Alice Frigerio

Port-wine stains (PWS) are capillary malformations, typically located in the dermis of the head and neck, affecting 0.3% of the population. Current theories suggest that port-wine stains are caused by somatic mutations that disrupt vascular development. Understanding PWS genetic determinants could provide insight into new treatments. Our study used a custom next generation sequencing (NGS) panel and digital polymerase chain reaction to investigate genetic variants in 12 individuals with isolated port-wine stains. Importantly, affected and healthy skin tissue from the same individual were compared. A subtractive correction method was developed to eliminate background noise from NGS data. This allowed the detection of a very low level of mosaicism. A novel somatic variant GNAQ, c.547C>G, p.Arg183Gly was found in one case with 4% allele frequency. The previously reported GNAQ c.548G>A, p.Arg183Gln was confirmed in 9 of 12 cases with an allele frequency ranging from 1.73 to 7.42%. Digital polymerase chain reaction confirmed novel variants detected by next generation sequencing. Two novel somatic variants were also found in RASA1, although neither was predicted to be deleterious. This is the second largest study on isolated, non-syndromic PWS. Our data suggest that GNAQ is the main genetic determinant in this condition. Moreover, isolated port-wine stains are distinct from capillary malformations seen in RASA1 disorders, which will be helpful in clinical evaluation.

The choice of the motor donor nerve is a crucial point in free flap transfer algorithms. In the case of unilateral facial paralysis, the contralateral healthy facial nerve can provide coordinated smile animation and spontaneous emotional expression, but with unpredictable axonal ingrowth into the recipient muscle. Otherwise, the masseteric nerve ipsilateral to the paralysis can provide a powerful neural input, without a spontaneous trigger of the smile. Harvesting a bulky muscular free flap may enhance the quantity of contraction but esthetic results are unpleasant. Therefore, the logical solution for obtaining high amplitude of smiling combined with spontaneity of movement is to couple the neural input: the contralateral facial nerve plus the ipsilateral masseteric nerve. Thirteen patients with unilateral dense facial paralysis underwent a one-stage facial reanimation with a gracilis flap powered by a double donor neural input, provided by both the ipsilateral masseteric nerve (coaptation by an end-to-end neurorrhaphy with the obturator nerve) and the contralateral facial nerve (coaptation through a cross-face nerve graft: end-to-end neurorrhaphy on the healthy side and end-to-side neurorrhaphy on the obturator nerve, distal to the masseteric/obturator neurorrhaphy). Their facial movements were evaluated with an optoelectronic motion analyzer. Before surgery, on average, the paretic side exhibited a smaller total three-dimensional mobility than the healthy side, with a 52% activation ratio and >30% of asymmetry. After surgery, the differences significantly decreased (analysis of variance (ANOVA), p < 0.05), with an activation ratio between 75% (maximum smile) and 91% (maximum smile with teeth clenching), and <20% of asymmetry. Similar modifications were seen for the performance of spontaneous smiles. The significant presurgical asymmetry of labial movements reduced after surgery. The use of a double donor neural input permitted both movements that were similar in force to that of the healthy side, and spontaneous movements elicited by emotional triggering.

To quantify the threshold for human perception of asymmetry for eyebrow elevation, eye closure, and smile, and to ascertain whether asymmetry detection thresholds and perceived severity of asymmetry differ in distinct facial zones. Online survey. Photographs of a female volunteer performing eyebrow elevation, eye closure, and smile were digitally manipulated to introduce left-to-right asymmetry in 1-mm increments from 0 mm to 6 mm. One hundred and forty-five participants viewed these photographs using an online survey, measuring accuracy of asymmetry detection and perceived expression unnaturalness (on a scale of 1-5). Photographs of facial asymmetries were correctly judged as asymmetrical over 90% of the time for 2 mm or more of asymmetry in eyelid closure, and 3 mm or more of asymmetry during smiling. Identification of eyebrow elevation asymmetry gradually rose from 23% correct to 97% correct across the range of 1 mm to 6 mm of asymmetry. Greater degrees of asymmetry were ranked as significantly more unnatural across all expressions (3 tests; X(2) (6, N = 145) = 405.52 to 656.27, all P <0.001). Thresholds for asymmetry detection vary across different zones of the face; once detected, asymmetry in eyelid position is perceived as more unnatural than asymmetries in either brow elevation or smile. These data will inform counseling of patients with segmental facial weakness and may provide more objective goals for facial reanimation procedures. 4.

One-stage free-flap facial reanimation may be accomplished by using a gracilis transfer innervated by the masseteric nerve, but this technique does not restore the patient's ability to smile spontaneously. By contrast, the transfer of the latissimus dorsi innervated by the contralateral facial nerve provides the correct nerve stimulus but is limited by variation in the quantity of contraction. The authors propose a new one-stage facial reanimation technique using dual innervation; a gracilis muscle flap is innervated by the masseteric nerve, and supplementary nerve input is provided by a cross-face sural nerve graft anastomosed to the contralateral facial nerve branch. Between October 2009 and March 2010, four patients affected by long-standing unilateral facial paralysis received gracilis muscle transfers innervated by both the masseteric nerve and the contralateral facial nerve. All patients recovered voluntary and spontaneous smiling abilities. The recovery time to voluntary flap contraction was 3.8 months, and spontaneous flap contraction was achieved within 7.2 months after surgery. According to Terzis and Noah's five-stage classification of reanimation outcomes, two patients had excellent outcomes and two had good outcomes. In this preliminary study, the devised double-innervation technique allows to achieve a good grade of flap contraction as well as emotional smiling ability. A wider number of operated patients are needed to confirm those initial findings.

Long-standing unilateral facial palsy is treated primarily with free-flap surgery using the masseteric or contralateral facial nerve as a motor source. The use of a gracilis muscle flap innervated by the masseteric nerve restores the smiling function, without obtaining spontaneity. Because emotional smiling is an important factor in facial reanimation, the facial nerve must serve as the motor source to achieve this fundamental target. From October 1998 to October 2009, 50 patients affected by long-standing unilateral facial paralysis underwent single-stage free-flap reanimation procedures to recover smiling function. A latissimus dorsi flap innervated by the contralateral facial nerve was transplanted in 40 patients, and a gracilis muscle flap innervated by the masseteric nerve in 10 patients. All patients underwent a clinical examination that analyzed voluntary and spontaneous smiling. All patients who received a latissimus dorsi flap innervated by the contralateral facial nerve and recovered muscle function (92.5%) showed voluntary and spontaneous smiling abilities. All patients who received a gracilis free flap innervated by the masseteric nerve recovered function, but only 1 (10%) showed occasional spontaneous flap activation. During those rare activations, much less movement was visible on the operated side than when the patient was asked to smile voluntarily. The masseteric nerve is a powerful motor source that guarantees free voluntary gracilis muscle activation; however, it does not guarantee any spontaneous smiling. Single-stage procedures that use a latissimus dorsi flap innervated by the contralateral facial nerve have a lower success rate and obtain less movement; however, spontaneous smiling is always observed.

Early repair of facial nerve paralysis when cortical neural input cannot be provided by the facial nerve nucleus, is generally accomplished anastomozing the extracranial stump of the facial nerve to a motor donor nerve. That is generally the hypoglossus, which carries a variable degree of morbidity. The present work aims to demonstrate the effectiveness of the masseteric nerve as donor for early facial reanimation, with the advantage that harvesting is associated with negligible morbidity. Between October 2007 and August 2009, 7 patients (2 males, 5 women) with unilateral facial paralysis underwent a masseter-facial nerves anastomosis with an interpositional nerve graft of the great auricular nerve. The interval between the onset of paralysis and surgery ranged from 8 to 48 months (mean 19.2 months). All patients included in the study had signs of facial mimetic muscle fibrillations on electromyography. The degree of preoperative facial nerve dysfunction was grade VI following the House-Brackmann scale for all patients. At the time of the study, all the patients with a minimum follow-up time of 12 months after the onset of mimetic function had recovered facial animation. Facial muscles showed signs of recovery within 2-9 months, mean 4.8 months, with the restoration of facial symmetry at rest. Facial movements appeared while the patients activated their chewing musculature. Morbidity related to this intervention is only the loss of sensitivity of earlobe and preauricular region. The present technique seems to be a valid alternative to classical hypoglossal-facial nerve anastomosis because of similar facial nerve recovery and lower morbidity.

Between April 1999 and April 2008, 37 patients with long-standing facial paralysis underwent a one-stage facial reanimation with neuromuscular free flaps: 28 patients (group A) underwent flap transposition only; 9 patients (group B) underwent a deep-planes lift (DPL) composed of the superficial muscoloaponeurotic system + parotid fascia at the time of facial reanimation. The postoperative and final results were compared between groups A and B, following the classification of Terzis and Noah (1997). Before the onset of contraction, only group B patients (100%) showed good or moderate symmetry at rest, while none of the patients of group A had a symmetric face. The respective final results for patients in groups A and B who already showed the onset of flap contraction were excellent in 28.6% and 44.5%, good in 42.9% and 33.3%, moderate in 10.7% and 22.2%, and fair or poor and fair in 17.8% and 0% of patients, respectively. The DPL allows immediate symmetry of the face at rest and contributes to upgrading the final static and dynamic results in facial reanimation with free muscular flaps.

Surgical treatment of parotid malignancies may frequently involve facial nerve amputation to achieve oncological radical resection. The entire facial nerve branching from its exit from the stylomastoid foramen to the periphery of the gland is often sacrificed. The first reconstructive strategy is the immediate reconstruction of the facial nerve by directly anastomosing the trunk of the facial nerve to its distal branches by interpositional nerve grafting. The present study was performed to determine the adequacy of thoracodorsal nerve grafting for immediate repair of the facial nerve. The anatomical features of the thoracodorsal nerve make it particularly appropriate to match its trunk to the stump of the facial nerve at its exit from the stylomastoid foramen. Up to seven branches of the thoracodorsal nerve may be distally anastomosed to the severed distal branches of the facial nerve. More complex reconstruction may be addressed simultaneously by contemporary harvesting a de-epithelialized free flap from the same site based on thoracodorsal vessel perforators and preparing a rib graft from the same donor site. Between October 2003 and August 2010, seven patients affected by parotid tumors (6 with parotid malignancies and 1 with multiple recurrences of pleomorphic adenoma) underwent radical parotidectomy with intentional sacrifice of the facial nerve to obtain oncological radical resection. In all patients, the facial nerve was reconstructed with an interpositional thoracodorsal nerve graft. In four patients, a de-epithelialized free flap based on the latissimus dorsi was transposed to cover soft tissue defects. Moreover, two of these patients also required a rib graft to reconstruct both the condyle and ramus of the mandible. With the exception of one patient affected by recurrent pleomorphic adenoma, all patients underwent radiotherapy after surgical treatment. All patients in our study recovered mimetic facial function. Facial muscles showed clinical signs of recovery within 5-14 (mean: 7.8) months, with varying degrees of mimetic restoration, and almost complete facial symmetry at rest in all patients. The House-Brackmann final score was I in two patients, II in two patients, and III in three patients. A thoracodorsal nerve graft to replace extratemporal facial nerve branching is a valid alternative technique to multiple classical nerve grafts, with good matching at both the proximal and distal anastomoses.

To quantify the effects of facial palsy reanimation, 14 patients aged 17-66 years were analysed. All patients had unilateral facial paralysis, and were candidates for surgical masseteric to facial nerve anastomosis. Two patient groups were measured: seven patients were waiting for surgery, the other seven patients had already been submitted to surgery, and had regained facial mimicry. Each patient performed three facial animations: brow raise; free smile; lip purse. These were recorded using an optoelectronic motion analyser. The three-dimensional coordinates of facial landmarks were obtained, their movements were computed, and asymmetry indices calculated (differential movements between the two hemi-faces: healthy and paretic/rehabilitated). Before surgery, mobility was larger in the healthy than in the paretic side; after surgery, the differences were reduced (brow raise and lip purse), or even reversed (smile). Before surgery, lip purse was performed with significant labial asymmetry (p=0.042; larger healthy side movement). After surgery, asymmetry indices reduced. Total labial asymmetry during smiling was significantly different from 0 before surgery (p=0.018, larger healthy side movement). After surgery, all asymmetry indices became non-significant. Before surgery the lateral displacements of all labial landmarks were towards the healthy side, while they normalized after surgery.

Surgical removal of large cervicofacial venous malformations might be hampered by massive intraoperative bleeding. Moreover, these lesions often insinuate within normal surrounding tissue, making complete resection impossible without causing significant morbidity. Two patients affected by facial venous malformations nonresponsive to sclerotherapy underwent surgery. Bleeding and critical branching of the facial nerve within the lesion prevented the surgeons from proceeding with the removal. The unresectable malformation was decompressed by means of a number of nonresorbable stitches from the surface of the lesion to the periosteum, tailoring a permanent pressure dressing. Outcomes at 12-month follow-up were stable, with good cosmetic results and satisfaction reported by both patients. No long-term side effects related to the procedure were observed. Decompression of large venous malformations by means of a strangling technique might represent a safe and effective procedure for those cases where a removal cannot be accomplished.

To present the combined treatment of fusiform basilar artery aneurysms consisting of a surgical posterior fossa decompressive craniectomy and ventriculoperitoneal (VP) shunt operation at the same sitting, before the endovascular procedure with telescopic stenting of the aneurysmatic vessel segment in four cases. Combined treatment involving surgical procedure consisting of ventriculoperitoneal shunt placement for hydrocephalus and an occipital bone craniectomy and C1 vertebrae posterior laminectomy to decompress the posterior fossa in the same session. After surgery, the patients were loaded with acetylsalicylic acid and clopidogrel, and then the endovascular treatment was performed. All of the procedures were performed successfully without technical difficulty. The patients tolerated the procedures well and all cases showed remodelling with the overlapping stent technique. The patients were discharged home with baseline neurological situation and computed tomography (CT) angiography was performed at the 3rd month. This technique is a safer endovascular approach to treating symptomatic fusiform basilar artery aneurysms by protecting patients from both the haemorrhagic complications of anticoagulant therapy and thrombotic complications due to the interruption of anticoagulant therapy, while treating the hydrocephalus and compression by surgical means.

Elicitation of eye closure and other movements via electrical stimulation may provide effective treatment for facial paralysis. The authors performed a human feasibility study to determine whether transcutaneous neural stimulation can elicit a blink in individuals with acute facial palsy and to obtain feedback from participants regarding the tolerability of surface electrical stimulation for daily blink restoration. Forty individuals with acute unilateral facial paralysis, HB grades 4 through 6, were prospectively studied between 6 and 60 days of onset. Unilateral stimulation of zygomatic facial nerve branches to elicit eye blink was achieved with brief bipolar, charge-balanced pulse trains, delivered transcutaneously by adhesive electrode placement; results were recorded on a high-speed video camera. The relationship between stimulation parameters and cutaneous sensation was analyzed using the Wong-Baker Faces Pain Rating Scale. Complete eye closure was achieved in 55 percent of pa...