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Dr. Salinas and colleagues examined the association of loneliness at baseline with 10-year all-cause dementia risk and early cognitive and neuroanatomic imaging markers of Alzheimer disease and related dementia (ADRD) vulnerability in 2,308 participants in the population-based Framingham study cohorts. They found that loneliness was associated with increased dementia risk, with the risk tripling in adults whose baseline risk would otherwise be fairly low on the basis of age and genetic risk and that loneliness was also associated with worse markers of ADRD vulnerability, implying a potential early pathogenetic role. In response, Dr. Daly notes that a similar association was seen between frailty and 10-year dementia risk. He suggests studying the relationship between longitudinal changes in loneliness and neuroanatomical or neuropathologic measures, and the relationship of loneliness to frailty. He also emphasizes the importance of taking action against loneliness in society, which was aggravated by the COVID-19 pandemic especially among lower socioeconomic strata, to mitigate further social disparities in dementia risk. Responding to these comments, Dr. Salinas notes that the study team has begun exploring longitudinal associations of loneliness with dementia-related measures in another cohort, and points to compelling findings of greater cortical amyloid and entorhinal tau accumulation in patients with loneliness in the Harvard Aging Brain Study. Dr. Salinas echoes the need for interventions targeting loneliness and social isolation. This correspondence underscores our growing understanding of the role that psychosocial determinants of health play in the development of dementia. Although it seems clear that a social brain fares better than a lonely one over time, the question remains as to whether the lonely brain can be "rescued" by social interventions.
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Objective: To determine the frequency of post-acute COVID-19 sequelae (PASC) symptoms in an outpatient neurology setting. Background: Symptoms of fatigue, headaches, and memory impairment have been reported in patients with PASC. Design/Methods: This is an observational study of the PASC experience of 98 non-hospitalized COVID-positive patients in neurology outpatient clinics. Participants completed a survey regarding persistent symptoms, after acute infection. Scales of quality of life and cognition were obtained and included the Montreal Cognitive Assessment (MoCA) and Neuro-QOL (Anxiety, fatigue, depression). Results: Of 98 participants recruited, 68% of participants were seen in neurology clinic specifically for PASC while 31% were seen for non-COVID related complaints but had a prior positive COVID-19 test. Mean age was 50.5±15.1 and 65% were female. Median time post-acute infection was 9.0 (IQR 4.7-11.7/range 0.5 - 16.8) months. Of the 93 participants with symptoms after 6 weeks, the most frequent symptoms reported were fatigue (67%), headaches (49%), muscle aches (48%), word-finding difficulty (48%), difficulty sleeping (47%), shortness of breath (47%), and change in memory (46%). The most common pre-morbid conditions were anxiety/depression (32%), hypertension (26%), pulmonary disease (23%), and autoimmune (17%). BMI>25 was present in 68%. 41% had a prior neurological condition with migraines being the most common (18%). There was no statistically significant difference in reported symptoms, pre-morbid conditions, sex, and age between participants who presented with PASC versus other neurological complaints. Patients reporting persistent fatigue (n=64) had a mean Neuro-QOL fatigue score of 53.3±9.9. Normal mean MoCA scores were present in patients reporting word finding difficulty or memory change (19.3±2.4 points) and in participants with abnormal Neuro-QOL scores (19.4±2.1 points). Conclusions: Patients with PASC in a neurology outpatient clinic report persistent neurological, systemic symptoms that affect their quality of life on multiple validated measures. The MoCA test may not be able to detect subtle cognitive deficits in this population.
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Objective: We sought to describe PASC-related headache severity and quality of life in a cohort of non-hospitalized individuals presenting to our outpatient neurology practices (PASC) Background: People with post-acute sequelae of COVID-19 (PASC) have reported many neurological symptoms such as brain fog, memory difficulties, and headache. Design/Methods: Participants with evidence of prior COVID-19 infection were asked to complete symptom scales, Neuro-QOL (anxiety, depression, and fatigue), and validated headache questionnaires: Headache Impact Test-6 and American Migraine Prevalence and Prevention questionnaire. Results: Among 98 participants reporting PASC symptoms after acute illness, mean age was 50.5±15.1 and 65% were female. Headache (49%) was the second most frequent neurologic symptom reported after fatigue (67%). 18% (18/98) had a prior history of migraine headaches. 38.9% (7/18) of participants with pre-morbid migraine reported more than 15 symptomatic headache days per month. When controlling for age and sex, there was a statistically significant difference (p=0.011) between in participants with a prior migraine history indicating more frequent headaches in the last 3 months (mean 39.0±28.5 headaches) compared to participants without prior migraine (mean 18.5±25.3 headaches). HIT-6 scores were also significantly greater (p=0.005) in participants with a migraine history after adjusting for age and sex, (58.6±13.2) versus 47±12.2) indicating worse quality of life related to headaches. In participants with HIT-6 scrores>=56 indicating substantial or severe impact on quality of life and AMPP scores meeting criteria for chronic migraine, NeuroQOL scores for depression, anxiety, and fatigue were also elevated/worse. Conclusions: People with PASC in a neurology outpatient practice, with a prior migraine history report elevated headache frequency, worse quality of life related to their headaches as indicated by the HIT-6 test and Neuro-QOL. These data support the inclusion of headache specific measures in studies of PASC in larger samples and suggests that COVID-19 infection can impact headaches.
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Objective: Given the reductions in in-person visits and the increases in teleneurology visits, we sought to determine whether patients increased their use of virtual complementary and integrative therapies. Background: Patients with neurological disorders may seek treatment options in addition to those recommended by their providers. Prior to the COVID-19 pandemic, about half of patients from populations that sought care in neurology tried complementary and integrative therapies (CITs). Design/Methods: By examining two separate datasets that included cohorts of patients with neurological disorders, we assessed patients' use of virtual (and non-virtual) CITs and determined whether there were clinical characteristics that predicted their use. The two studies that comprised this report included one that examined patient and provider experiences with teleneurology visits, and another that assessed patients with a history of COVID-19 infection who presented for neurologic evaluation. Results: Patients who postponed medical treatment for non-COVID-19-related problems during the pandemic were more likely to seek CITs. Virtual exercise, virtual psychotherapy and relaxation/meditation smartphone applications were the most frequent types of virtual CITs chosen by patients. In both studies, age was a key demographic factor associated with mobile/virtual CIT usage. Conclusions: Data from our investigations demonstrated that, in addition to its other roles in teleneurology, CIT-related technologies may be utilized in the treatment of neurologic conditions.
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Objective: We sought to describe post-acute symptoms of COVID-19 (PASC)-related visual symptoms in a cohort of non-hospitalized individuals presenting to our outpatient neurology practices and undergoing vision-specific quality of life assessments. Background: Infection with SARS-CoV-2 (COVID-19) involves multiple systems, including those for vision. People with post-acute sequelae of COVID-19 (PASC) have reported many neurological symptoms such as brain fog, memory difficulties, and headache, as well as vision related complaints. Design/Methods: Participants completed standardized and well-validated vision-specific quality of life questionnaires, including the 25-Item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) and the 10-Item Neuro-Ophthalmic Supplement to the NEI-VFQ-25 (NOS). Patient scores were compared to those of disease-free controls within the same age groups. Results: Among 50 participants reporting persistent COVID-related symptoms more than 6 weeks after acute illness, the average age was 49.3 ± 14.6 years;33/50 (65%) were female. Symptoms reported by patients were mostly general and not visual. However, vision-specific quality of life scores were significantly lower than values for normal healthy controls with no history of neurological or ophthalmological disease (p<0.0001 for both the NEI-VFQ-25 and NOS composite scores, two-sample t-tests). Mean NEI-VFQ-25 composite score was 89.5 ± 12.7 compared to 98.2 ± 2.1 for healthy controls. Mean NOS score was 82.7 ± 16.0 compared to 96.5 ± 5.2 for controls. Conclusions: People with post-acute sequelae of COVID-19 (PASC) in a neurology outpatient practice, even among those without visual symptoms that bring them to medical attention, report persistent visual quality of life impairment. These data support the inclusion of vision-specific outcome measures and symptom scales in studies of PASC, and confirm that COVID-19 infection may impair visual function.
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Objective: Early neurorehabilitation improves outcomes in patients with disorders of consciousness after brain injury, but its applicability in COVID-19 is unknown. We demonstrate the feasibility of an early neurorehabilitation protocol for patients with COVID-19-associated disorders of consciousness in the intensive care unit (ICU) and evaluate factors associated with recovery. Methods: Between March 10 and May 20, 2020, we prospectively enrolled 21 ICU patients with delayed recovery of consciousness after severe COVID-19 in a pilot early neurorehabilitation protocol including serial Coma Recovery Scale - Revised (CRS-R) assessments and multimodal treatment. We retrospectively compared clinical features of patients who did and did not achieve a CRS-R total score (TS) ≥8, consistent with minimally conscious state, before discharge. We additionally present preliminary 6-month follow-up data for 8 patients who survived to discharge. Results: Patients underwent CRS-R a median of 6 (interquartile range [IQR] 3-10) times before discharge, beginning a median of 48 days (IQR 40-55) from admission. Twelve (57%) patients achieved at least one CRS-R TS ≥8, after a median of 8 days (IQR 2-14) off continuous sedation;they had lower body mass index (p = 0.009), lower peak serum C-reactive protein (p = 0.023), higher minimum arterial partial pressure of oxygen (p = 0.028) and earlier fentanyl discontinuation (p = 0.018). CRS-R scores fluctuated over time and best CRS-R TS was significantly higher than last CRS-R TS (median 8 [IQR 5- 23] vs 5 [IQR 3-18], p = 0.002). Earlier fentanyl (p = 0.001) and neuromuscular blockade (p = 0.015) discontinuation correlated with higher last CRS-R TS. Six-month follow-up data was obtained for 8 of 12 patients who survived to hospital discharge: of these, one patient (13%) had expired;3 (38%) remained in a disorder of consciousness;one (13%) was conscious but moderately disabled;and 3 (38%) achieved functional independence. Conclusion: It is feasible to provide early neurorehabilitation to patients with impaired consciousness after severe COVID-19 in the ICU. These patients can recover, but hypoxia, systemic inflammation, sedation and neuromuscular blockade may impact CRS-R scores and short-term outcomes. Return to functional independence is possible for some patients. Further research should evaluate factors influencing longer-term neurologic recovery and benefits of early rehabilitation in patients with severe COVID-19.
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PURPOSE: To report 3 otherwise healthy patients with Herpes zoster reactivation shortly after administration of a mRNA vaccine against the novel COVID-19 virus. OBSERVATIONS: Patient 1 is a 54 year old who presented with Herpes zoster meningitis complicated by enhancing nodular leptomeningeal lesions of the spinal cord. The subsequent two patients had Herpes zoster ophthalmicus of the cornea (Case 2) and eyelid (Case 3). All three presented within 2 weeks of receiving the Pfizer/BioNTech COVID-19 vaccine. CONCLUSIONS: Herpes zoster may be a side effect of m RNA vaccination against the Sars-CoV2 vaccine and requires further investigation.
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BACKGROUND AND PURPOSE: Various patterns of leukoencephalopathy have been described in coronavirus disease 2019 (COVID-19). In this article, we aimed to describe the clinical and imaging features of acute disseminated leukoencephalopathy in critically ill patients with COVID-19 and the imaging evolution during a short-term follow-up. MATERIALS AND METHODS: We identified and reviewed the clinical data, laboratory results, imaging findings, and outcomes for 8 critically ill patients with COVID-19 with acute disseminated leukoencephalopathy. RESULTS: All patients demonstrated multiple areas of white matter changes in both cerebral hemispheres; 87.5% (7/8) of patients had a posterior predilection. Four patients (50%) had short-term follow-up imaging within a median of 17 days after the first MR imaging; they developed brain atrophy, and their white matter lesions evolved into necrotizing cystic cavitations. All (8/8) patients had inflammatory cytokine release syndrome as demonstrated by elevated interleukin-6, D-dimer, lactate dehydrogenase, erythrocyte sedimentation rate, C-reactive protein, and ferritin levels. Most (7/8; 87.5%) patients were on prolonged ventilator support (median, 44.5 days; interquartile range, 20.5 days). These patients had poor functional outcomes (6/8 [75%] patients were discharged with mRS 5) and high mortality (2/8, 25%). CONCLUSIONS: Critically ill patients with COVID-19 can develop acute disseminated leukoencephalopathy that evolves into cystic degeneration of white matter lesions with brain atrophy during a short period, which we dubbed virus-associated necrotizing disseminated acute leukoencephalopathy. This may be the result of COVID-19-related endothelial injury, cytokine storm, or thrombotic microangiopathy.