The use of platelet-rich plasma in treatment of olfactory dysfunction: A pilot study.

BackgroundOlfactory dysfunction is a prevalent problem with a significant impact on quality of life and increased mortality. Limited effective therapies exist. Platelet-rich plasma (PRP) is an autologous biologic product with anti-inflammatory and neuroprotective effects. This novel pilot study evaluated the role of PRP on olfactory neuroregeneration in patients with hyposmia.MethodsSeven patients who had olfactory loss greater than 6 months in duration, no evidence of sinonasal inflammatory disease, and no improvement with olfactory training and budesonide topical rinses were enrolled in this preliminary study. Patients received a single intranasal injection of PRP into the mucosa of the olfactory cleft. The Sniffin' Sticks olfactory test consisting of threshold, discrimination, and identification measurements (TDI) was administered at the beginning of the study and at 1 and 3 months.ResultsAll patients reported a subjective improvement of their smell shortly after injection but then stabilized. At 3-month post-treatment, two patients with functional anosmia (TDI < 16) did not improve significantly. Five patients with hyposmia (TDI > 16 but <30) showed an improvement with 60% achieving normosmia (TDI > 30) at 3-month follow-up. On average, patients with baseline TDI > 16 improved by 5.85 points with the most significant improvement in the threshold subcomponent. There were no adverse outcomes from intranasal PRP injections.ConclusionPRP appears safe for use in the treatment of olfactory loss, and preliminary data suggest possible efficacy, especially for those with moderate yet persistent loss. Further studies will help determine optimal frequency and duration of use.Level of evidence 2

A systematic review of therapeutic options for non-conductive olfactory dysfunction

Background: Olfactory dysfunction affects a significant proportion of the population but appears to be more common in the elderly population (>20% of adults over 60 years old). Unfortunately, many sufferers face an apparent lack of therapeutic options when consulting with medical professionals. Method: We searched various electronic medical databases for the treatment of non-conductive olfactory dysfunction. After careful review of the abstracts and the full articles, we included publications that fulfilled our inclusion criteria and analysed the results. Results: A total of 38 publications were included in our review including 6 randomised control trials, 14 cohort studies and 18 observational studies. Conclusion: Olfactory training appears to improve non-conductive olfactory dysfunction irrespective of the aetiology. Steroids appear to have some benefit, but this may be aetiology dependent and Vitamin A and sodium citrate have shown some promise. High quality randomised control trials are still required to determine their place in managing this patient population

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

A Review on the Cognitive Neuroscience of Autism

With increased recognition in the media, heightened prevalence, and advances in research technologies, investigation into the causes of autism has broadened in recent years. Studies at the molecular, structural, and behavioral levels have resulted in significant findings, linking autism to qualitative differences in neurological function and an alteration of early development. Familial aggregation of autism demonstrate a strong genetic factor, although genetics can not completely account for its pathogenesis. Studies show autism having one of the most complex pathologies among neurodevelopmental disorders. Future studies applying sophisticated methodologies in new areas may shed light on current mysteries surrounding the disorder

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

Olfactory Training and Oral CorticosteroidTherapy for Persistent Postinfectious Hyposmia

Introduction Postinfectious hyposmia gained special attention in the postpandemic era, and persistent cases are particularly difficult to treat. Many unproven therapies are used in clinical practice, including corticosteroids, with insufficient evidence. Objective To establish the effectiveness of systemic corticosteroid therapy, associated with olfactory training, for persistent postinfectious hyposmia. Methods Patients with persistent postinfectious hyposmia were divided, based on comorbidities, into control group (submitted to olfactory training alone) and test group (associated 7-day course of prednisone 40 mg). Olfactory evaluations were performed (visual analogue scale, Alcohol Sniff Test, and Connecticut Olfactory Test), at baseline, and at the 3- and 6-month follow-ups. Results There was no statistically significant difference between the test (n¼10) and control (n¼7) groups (p>0.05) for primary outcomes (visual analogue scale, Alcohol Sniff Test, and Connecticut Olfactory Test), although there was statistically significant improvement of Alcohol Sniff Test scores in both groups at 6 months (p>0.05). The study’s statistical power was reduced due to the small sample size. Even without randomization, the groups were not comparable only in terms of age (p>0.05). Although no statistically significant association was found, there was a clear tendency for improvement in the overall olfactory function, which may be spontaneous or due to olfactory training. No side effects were reported. Conclusion There was no statistically significant benefit of systemic corticosteroid therapy for patients with persistent postinfectious hyposmia (p>0.05). Treatment with systemic corticosteroids should be individualized, and there is no consensus in the literature.Introduction Postinfectious hyposmia gained special attention in the postpandemic era, and persistent cases are particularly difficult to treat. Many unproven therapies are used in clinical practice, including corticosteroids, with insufficient evidence. Objective To establish the effectiveness of systemic corticosteroid therapy, associated with olfactory training, for persistent postinfectious hyposmia. Methods Patients with persistent postinfectious hyposmia were divided, based on comorbidities, into control group (submitted to olfactory training alone) and test group (associated 7-day course of prednisone 40 mg). Olfactory evaluations were performed (visual analogue scale, Alcohol Sniff Test, and Connecticut Olfactory Test), at baseline, and at the 3- and 6-month follow-ups. Results There was no statistically significant difference between the test (n¼10) and control (n¼7) groups (p>0.05) for primary outcomes (visual analogue scale, Alcohol Sniff Test, and Connecticut Olfactory Test), although there was statistically significant improvement of Alcohol Sniff Test scores in both groups at 6 months (p>0.05). The study’s statistical power was reduced due to the small sample size. Even without randomization, the groups were not comparable only in terms of age (p>0.05). Although no statistically significant association was found, there was a clear tendency for improvement in the overall olfactory function, which may be spontaneous or due to olfactory training. No side effects were reported. Conclusion There was no statistically significant benefit of systemic corticosteroid therapy for patients with persistent postinfectious hyposmia (p>0.05). Treatment with systemic corticosteroids should be individualized, and there is no consensus in the literature

Viral Encephalitis: Etiology, Clinical Features, Diagnosis and Management

8openSergio Ferrari; Antonio Toniolo; Salvatore Monaco; Filippo Luciani; Francesca Cainelli; Andreina Baj; Zelalem Temesgen; Sandro VentoSergio, Ferrari; Toniolo, Antonio; Salvatore, Monaco; Filippo, Luciani; Francesca, Cainelli; Baj, Andreina; Zelalem, Temesgen; Sandro, Vent

Intensive Olfactory Training in Post-COVID Patients: A Randomized Multicenter Clinical Trial

Introduction: Olfactory dysfunction (OD) is one of the most reported symptoms of COVID -19. Previous studies have identified olfactory training (OT) as an important treatment for postinfectious OD, but little is known about its effect after SARS-CoV-2 infection and how it can be optimized. Objective: To assess whether OT can be optimized if performed intensively, with more fragrances over a shorter period in patients with persistent OD after COVID -19. Also, to determine the presence of other variables related to OD and treatment response in this population. Method: This multicenter randomized clinical trial recruited 80 patients with persistent OD with previous COVID-19 for less than three months. The patients were divided into two groups, who received treatment with 4 and 8 essences over four weeks. Subjective assessments and the University of Pennsylvania Smell Identification Test (UPSIT) were performed before and after treatment. Results: A significant improvement in olfaction was measured subjectively and on UPSIT in both groups, but without significant differences between groups. In addition, the presence of olfactory fluctuation was associated with higher UPSIT scores. Conclusion: These data suggest that intensifying the training by increasing the number of essences for 4 weeks does not show superiority over the classical method. Moreover, a fluctuating olfactory ability seems to be related to a better score in the UPSIT

Terpene-Centered Olfactory Training in Postinfectious Olfactory Dysfunction: A Dual-Route Approach

ABSTRACT Objective: To compare the efficacy of classical olfactory training (COT) protocols with a novel dual-route method targeting both orthonasal and retronasal pathways in the management of postinfectious olfactory dysfunction (PIOD), and to explore the neurotherapeutic potential of terpene-based odorants. Methods: One hundred and seventeen patients diagnosed with PIOD received either conventional olfactory training or a modi- fied protocol that integrates retronasal stimulation. The terpene profile of administered odorants was evaluated for its contribu- tion to olfactory and cognitive outcomes. Results: This study had five major findings: (1) The Terpene-Centered Orthonasal and Retronasal Olfactory Training (TCOT) group showed significantly greater improvements in Sniffin' Sticks TDI and odor identification scores at the 9th and 12th months compared to the COT and Modified Olfactory Training (MOT) groups (p<0.001); (2) Retronasal olfactory scores improved sig- nificantly more in the TCOT group at the 9th and 12th months (p<0.001); (3) Clinically meaningful improvement (≥6-point TDI gain) was most frequent in TCOT participants at all time points beyond 6months; (4) TCOT participants exhibited the greatest re- ductions in parosmia severity at 6, 9, and 12months (p<0.05); (5) Cognitive complaints, as measured by CFQ-5 scores, improved most markedly in the TCOT group, with significant differences at the 6th (p<0.001) and 12th (p=0.02) months. Conclusion: Incorporating retronasal training and terpene-rich odorants in olfactory rehabilitation may improve outcomes in PIOD. These findings support the integration of terpene-centered, multimodal olfactory training into clinical rehabilitation strategies for PIOD. Level of Evidence: Level 2

Post-viral olfactory loss and parosmia

The emergence of SARS-CoV-2 has brought olfactory dysfunction to the forefront of public awareness, because up to half of infected individuals could develop olfactory dysfunction. Loss of smell—which can be partial or total—in itself is debilitating, but the distortion of sense of smell (parosmia) that can occur as a consequence of a viral upper respiratory tract infection (either alongside a reduction in sense of smell or as a solo symptom) can be very distressing for patients. Incidence of olfactory loss after SARS-CoV-2 infection has been estimated by meta-analysis to be around 50%, with more than one in three who will subsequently report parosmia. While early loss of sense of smell is thought to be due to infection of the supporting cells of the olfactory epithelium, the underlying mechanisms of persistant loss and parosmia remain less clear. Depletion of olfactory sensory neurones, chronic inflammatory infiltrates, and downregulation of receptor expression are thought to contribute. There are few effective therapeutic options, so support and olfactory training are essential. Further research is required before strong recommendations can be made to support treatment with steroids, supplements, or interventions applied topically or injected into the olfactory epithelium in terms of improving recovery of quantitative olfactory function. It is not yet known whether these treatments will also achieve comparable improvements in parosmia. This article aims to contextualise parosmia in the setting of post-viral olfactory dysfunction, explore some of the putative molecular mechanisms, and review some of the treatment options available