Spontaneous Improvement Research Articles

Natural History and Treatment of Brown’s Syndrome: Long-Term Experience

Purpose: Brown’s Syndrome (BS) is a restrictive strabismus characterized by a limitation of elevation in adduction. Several etiologies have been described, usually involving the superior oblique muscle. Spontaneous improvement has been reported in several studies, so surgery is reserved for a minority of cases. Our purpose is to review the characteristics, natural history and treatment of this pathology and present the experience of the Instituto de Oftalmologia Dr. Gama Pinto (IOGP). Methods: A consecutive retrospective series of BS patients seen at the Strabismus Department of IOGP between 1983 and 2014 was reviewed. All patients with complete clinical data were included in this study. The epidemiologic characteristics, clinical features, treatment, and clinical progression were reviewed. Results: Thirty-nine cases were selected, with a mean age at first diagnosis of 6.5 years. Of the thirty-nine cases, 6 were iatrogenic and the remainder idiopathic. Thirty-six cases were followed for a mean period of 6.1 years. Surgical intervention for BS was performed in 11 patients, using different approaches. Of these, 9 cases were considered successful. The remaining 25 cases were kept under observation without surgery, of which 17 showed spontaneous improvement and the other 7 remained unchanged. Conclusions: The surgical success rate was 82%, which demonstrates the good efficacy of the surgery despite the complexity and variety of pathophysiological mechanisms of the syndrome. In the patients kept under observation there was spontaneous improvement in 68%, confirming that a conservative approach seems to be adequate in most cases.

Clinical profile and predictors of visual outcome in nonarteritic anterior ischemic optic neuropathy

Background: Nonarteritic anterior ischemic optic neuropathy (NAION) is a disorder of the optic nerve head causing acute painless visual loss in the elderly. Several ocular and systemic risk factors predispose to optic nerve head ischemia. Patients usually have a moderate visual loss which tends to stabilize in a few months, but complete recovery may not occur. Aim: This study aimed to study the clinical profile of NAION and to find the predictors of visual outcome in the study group. Materials and Methods: This prospective case series study included 25 patients with unilateral acute visual loss and clinical features suggestive of NAION. Detailed history and investigations were done to detect the risk factors implicated for the disease Patients were followed up for 6 months. Initial and final vision were analysed to assess the visual outcome. Statistical analysis was performed using SPSS. Results: Mean age was 58.08 ± 8.118 years. There was no gender predilection. The most common type of disc edema was diffuse hyperemic, and the most common field defect was inferior altitudinal. Systemic comorbid conditions such as dyslipidemia, smoking, hypotension, diabetes, and hypertension had higher odds of developing NAION even though not statistically significant. Correlation between initial vision and visual acuity at 6 months was statistically significant and spontaneous improvement in vision was seen in 16% of patients. Conclusion: Pallid disc edema and poor initial visual acuity were predictors of poor visual outcome. Female gender, hyperemic disc edema, and superior field defect had a favorable outcome. Associated comorbidities increased the risk of visual loss.

Clinical trial of celecoxib for recurrent respiratory papillomatosis

Recurrent respiratory papillomatosis (RRP), caused by HPV 6/11, is managed by surgery but papilloma frequently recur. COX-2 and its product PGE2 are overexpressed in RRP. Celecoxib, a COX-2 inhibitor, reduces papilloma cell proliferation, increases apoptosis and reduces HPV E6 and E7 expression. A pilot study of celecoxib therapy showed 2 of 3 patients with complete disease remission. We have now conducted a doubleblind placebo-controlled phase II clinical trial of the efficacy of celecoxib for RRP. Patients with moderate-tosevere disease were randomized to celecoxib or placebo for 1 year, then switched to the alternate treatment for 1 year. Surgery was performed every 3 months to remove all papilloma and assess rate of regrowth, with biopsies and blood collected at each surgery. Clinical response was defined as reduction in rate of regrowth of ≥50% for at least 6 months. Persistence of HPV was measured by qPCR. Fifty-one patients were enrolled, 33 competed the study. 64% had HPV6 and 36% had HPV11. 36% of patients improved on celecoxib, but there was no statistical difference between treatment and placebo groups. The rate of spontaneous improvement was much greater than expected. There was no correlation between Citation: Dr. Mark Shikowitz, Clinical trial of celecoxib for recurrent respiratory papillomatosis. Journal of Plastic Surgery and Case Studies Clinical trial of celecoxib for recurrent respiratory papillomatosis Mark Shikowitz The Feinstein Institute of Medical Research, USA. HPV type, duration of disease, gender, other demographic characteristics or celecoxib plasma levels and response. Patients with complete response still had latent HPV DNA in their airway epithelium. Immunology studies are in progress. In conclusion, we suspect celecoxib at this dose alone is not an effective treatment of RRP. However, combined with properly performed frequent surgery may positively impact immune response and the course of the disease.

Rodent Neural Progenitor Cells Support Functional Recovery after Cervical Spinal Cord Contusion.

Previously, we and others have shown that rodent neural progenitor cells (NPCs) can support functional recovery after cervical and thoracic transection injuries. To extend these observations to a more clinically relevant model of spinal cord injury, we performed unilateral midcervical contusion injuries in Fischer 344 rats. Two-weeks later, E14-derived syngeneic spinal cord-derived multi-potent NPCs were implanted into the lesion cavity. Control animals received either no grafts or fibroblast grafts. The NPCs differentiated into all three neural lineages (neurons, astrocytes, oligodendrocytes) and robustly extended axons into the host spinal cord caudal and rostral to the lesion. Graft-derived axons grew into host gray matter and expressed synaptic proteins in juxtaposition with host neurons. Animals that received NPC grafts exhibited significant recovery of forelimb motor function compared with the two control groups (analysis of variance p < 0.05). Thus, NPC grafts improve forelimb motor outcomes after clinically relevant cervical contusion injury. These benefits are observed when grafts are placed two weeks after injury, a time point that is more clinically practical than acute interventions, allowing time for patients to stabilize medically, simplifying enrollment in clinical trials, and enhancing predictability of spontaneous improvement in control groups.

Treatment for ventricular arrhythmias in the absence of structural heart disease: from guidelines to clinical practice

To determine criteria for choosing management tactics in patients with ventricular arrhythmias (VA) in the absence of structural heart disease from the point of view of physicians and patients in clinical practice and to compare the immediate results of antiarrhythmic drug therapy (ADT) and radiofrequency ablation (RFA) with the trends in arrhythmic syndrome in the non-treatment group. Examinations were made in 90 patients (23 men and 67 women) (mean age, 44 (31; 57) years) with VA in the absence of structural heart disease. Preference was given to RFA (n = 32 (36%)), ADT (n = 37 (41%)), and follow-up tactics (n = 21 (23%)). At baseline and 1 month, Holter ECG monitoring was done; quality of life (QOL) was assessed; and anxiety and depression levels were detected using the SF-36 and HADS questionnaires. In addition, 71 physicians were surveyed about their preferences to the treatment of VA in individuals without structural heart disease. In the total group of patients, VA was unambiguously accompanied by the symptoms only in 47%. The signs of anxiety and depression were identified in 41 and 14% of cases, respectively. The efficiency of RFA was comparable to that of ADT (p > 0.1): a positive antiarrhythmic effect was observed in 71.9% of the patients in the RFA group and in 67.6% in the ADT group. During one month, 38.1% of the patients in the follow-up group showed a spontaneous substantial reduction in the number of ventricular premature beats (VPBs) or disappearance of unstable ventricular tachycardia (UVT), which met the criteria for a positive effect. At baseline, the QOL indicators on a social functioning scale in the RFA group were worse than those in the ADT group. At the same time, most QOL indicators in the patients who have chosen a wait-and-see tactic were significantly higher than those in the RFA and ADT subgroups. The patients treated with ethacyzin in the ADT group more frequently achieved a positive effect. In the interviewed physicians' opinion, the choice of a tactic depended on the impact of arrhythmia on health status (68%), the number of VPBs per day (61%), and the presence of UVT (56%). RFA or ADT was most often recommended when there were 10,000-15,000 or more VPBs per day ((49 and 35% of the respondents, respectively). 46.5% of the respondents stated that β-blockers were the drug of choice for idiopathic frequent VPBs. Only 30% of the respondents considered it appropriate to restrict to a follow-up in the presence of asymptomatic VPBs. Patient management in clinical practice generally complies with the current guidelines; however, much importance is attached to the severity of arrhythmia (the number of VPBs per day, the presence of UVT) in addition to the presence of symptoms. In the opinion of most physicians, the initiation of treatment is justified when there are 10,000-15,000 and more per day. QOL assessment may be promising in choosing the optimal management tactics for these patients. Treatment should not be initiated immediately in patients with a high level of QOL, especially in those with arrhythmia lasting less than 12 months, by taking into account that there can be a spontaneous improvement in 38% of cases within the next month. The immediate results of ADT and RFA are comparable in patients with VA in the absence of structural heart disease. The Class IC antiarrhythmic drug ethacyzin is the most effective agent that ensures positive changes in arrhythmic syndrome in 66.7% of cases with the rate of side effects being in 17.8%.

Percutaneous endoscopic colostomy for adults with chronic constipation: Retrospective case series of 12 patients.

Percutaneous endoscopic colostomy (PEC) is a technique derived from percutaneous endoscopic gastrostomy. When conservative treatment of chronic obstipation fails, colon irrigation via PEC seems less invasive than surgical interventions. However, previous studies have noted high complication rates of PEC, mostly related to infections. Our aim was to report our experiences with PEC in patients with chronic refractory constipation. Retrospective analysis of all patients who underwent PEC for refractory constipation in our secondary referral hospital between 2009 and 2016. Twelve patients received a PEC for chronic, refractory constipation. Short-term efficacy for relief of constipation symptoms was good in 8 patients and moderate in 4 patients. Two patients had the PEC removed because of spontaneous improvement of constipation. Three patients, who initially noticed a positive effect, preferred an ileostomy over PEC after 1-5years. One PEC was removed because of an abscess. Long-term efficacy is 50%: 6 patients still use their PEC after 3.3years of follow-up. No mortality occurred. PEC offers a technically easily feasible and safe treatment option for patients with chronic constipation not responding to conventional therapy. Long-term efficacy of PEC in our patients is 50%.

Bamboo Nodes on a Series of 15 Patients: Vocal Fold Lesion as a Sign of Autoimmune Disease and Microphonotrauma

Bamboo nodes are band-like submucosal deposits of the middle third of the vocal fold. They are often related to connective tissue disorders, but can also precede them. The aim of this study was to report our experience with conservative treatment of those rare lesions. This is a retrospective series of 15 patients consulting for hoarseness and presenting bamboo nodes from 2010 to 2016. All patients were women of mean age of 38 years with a moderate or high degree of daily vocal effort. Nine patients (60%) presented with known autoimmune disease at the phoniatric appointment. The other patients (40%) benefited from a systematic biological research for autoimmune disease, which retrieved two poorly symptomatic connective tissue disorders. Patients were clinically improved by speech therapy (53%) or by an optimization or introduction of immunosuppressive treatment (46%). A spontaneous improvement was observed for three patients after voice rest (one after retirement, one after professional change, and last one after resuming professional singing). In our series, no phonosurgery was performed. The vocal profile at last appointment found a moderate Voice Handicap Index at 35.3/120, a low maximum time of phonation at 13.6 seconds, and a high jitter at 1.4, sign of instability of the vibrator. This series emphasizes the importance of diagnosing bamboo nodes in middle-aged female presenting an autoimmune disease. Vice versa for each patient with bamboo nodes, a systematic autoimmune check-up has to be realized to detect a biological asymptomatic autoimmune disease.

Fat embolism: a rare cause of perioperative renal transplant dysfunction

Fat embolism is a recognised complication of bony injury and orthopaedic surgery, commonly involving the long bones and pelvis. We report on the case of a 68-year-old renal transplant recipient...

Spontaneous improvement in both obstructive sleep apnea and cognitive impairment after stroke

Spontaneous improvement in both obstructive sleep apnea and cognitive impairment after stroke

Low-Intensity Extracorporeal Shockwave Therapy – A New Approach in the Treatment of Erectile Dysfunction after Radical Prostatectomy

Summary The experience accumulated with low-intensity extracorporeal shock wave therapy (LI-ESWT) from international clinical trials has demonstrated its safety, efficacy and good tolerance in treatment of erectile dysfunction (ED). The aim of this retrospective study was to investigate the effect of LI-ESWT in patients with ED after bilateral nerve sparing radical surgery for prostate cancer. Twenty-seven patients underwent bilateral nerve sparing radical retropubic prostatectomy (BNSRRP) at the clinic of urology of the university hospital in Pleven between January 2016 and December 2016. Twenty-one of these patients had pre-operative preserved erectile function (EF), as reported according to the International Index of Erectile Function (IIEF-5). Postoperatively, these 21 patients experienced a mild (18-21 points) impairment of EF. In 10 patients (group 1), LI-ESWT was performed. The procedure was performed once a week for 6 weeks with a LI-ESWT (BTL 6000 SWT Topline) instrument. The reading was obtained with IIEF-5 on the third and sixth month after the end of therapy. The other 11 patients (group 2) were used as a control group and did not receive treatment. In 5 patients in group 1, a recovery of EF (&gt; 21 points) as per IIEF-5 was recorded at the third month after treatment. In two patients, the same score was recorded at the sixth month. No improvement was seen in three men in group 1. In the controls (group 2), a spontaneous EF improvement in four patients at sixth month was registered. Despite the small number of patients and their short-term follow-up, our initial results indicate that LI-ESWT is effective, safe and well-tolerated. It could be an alternative for early penis rehabilitation in patients who have undergone BNSRRP.

Paradoxical Adipose Hypertrophy (PAH) After Cryolipolysis.

Cryolipolysis is a minimally invasive technique used to decrease local adipose tissue by thermal cooling. Paradoxical adipose hypertrophy (PAH) is a rare complication of cryolipolysis with important aesthetic consequences. The objective of this study was to describe four cases of PAH after a cryolipolysis treatment. Between January 2014 and January 2017, all patients who had undergone a cryolipolysis treatment in a single center were reviewed. The device used was a CoolSculpting device and the same operator performed all the cryolipolysis treatments. We retrospectively included all patients who had a suspicion of PAH. In our study, 398 patients underwent a session of cryolipolysis. Four patients presented with a voluminous painless swelling in the treated area, between 2 and 4 months after the cryolipolysis session. One patient was treated with liposuction. Histological analysis of the adipose tissue in this patient revealed a nonspecific panniculitis. The other three patients did not receive any additional treatment, and their symptoms stabilized after several months. Although cryolipolysis generally yields good results, it can be complicated with PAH, which tends to occur a few months after the cryolipolysis treatment. Patients should be informed of the possibility of developing this complication and encouraged to attend regular follow up for at least 6 months, so that this condition can be readily detected. Surgical treatment should be offered if there is no spontaneous improvement of the symptoms.

Early Rehabilitation After Stroke: a Narrative Review.

Despite current rehabilitative strategies, stroke remains a leading cause of disability in the USA. There is a window of enhanced neuroplasticity early after stroke, during which the brain's dynamic response to injury is heightened and rehabilitation might be particularly effective. This review summarizes the evidence of the existence of this plastic window, and the evidence regarding safety and efficacy of early rehabilitative strategies for several stroke domain-specific deficits. Overall, trials of rehabilitation in the first 2weeks after stroke are scarce. In the realm of very early mobilization, one large and one small trial found potential harm from mobilizing patients within the first 24h after stroke, and only one small trial found benefit in doing so. For the upper extremity, constraint-induced movement therapy appears to have benefit when started within 2weeks of stroke. Evidence for non-invasive brain stimulation in the acute period remains scant and inconclusive. For aphasia, the evidence is mixed, but intensive early therapy might be of benefit for patients with severe aphasia. Mirror therapy begun early after stroke shows promise for the alleviation of neglect. Novel approaches to treating dysphagia early after stroke appear promising, but the high rate of spontaneous improvement makes their benefit difficult to gauge. The optimal time to begin rehabilitation after a stroke remains unsettled, though the evidence is mounting that for at least some deficits, initiation of rehabilitative strategies within the first 2weeks of stroke is beneficial. Commencing intensive therapy in the first 24h may be harmful.

Improvement of portal venous pressure in cirrhotic rat livers by systemic treatment with adipose tissue–derived mesenchymal stromal cells

Background aimsPortal hypertension is the main cause of complications in cirrhosis caused primarily by extensive fibrosis. Both anti-fibrotic and pro-fibrotic properties of mesenchymal stromal cells (MSCs) have been described in various animal models of liver fibrosis. Therefore, the impact of MSCs on portal hypertension and fibrosis should be investigated in an animal model of liver cirrhosis. MethodsThe effect of systemic treatment with adipose tissue–derived MSCs, pre-differentiated into hepatocytic cells, was investigated in a rat model of liver cirrhosis induced by chronic inhalation of carbon tetrachloride. ResultsChronic intoxication with carbon tetrachloride increased the portal venous pressure, which was significantly attenuated by the treatment with MSCs. Consistent with the increase in portal and sinusoidal resistance in the cirrhotic liver, the splenic weight increased, which was again attenuated by the MSCs. The cells had no impact on the spontaneous improvement of liver dysfunction after cessation of treatment with carbon tetrachloride. However, fibrosis was significantly improved as assessed by image quantification of collagen stained with Sirius red. However, hydroxyproline was unchanged indicating that fibrillary collagen content was not affected. That was in line with the finding that the activation of hepatic stellate cells, mainly contributing to excess collagen production in liver cirrhosis, was not affected by the MSCs. The expression of metalloproteinases and their inhibitors did also not change. DiscussionIt is suggested that hepatocytic differentiated MSCs improved portal blood flow in the cirrhotic liver rather by the physical reestablishment of liver architecture than by biochemical repair.

Postoperative Changes After Closed Reduction of Nasal Fracture.

Nasal bone fracture is the most common facial fracture; however, surgery does not guarantee reduction and complications, such as undercorrection, overcorrection, and deviation, may occur. By analyzing findings of computed tomography (CT) immediately and at 3 months postoperatively, we evaluated the accuracy of reduction and long-term changes to the nasal bone.Patients with pure nasal bone fracture were evaluated from January 1, 2010 to December 31, 2011. First, we categorized fracture types according to the Stranc-Robertson classification system, using preoperative CT findings (ie, F1, F2, L1, and L2). We categorized each result of reduction by immediate postoperative CT scan findings as "Excellent," "Good," "Fair," and "Poor," with "Excellent" and "Good" ratings being considered a "Success." We evaluated changes to the nasal bone at 3 months after reduction, using the same grade.A total of 128 patients were analyzed. The results of patients in the F1 group were better than those of other patients immediately postoperatively, whereas those of the L2 group were worse. The overall success rate was 49.2% (58/118). At 3 months postoperatively, 33 cases exhibited an improvement to a higher grade, whereas 25 cases improved from an unacceptable outcome to a successful outcome, with the overall success rate being 70.3% (83/118).Immediately postoperative CT scans can be helpful for surgeons in determining whether a secondary adjustment is necessary. Incompletely reduced nasal bone showed spontaneous improvement in bony arrangement according to our study, so simple observation could be a choice.

Generalised idiopathic benign acanthosis nigricans with onset during infancy: report of two patients

&lt;p&gt;Generalised acanthosis nigricans (AN) is usually seen in association with insulin resistance or internal malignancy in adults. Very rarely, this may occur in children without any evidence of systemic disease and runs a benign course. Its management requires only watchful waiting. Here, we report two children with benign AN who had onset of AN during infancy and showed spontaneous improvement during follow up for a mean duration of 7.7±0.14 years.&lt;/p&gt;

Weaning from long term continuous positive airway pressure or noninvasive ventilation in children.

A significant number of children are able to discontinue long term continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV) but the underlying disorders, weaning criteria, and outcome of these children have not been studied. Retrospective cohort follow up. Consecutive children who were weaned from long term CPAP/NIV between October 2013 and January 2016. Underlying disorders, weaning criteria, and clinical outcome were analyzed. Fifty eight (27%) of the 213 patients on long term CPAP/NIV could be weaned from CPAP/NIV with 50 patients being weaned from CPAP and 8 from NIV. Most patients were young children with upper airway anomalies, Prader Willi syndrome or bronchopulmonary dysplasia. CPAP/NIV was discontinued following spontaneous improvement of sleep-disordered breathing in 33 (57%) patients, upper airway surgery (n = 14, 24%), maxillofacial surgery (n = 6, 11%), neurosurgery (n = 1, 2%), upper airway and neurosurgery (n = 2, 3%), or switch to oxygen therapy (n = 2, 3%). CPAP/NIV was discontinued due to normal nocturnal gas exchange during spontaneous breathing in all patients, with an obstructive apnea-hypopnea index ≤6 events/h on a combined poly(somno)graphy in 27 patients. A relapse of obstructive sleep apnea was observed after a median delay of 2 years in six patients who resumed CPAP and in one patient who underwent midface distraction. Weaning from CPAP/NIV is possible in children treated with long term CPAP/NIV but is highly dependent on the underlying disorder. Spontaneous improvement is possible but most children need specific surgery. Long term follow-up is necessary in children with underlying disorders.

Postoperative Changes in Strabismus, Ductions, Exophthalmometry, and Eyelid Retraction After Orbital Decompression for Thyroid Orbitopathy.

Surgical rehabilitation of thyroid orbitopathy involves reducing proptosis, treating strabismus, lengthening the eyelids, and managing aesthetic changes. Not all are necessary in each patient; however, they often are. The current investigation intends to describe postdecompression changes that may influence the staging of these procedures. In this retrospective cohort study, records of 169 patients who underwent orbital decompression between 1983 and 2001 were reviewed. A single orbital specialist confirmed all measurements. Time to follow up was defined as the most recent follow up after decompression and prior to any secondary procedures. No strabismus or eyelid surgery was performed at the time of decompression. Strabismus was measured with alternating prism cover test. Ductions were estimated utilizing Hirschberg's method. Exophthalmometry was measured with Hertel. Eyelid positions were defined relative to the pupillary light reflex. Strabismus data were analyzed within eye pairs. Ductions, exophthalmometry and eyelid position were analyzed for each eye. T-test for paired data was utilized to compare means pre- and postoperatively. The study population was on average 45 years old and 73.4% women. Average length of follow up was 1.2 years. Esotropia was significantly increased after decompression by an average of 8.1 prism diopters (p < 0.01). Exotropia and vertical deviations were not significantly altered. Ductions decreased by >5 degrees in at least one meridian for 68.1% of the population. Upper eyelid retraction remained unchanged; however, lower eyelid retraction improved by 50% from 1.4 mm to 0.7 mm (p < 0.01). Exophthalmometry improved from 23.5 mm to 19.7 mm (p < 0.01), and this result was correlated with the number of walls removed (Pearson r = -0.302, p < 0.01). On average, esotropia and ductions tend to worsen with decompression surgery. This result supports the clinical dictum to avoid strabismus surgery until after decompression. The improvement in lower eyelid retraction suggests that at least lower eyelid-lengthening surgery should be reserved for after decompression, as there may be significant spontaneous improvement, while the same may not be true for upper eyelid retraction, which does not tend to change with decompression.

Dentoalveolar and arch dimension changes in patients treated with miniplate-anchored maxillary protraction.

The aim of this study was to evaluate dentoalveolar and arch dimension changes in 2 miniplate-anchored maxillary protraction protocols in relation to an untreated control group using 3-dimensional digital models. Thirty growing Class III subjects with maxillary deficiency in the late mixed or early permanent dentition phase were randomly divided into 3 groups. In group 1 (n=10), patients were treated with skeletally anchored facemasks anchored with miniplates placed at the zygomatic buttress. In group 2 (n=10), patients were treated with Class III elastics extending from infrazygomatic miniplates in the maxilla to symphyseal miniplates in the mandible. Group 3 (n=10) was an untreated control group. The decision to discontinue orthopedic treatment was made when the patients had 3 to 4mm of positive anterior overjet. Pretreatment, posttreatment, and observation 3-dimensional digital models were analyzed, superimposed, 3 dimensionally mapped, and sectioned. In this study, there were no significant changes in maxillary arch depth and maxillary or mandibular intermolar width before and after maxillary protraction or after the observation period in the control group. The mandibular arch depth decreased by a small but statistically significant amount only in groups 1and 3. Superimposition of the pretreatment and posttreatment or observation maxillary 3-dimensional digital models showed minimal clinically significant dentoalveolar changes. Miniplate-anchored maxillary protraction protocols can accomplish maxillary advancement by eliminating movements of teeth and dentoalveolarchanges. No spontaneous improvement in transverse deficiency was detected after correction of the anteroposterior deficiency at this age. Consequently, patients with transverse maxillary deficiency should have rapid maxillary expansion before or during the miniplate-anchored protraction period to improve the transverse deficiency.

ADCY5-related movement disorders: Frequency, disease course and phenotypic variability in a cohort of paediatric patients

IntroductionADCY5 mutations have been recently identified as an important cause of early-onset hyperkinetic movement disorders. The phenotypic spectrum associated with mutations in this gene is expanding. However, the ADCY5 mutational frequency in cohorts of paediatric patients with hyperkinetic movement disorders has not been evaluated. MethodsWe performed a screening of the entire ADCY5 coding sequence in 44 unrelated subjects with genetically undiagnosed childhood-onset hyperkinetic movement disorders, featuring chorea alone or in combination with myoclonus and dystonia. All patients had normal CSF analysis and brain imaging and were regularly followed-up in tertiary centers for paediatric movement disorders. ResultsWe identified five unrelated subjects with ADCY5 mutations (11% of the cohort). Three carried the p. R418W mutation, one the p. R418Q and one the p. R418G mutation. Mutations arose de novo in four cases, while one patient inherited the mutation from his similarly affected father. All patients had delayed motor and/or language milestones with or without axial hypotonia and showed generalized chorea and dystonia, with prominent myoclonic jerks in one case. Episodic exacerbations of the baseline movement disorder were observed in most cases, being the first disease manifestation in two patients. The disease course was variable, from stability to spontaneous improvement during adolescence. ConclusionMutations in ADCY5 are responsible for a hyperkinetic movement disorder that can be preceded by episodic attacks before the movement disorder becomes persistent and is frequently misdiagnosed as dyskinetic cerebral palsy. A residual degree of neck hypotonia and a myopathy-like facial appearance are frequently observed in patients with ADCY5 mutations.

Evaluation of a Minimally Disruptive Treatment Protocol for Frontal Sinus Fractures

Despite common goals of frontal sinus fracture treatment (restoring forehead contour and creating a safe sinus), there remains significant variability in evaluation and treatment. To describe our experience with a minimally disruptive treatment protocol for the treatment of frontal sinus fractures. Analysis of prospectively collected data from 2010 through 2015 at a level 1 trauma center. All patients with frontal sinus fractures treated with our protocol from January 2010 to December 2015. Patients with poor follow-up and/or incomplete medical records were excluded from analysis. Presence of an aerated frontal sinus and aesthetically acceptable forehead contour. Secondary outcome measures were complications related to frontal sinus fractures. A total of 39 patients were treated under our minimally disruptive protocol, and 25 patients were included in the study; 18 (72%) were male and 7 (28%) were female. Their ages ranged from 6 to 62 years. After review, 22 patients had both clinical and radiographic follow-up. No patients underwent immediate frontal sinus repair. Five of 22 patients underwent surgery for indications other than their frontal sinus fracture: 1 of 5 patients underwent immediate surgical repair due to bilateral LeFort fractures, and 4 of 5 underwent delayed surgery due to nasal polyps (1 patient), scar revision (1 patient), and concomitant LeFort fractures (2 patients). Two of 22 patients (9%) underwent frontal sinus repair after outpatient surveillance due to persistent cerebrospinal fluid leak (1 patient) and orbital roof fracture (1 patient). The remaining 20 patients were treated nonoperatively, and 19 of 20 (95%) had spontaneous improvement in opacification and/or contour deformity. Twelve of 20 patients (60%) had improvement or resolution in both. One patient had ongoing partial opacification and deformity at the 3-month follow-up but was asymptomatic and had bony contour that was aesthetically acceptable to the patient. There were no complications. The median of all follow-up was 3 months. Frontal sinus fractures treated nonoperatively had a high rate of spontaneous ventilation and bony autoreduction with aesthetically acceptable frontal bone remodeling. There were no complications in the nonoperative group. The initial results of this study support further study of the safety and efficacy of a minimally disruptive protocol for frontal sinus fractures. 4.