Assessment and Scientific Progresses in the Analysis of Olfactory Evoked Potentials

The human sense of smell is important for many vital functions, but with the current state of the art, there is a lack of objective and non-invasive methods for smell disorder diagnostics. In recent years, increasing attention is being paid to olfactory event-related potentials (OERPs) of the brain, as a viable tool for the objective assessment of olfactory dysfunctions. The aim of this review is to describe the main features of OERPs signals, the most widely used recording and processing techniques, and the scientific progress and relevance in the use of OERPs in many important application fields. In particular, the innovative role of OERPs is exploited in olfactory disorders that can influence emotions and personality or can be potential indicators of the onset or progression of neurological disorders. For all these reasons, this review presents and analyzes the latest scientific results and future challenges in the use of OERPs signals as an attractive solution for the objective monitoring technique of olfactory disorder

Uncovering the Correlation between COVID-19 and Neurodegenerative Processes: Toward a New Approach Based on EEG Entropic Analysis

COVID-19 is an ongoing global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Although it primarily attacks the respiratory tract, inflammation can also affect the central nervous system (CNS), leading to chemo-sensory deficits such as anosmia and serious cognitive problems. Recent studies have shown a connection between COVID-19 and neurodegenerative diseases, particularly Alzheimer’s disease (AD). In fact, AD appears to exhibit neurological mechanisms of protein interactions similar to those that occur during COVID-19. Starting from these considerations, this perspective paper outlines a new approach based on the analysis of the complexity of brain signals to identify and quantify common features between COVID-19 and neurodegenerative disorders. Considering the relation between olfactory deficits, AD, and COVID-19, we present an experimental design involving olfactory tasks using multiscale fuzzy entropy (MFE) for electroencephalographic (EEG) signal analysis. Additionally, we present the open challenges and future perspectives. More specifically, the challenges are related to the lack of clinical standards regarding EEG signal entropy and public data that can be exploited in the experimental phase. Furthermore, the integration of EEG analysis with machine learning still requires further investigatio

Smell and taste disorders

Smell and taste disorders can markedly affect the quality of life. In recent years we have become much better in the assessment of the ability to smell and taste. In addition, information is now available to say something about the prognosis of individual patients. With regard to therapy there also seems to be low but steady progress. Of special importance for the treatment is the ability of the olfactory epithelium to regenerate

Smell and taste disorders

Smell and taste disorders can markedly affect the quality of life. In recent years we have become much better in the assessment of the ability to smell and taste. In addition, information is now available to say something about the prognosis of individual patients. With regard to therapy there also seems to be low but steady progress. Of special importance for the treatment is the ability of the olfactory epithelium to regenerate

Position Paper on Olfactory Dysfunction

Background: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst full recommendations are outlined in the main document, key points include: -Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy. -Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. -Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. -Comprehensive chemosensory assessment should include gustatory screening. -Smell training can be helpful in patients with olfactory loss of several aetiologies. Conclusions: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field

Objektivierung von funktionellen und strukturellen Beeinträchtigungen sensorischer Afferenzen bei neuroimmunologischen Krankheitsbildern

In dieser kumulativen Habilitationsschrift werden eigene Arbeiten zusammengefasst, die sich thematisch mit der Objektivierung sensorischer Afferenzstörungen bei neuroimmunologischen Krankheitsbildern befassen. B-mode Ultraschall, eine in der klinischen Routine weit verbreitete Methode, wurde als objektives Untersuchungsverfahren zur Beurteilung der Pupillenfunktion etabliert, Normwerte von Pupillendurchmessern und Pupillenkonstriktionszeiten wurden für verschiedene Altersgruppen publiziert. Das frühzeitige Erkennen und Behandeln einer ON ist entscheidend, um irreversible Schäden des N. opticus zu verhindern. Eine Funktionsstörung des afferenten visuellen Systems bei Patienten mit ON ließ sich gut mittels B-mode Ultraschall objektivieren und quantifizieren. B-mode Ultraschall könnte als bildgebender Biomarker für ein RAPD und als Surrogat-Parameter für eine Läsion des N. opticus in klinischen Studien und in der Routinediagnostik Anwendung finden. In einer weiteren Studie wurde die visuelle Lebensqualität bei NMOSD und MS Patienten mit Zustand nach ON untersucht. Die Einschränkung an visueller Lebensqualität korrelierte mit dem Ausmaß an funktioneller und struktureller Schädigung des afferenten visuellen Systems, gemessen mittels OCT und Visus. Die Integrität des afferenten olfaktorischen Systems wurde bei der NMOSD, PPMS und AE in eigenen Arbeiten erstmals untersucht. Zusammenfassend erwies sich das Riechvermögen bei diesen seltenen neuroimmunoloigschen Krankheitsbildern als deutlich eingeschränkt, wobei wir dabei von unterschiedlichen Pathomechanismen ausgehen. Riechstörungen sind möglicherweise ein weiteres Symptom dieser phänotypisch sehr heterogenen Krankheitsbilder. Eine niederschwellige Riechtestung im Rahmen der differentialdiagnostischen Zuordnung sollte bei den untersuchten Krankheitsbildern in Erwägung gezogen werden

Sensory Involvement in Amyotrophic Lateral Sclerosis

Although amyotrophic lateral sclerosis (ALS) is pre-eminently a motor disease, the existence of non-motor manifestations, including sensory involvement, has been described in the last few years. Although from a clinical perspective, sensory symptoms are overshadowed by their motor manifestations, this does not mean that their pathological significance is not relevant. In this review, we have made an extensive description of the involvement of sensory and autonomic systems described to date in ALS, from clinical, neurophysiological, neuroimaging, neuropathological, functional, and molecular perspectives

Longitudinal Testing of Olfactory and Gustatory Function in Patients with Multiple Sclerosis

Background The aim of the study was to investigate changes of the olfactory and gustatory capacity in patients with multiple sclerosis (MS). Methodology 20 MS patients were tested longitudinally for 3 years after initial testing. The Threshold Discrimination Identification test (TDI) was used for subjective olfactometry. Objective olfactometry was performed by registering olfactory evoked potentials (OEP) by EEG. The Taste Strip Test (TST) was used for gustatory testing. Results 45% of the patients showed olfactory dysfunction in the follow-up TDI test and 50% showed delayed OEP´s. 20% of the patients showed gustatory dysfunction on follow-up visit. The patients showed mild disease activity with 0,3 ± 0,5 relapses over the testing period and no significant change of their olfactory and gustatory capacity. The olfactory capacity for the discrimination of odors correlated inversely with the number of relapses (r = -0.5, p ≤ 0.05). The patients were aware of their olfactory deficit. Conclusions Olfactory and gustatory dysfunction is a symptom in MS patients and may be a useful parameter to estimate disease progression in MS patients. As the discrimination of odors is processed in higher central regions of the central nervous system (CNS), the results suggest that olfactory dysfunction could be due to CNS damage

Neurodegeneration associated-proteins in human olfactory epithelium: immunocytochemical and biomolecular study in healthy subjects and patients with synucleinopathies

Olfactory impairment is considered an initial disturbance of several neurodegenerative diseases (NDs), including Parkinson\u2019s disease (PD) and Alzheimer\u2019s disease (AD). In addition, smell impairment precedes a decade, or even longer, the onset of motor or cognitive symptoms. Olfactory signals are detected by olfactory receptor proteins (ORPs) expressed in the cilia of olfactory receptor neurons (ONs). ONs are the distinctive cellular components of the peripheral olfactory epithelium (OE) and lie in the nasal vault. ONs axons pass the cribriform plate and reach the olfactory bulb (OB) where the olfactory stimuli are processed and sent to the superior nuclei of the CNS. Previous studies in AD and other neurodegenerative disorders have shown the presence of \u3b2-amyloid deposits in the OB, neurofibrillary tangles, as well as Lewy body pathology. OB represents the brain area earlier involved in the neuropathological process, decades before the development of clinical symptoms. Therefore, OB can be considered a target in the study of neurodegenerative diseases in their early molecular processes. Moreover, the OB of healthy subjects presents deposits of aggregated proteins confirming that these aggregates are deposited in a prodromal disease stage. Since the OB is an early accumulation site of aggregated proteins and the synapses derive from the ONs, it is possible that the first event of protein aggregation occurs in OE. ONs are directly exposed to the external environment including chemical/physical toxic injuries and such micro-environment predisposes to abnormal protein processing and folding (Sammeta and McClintock 2010). In addition, ONs and all other mature cell components have a half-life of three months and programmed apoptosis. The neural activity is maintained by a constant cellular turn-over, which is sustained by the basal stem cells. This regeneration process is persistent during the whole life of an individual, albeit with a decreasing rate with aging. Extensive scientific literature indicates the neuronal damage as the consequence of exposure to toxic injuries leading to neurodegeneration and ONs are a natural model of this noxious process (Lema Tom\ue9, Tyson et al. 2013). The hypothesis of this pathological pathway is supported by several studies, in which aggregated forms of \u3b1-synuclein, tau and \u3b2-amyloid are detected in olfactory mucosa (OM) biopsies as well as in autoptic samples of patients with Parkinson\u2019s disease (PD), Lewy body dementia (LBD), Frontotemporal dementia (FTD) and Alzheimer disease (AD) (Funabe, Takao et al. 2013) (Saito, Shioya et al. 2016) (Tabaton, Cammarata et al. 1991) (Talamo, Rudel et al. 1989) (Crino, Greenberg et al. 1995) (Arnold, Lee et al. 2010). In this study, we investigated for the first-time primary ONs sampled ex vivo using olfactory brushing (OBg) in normal subjects and patients with different neurodegenerative disorders. Because of its convenient location, OE is easily accessible and can be sampled to obtain the ONs in the tissue outer layer. This sampling method is harmless and non-invasive, bypassing potential artifacts due to post mortem specimens as well as avoiding the invasiveness of biopsy procedures. Recently, we showed that OBg procedure in Creutzfeldt-Jakob Disease (CJD) patients allows efficient OM sampling for the Real-Time Quaking-Induced Conversion (RT-QuIC) assay. We specifically amplified pathological prion protein (PrPSc) providing a diagnostic intra vitam test with sensitivity and specificity nearly to 100% (Orr\ufa, Bongianni et al. 2014). For the purpose of our study, we firstly defined the phenotypic characterization of the human olfactory cells sampled with OBg from healthy subjects. Distinct antibodies were selected to analyze the olfactory epithelium cells: olfactory marker protein (OMP), neuron-specific class III \u3b2-tubulin (TUJ-1), protein gene product 9.5 (PGP 9.5), Pan-Cytokeratin (PCK). Secondly, we aimed to determine the expression patterns of the major misfolded proteins involved in the main neurodegenerative diseases. In particular, the selected proteins were: \u3b1-synuclein, APP/beta-amyloid, tau, and TDP-43. The identification of the expression patterns of these proteins in the ONs might provide information to understand the abnormal molecular mechanisms in the initial misfolding species involved in the pathological process. Moreover, in this study, we speculated on the subcellular locale where the protein aggregation may occur. Furthermore, by demonstrating the constitutive expression of the native NDs-associated proteins in the OE, we could assume that they may represent a potential template for triggering the aggregation process. Based on the immunocytochemistry analysis, we investigated the \u3b1-synuclein expression in patients affected by different synucleinopathies. In fact, \u3b1-synuclein misfolding and aggregation mechanisms are involved in the pathogenesis of neurodegenerative disorders such as Parkinson's disease (PD), dementia with Lewy bodies (LBD) and multiple system atrophy (MSA), which are all characterized by \u3b1-synuclein fibrils deposition (Spillantini, Schmidt et al. 1997). Finally, we analyzed the immunocytochemistry results in OM samples tested by \u3b1-synuclein RT-QuIC (\u3b1-syn RT-QuIC)