Photobiomodulation therapy for treatment olfactory and taste dysfunction COVID-19-related: A case report.

It is postulated that the inflammatory process resulting from SARS-CoV-2 infection is the main cause of smell and taste dysfunctions in patients. In view of this, photobiomodulation, due to its anti-inflammatory and antioxidant effects, may be a promising therapeutic modality to treat these disorders. In the present case report, we observed clinical improvement in the symptoms of anosmia and ageusia related to COVID-19 after treatment with photobiomodulation. Due to the inflammatory nature of COVID-19 and the anti-inflammatory effects, photobiomodulation antioxidants already proven in the literature make it a promising therapeutic modality, especially sequela COVID-related, including olfactory (anosmia) and taste (ageusia) dysfunction. In the present case report, the patient's olfactory and gustatory functions were re-established after 10 treatment sessions with photobiomodulation.

Treatment of COVID-19-Related Olfactory Disorder Promoted by Kakkontokasenkyushin'i: A Case Series.

Olfactory disorders are one of the characteristic symptoms of the coronavirus disease of 2019 (COVID-19), which causes infection and inflammation of the upper and lower respiratory tract. To our knowledge, there are no treatments for COVID-19-related olfactory disorder. Here, we report five olfactory disorder cases in COVID-19, treated using the Japanese traditional (Kampo) medicine, kakkontokasenkyushin'i. We treated five patients with mild COVID-19 at an isolation facility using Kampo medicine, depending on their symptoms. Patients with the olfactory disorder presented with a blocked nose, nasal discharge or taste impairment. Physical examination using Kampo medicine showed similar findings, such as a red tongue with red spots and sublingual vein congestion, which presented as blood stasis and inflammation; thus, we prescribed the Kampo medicine, kakkontokasenkyushin'i. After administration, the numeric rating scale scores of the smell impairment improved within 3 days from 9 to 3 in case 1, from 10 to 0 in case 2, from 9 to 0 in case 3, from 5 to 0 in case 4, and from 9 to 0 within 5 days in case 5. Following the treatment, other common cold symptoms were also alleviated. Kakkontokasenkyushin'i can be used for treating nasal congestion, rhinitis, and inflammation in the nasal mucosa. The olfactory disorder in COVID-19 has been reportedly associated with inflammation and congestion, especially in the olfactory bulb and olfactory cleft. Kakkontokasenkyushin'i may be one of the treatment alternatives for the olfactory disorder with rhinitis in patients with COVID-19.

Transient Anosmia Induces Depressive-like and Anxiolytic-like Behavior and Reduces Amygdalar Corticotropin-Releasing Hormone in a ZnSO4-Induced Mouse Model.

Olfactory loss is known to affect both mood and quality of life. Transient anosmia was induced in mice to study the resulting changes in mood, behavior, and on a molecular level. Transient anosmia was induced by a single intranasal instillation of ZnSO4 in BALB/c mice. Hematoxylin and eosin (HE) staining, and potato chip finding test were performed to confirm olfactory loss. Tail suspension, forced swim, and splash tests were performed to evaluate depression-related behavior; while the open field, and elevated plus maze tests were used to evaluate anxiety-related behavior. The mRNA levels of amygdalar corticotropin-releasing hormone (CRH) and hypothalamic glucocorticoid receptor (GR) were quantified using real-time PCR to confirm relevant molecular change. Olfactory loss was confirmed 1-2.5 weeks after induction, and this loss was subsequently reversed over time. The results of the behavioral tests indicated increased depression-like and reduced anxiety-like behavior at week 1. Accordingly, PCR data identified decreased amygdalar CRH expression at week 1. These results suggest that transient anosmia induces both depressive and anxiolytic behavior as a result of decreased amygdalar CRH in a mouse model of anosmia.

Ocular myasthenia gravis accompanied by anosmia.

We report a case of ocular myasthenia gravis (MG) accompanied by anosmia. A 76-year-old man had idiopathic anosmia of 2-year duration. Four months before consultation, he began to have drooping in the right upper eyelid along with muscle soreness, distension, and pain in the nape. His tongue was dark-red with a thin and white coating; his pulse was wiry and slippery. According to Traditional Chinese Medicine, eyelid drooping and anosmia are the main signs of liver constraint and spleen deficiency. In Western Medicine, the diagnosis was ocular MG and idiopathic anosmia. Our patient, along with the literature, suggests that anosmia may be an early symptom before MG. MG accompanied by anosmia could be a special subtype of MG according to antibody production and symptoms.

Smell identification in individuals at clinical high risk for schizophrenia.

Smell identification deficits exist in schizophrenia, and may be associated with its negative symptoms. Less is known about smell identification and its clinical correlates in individuals at clinical high risk (CHR) for schizophrenia and related psychotic disorders. We examined smell identification, symptoms and IQ in 71 clinical high-risk (CHR) subjects and 36 healthy controls. Smell identification was assessed using both the 40-item University of Pennsylvania Smell Identification Test (UPSIT; Doty, R.L., Shaman, P., Kimmelman, C.P., Dann, M.S., 1984. University of Pennsylvania Smell Identification Test: a rapid quantitative olfactory function test for the clinic. Laryngoscope 94, 176-178) and its extracted 12-item Brief Smell Identification Test (Goudsmit, N., Coleman, E., Seckinger, R.A., Wolitzky, R., Stanford, A.D., Corcoran, C., Goetz, R.R., Malaspina, D., 2003. A brief smell identification test discriminates between deficit and non-deficit schizophrenia. Psychiatry Research 120, 155-164). Smell identification did not significantly differ between CHR subjects and controls. Among CHR subjects, smell identification did not predict schizophrenia (N=19; 27%) within 2 years, nor was it associated with negative or positive symptoms. This is the third prospective cohort study to examine smell identification in CHR subjects, and overall, findings are inconclusive, similar to what is found for other disorders in adolescents, such as autism spectrum, attention deficit and anxiety disorders. Smell identification deficit may not have clear utility as a marker of emergent schizophrenia and related psychotic disorders.

Idiopathic hypogonadotrophic hypogonadism associated with arachnoid cyst of the middle fossa and forebrain anomalies: presentation of an unusual case.

We report a 22-yr-old male patient with hypogonadotrophic hypogonadism (HH) associated with a giant middle fossa arachnoid cyst (AC) diagnosed by magnetic resonance imaging (MRI). He presented with pubertal and growth delay. He also had learning disabilities and anosmia. Laboratory investigation revealed pre-pubertal levels of testosterone and normal results of the combined test of anterior pituitary function, except for in GnRH acute and prolonged test. Cranial MRI showed an AC in left middle fossa with expansion to suprasellar cisterna and several abnormalities like left temporal lobe hypoplasia, left optic tract and bilateral olfactory bulb hypoplasia and left hypothalamic hypoplasia.

[GnRH deficiency: new insights from genetics]. / Déficience en GnRH: le nouvel eclairage apporté par la génétique.

The acquisition of a sexually dimorphic phenotype is a critical event in mammalian development. Hypogonadotropic hypogonadism (HH) results from impaired secretion of GnRH. The patients display with delayed puberty, micropenis and cryptorchidism in the male reflecting gonadotropin insufficiency, and amenorrhea in the female. Kallmann's syndrome (KS) is defined by the association of HH and anosmia or hyposmia (absent smelling sense). Segregation analysis in familial cases has demonstrated diverse inheritance patterns, suggesting the existence of several genes regulating GnRH secretion. The X-linked form of the disease was associated with a genetic defect in the KALI gene located on the Xp22.3 region. KAL1 gene encodes an extracellular matrix glycoprotein anosmin-1, which facilitates neuronal growth and migration. Abnormalities in the migratory processes of the GnRH neurons with the olfactory neurons explain the association of HH with anosmia. Recently, mutations in the FGF recepteur 1 (FGFR1) gene were found in KS with autosomal dominant mode of inheritance. The role of FGFR1 in the function of reproduction requires further investigation. Besides HH with anosmia, there are isolated HH (IHH). No human GnRH mutations have been reported although hypogonadal mice due to a GnRH gene deletion exist. In patients with idiopathic HH and without anosmia an increasing number of GnRH receptor (GnRHR) mutations have been described which represent about 50% of familial cases. The clinical features are highly variable and there is a good relationship between genotype and phenotype. A complete loss of function is associated with the most severe phenotype with resistance to pulsatile GnRH treatment, absence of puberty and cryptorchidism in the male. In contrast, milder loss of function mutations causes incomplete failure of pubertal development. The preponderant role of GnRH in the secretion of LH by the gonadotrophs explains the difference of the phenotype between male and female with partial GnRH resistance. Affected females can have spontaneous telarche and normal breast development while affected males exhibit no pubertal development but normal testis volume, a feature described as "fertile-eunuch". High-dose pulsatile GnRH has been used to induce ovulation. Another gene, called GPR54, responsible for idiopathic HH has been recently described by segregation analysis in two different consanguineous families. The GPR54 gene is an orphan receptor, and its putative ligand is the product of the KISS-1 gene, called metastine. Their roles in the function of reproduction are still unknown.

Kallmann's syndrome and schizophrenia.

OBJECTIVE: Kallmann's Syndrome is a heritable disorder characterized by the association of hypogonadotropic hypogonadism and anosmia or hyposmia. A common pathogenesis for KS and schizophrenia had been proposed based on shared pathologies of these two disorders, although no such clinical associations have ever been reported. METHOD: We report a 35 year old man with schizophrenia and Kallmann's Syndrome. The patient presented with signs and symptoms of hypogonadism, severe hyposmia and normal endocrine functions of the anterior pituitary. Hyposmia has been attributed to the absence of the olfactory bulbs and tracts and atrophy of the olfactory gyri, but normal olfactory mucosa. The patient presented with paranoid schizophrenia with persecutory delusions, auditory hallucinations, thought disorder, depersonalization, and gradual but marked global deterioration. RESULTS: Psychiatric evaluation revealed an entirely different psychopathological and personality profile between the patient and the six other Kallmann patients studied. Cycle sequencing analysis revealed a normal sequence of all 14 exons of the KAL gene. In conclusion, based on the presented case, Kallmann's Syndrome and schizophrenia represent a rare clinical association rather than a syndrome with a common pathogenesis, which if present should be confined to the olfactory dysfunction.

[Pulsatile GnRH substitution in Kallmann's syndrome in women]. / Pulsatile GnRH-Substitution beim Kallmann-Syndrom der Frau.

Anosmia and primary amenorrhoea are guiding symptoms of Kallmann's syndrome (olfacto-genital syndrome) in which agenesis of the olfactory lobe is associated with congenital defects in the mediobasal region of the hypothalamus, thus preventing a sufficient GnRH synthesis. In three patients with Kallmann's syndrome, the secretion of gonadotropins on bolus injection of 25 micrograms GnRH was comparable with prepubertal reaction. In one patient, the hypophyseal function was normalized, and ovulatory cycles were induced by pulsatile GnRH substitution via a portable computerized pump (Zyklomat). Pregnancy occurred. The duration of treatment required to induce ovulation was identical during two subsequent treatment cycles, contrary to observations in functional hypothalamic amenorrhoeas. The marked ovarian reaction shows that even if there is no endogenous GnRH secretion, a pulsatile dose of less than 20 micrograms seems to be sufficient.

Hypothalamic and pituitary function in hypogonadotropic hypogonadism.

Hypogonadotropic hypogonadism has been identified as a cause of partial or complete failure of puberty, may be familial and may have other associated abnormalities of hyposmia, intellectual retardation, perceptive deafness, color blindness, skeletal deformities, and gynecomastia. Pituitary function is usually normal with the primary defect believed to be hypothalamic. A twenty-year-old white male with a clinical diagnosis of hypogonadotropic hypogonadism and anosmia under-went complete endocrine evaluation with evaluation of the pituitary response to luteinizing hormone-releasing hormone. FSH (follicle-stimulating hormone) and LH (luteinizing hormone) release after luteinizing hormone-releasing hormone did occur, but the response was less than that seen in normal controls. Evaluation demonstrated that the pituitary-gonadal axis was intact with the hypothalamic-pituitary axis being defective. Therapy with the synthetic decapeptide (luteinizing hormone-releasing hormone) is correct theoretically and may be superior to therapy with exogenous gonadotropins.