The neurology of COVID-19 revisited: A proposal from the Environmental Neurology Specialty Group of the World Federation of Neurology to implement international neurological registries
Gustavo C. RománPeter S. SpencerJ. ReisAlain BuguetMostafa El Alaoui FarisSarosh M. KatrakMiguel J. A. LáinezMarco T. MedinaSarita Gajbhiye MeshramHidehiro MizusawaŞerefnur ÖztürkMohammad Wasay
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Abstract:
A comprehensive review of the neurological disorders reported during the current COVID-19 pandemic demonstrates that infection with SARS-CoV-2 affects the central nervous system (CNS), the peripheral nervous system (PNS) and the muscle. CNS manifestations include: headache and decreased responsiveness considered initial indicators of potential neurological involvement; anosmia, hyposmia, hypogeusia, and dysgeusia are frequent early symptoms of coronavirus infection. Respiratory failure, the lethal manifestation of COVID-19, responsible for 264,679 deaths worldwide, is probably neurogenic in origin and may result from the viral invasion of cranial nerve I, progressing into rhinencephalon and brainstem respiratory centers. Cerebrovascular disease, in particular large-vessel ischemic strokes, and less frequently cerebral venous thrombosis, intracerebral hemorrhage and subarachnoid hemorrhage, usually occur as part of a thrombotic state induced by viral attachment to ACE2 receptors in endothelium causing widespread endotheliitis, coagulopathy, arterial and venous thromboses. Acute hemorrhagic necrotizing encephalopathy is associated to the cytokine storm. A frontal hypoperfusion syndrome has been identified. There are isolated reports of seizures, encephalopathy, meningitis, encephalitis, and myelitis. The neurological diseases affecting the PNS and muscle in COVID-19 are less frequent and include Guillain-Barré syndrome; Miller Fisher syndrome; polyneuritis cranialis; and rare instances of viral myopathy with rhabdomyolysis. The main conclusion of this review is the pressing need to define the neurology of COVID-19, its frequency, manifestations, neuropathology and pathogenesis. On behalf of the World Federation of Neurology we invite national and regional neurological associations to create local databases to report cases with neurological manifestations observed during the on-going pandemic. International neuroepidemiological collaboration may help define the natural history of this worldwide problem.Keywords:
Hyposmia
Deficits in smell and/or taste are possible neurological manifestations of coronavirus disease-2019 (COVID-19). The study aims to determine the incidence of hyposmia and hypoguesia in patients infected with COVID-19 in Shifa-14 Hospital, Kirkuk, Iraq. Data for this study were taken from the patients' registries. The results showed that out of 117 patients, 73 (62.4%) had hyposmia or hypoguesia, or both. Most of the patients were males 71 (60.7%) with different age groups. The majority of patients was smokers 72 (61.5%) and had mild infection 61 (52.1 %). Men, smoking, and disease seriousness had a vastly significant association with hyposmia and hypoguesia. We concluded that lack of smell and taste was a common symptom of COVID-19. Males, smoking, and severe infection were risk factors hyposmia or hypoguesia in the COVID-19 cases.
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Hyposmia is an early feature in neurodegenerative diseases, most notably Parkinson's disease (PD). Using abbreviated smell tests could provide a cost-effective means for large-scale hyposmia screening. It is unclear whether short smell tests can effectively detect hyposmia in patient populations.To test the ability of short smell combinations to "prescreen" for probable hyposmia in people with PD and target administration of more extensive tests, such as the University of Pennsylvania Smell Identification Test.We assessed the screening performance of a short 4-smell combination previously derived from use of the 40-item University of Pennsylvania Smell Identification Test in healthy older people and its ability to detect hyposmia in a large cohort of PD patients.The novel 4-smell combination included menthol, clove, onion, and orange and had a sensitivity of 87.1% (95% confidence interval, 84.9%-89.2%) and specificity of 69.7% (63.3%-75.5%) for detecting hyposmia in patients with PD. A different (also novel) 4-item combination developed using a data-driven approach in PD patients only achieved 81.3% (78.2%-84.4%) sensitivity for equivalent specificity.A short 4-smell combination derived from a healthy population demonstrated high sensitivity to detect those with hyposmia and PD.
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Smell acuity has been measured by many different methods using a variety of techniques and stimuli. The most clinically practical technique involves psychophysical measurement of smell acuity. Using this technique with signal detection, single or multiple stimuli or other methods it has been possible to distinguish subjects with normal smell function from those with smell loss (hyposmia). Using these traditional techniques measurements have been used to obtain sensory thresholds [detection (DT) and recognition (RT)] and estimates of magnitude estimation (ME). However, most investigators currently using these techniques have not established standards by which patient pathology can be defined either with respect to initial hyposmia or to changes on treatment. We have established standards for both normal subjects and patients with hyposmia and have used them to define both initial hyposmia and treatment efficacy. Type I hyposmia is defined by absent RT and ME but preservation of DT. Type II hyposmia is defined by decreased DT, RT and ME. With these parameters as a clinical basis 233 patients with smell loss were evaluated and then treated with the generalized phosphodiesterase inhibitor theophylline at daily doses of 200–1000 mg for 2–24 months. Results indicate that 40 % of patients with Type I hyposmia and 70 % of patients with Type II hyposmia demonstrated improved smell acuity. By use of these specific clinical measurements it is now possible to predict clinical outcome based upon initial hyposmia measurements. These results also demonstrate that measurement standards of olfactory acuity have now been established similar to standards measuring pathology of metabolic processes using blood or urine.
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Objectives. To measure the prevalence of and identify the clinical characteristics associated with olfactory decline in patients with chronic rhinosinusitis. Methods and Materials. There is analytical, prospective, and observational study in adult patients with a diagnosis of chronic rhinosinusitis. The olfactory test used was the Connecticut Chemosensory Clinical Research Center (CCCRC). Results. They are 33 patients total. Within the group of patients aged 18 to 39, 9% had normosmia, 73% hyposmia, and 18% anosmia (P < 0.001). Between 40 and 64 years old, there was no patient with normosmia, 63% hyposmia, and 37% anosmia (P < 0.001). Of patients older than 65 years old, 33% showed mild hyposmia, 34% severe hyposmia, and 33% anosmia (P < 0.001). 52% were females, and 48% were males. Conclusion. Nasal polyposis, asthma, septal deviation, turbinate hypertrophy, tobacco, and allergic rhinitis are predicting factors of olfactory dysfunction. Antecedents of previous endoscopic surgeries, age, and gender would not be associated with olfactory loss.
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To evaluate nasal mucus levels of cAMP and cGMP in patients with taste and smell dysfunction with respect to severity of their smell loss.cAMP and cGMP were measured in nasal mucus using a sensitive spectrophotometric 96 plate ELISA technique. Smell loss was measured in patients with taste and smell dysfunction by standardized psychophysical measurements of olfactory function and classified by severity of loss into four types from most severe to least severe such that anosmia > Type I hyposmia > Type II hyposmia > Type III hyposmia. Measurements of nasal mucus cyclic nucleotides and smell loss were made independently.As smell loss severity increased stepwise cAMP and cGMP levels decreased stepwise [cAMP, cGMP (in pmol/ml); anosmia - 0.004, 0.008: Type I hyposmia - 0.12+/-0.03, 0.10+/-0.03: Type II hyposmia - 0.15+/-0.02, 0.16+/-0.01: Type III hyposmia - 0.23+/-0.05, 0.20+/-0.15].These results confirm the association of biochemical changes in cyclic nucleotides with systematic losses of smell acuity. These results confirm the usefulness of the psychophysical methods we defined to determine the systematic classification of smell loss severity. These changes can form the basis for the biochemical definition of smell loss among some patients with smell loss as well as for their therapy.
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Neurological dysfunction in AIDS is common, occurring in as many as eighty percent of children. Thus, it is important to recognize the central nervous system imaging appearance of HIV, in particular those of HIV encephalopathy, as this is an AIDS defining illness and with distinct neuro-imaging features essential for early diagnosis and timely therapeutic interventionTo identify the clinical features in HIV-1 infection of the central nervous system and their associated neuroradiological correlates.Retrospective review of the records of all children with HIV-1 encephalopathy identified among children with neurological and developmental problems and who were on follow up at a child development and neurology clinic in an African city.A total of 22 children (10 male and 12 female) with HIV-1 encephalopathy were identified among 2382 children with various forms of neurological and developmental problems and who were on follow up at a child development and neurology clinic for a little bit over eight years period. All the children acquired the infection vertically. The age range of these children was between 10 months to 14 years. The median age was 5.6 years. The mean duration of symptom was 3.2 years. Global delay or regression in development along with signs of pyramidal tract involvement and seizures were the commonest clinical signs observed in these children. Neuro-behavioral problems were commonly observed among preschool and school aged children. In older children and preadolescents focal seizures with or with out neurologic deficit and neuroradiological findings were common. Nonhemorrhagic stroke was rare and occurred in one child and another child had cortical blindness. Three children had no neurological deficit. Rapid progression of the disease carried grave prognosis. Opportunistic infections and tumors of the central nervous system were also uncommon among these children. Brain volume loss with dilatation of the lateral ventricle, bilateral symmetrical or asymmetrical calcification of the basal ganglia and periventricular involvement of the white matter were the commonest neuro-radiological findings observed in these children.Atrophy of the brain with dilatation of the lateral ventricles and calcification of the basal ganglia and peri-ventricular involvement of the white matter were the commonest neuro-radiological findings in children with HIV-1 encephalopathy. Similarly global delay or regression in development along with pyramidal tract signs and seizures were the commonest neurological findings. Behavioral problems were common in preschool and school aged children. Focal seizures were common in older children and preadolescents. Rapid progression of the disease carried grave prognosis.
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Background and Objectives Although patients with chronic rhinosinusitis (CRS) present a similar degree of olfactory dysfunction, their impairments in threshold, discrimination, and identification test results may vary. We investigated factors related to each of these components using the Korean version of the Sniffin’ Sticks test II in CRS patients.<br/>Subjects and Method A total of 120 CRS patients with olfactory dysfunction were enrolled and assigned to hyposmia and anosmia groups. Correlation between the three components were examined in both groups. We also subdivided patients into higher- and lower-score groups according to the threshold, discrimination, and identification scores within the hyposmia and anosmia groups to determine associated factors among the demographic factors, CRS severity on computed tomography (CT) and endoscopic findings.<br/>Results Threshold, discrimination, and identification scores were significantly correlated in hyposmia patients. Age [odds ratio (OR), 0.94] was associated with the threshold score, and the anterior olfactory cleft opacification score (OR, 1.31) on CT was associated with identification difficulties in hyposmia patients. The posterior olfactory cleft opacification score was associated with threshold (OR, 2.76) and identification difficulties (OR, 1.68) in anosmia patients. However, we could not identify significant risk factors for discrimination in both groups.<br/>Conclusion We demonstrated that the three components of the olfactory function test for CRS are significantly correlated in patients with hyposmia. Age was associated with threshold score in hyposmia patients and CRS severity, and with discrimination scores in both hyposmia and anosmia patients. These findings will help the understanding of pathophysiology of CRSrelated olfactory dysfunction.<br/>Korean J Otorhinolaryngol-Head Neck Surg 2020;63(8):358-68
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Hyposmia is often undiagnosed despite the known negative effect on taste, appetite and life quality. However, a new focus on the first cranial nerve has emerged as a consequence of a discovered connection between neurodegenerative disorders and hyposmia. In Parkinson's disease and Alzheimer's disease hyposmia is not only one of the earliest clinical presentations, the degree of hyposmia also correlates with the later progression of these two conditions. Hyposmia should not be ignored nor accepted; instead it should be integrated in any neurological examination, especially in elderly patients.
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