CSF of SARS-CoV-2 patients with neurological syndromes reveals hints to understand pathophysiology

ObjectiveCoronavirus disease (COVID-19) has been associated with a large variety of neurological disorders. However the mechanisms underlying these neurological complications remain elusive. In this study we aimed at determining whether neurological symptoms were caused by SARS-CoV-2 direct infection or by either systemic or local pro-inflammatory mediators. MethodsWe checked for SARS-CoV-2 RNA by RT-qPCR, SARS-CoV-2-specific antibodies and for 49 cytokines/chemokines/growth factors (by Luminex) in the cerebrospinal fluids (CSF) +/-sera of a cohort of 22 COVID-19 patients with neurological presentation and 55 neurological control patients (inflammatory [IND], non-inflammatory [NIND], multiple sclerosis [MS]). ResultsWe detected SARS-CoV-2 RNA and virus-specific antibodies in the CSF of 0/22 and 10/21 COVID-19 patients, respectively. Of the four categories of tested patients, the CSF of IND exhibited the highest level of cytokines, chemokines and growth factors. In contrast, COVID-19 patients did not present overall upregulation of inflammatory mediators in the CSF. However, the CSF of patients with severe COVID-19 (ICU patients) exhibited higher concentrations of CCL2, CXCL8, and VEGF-A in the CSF than patients with a milder form of COVID-19. In addition, we could show that intrathecal CXCL8 synthesis was linked to an elevated barrier index and correlated to the increase of peripheral inflammation (serum HGF and CXCL10). ConclusionOur results point at an absence of massive SARS-CoV-2 infection or inflammation of the central nervous system, but highlight a specific impairment of the neurovascular unit linked to intrathecal production of CXCL8.

Two patients with acute meningo-encephalitis concomitant to SARS-CoV-2 infection

Human coronaviruses are known for their tropism for central nervous system and to be associated with neurological complications. SARS-CoV-2 pandemy represent a major health issue and if respiratory symptoms are at the forefront, neurological symptoms should be expected. Here we report the case of two patient that developed encephalitic symptoms with neuropsychological impairment and pathologic cerebrospinal fluid features concomitantly to SARS-CoV-2 documented infection. Both patient recovered promptly without treatment. This report raises the question of central nervous system involvement in SARS-CoV-2 infection and the need for investigation of neuropsychological complications in infected patient.

[From anomalies to abnormalities. Therapeutic considerations]. / De l'anomalie à la malformation. Réflexion et attitude thérapeutique.

The proper timing prior to any treatment should be the therapeutic decision. This concept seems to us particularly opportune as we deal, in the exercise of our disciplines, with facial morphology, a topic that is nowadays affected by excessive expectations and by the dictates of fashion, body image and appearance, all stirred up to a fever pitch by the media.

Nipple reconstruction: technical aspects and evolution in 14 patients.

BACKGROUND: During breast reconstruction after mastectomy, the long-term deterioration of the projection of neonipples led the authors to modify Thomas's technique in its design and use. METHODS: The results were evaluated after at least 10 months, in 14 patients, by comparative measurement of diameters and projection of the neonipple and contralateral nipple. RESULTS: In two cases, the authors had a 3-mm loss of height; in six cases, the authors had a variation of 1 mm compared with the referent nipple; and the heights appeared identical in the six other cases. The height variation was thus lower or equal to 1 mm compared with the contralateral nipple in 80 percent of cases. There was no or little diameter variation of approximately 1 mm in 12 cases (85.7 percent). CONCLUSION: This technique allows rebuilding of a nipple that remains identical to the contralateral nipple over the long run.

Sphincter pharyngoplasty as a treatment of velopharyngeal incompetence in young people: a prospective evaluation of effects on sleep structure and sleep respiratory disturbances.

BACKGROUND: Sphincter pharyngoplasty (SP) appears to be the more "physiologic" surgical technique to treat velopharyngeal incompetence (VPI). This procedure creates a dynamic sphincter of variable diameter and keeps the flexibility of the soft palate. SP also induces velopharyngeal size reduction, mainly in the transverse diameter, which may cause upper airway (UA) occlusions during sleep. AIM: To prospectively evaluate the effects of SP by a modified Orticochea procedure on sleep structure and sleep respiratory disturbances. METHODS: Polysomnographic studies before and after surgery in 17 consecutive patients treated by a modified Orticochea procedure SP for VPI. RESULTS: For the whole group, SP did not induce significant impairment of apnea-hypopnea index or nocturnal oxygen saturation. Slow-wave sleep (SWS) was significantly reduced after surgery (25 +/- 9% of total sleep time [TST] vs 28 +/- 9% of TST before SP [p = 0.04]). Following surgery, there was a trend for an increase in the microarousal index) (p = 0.09) and more specifically in respiratory-related microarousals. CONCLUSION: SP, although creating a clinically obvious reduction of velopharyngeal diameter, generally did not lead to the occurrence of an obstructive sleep apnea syndrome. However, we found a significant reduction of SWS quantity and a trend toward an increase in the number of cortical microarousals. These findings suggest that the reduction of UA diameter associated with the surgical technique leads to increases in respiratory effort sufficient to induce sleep fragmentation and SWS reduction, even in the absence of apneas or hypopneas.

Mandibular advancement devices: rate of contraindications in 100 consecutive obstructive sleep apnea patients.

Mandibular advancement devices (MAD) should be contraindicated (Clark GT, Sleep Med Rev 1998;2:163-174) if there are: (1) insufficient teeth to support the device, (2) periodontal problems inducing tooth mobility, (3) active temporomandibular joint (TMJ) disorder, and (4) limited maximum protrusive distance (< 6 mm). The aim of the present study was to evaluate the proportion of the obstructive sleep apnea population that exhibits any contraindication (CI) to MAD. For this study there were 100 unselected adult patients consecutively diagnosed by polysomnography in a tertiary sleep laboratory. Clinical and radiologic evaluation of the dental, periodontal, and TMJ status of these 100 patients were performed by two expert maxillofacial surgeons, blind to each other, permitting the identification of MAD CIs. The two maxillofacial surgeons agreed on MAD absolute CIs in 96 of the 100 patients. CIs were identified in 34% of the patients. The nature of the CIs systematically referred to an insufficient number of remaining teeth (mean number of teeth lost: 7.8 +/- 6.1 with 31 patients having had more than 10 teeth removed). The tooth avulsions were significantly higher in contraindicated compared with noncontraindicated patients (16 +/- 8 versus 4 +/- 3, p < 0.00001). Periodontal abnormalities coexisted with dental CI in approximately half of the patients. A TMJ disorder was considered as significant enough to lead to CI in two patients. Dental and periodontal care was needed in 16 patients before the use of MAD could be considered. Conclusions were that primary CIs were present in 34% of 100 consecutive patients, mainly owing to dental problems. Moreover, another subgroup of patients (16%) required close supervision and follow-up to avoid impairment of preexisting TMJ and dental problems. Such a high rate of CI should be considered when the overall efficacy of oral appliances is compared with other treatments, such as surgery or nasal continuous positive airway pressure.

Computer-assisted orthognathic surgery: clinical evaluation of a mandibular condyle repositioning system.

PURPOSE: The purpose of this study was to evaluate a new method for positioning the mandibular condyle during orthognathic surgery based on 3-dimensional optical localization of infrared emitting diodes. PATIENTS AND METHODS: Eleven patients ("empirical group") underwent condylar repositioning using the empirical repositioning method (standard technique) and were considered controls. In 10 patients ("active group"), the computer-assisted system was used to replace the condyle-bearing fragment in its sagittal preoperative position. In these patients, the condylar torque was not controlled. In the third group of 10 patients ("graft group"), the computer-assisted system was used to replace the condyle in all 3 directions. Very often it was necessary in this group to fill the osteotomy gap with a bone graft. The clinical evaluation was based on 4 major criteria: the quality of the postoperative occlusion, the stability of skeletal position on successive cephalometric radiographs, the occurrence of temporomandibular dysfunction (TMD), and the preservation of mandibular motion. Clinical assessment was made at 1, 3, 6, and 12 months follow-up. RESULTS: Forty-five percent of the "empirical group" did not have the expected postoperative occlusion, 5 patients showed evidence of clinical relapse at 1 year, 45% had worsened TMD status, and only 63.37% of mandibular motion had been recovered at 6 months. All the patients in the "active group" had the expected occlusion and only 1 patient exhibited a mild relapse and TMD symptoms; however the average mandibular motion recovery was only 62.65% at 6 months. All the patients in the "graft group" had a good occlusion and no relapse or TMD. Their percentage of mandibular motion recovery was 77.58%. CONCLUSION: The quality of sagittal repositioning is the main factor contributing to a good occlusion and bone stability. Functional results (in particular, recovery of mandibular motion) are more related to limiting condylar torque.