Is pre-operative electromyography a reliable tool in differentiating acute and chronic facial palsy? A preliminary evaluation in patients treated with triple innervation facial reanimation.

Electromyographic evaluation is a reliable tool for confirming facial palsy and assessing its severity. It allows differentiating facial paresis and paralysis, and further distinguishes acute palsies, still showing muscle fibrillations, from chronic cases. This article aims to show that EMG fibrillations might represent a better criterion to differentiate acute and chronic palsies than the standard 18-24 months' cut-off usually employed for classification and treatment purposes. We performed a cohort study using the eFACE tool for comparing triple innervation facial reanimation results in patients with EMG fibrillation treated <12 months, 12-18 months, and >18 months from paralysis onset. Patients showed a statistically significant post-operative improvement in all eFACE items, both in the whole sample and in the three groups. Only the deviation from the optimal score for the gentle eye closure item in group 2 didn't reach statistical significance (p = 0.173). The post-operative results were comparable in the three groups, as the Kruskal-Wallis test showed a difference only for the platysmal synkinesis item scores, which were significantly lower in group 3 (p = 0.025).

Long-term treatment of hereditary transthyretin amyloidosis with patisiran: multicentre, real-world experience in Italy.

BACKGROUND: Hereditary transthyretin (ATTRv, v for variant) amyloidosis with polyneuropathy is a rare disease caused by mutations in the transthyretin gene. In ATTRv amyloidosis, multisystem extracellular deposits of amyloid cause tissue and organ dysfunction. Patisiran is a small interfering RNA molecule drug that reduces circulating levels of mutant and wild-type TTR proteins. Prior to its regulatory approval, patisiran was available in Italy through a compassionate use programme (CUP). The aim of this study was to analyse the long-term outcomes of patients who entered into the CUP. METHODS: This was a multicentre, observational, retrospective study of patients with ATTRv amyloidosis treated with patisiran. The analysis included change from baseline to 12, 24, 36 and 48 months in familial amyloid polyneuropathy (FAP) stage, polyneuropathy disability (PND) class, neuropathy impairment score (NIS), modified body mass index (mBMI), Compound Autonomic Dysfunction Test (CADT), Karnofsky Performance Status (KPS) scale and Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) questionnaire. Safety data were also analysed. RESULTS: Forty patients from 11 Italian centres were enrolled: 23 in FAP 1 (6 in PND 1 and 17 in PND 2) and 17 in FAP 2 (8 in PND 3a and 9 in PND 3b) stage. In this population, the mean NIS at baseline was 71.4 (± 27.8); mBMI, 917.1 (± 207) kg/m2; KPS, 67.1 (± 14.0); Norfolk QoL-DN, 62.2 (± 25.2); and CADT, 13.2 (± 3.3). Statistical analysis showed few significant differences from baseline denoting disease stability. No new safety signals emerged. CONCLUSIONS: Patisiran largely stabilised disease in patients with ATTRv amyloidosis.

Magnetic resonance neurography and diffusion tensor imaging of the sciatic nerve in hereditary transthyretin amyloidosis polyneuropathy.

The therapeutic advance in hereditary transthyretin amyloidosis (ATTRv amyloidosis) requires quantitative biomarkers of nerve involvement in order to foster early diagnosis and monitor therapy response. We aimed at quantitatively assessing Magnetic Resonance Neurography (MRN) and Diffusion Tensor Imaging (DTI) properties of the sciatic nerve in subjects with ATTRv-amyloidosis-polyneuropathy (ATTRv-PN) and pre-symptomatic carriers (ATTRv-C). Twenty subjects with pathogenic variants of the TTR gene (mean age 62.20 ± 12.04 years), 13 ATTRv-PN, and 7 ATTRv-C were evaluated and compared with 20 healthy subjects (mean age 60.1 ± 8.27 years). MRN and DTI sequences were performed at the right thigh from the gluteal region to the popliteal fossa. Cross-sectional-area (CSA), normalized signal intensity (NSI), and DTI metrics, including fractional anisotropy (FA), mean (MD), axial (AD), and radial diffusivity (RD) of the right sciatic nerve were measured. Increased CSA, NSI, RD, and reduced FA of sciatic nerve differentiated ATTRv-PN from ATTRv-C and healthy subjects at all levels (p < 0.01). NSI differentiated ATTRv-C from controls at all levels (p < 0.05), RD at proximal and mid-thigh (1.04 ± 0.1 vs 0.86 ± 0.11 p < 0.01), FA at mid-thigh (0.51 ± 0.02 vs 0.58 ± 0.04 p < 0.01). According to receiver operating characteristic (ROC) curve analysis, cutoff values differentiating ATTRv-C from controls (and therefore identifying subclinical sciatic involvement) were defined for FA, RD, and NSI. Significant correlations between MRI measures, clinical involvement and neurophysiology were found. In conclusion, the combination of quantitative MRN and DTI of the sciatic nerve can reliably differentiate ATTRv-PN, ATTRv-C, and healthy controls. More important, MRN and DTI were able to non-invasively identify early subclinical microstructural changes in pre-symptomatic carriers, thus representing a potential tool for early diagnosis and disease monitoring.

Muscle quantitative MRI as a novel biomarker in hereditary transthyretin amyloidosis with polyneuropathy: a cross-sectional study.

BACKGROUND: The development of reproducible and sensitive outcome measures has been challenging in hereditary transthyretin (ATTRv) amyloidosis. Recently, quantification of intramuscular fat by magnetic resonance imaging (MRI) has proven as a sensitive marker in patients with other genetic neuropathies. The aim of this study was to investigate the role of muscle quantitative MRI (qMRI) as an outcome measure in ATTRv. METHODS: Calf- and thigh-centered multi-echo T2-weighted spin-echo and gradient-echo sequences were obtained in patients with ATTRv amyloidosis with polyneuropathy (n = 24) and healthy controls (n = 12). Water T2 (wT2) and fat fraction (FF) were calculated. Neurological assessment was performed in all ATTRv subjects. Quantitative MRI parameters were correlated with clinical and neurophysiological measures of disease severity. RESULTS: Quantitative imaging revealed significantly higher FF in lower limb muscles in patients with ATTRv amyloidosis compared to controls. In addition, wT2 was significantly higher in ATTRv patients. There was prominent involvement of the posterior compartment of the thighs. Noticeably, FF and wT2 did not exhibit a length-dependent pattern in ATTRv patients. MRI biomarkers correlated with previously validated clinical outcome measures, Polyneuropathy Disability scoring system, Neuropathy Impairment Score (NIS) and NIS-lower limb, and neurophysiological parameters of axonal damage regardless of age, sex, treatment and TTR mutation. CONCLUSIONS: Muscle qMRI revealed significant difference between ATTRv and healthy controls. MRI biomarkers showed high correlation with clinical and neurophysiological measures of disease severity making qMRI as a promising tool to be further investigated in longitudinal studies to assess its role at monitoring onset, progression, and therapy efficacy for future clinical trials on this treatable condition.

Real-life experience with inotersen in hereditary transthyretin amyloidosis with late-onset phenotype: Data from an early-access program in Italy.

BACKGROUND AND PURPOSE: Hereditary transthyretin (TTR) amyloidosis (ATTRv) is a dominantly inherited, adult-onset, progressive, and fatal disease caused by mutations in the transthyretin gene. Therapeutic agents approved for this disease include the TTR stabilizer tafamidis and the gene-silencing drugs patisiran and inotersen. Inotersen is an antisense oligonucleotide that suppresses the hepatic production of transthyretin. After European Medical Agency approval in 2018, an early-access program was opened in Italy, and in this article, we present the long-term outcome of a cohort of Italian ATTRv patients who received inotersen within this program. METHODS: This is a multicenter, observational, retrospective study of patients affected by ATTRv that started inotersen during the early-access program. The primary end point was safety. Secondary end points included change from baseline in familial amyloid polyneuropathy (FAP) stage, Polyneuropathy Disability, Neuropathy Impairment Scale, Compound Autonomic Dysfunction Test, Norfolk Quality of Life-Diabetic Neuropathy, troponin, N-terminal pro-brain natriuretic peptide, interventricular septum thickness, and body mass index. RESULTS: In total, 23 patients were enrolled. No patient permanently discontinued the treatment because of thrombocytopenia, and no cases of severe thrombocytopenia were observed. Five patients discontinued the treatment permanently because of voluntary withdrawal (two patients), renal failure after infective pyelonephritis, not related to inotersen, drug-related hypotension, and amyloid-negative crescentic glomerulonephritis. In seven patients, dosing frequency was reduced to every 2 weeks due to recurrent thrombocytopenia. Considering the FAP stage, only two patients worsened, whereas the other 21 patients remained stable until the last follow-up available. CONCLUSIONS: The long-term safety profile of inotersen is favorable. Neurologic disease severity at baseline is the main factor associated with progression.

Progressive brachial plexus enlargement in hereditary transthyretin amyloidosis.

Axonal polyneuropathy is the main feature of hereditary transthyretin amyloidosis (ATTRv). Nerve morphological abnormalities have been reported, but longitudinal changes have never been assessed. We performed a prospective widespread nerve ultrasound evaluation and nerve cross-sectional area (CSA) was compared with baseline data in both ATTRv patients and pre-symptomatic carriers. Thirty-eight subjects were evaluated (mean follow-up 17.1 months), among them 21 had polyneuropathy while 17 were pre-symptomatic carriers. CSA significantly increased at brachial plexus in both groups (p = 0.008 and p = 0.012) pointing to progressive brachial plexus enlargement as a longitudinal biomarker of both disease progression and disease occurrence in pre-symptomatic carriers.

Nerve ultrasound in hereditary transthyretin amyloidosis: red flags and possible progression biomarkers.

BACKGROUND: Diagnostic delay of hereditary transthyretin amyloidosis (ATTRv, v for variant) prevents timely treatment and, therefore, concurs to the mortality of the disease. The aim of the present study was to explore with nerve ultrasound (US) possible red flags for early diagnosis in ATTRv patients with carpal tunnel syndrome (CTS) and/or polyneuropathy and in pre-symptomatic carriers. METHODS: Patients and pre-symptomatic carriers with a TTR gene mutation were enrolled from seven Italian centers. Severity of CTS was assessed with neurophysiology and clinical evaluation. Median nerve cross-section area (CSA) was measured with US in ATTRv carriers with CTS (TTR-CTS). One thousand one hundred ninety-six idiopathic CTS were used as controls. Nerve US was also performed in several nerve trunks (median, ulnar, radial, brachial plexi, tibial, peroneal, sciatic, sural) in ATTRv patients with polyneuropathy and in pre-symptomatic carriers. RESULTS: Sixty-two subjects (34 men, 28 women, mean age 59.8 years ± 12) with TTR gene mutation were recruited. With regard to CTS, while in idiopathic CTS there was a direct correlation between CTS severity and median nerve CSA (r = 0.55, p < 0.01), in the subgroup of TTR-CTS subjects (16 subjects, 5 with bilateral CTS) CSA did not significantly correlate with CTS severity (r = - 0.473). ATTRv patients with polyneuropathy showed larger CSA than pre-symptomatic carriers in several nerve sites, more pronounced at brachial plexi (p < 0.001). CONCLUSIONS: The present study identifies nerve morphological US patterns that may help in the early diagnosis (morpho-functional dissociation of median nerve in CTS) and monitoring of pre-symptomatic TTR carriers (larger nerve CSA at proximal nerve sites, especially at brachial plexi).

Direct Versus Indirect Corneal Neurotization for the Treatment of Neurotrophic Keratopathy: A Multicenter Prospective Comparative Study.

PURPOSE: To analyze the comparative safety and efficacy of two techniques of corneal neurotization (CN) (direct corneal neurotization [DCN] vs indirect corneal neurotization [ICN]) for the treatment of neurotrophic keratopathy (NK). DESIGN: Multicenter interventional prospective comparative case series. METHODS: This study took place at ASST Santi Paolo e Carlo University Hospital, Milan; S.Orsola-Malpighi University Hospital, Bologna; and Santa Maria alle Scotte University Hospital, Siena, Italy. The study population consisted of consecutive patients with NK who underwent CN between November 2014 and October 2019. The intervention procedures included DCN, which was was performed by transferring contralateral supraorbital and supratrochlear nerves. ICN was performed using a sural nerve graft. The main outcome measures included NK healing, corneal sensitivity, corneal nerve fiber length (CNFL) measured by in vivo confocal microscopy (IVCM), and complication rates. RESULTS: A total of 26 eyes in 25 patients were included: 16 eyes were treated with DCN and 10 with ICN. After surgery, NK was healed in all patients after a mean period of 3.9 months without differences between DCN and ICN. Mean corneal sensitivity improved significantly 1 year after surgery (from 3.07 to 22.11 mm; P < .001) without differences between the 2 groups. The corneal sub-basal nerve plexus that was absent before surgery in all patients, except 4, become detectable in all cases (mean CNFL: 14.67 ± 7.92 mm/mm2 1 year postoperatively). No major complications were recorded in both groups. CONCLUSIONS: CN allowed the healing of NK in all patients as well as improvement of corneal sensitivity in most of them thanks to nerve regeneration documented by IVCM. One year postoperatively, DCN and ICN showed comparable outcomes.

In Vivo and Ex Vivo Comprehensive Evaluation of Corneal Reinnervation in Eyes Neurotized With Contralateral Supratrochlear and Supraorbital Nerves.

PURPOSE: To use an automated morphometric analysis system of in vivo confocal microscopy (IVCM) images for evaluating reinnervation occurring at the subbasal nerve plexus (SNP) after direct corneal neurotization (DCN) and to further report neurophysiological and histopathological findings. METHODS: Prospective interventional case series including 3 eyes with neurotrophic keratitis that underwent DCN. Deep anterior lamellar keratoplasty was performed 18 months after DCN in patient 1. The following evaluations were performed before and at 3, 6, and 12 months after DCN: clinical evolution of keratitis; corneal sensitivity; IVCM images of the SNP analyzed with "ACCMetrics;" neurophysiological study of corneal reflex. Protein gene product 9.5 immunofluorescence staining assay and transmission electron microscopy were conducted on the neurotized button excised during deep anterior lamellar keratoplasty. RESULTS: Complete healing was obtained in all patients by 3 months postoperatively. Corneal sensitivity was absent preoperatively in all eyes and improved after surgery, reaching an average value of 30 mm 1 year postoperatively. The corneal SNP was not visible at IVCM in any of the cases preoperatively and became visible by 3 months postoperatively, showing IVCM metrics comparable to normal contralateral eyes at 1 year. In all cases, neurophysiological evaluation showed a partial recovery of the electrical activity of the cornea. In patient 1, protein gene product (PGP) 9.5 staining of neurotized cornea showed nerve fascicles at the SNP, whereas transmission electron microscopy showed amyelinic nerve axons and nerve endings. CONCLUSIONS: The corneal SNP exhibited IVCM metrics comparable to the normal contralateral eye 1 year after DCN. Ex vivo histopathological assessment of neurotized corneas confirmed the presence of nerves with normal ultrastructure.

Use of the masseteric nerve to treat segmental midface paresis.

Segmental midface paresis with or without synkinesis reflects incomplete recovery from Bell's palsy, operations on the cranial base or parotid, or trauma, in 25%-30% of cases. To correct the deficit, the masseteric nerve was used to deliver a powerful stimulus to the zygomatic muscle complex, with the addition of a cross-face sural nerve graft to ensure more spontaneous smiling. By doing this, the orbicularis oculi muscle continues to have an appropriate stimulus from the facial nerve, and the zygomatic muscle complex is separately innervated, which considerably reduces synkinesis between the two muscle compartments. For those patients with muscular contractures of the midface, the new healthy neural stimulus relaxes muscles at rest. From January 2011 to March 2017, 20 patients presented with segmental facial paresis of the midface and were operated on using this new technique. All patients were evaluated before and after operation using Clinician-Graded Electronic Facial Paralysis Assessment (eFACE), and they showed considerable postoperative improvements in static, dynamic, and synkinetic variables. Our proposed use of the masseteric nerve to treat segmental facial paresis produces favourable results, but our initial data require confirmation by further studies.

Objective Assessment of Lingual Nerve Microsurgical Reconstruction.

Lingual nerve (LN) injury is one of the most serious consequences of oral surgery. Prompt microsurgical reconstruction of the nerve can alleviate most of those symptoms leading to satisfactory functional recovery.Thirty-five patients with partial to complete LN injury underwent surgery in the period between January 2006 and May 2015. All patients underwent a preoperative clinical and neurological evaluation with the assessment of lingual tactile and pain sensory thresholds and masseteric inhibitory reflex.All patients underwent explorative surgery and direct microneurorrhaphy of distal and proximal stumps in case of complete lesion, while the removal of traumatic neuroma and the following microneurorrhaphy of distal and proximal stumps of the injured nerve was performed in case of incomplete lesion. Nerve grafting has always been avoided because of distal stump mobilization obtained by severing the submandibular branch of the LN.All patients but 1 exhibited good recovery of tongue sensation, never complete, both clinically and electrophysiologically: recovery of the excitability of masseteric inhibitory reflex suppression components SP1 and SP2 was observed, often with increased latencies but consistent with a functional recovery.All patients feeling pain preoperatively experienced complete relief of algic symptoms.The early microsurgical approach is the most suitable choice for the treatment of LN injuries.

Monocentric Prospective Study into the Sustained Effect of Incobotulinumtoxin A (XEOMIN®) Botulinum Toxin in Chronic Refractory Migraine.

Refractory chronic migraine is a disabling disorder impacting quality of life. BOTOX® (Onabotulinumtoxin A) is approved as a prophylactic treatment of chronic migraine in patients unresponsive to at least three prior preventive treatments. The objective of this study was to determine the prophylactic effect of 145 U XEOMIN® (Incobotulinumtoxin A) injected at 31 specific sites in adult patients with refractory chronic migraine. Sixty-one patients (8 men and 53 women, mean age 50) with migraine were recruited, including 20 patients with isolated chronic migraine, 18 patients with chronic migraine associating tension-type headache, 12 patients with migraine associating medication overuse headache, and 11 patients with episodic disabling migraine. The mean number of injections and duration of treatment per patient was 3.5 (range 2⁻13) and 21 (6⁻68) months, respectively. From baseline to first injection, 44 patients (73%) had >50% reduction in frequency of migraine episodes, 29 patients (48%) showed >50% reduction in number of headache days, and 28 patients (46%) had a >50% reduction in drug intake. Stable response for all three parameters was observed after the last injection. XEOMIN® thus seems to represent an effective and sustained prophylactic treatment of chronic migraine.

Mixed facial reanimation technique to treat paralysis in medium-term cases.

Recent facial paralyses, in which fibrillations of the mimetic muscles are still detectable by electromyography (EMG), allow facial reanimation based on giving new neural stimuli to musculature. However, if more time has elapsed, mimetic muscles can undergo irreversible atrophy, and providing a new neural stimulus is simply not effective. In these cases function is provided by transferring free flaps into the face or transposing masticatory muscles to reinstitute major movements, such as eyelid closure and smiling. In a small number of cases, patients affected by paralysis are referred late - more than 18 months after onset. In these cases, reinnervating the musculature carries a high risk of failure because some or all of the mimetic muscles may atrophy irreversibly while axonal ingrowth is taking place. A mixed reanimation technique to address this involves a neurorrhaphy between the masseteric nerve and a facial nerve branch for the orbicularis oculi, to ensure a stronger innervation to that muscle, associated with the transposition of the temporalis muscle to the nasiolabial sulcus. This gives good symmetry in the rest of the midface, while smiling movement is achievable, but not guaranteed. This one-time facial reanimation is particularly indicated for those who refuse major free-flap surgery or when that may be risky, as in previously operated and irradiated fields. More extensive procedures based on utilizing a free flap to recover smiling, while adding a cross-face nerve graft to restore blinking, may be proposed for motivated patients. Between 2010 and 2015, five patients affected by complete unilateral facial palsy underwent this technique in the Maxillofacial Surgery Department, San Paolo Hospital (Milan, Italy). Symmetry of the middle-third of the face at rest and recovery of smiling was quite good. Complete voluntary eyelid closure was obtained in all cases. Combining temporalis flap rotation and a masseteric-to-orbicularis-oculi-facial-nerve branch neurorrhaphy seems to be a valid solution for those medium-term referred patients.

Surgical treatment of synkinesis between smiling and eyelid closure.

Synkinetic movements are common among patients with incomplete recovery from facial palsy, with reported rates ranging from 9.1% to almost 100%. The authors propose the separation of the neural stimulus of the orbicularis oculi from that of the zygomatic muscular complex to treat eyelid closure/smiling synkinesis. This technique, associated with an anastomosis between the masseteric nerve and a central branch of the facial nerve, as well as with the use of a cross-facial nerve graft, resolves most of the spasms of the midface musculature, leading to a more relaxed tone when the mimic muscle is at rest and enhancing muscle excursion during voluntary and spontaneous smiling. Between 2011 and 2016, 18 patients affected by segmental paresis of the middle of the face underwent surgical treatment at the Maxillofacial Surgery Department of the San Paolo Hospital (Milan, Italy). Of these patients, 72.22% of cases with hypertone obtained partial to complete relaxation. Synkinesis was completely resolved in 83.33% of cases, and a significant improvement in facial movement was achieved in all patients. Neurorrhaphy of the masseteric nerve and the central branch of the facial nerve appears to produce favorable results. These initial data should be confirmed by further studies.

Surgical treatment of painful inferior alveolar nerve injuries following endodontic treatment: a consecutive case series of seven patients.

PURPOSE: Injuries of the inferior alveolar nerve (IAN) related to endodontic treatment are being increasingly reported. However, consensus on the preferred intervention and the timing of and indications for surgical treatment is lacking. Here, we describe our experience with painful IAN injuries arising from endodontic treatment and requiring prompt microsurgical treatment. METHODS: Seven consecutive patients with painful IAN injuries were referred to the Maxillofacial Surgery Unit of San Paolo Hospital in Milan. All patients had undergone root canals endodontic treatment in the mandibular molar or premolar between 2007 and 2014. The time elapsed between injury and referral for surgical treatment ranged from 10 days to 20 months. Each patient was treated by one of several different microsurgical procedures, described herein. RESULTS: Overall, neurosensory status and IAN-related pain improved in all seven patients. The best results were obtained by IAN replacement with a sural nerve graft. However, complete sensory recovery was not achieved in any of the patients. CONCLUSIONS: Although our sample includes only seven patients, early surgical treatment with an interpositional sural nerve graft seems to allow neurosensory recovery. Less satisfactory results are achieved in patients with IAN injuries of > 12 months duration.

Autoantibodies to nodal isoforms of neurofascin in chronic inflammatory demyelinating polyneuropathy.

Chronic inflammatory demyelination polyneuropathy is a heterogeneous and treatable immune-mediated disorder that lacks biomarkers to support diagnosis. Recent evidence indicates that paranodal proteins (contactin 1, contactin-associated protein 1, and neurofascin-155) are the targets of autoantibodies in subsets of patients showing distinct clinical presentations. Here, we identified neurofascin-186 and neurofascin-140 as the main targets of autoantibodies in five patients presenting IgG reactivity against the nodes of Ranvier. Four patients displayed predominantly IgG4 antibodies, and one patient presented IgG3 antibodies that activated the complement pathway in vitro. These patients present distinct clinical features compared to those with anti-neurofascin-155 IgG4. Most patients had a severe phenotype associated with conduction block or decreased distal motor amplitude. Four patients had a subacute-onset and sensory ataxia. Two patients presented with nephrotic syndromes and one patient with an IgG4-related retroperitoneal fibrosis. Intravenous immunoglobulin and corticosteroids were effective in three patients, and one patient remitted following rituximab treatment. Clinical remission was associated with autoantibody depletion and with recovery of conduction block and distal motor amplitude suggesting a nodo-paranodopathy. Our data demonstrate that the pathogenic mechanisms responsible for chronic inflammatory demyelination polyneuropathy are broad and may include dysfunctions at the nodes of Ranvier in a subgroup of patients.

Masseteric-facial nerve neurorrhaphy: results of a case series.

OBJECTIVE Facial palsy is a well-known functional and esthetic problem that bothers most patients and affects their social relationships. When the time between the onset of paralysis and patient presentation is less than 18 months and the proximal stump of the injured facial nerve is not available, another nerve must be anastomosed to the facial nerve to reactivate its function. The masseteric nerve has recently gained popularity over the classic hypoglossus nerve as a new motor source because of its lower associated morbidity rate and the relative ease with which the patient can activate it. The aim of this work was to evaluate the effectiveness of masseteric-facial nerve neurorrhaphy for early facial reanimation. METHODS Thirty-four consecutive patients (21 females, 13 males) with early unilateral facial paralysis underwent masseteric-facial nerve neurorrhaphy in which an interpositional nerve graft of the great auricular or sural nerve was placed. The time between the onset of paralysis and surgery ranged from 2 to 18 months (mean 13.3 months). Electromyography revealed mimetic muscle fibrillations in all the patients. Before surgery, all patients had House-Brackmann Grade VI facial nerve dysfunction. Twelve months after the onset of postoperative facial nerve reactivation, each patient underwent a clinical examination using the modified House-Brackmann grading scale as a guide. RESULTS Overall, 91.2% of the patients experienced facial nerve function reactivation. Facial recovery began within 2-12 months (mean 6.3 months) with the restoration of facial symmetry at rest. According to the modified House-Brackmann grading scale, 5.9% of the patients had Grade I function, 61.8% Grade II, 20.6% Grade III, 2.9% Grade V, and 8.8% Grade VI. The morbidity rate was low; none of the patients could feel the loss of masseteric nerve function. There were only a few complications, including 1 case of postoperative bleeding (2.9%) and 2 local infections (5.9%), and a few patients complained about partial loss of sensitivity of the earlobe or a small area of the ankle and foot, depending on whether great auricular or sural nerves were harvested. CONCLUSIONS The surgical technique described here seems to be efficient for the early treatment of facial paralysis and results in very little morbidity.

Nucleotide variation in Sabin type 3 poliovirus from an Albanian infant with agammaglobulinemia and vaccine associated poliomyelitis.

BACKGROUND: Vaccine-associated paralytic poliomyelitis (VAPP) and immunodeficient long-term polio excretors constitute a significant public health burden and are a major concern for the WHO global polio eradication endgame. CASE PRESENTATION: Poliovirus type 3 characterized as Sabin-like was isolated from a 5-month-old Albanian child with X-linked agammaglobulinemia and VAPP after oral polio vaccine administration. Diagnostic workup and treatment were performed in Italy. Poliovirus replicated in the gut for 7 months. The 5' non coding region (NCR), VP1, VP3 capsid proteins and the 3D polymerase genomic regions of sequential isolates were sequenced. Increasing accumulation of nucleotide mutations in the VP1 region was detected over time, reaching 1.0 % of genome variation with respect to the Sabin reference strain, which is the threshold that defines a vaccine-derived poliovirus (VDPV). We identified mutations in the 5'NCR and VP3 regions that are associated with reversion to neurovirulence. Despite this, all isolates were characterized as Sabin-like. Several amino acid mutations were identified in the VP1 region, probably involved in growth adaptation and viral persistence in the human gut. Intertypic recombination with Sabin type 2 polio in the 3D polymerase region, possibly associated with increased virus transmissibility, was found in all isolates. Gamma-globulin replacement therapy led to viral clearance and neurological improvement, preventing the occurrence of persistent immunodeficiency-related VDPV. CONCLUSIONS: This is the first case of VAPP in an immunodeficient child detected in Albania through the Acute Flaccid Paralysis surveillance system and the first investigated case of vaccine associated poliomyelitis in Italy since the introduction of an all-Salk schedule in 2002. We discuss over the biological and clinical implications in the context of the Global Polio Eradication Program and emphasize on the importance of the Acute Flaccid Paralysis surveillance.