may occur. The ongoing pain may be described by a large number of adjectives such as burning, aching, throbbing, sore, cutting, but there is no pain descriptor which is diagnostic for neuropathic pain. Pain may usually be evoked by lightly touching the skin or by exposure to cold. A clinical neurological examination is necessary in the evaluation of the level of injury, possibly also electromyography/neurography in case of peripheral nerve lesions or CT/MR in case of central lesions. Neuropathic pain is almost always characterised by changes in sensibility, usually involving the thin-fibre system (peripheral nerve fibres or central projections). Special emphasis is put on the examination of sensory dysfunction.

Is speech and language therapy meeting the needs of language minorities? The case of deaf people with neurological impairments.

The cultural diversity of the UK poses a challenge for speech and language therapists. Work with children from language minorities has been documented, but less so with adults. This raises the question of whether adults from minority communities are gaining access to services. Deaf people who use British Sign Language (BSL) are one language minority. It is known that sign language is vulnerable to neurological damage. Of interest is whether Deaf people with such damage are referred to speech and language therapy (SLT). The aim was to find out how many deaf people were referred to SLT services in the UK over the last 5 years, and reasons for the referrals. We also explored the service offered to Deaf referrals, and whether SLT teams had access to BSL skills, either internally or via interpreters. A brief questionnaire was sent to the managers of all SLT services in the UK (n=264). There was as 60% response rate. Only 34 services received referrals of Deaf patients, with a total of 39 Deaf people seen. This is substantially below the predicted rates. Most referrals were for dysphagia, or dysphagia with communication impairments. In line with this, dysphagia management was the dominant service, although most referrals also received language assessment. Most teams did not have signing staff members and access to interpreters was variable. The results suggest that many Deaf people are not gaining access to SLT after neurological impairment. Those who are referred are unlikely to receive language therapy. The instigation of a national team specializing in BSL impairments is recommended.

Diagnostic patterns and temporal trends in the evaluation of adult patients hospitalized with syncope.

BACKGROUND: Syncope is a common clinical problem that is often difficult and expensive to diagnose. We examined diagnostic patterns and trends and use of specialty consultations in the evaluation of syncope. METHODS: We retrospectively reviewed the medical records of consecutive adult patients hospitalized with the principal diagnosis of syncope (International Classification of Diseases, Ninth Revision, code 780.2) during 1994 and 1998 at 2 community teaching hospitals. RESULTS: A total of 649 patients (57% female) with a mean (+/-SD) age of 68 +/- 15 years were identified in 1994 (n = 451) and 1998 (n = 198). Three hundred forty-one patients (53%) underwent at least 1 neurologic test, including brain computed tomographic (CT) scan (n = 283), electroencephalography (n = 253), carotid Doppler echocardiography (n = 185), and brain magnetic resonance imaging (n = 10). Only brain CT scan and electroencephalography yielded diagnoses in 5 (2%) and 6 patients (2%), respectively with history consistent with seizures or stroke. Cardiovascular tests providing the highest diagnostic yields (postural blood pressure check in 52 [30%], head-up tilt-table test in 32 [24%], and electrophysiologic study in 5 [16%]) were used in 176 (27%), 132 (20%), and 31 patients (5%), respectively. Differences in the use of some tests were noted at the participating hospitals and over time (1994 vs 1998). The total number of diagnosed cases was similar for patients undergoing evaluation by primary care physicians alone (65/103 [63%]), compared with cardiology (48/85 [56%]), neurology (29/48 [60%]), or both (81/141 [57%]). After a mean (+/-SD) length of stay of 5 +/- 4 days, 320 (49%) of 649 cases remained undiagnosed. CONCLUSIONS: Despite a reduction in the use of some tests (eg, brain CT scan and carotid Doppler) over time, lower-yield neurologic tests were overused and higher-yield cardiovascular tests were likely underused. The untargeted, seemingly random use of specialty evaluations did not seem to contribute to an increase in the overall number of diagnosed cases. Increased use of specific tests directed by history and results of physical examination may improve diagnostic yield and decrease the cost of evaluating syncope.

Variation in the influence of selected sociodemographic risk factors for mental retardation.

OBJECTIVES: This study explored the utility of subdividing mental retardation into groups based on the presence of other neurological conditions. METHODS: Data were abstracted from birth certificates as part of a case-control study of mental retardation among 10-year-old children. The study sample included 458 case children and 563 control children selected from public schools. Case children were subdivided on the basis of intelligence quotient (IQ) score and the presence of other neurological conditions. RESULTS: Other neurological conditions were more common with severe mental retardation than with mild mental retardation. Regardless of IQ level or the presence of other neurological conditions, boys were more likely than girls to have mental retardation. Older mothers were more likely than younger mothers to have a child with mental retardation accompanied by another neurological condition. High birth order, Black race, and low maternal education were associated with a higher prevalence of isolated mental retardation. CONCLUSIONS: These findings suggest that sociodemographic risk factors for mental retardation vary according to the presence of other neurological conditions and that subdivisions based on medical or physical criteria may be useful in epidemiologic studies of mental retardation.

Electrophysiological assessment of spinal cord lesions by means of transcranial cortical stimulation.

Central Motor Conduction Time (CMCT) was assessed in 30 healthy volunteers and 22 patients with spinal cord lesions due to compressive, degenerative and demyelinating disease. To obtain the CMCT, electrical Transcranial Stimulation and Percutaneous Spinal Stimulation or F wave calculations were employed. Pyramidal Tract (PT) conduction was always abnormal in the clinically impaired corticospinal tracts of all the studied patients. This results correlated with the degree of muscle weakness specially in those having compressive lesions. Subclinical evidence of pyramidal damage was also observed in two patients with Multiple Sclerosis. As opposed to the other groups, patients with degenerative spinal disease, showed essentially symmetric abnormalities. An important overlap of CMCT slowness was seen among the three studied groups, suggesting that this isolated clue is not valuable enough for aetiological suspicion. Double muscle responses due to single TCS were obtained, during rest, in some patients from each group, but never in controls. This pathological feature, not reported by others, could represent the excitation of indirect corticospinal connections, partially responsible for the residual motor function after PT damage.

Acquired mutism: physiopathy and assessment.

The speechless patient presents a unique challenge to the clinician working with neurologically impaired adults. Acquired speechlessness, or mutism, has been associated with a variety of clinical states and syndromes after damage to central and peripheral nervous system structures. The intent of this paper is to summarize the reported states and syndromes associated with acquired mutism (eg, persistent vegetative state, akinesia), and to organize this information in a framework for clinical assessment of the speechless patient. For the purpose of discussion, speech production is divided into five interrelated processes: arousal; cognitive processing; affect and drive; motor initiation, planning, programming, and coordination; and execution of movement. Disorders characterized by mutism are classified according to the process or processes of speech production that primarily are affected. Each subtype of acquired mutism is characterized by a cluster of neurologic signs, which has been incorporated into a decision-making framework for use in a clinical setting.

Assessment of the person with AIDS in the emergency department.

It is difficult to describe a "typical" clinical picture of a person with acquired immunodeficiency syndrome (AIDS) who is seen in the emergency department. The clinical course and the early clinical manifestations that lead to the initial diagnosis of AIDS vary greatly. Variability is the rule, because the patient with AIDS may manifest a wide range of signs and symptoms--from those associated with a minor illness to those indicative of a critical near-death state. Indeed, some patients with AIDS have no complaints or relatively minor constitutional complaints before becoming acutely compromised as a result of an overwhelming opportunistic infection. Other patients have a relatively short history (weeks to months) of vague, nonspecific complaints.

Assessment of head shaking test in neuro-otological practice.

The head shaking test (HST) is an important test in neuro-otological diagnosis. In our study of 277 patients complaining of dizziness we verified this importance. The results thus obtained were compared with the results recorded in 73 normal subjects. Head shaking nystagmus was observed in 73 patients. Of these 73 cases, 42 involved central diseases and 31 cases involved peripheral diseases. Head shaking nystagmus was observed in 7 subjects of the control group. A highly significant correlation was noted between head shaking nystagmus and positional nystagmus, between head shaking nystagmus and the caloric test and between head shaking nystagmus and all the other spontaneous types of nystagmus that were investigated (eyes open in light/gaze straight ahead; eyes open behind Frenzel's glasses; eyes closed; eyes open in darkness). No correlation was found between head shaking nystagmus and cervical nystagmus and positioning nystagmus. The sensitivity of head shaking nystagmus, in comparison with other types of spontaneous nystagmus, was found to be slightly higher in cases with peripheral lesions than in those with central lesions. These data confirm the diagnostic importance of this simple test. It is also important to keep in mind that the HST has no importance for topodiagnostic purposes.