Noncoding variants alter GATA2 expression in rhombomere 4 motor neurons and cause dominant hereditary congenital facial paresis.

Hereditary congenital facial paresis type 1 (HCFP1) is an autosomal dominant disorder of absent or limited facial movement that maps to chromosome 3q21-q22 and is hypothesized to result from facial branchial motor neuron (FBMN) maldevelopment. In the present study, we report that HCFP1 results from heterozygous duplications within a neuron-specific GATA2 regulatory region that includes two enhancers and one silencer, and from noncoding single-nucleotide variants (SNVs) within the silencer. Some SNVs impair binding of NR2F1 to the silencer in vitro and in vivo and attenuate in vivo enhancer reporter expression in FBMNs. Gata2 and its effector Gata3 are essential for inner-ear efferent neuron (IEE) but not FBMN development. A humanized HCFP1 mouse model extends Gata2 expression, favors the formation of IEEs over FBMNs and is rescued by conditional loss of Gata3. These findings highlight the importance of temporal gene regulation in development and of noncoding variation in rare mendelian disease.

The Alterations and Significance of Intercellular Adhesion Molecule-1 in Mouse Brainstem During Herpes Simplex Virus Type 1-Induced Facial Palsy.

Herpes simplex virus type 1 (HSV-1) results in the development of Bell's pals but still, the pathophysiology of the facial nerve paralysis is still not fully studied. The main objective is to establish an animal model of type 1 herpes simplex virus (HSV-1)-induced face paralysis in the mouse and to investigate the pattern of changes in intercellular adhesion molecule -1(ICAM-1) expression in the facial nucleus of the brain stem in mice with facial paralysis as well as the effects of glucocorticoids on intercellular adhesion molecule -1(ICAM-1) expression. A total of 170 4-week-old Balb/c male mice were randomly divided into the virus inoculation group (n = 135), saline control group (n = 26), and blank control group (n = 9). Mice in the virus inoculation group that showed facial paralysis were divided into A, B, and C subgroups. The A group did not receive any treatments, the B group received methylprednisolone sodium succinate (MPSS) intervention, and the C group received MPSS + RU486 treatment. The mouse model of facial paralysis was established by inoculating HSV-1 to the skin at the back of the ears. The facial nerve function of mice was assessed, and real-time PCR and western blot were used to assess ICAM-1 expression in the facial nucleus of the brain stem in mice with facial paralysis after drug intervention. In the virus inoculation group, 95 mice (55.88%) showed varying degrees of facial paralysis symptoms within 2-5 days after inoculation. The ICAM-1 gene and protein expression levels remained at low levels in the facial nucleus of the brain stem of mice in the saline group, which showed no significant difference compared to the normal control group (P > 0.05). However, for mice of the virus inoculation group, ICAM-1 expression increased at 6 h after the occurrence of facial paralysis and peaked after 2 days, differing significantly from the blank control group (P < 0.01). ICAM-1 expression subsequently decreased gradually. In the HSV-1 + MPSS group, ICAM-1 protein expression decreased significantly on the 2nd day after facial paralysis. In the HSV-1 + MPSS + RU486 group, MPSS inhibition of ICAM-1 protein expression was reduced. The results suggested that ICAM-1 is involved in the pathological processes by which HSV-1 induces facial paralysis in mice, and the treatment effects of MPSS for Bell's palsy can be achieved by the inhibition of MCP-1.

The association between ear involvement and clinical features and prognosis in ANCA-associated vasculitis.

OBJECTIVE: The concept of otitis media with ANCA-associated vasculitis (OMAAV) was recently proposed by the study group of the Japan Otological Society. However, little is known about the effect of ear involvement on the clinical features and prognosis of AAV. We investigate this issue in this study. METHODS: We retrospectively examined 36 patients diagnosed with OMAAV and 44 patients diagnosed with AAV without ear involvement (non-OMAAV) at Ehime University Hospital from 2013 to 2018. We collected serological findings including ANCA type and titer, C-reactive protein (CRP), serum creatinine level, organ involved at initial diagnosis, treatment, remission, disease relapse, and mortality from medical records. We investigated whether clinical features and outcomes differed between the OMAAV and non-OMAAV groups. RESULTS: Age, ANCA titer, and CRP at initial diagnosis were not significantly different between the two groups, and the rate of intravenous cyclophosphamide (IVCY) use also did not differ. The proportions of patients with concurrent eye involvement, facial palsy (FP), and hypertrophic pachymeningitis (HCP) were significantly higher in the OMAAV than in the non-OMAAV group (p = 0.005, 0.005 and 0.049, respectively), while both renal and peripheral nerve involvement were significantly less common in OMAAV patients (p = 0.04). Among the 30 patients with renal involvement, serum creatinine level at diagnosis was significantly lower in the OMAAV group (p = 0.04). The mortality rate was 8.3% in OMAAV and 6.8% in non-OMAAV cases, but this difference was not significant. The rate of relapse was 33.3% in OMAAV and 13.6% in non-OMAAV cases; this difference was significant (p = 0.04). CONCLUSIONS: Serological measurements of disease activity did not differ between the groups. Eye involvement, FP, and HCP, however, were significantly more common in AAV with ear involvement. In addition, renal involvement was less common and renal impairment was milder in AAV with ear involvement. These findings can be considered clinical features. The relapse rate was significantly higher in AAV with ear involvement.

Role of Biomarkers as Prognostic Factors in Acute Peripheral Facial Palsy.

Acute peripheral facial palsy (APFP), including Bell's palsy and Ramsay Hunt syndrome, is a disease that affects daily life through facial motor dysfunction, causing psychological problems. Various tests to evaluate prognosis have been studied; however, there are no validated predictive biomarkers to guide clinical decision making. Therefore, specific biomarkers that respond to treatment are required to understand prognostic outcomes. In this review, we discuss existing literature regarding the role of APFP biomarkers in prognosis and recovery. We searched the PubMed, EMBASE, and Cochrane Library databases for relevant papers. Our screening identified relevant studies and biomarkers correlating with the identification of predictive biomarkers. Only studies published between January 2000 and October 2021 were included. Our search identified 5835 abstracts, of which 35 were selected. All biomarker samples were obtained from blood and were used in the evaluation of disease severity and prognosis associated with recovery. These biomarkers have been effective prognostic or predictive factors under various conditions. Finally, we classified them into five categories. There is no consensus in the literature on the correlation between outcomes and prognostic factors for APFP. Furthermore, the correlation between hematologic laboratory values and APFP prognosis remains unclear. However, it is important to identify new methods for improving the accuracy of facial paralysis prognosis prediction. Therefore, we systematically evaluated prognostic and potentially predictive APFP biomarkers. Unfortunately, a predictive biomarker validating APFP prognosis remains unknown. More prospective studies are required to reveal and identify promising biomarkers providing accurate prognosis.

Accelerated outgrowth in cross-facial nerve grafts wrapped with adipose-derived stem cell sheets.

In this study, we devised a novel cross-facial nerve grafting (CFNG) procedure using an autologous nerve graft wrapped in an adipose-derived stem cell (ADSC) sheet that was formed on a temperature-responsive dish and examined its therapeutic effect in a rat model of facial palsy. The rat model of facial paralysis was prepared by ligating and transecting the main trunk of the left facial nerve. The sciatic nerve was used for CFNG, connecting the marginal mandibular branch of the left facial nerve and the marginal mandibular branch of the right facial nerve. CFNG alone, CFNG coated with an ADSC suspension, and CFNG wrapped in an ADSC sheet were transplanted in eight rats each, designated the CFNG, suspension, and sheet group, respectively. Nerve regeneration was compared histologically and physiologically. The time to reinnervation, assessed by a facial palsy scoring system, was significantly shorter in the sheet group than in the other two groups. Evoked compound electromyography showed a significantly higher amplitude in the sheet group (4.2 ± 1.3 mV) than in the suspension (1.7 ± 1.2 mV) or CFNG group (1.6 ± 0.8 mV; p < .01). Toluidine blue staining showed that the number of myelinated fibers was significantly higher in the sheet group (2,450 ± 687) than in the suspension (1,645 ± 659) or CFNG group (1,049 ± 307; p < .05). CFNG in combination with ADSC sheets, prepared using temperature-responsive dishes, promoted axonal outgrowth in autologous nerve grafts and reduced the time to reinnervation.

Variants affecting diverse domains of MEPE are associated with two distinct bone disorders, a craniofacial bone defect and otosclerosis.

PURPOSE: To characterize new molecular factors implicated in a hereditary congenital facial paresis (HCFP) family and otosclerosis. METHODS: We performed exome sequencing in a four-generation family presenting nonprogressive HCFP and mixed hearing loss (HL). MEPE was analyzed using either Sanger sequencing or molecular inversion probes combined with massive parallel sequencing in 89 otosclerosis families, 1604 unrelated affected subjects, and 1538 unscreened controls. RESULTS: Exome sequencing in the HCFP family led to the identification of a rare segregating heterozygous frameshift variant p.(Gln425Lysfs*38) in MEPE. As the HL phenotype in this family resembled otosclerosis, we performed variant burden and variance components analyses in a large otosclerosis cohort and demonstrated that nonsense and frameshift MEPE variants were significantly enriched in affected subjects (p = 0.0006-0.0060). CONCLUSION: MEPE exerts its function in bone homeostasis by two domains, an RGD and an acidic serine aspartate-rich MEPE-associated (ASARM) motif inhibiting respectively bone resorption and mineralization. All variants associated with otosclerosis are predicted to result in nonsense mediated decay or an ASARM-and-RGD-truncated MEPE. The HCFP variant is predicted to produce an ASARM-truncated MEPE with an intact RGD motif. This difference in effect on the protein corresponds with the presumed pathophysiology of both diseases, and provides a plausible molecular explanation for the distinct phenotypic outcome.

A novel homozygous HOXB1 mutation in a Turkish family with hereditary congenital facial paresis.

Hereditary congenital facial paresis (HCFP) is characterized by isolated dysfunction of the facial nerve (CN VII) due to congenital cranial dysinnervation disorders. HCFP has genetic heterogeneity and HOXB1 is the first identified gene. We report the clinical, radiologic and molecular investigations of three patients admitted for HCFP in a large consanguineous Turkish family. High-throughput sequencing and Sanger sequencing of all patients revealed a novel homozygous mutation p.Arg230Trp (c.688C>T) within the HOXB1 gene. The report of the mutation brings the total number of HOXB1 mutations identified in HCFP to four. The results of this study emphasize that in individuals with congenital facial palsy accompanied by hearing loss and dysmorphic facial features, HOXB1 mutation causing HCFP should be kept in mind.

Facial paralysis induced by ear inoculation of herpes simplex virus in rat.

OBJECTIVE: Bell's palsy is caused by the reactivation of herpes simplex virus type 1 (HSV-1). Using Balb/c mice inoculated with the KOS strain of HSV-1, we previously developed an animal disease model that simulated mild Bell's palsy. The current study developed an animal disease model of more severe facial palsy than that seen in the mouse model. METHODS: Three-week-old female Wister rats weighing 60-80g were inoculated on the auricle with HSV-1 and acyclovir was administered intraperitoneally to deactivate the infected HSV-1. Instead of HSV-1, phosphate-buffered saline was used for inoculation as a negative control. Quantitative polymerase chain reaction (PCR), behavior testing (blink reflex), electroneuronography, histopathology of the peripheral nerve, and immunohistochemistry of the facial nerve nucleus were evaluated. RESULTS: Facial palsy occurred 3-5 days after virus inoculation, and the severity of the facial palsy progressed for up to 7 days. Quantitative PCR showed an increase in HSV-1 DNA copies in the facial nerve from 24 to 72h, suggesting that HSV-1 infection occurred in the nerve. Electroneuronography values were 33.0±15.3% and 110.0±18.0% in HSV-1-inoculated and control rats, respectively. The histopathology of the peripheral nerve showed demyelination and loss of the facial nerve, and the facial nerve nucleus showed degeneration. CONCLUSION: Facial palsy developed in Wister rats following inoculation of the KOS strain of HSV-1 onto the auricles. The behavioral, histopathological, and electroneuronography data suggested that the severity of facial palsy was greater in our rats than in animals in the previous mouse disease model.

Comparison of trophic factors' expression between paralyzed and recovering muscles after facial nerve injury. A quantitative analysis in time course.

After peripheral nerve injury, recovery of motor performance negatively correlates with the poly-innervation of neuromuscular junctions (NMJ) due to excessive sprouting of the terminal Schwann cells. Denervated muscles produce short-range diffusible sprouting stimuli, of which some are neurotrophic factors. Based on recent data that vibrissal whisking is restored perfectly during facial nerve regeneration in blind rats from the Sprague Dawley (SD)/RCS strain, we compared the expression of brain derived neurotrophic factor (BDNF), fibroblast growth factor-2 (FGF2), insulin growth factors 1 and 2 (IGF1, IGF2) and nerve growth factor (NGF) between SD/RCS and SD-rats with normal vision but poor recovery of whisking function after facial nerve injury. To establish which trophic factors might be responsible for proper NMJ-reinnervation, the transected facial nerve was surgically repaired (facial-facial anastomosis, FFA) for subsequent analysis of mRNA and proteins expressed in the levator labii superioris muscle. A complicated time course of expression included (1) a late rise in BDNF protein that followed earlier elevated gene expression, (2) an early increase in FGF2 and IGF2 protein after 2 days with sustained gene expression, (3) reduced IGF1 protein at 28 days coincident with decline of raised mRNA levels to baseline, and (4) reduced NGF protein between 2 and 14 days with maintained gene expression found in blind rats but not the rats with normal vision. These findings suggest that recovery of motor function after peripheral nerve injury is due, at least in part, to a complex regulation of lesion-associated neurotrophic factors and cytokines in denervated muscles. The increase of FGF-2 protein and concomittant decrease of NGF (with no significant changes in BDNF or IGF levels) during the first week following FFA in SD/RCS blind rats possibly prevents the distal branching of regenerating axons resulting in reduced poly-innervation of motor endplates.

Expression of aquaporin 2 following facial nerve crush in rats.

CONCLUSION: We demonstrated an early increase in aquaporin 2 (AQP2) expression in a motor nerve (extratemporal facial nerve, FN) following acute peripheral compression (crush), concomitant to effective development of motor dysfunction (facial palsy). The early increase in AQP2 expression that occurred concomitantly with the appearance of a deficit in a peripheral motor nerve suggests that this protein is involved in the physiological events associated with post-injury edema, similar to the already demonstrated behavior of AQP4 in the central nervous system (CNS). OBJECTIVE: The aim of this study was to assess the expression of AQP2 in the FN of rats up to 7 days after crush. METHODS: The extratemporal trunk of the right FN of rats was subjected to mechanical crush, and the expression of AQP2 in the affected (right) and non-affected (left) FN was measured by means of western blotting at days 1, 3, and 7 after injury. Behavioral analysis of the development of facial palsy was also performed over the same time period. RESULTS: Increased expression of AQP2 was shown in the affected FN compared with its corresponding control at day 1 after compression, simultaneously with the appearance of facial palsy.

Mitochondrial Cyclophilin D as a Potential Therapeutic Target for Ischemia-Induced Facial Palsy in Rats.

Many studies have demonstrated that ischemia could induce facial nerve (FN) injury. However, there is a lack of a suitable animal model for FN injury study and thus little knowledge is available about the precise mechanism for FN injury. The aims of this study were to establish a reliable FN injury model induced by blocking the petrosal artery and to investigate whether dysfunctional interaction between cyclophilin D (CypD) and mitochondrial permeability transition pore (MPTP) can mediate cell dysfunction in ischemic FN injury. The outcomes of ischemia-induced FN injury rat model were evaluated by behavioral assessment, histological observation, electrophysiology, and electron microscopy. Then the levels of CypD and protein that forms the MPTP were evaluated under the conditions with or without the treatment of Cyclosporin A (CsA), which has been found to disrupt MPTP through the binding of CypD. The blocking of petrosal artery caused significant facial palsy signs in the ischemia group but not in the sham group. Furthermore, ischemia can induce the dysfunction of facial nucleus neurons and destruction of the myelin sheath and increase the protein levels of CypD and MPTP protein compared with sham group. Interestingly, treatment with CsA significantly improved neurological function and reversed the ischemia-induced increase of CypD and MPTP proteins in ischemia group. These results demonstrated that blocking of petrosal artery in rats can induce FN injury and the mechanism may be related to the disruption of MPTP by CypD.

The alteration of SHARPIN expression in the mouse brainstem during herpes simplex virus 1-induced facial palsy.

Bell's palsy presents a unilateral weakness or paralysis of the face due to acute dysfunction of the peripheral facial nerve with no readily identifiable cause. Although data show that herpes simplex virus type 1 (HSV-1) may be the possible causative agent of Bell's palsy, the precise mechanism of the paralysis is still unknown. SHANK-associated RH domain-interacting protein (SHARPIN) is thought to play a role in the control of inflammatory responses. In order to clarify the molecular pathway of SHARPIN involved in the facial palsy caused by HSV-1 in mice and the inhibitory effect of corticosteroids, we used 4-week-old Balb/c mice inoculated with HSV-1 for experiments. The expression and location of SHARPIN in the facial nucleus of brainstem were detected respectively by quantitative real-time polymerase chain reaction, western blot and immunofluorescence. Expression level of SHARPIN increased and peaked at 2 days and then decreased in the facial nucleus of brainstem after the manifestation of the facial paralysis. After the administration of MPSS, the protein expression of SHARPIN at the peak point was down-regulated. Our results suggest that SHRPIN were activated during the inflammatory reaction in the HSV-1-induced facial paralysis. MPSS can effectively inhibit the expression of SHARPIN that may contribute to attenuate HSV-1-mediated nervous system damage.

The alterations of matrix metalloproteinase-9 in mouse brainstem during herpes simplex virus type 1-induced facial palsy.

The aim of this study is to explore the changes of matrix metalloproteinase-9 (MMP9) in the mouse brainstem during the development of facial paralysis induced by herpes simplex virus type 1 (HSV-1) and the inhibitory effect of methylprednisolone sodium succinate (MPSS) on MMP9 expression. HSV-1 was inoculated into the surface of posterior auricle of mouse to establish a paralyzed animal model. The paralyzed mice were divided randomly into three groups. In one group without any treatment, mice were killed at different time points of 6 h, 1, 2, 3, and 7 days post-induction of facial paralysis; in the other two groups, mice were injected daily with MPSS and a combination of MPSS and glucocorticoid receptor blocker (RU486) for 2 days, respectively. The expression of MMP9 in the facial nucleus of brainstem was detected by Western blot, quantitative real-time polymerase chain reaction, and immunofluorescence technique. A total of 52.07 % of mice developed unilateral facial paralysis after inoculated with HSV-1. Both mRNA and protein expression of MMP9 were present at low levels in normal facial nucleus of brainstem and were increased significantly after facial paralysis with its peak time at 2 days post-induction of facial paralysis. Expression of MMP9 of paralyzed mice was inhibited by MPSS, and the inhibition could be blocked by RU486. Our findings suggest that MMP9 in mouse brainstem is involved in the evolution of facial palsy induced by HSV-1 and may play an important role in the pathogenesis of this disease. MPSS might effectively relieve HSV-1-mediated damages by inhibitory effect on expression of MMP9 in HSV-1-induced facial paralysis.

Myogenin expression in facial muscle following damage to the facial nerve.

CONCLUSION: Gene analysis of facial muscle may be a promising way to detect denervation of facial muscle, helping to determine the prognosis of a facial palsy early in its progression. OBJECTIVES: In the treatment of intratemporal facial palsy, early diagnosis of neural damage is important in deciding about therapeutic modalities. In this study, we investigated the relationship between the severity of facial palsy and the level of myogenin expressed in the facial muscle. METHODS: The animals were divided into two groups, depending on whether the facial nerve was resected or compressed. Expression of myogenin mRNA was examined using real-time PCR and in situ hybridization of the facial muscle following the nerve damage. RESULTS: Increased expression of myogenin was observed in the nerve resection group, while no such increase was seen in the nerve compression group. In situ hybridization indicated that myogenin was expressed exclusively in satellite cells around the denervated muscle fibers.

A Phe377del mutation in ANK leads to impaired osteoblastogenesis and osteoclastogenesis in a mouse model for craniometaphyseal dysplasia (CMD).

Craniometaphyseal dysplasia (CMD) is a rare genetic disorder with hyperostosis of craniofacial bones and widened metaphyses in long bones. Patients often suffer from neurological symptoms due to obstruction of cranial foramina. No proven treatment is available and the pathophysiology is largely unknown. A Phe377 (TTC(1130-1132)) deletion in exon 9 of the pyrophosphate (PPi) transporter ANK leads to CMD-like features in an Ank(KI/KI) mouse model. Here, we investigated the effects of CMD-mutant ANK on mineralization and bone mass at a cellular level. Ank(KI/KI) osteoblast cultures showed decreased mineral deposition. Expression of bone mineralization regulating genes Mmp13, Ocn, Osx and Phex was reduced in Ank(KI/KI) osteoblasts, while the Fgf23 mRNA level was highly elevated in Ank(KI/KI) calvarial and femoral bones. Since ANK is a known PPi transporter, we examined other regulators of Pi/PPi homeostasis Enpp1 and Tnap. Significantly increased ENPP1 activity may compensate for dysfunctional mutant ANK leading to comparable extracellular PPi levels in Ank(+/+) osteoblasts. Similar to Ank(KI/KI) bone marrow-derived macrophage cultures, peripheral blood cultures from CMD patients exhibited reduced osteoclastogenesis. Cell-autonomous effects in Ank(KI/KI) osteoclasts resulted in disrupted actin ring formation and cell fusion. In addition, Ank(KI/KI) osteoblasts failed to adequately support osteoclastogenesis. Increased bone mass could partially be rescued by bone marrow transplants supporting our hypothesis that reduced osteoclastogenesis contributes at least in part to hyperostosis. We conclude that the Phe377del mutation in ANK causes impaired osteoblastogenesis and osteoclastogenesis resulting in hypomineralization and a high bone mass phenotype.

Different conjunctival adaptive response in patients with aqueous-deficient and with mucous-deficient dry eyes.

PURPOSE: To describe the different cellular adaptive patterns found in the conjunctival epithelium from patients with aqueous-deficient and mucous-deficient dry eyes. METHODS: The authors studied different conjunctival areas, by impression cytology and by biopsy, 50 eyes with facial nerve paralysis (FNP), 50 eyes with ocular cicatricial pemphigoid (OCP), and 50 eyes from patients with primarily Sjögren syndrome (1SS). RESULTS: Eyes with FNP from the first clinical grade showed a progressive alteration of the nonsecretory cells, with a significant decrease in density goblet cells, generally with a PAS-positive staining. Eyes with OCP, during clinical grades 1 and 2, showed a slow deterioration of the nonsecretory cells; but from clinical grade 3, there was a significant increase of the cellular size and the thickness of the conjunctiva. Goblet cells showed a significant decrease in density from clinical grade 1, generally with a PAS-negative staining. Eyes with 1SS during clinical grades 1 and 2 showed a progressive alteration of the nonsecretory cells, with a significant decrease in density goblet cells, and a PAS-positive staining. From clinical grade 3 appeared a significant increase of nonsecretory cellular size and thickness of conjunctiva, with a significant decrease in goblet cell counts, and a PAS-negative staining. CONCLUSIONS: Patients with FNP (a primarily aqueous-deficient alteration) follow completely the squamous metaplasia process. Patients with OCP (a primarily mucous-deficient syndrome) have a hypertrophy and hyperplasia process along the ocular surface. Patients with 1SS (a primarily aqueous-deficient and mucin-deficient alteration) have a squamous metaplasia process, but from clinical grade 3 also appears a hypertrophy and hyperplasia process.

Long-term adaptation of human microneurovascular muscle flaps to the paralyzed face: an immunohistochemical study.

The purpose of this study was to characterize microneurovascular (MNV) muscle transplants immunohistochemically up to 10 years after transfer. Histological data was related to long-term functional outcome. The study comprised 17 patients with a mean age of 41 years suffering from complete unilateral long-lasting facial paralysis. A two-stage procedure was performed between 1986 and 2001. The gracilis, latissimus dorsi, and serratus muscles were used in four, eight, and five patients, respectively. Eighteen biopsy samples were taken from MNV muscle grafts during secondary refinement procedures. In one patient, the tissue samples were collected at two different time points. Immunohistochemistry testing revealed muscle fiber type distribution (anti-myosin fast), proliferating satellite cells (Ki-67), and reinnervation (S-100). Muscle atrophy was assessed histomorphometrically. In a recent study, patient characteristics and the function of the flap were evaluated. Histological data were compared with clinical data and long-term functional outcomes of the patients. In biopsy samples taken 1-10 (mean 31 months) years after MNV muscle transfer, the mean muscle fiber diameter was 38 (range 14-70) microm, indicating a 40% decrease compared with control values. Muscle atrophy was not type-specific and the mean percentage of type II fibers was not altered. Individual variation was, however, considerable. Proliferative activity of satellite cells was seen in 60% of the samples but it tended to decline with an increase in follow-up time. All samples showed intramuscular reinnervation. In statistical analysis severe atrophy correlated with prolonged intraoperative ischemia (P=0.04). The good long-term functional outcome correlated with dominance of fast fibers in muscle grafts (P=0.03). Atrophy tended to be more pronounced in the serratus than in the other muscles (ns). In summary, despite dense muscle reinnervation, morphology of the muscle is not fully restored after muscle transfer. Ischemia time affects muscle morphology. Adaptation of the graft to fast-twitch muscle activity favors better mimic function. The proliferative activity of satellite cells declines with prolonged follow-up time.

Facial nerve section induces transient changes in sensitivity to methacholine and in acetylcholine synthesis in the rat parotid gland.

Nerves exert long-term influences on the salivary glands as e.g. revealed by increases in sensitivity to secretagogues following nerve degeneration. The objective was to study the effect of unilateral facial nerve section on the sensitivity of the parotid secretory cells 2-3 weeks postoperatively, i.e. at a time when the sensitisation is thought to be fully developed. Comparisons were made between pair of glands. However, no increase in the secretory response to increasing intravenous doses of methacholine of the duct-cannulated gland on the operated side was found; neither were any decrease in the acetylcholine synthesizing capacity of the gland found. In contrast, a slight supersensitivity had developed 1 week postoperatively supporting the idea of a functional influence of the facial nerve on the secretory cells under normal conditions. Furthermore, the results combined with the previous finding of ours of decreased acetylcholine synthesis in the parotid gland 1 week after facial nerve section, suggest a rapid restitution of the nervous influence on the secretory cells between 1 and 2-3 weeks postoperatively.

Acute peripheral facial palsy in adults.

OBJECTIVE: To collect epidemiological data of peripheral facial palsy, and especially to chart the incidence and clinical characteristics of Lyme associated facial palsy. MATERIAL AND METHODS: We included consecutive adult patients presenting with peripheral facial palsy in Vest-Agder County from January 1997 to December 1998. The facial palsy was graded according to the House and Brackman facial function scoring system,and cerebrospinal fluid and serum samples were examined for Borrelia burgdorferi antibodies and virus antibodies. Final outcome was evaluated by follow up visits or telephone interview. RESULTS: Sixty nine patients were included and followed until complete recovery, or for 5 years. Ten per cent were caused by Lyme disease, 17% by virus infection, 4% by other causes and 68% were classified as Bell's palsy. All patients with Lyme facial palsy had additional neurological symptoms, and 87% reported constitutional complaints. The overall final outcome was good with complete recovery in 77%, slight sequelae in 20% and moderate sequelae in 3%. No patients experienced severe sequelae. Two of 28 patients examined with neurography had absent compound muscle action potentials in orbicularis oculi. Both made good recovery with only slight sequelae. CONCLUSIONS: Peripheral facial palsy is a common disorder with a favourable prognosis. Lyme disease seems to be an infrequent cause of facial palsy in patients without constitutional symptoms or additional neurological findings.