Botulinum toxin as an initial therapy for management of sixth nerve palsies caused by nasopharyngeal carcinomas.

PurposeThe purpose of this study is to evaluate the efficacy and safety of botulinum toxin injection as a primary treatment for strabismus in a cohort of patients with nasopharyngeal carcinoma (NPC)-related chronic sixth nerve palsy.Patients and methodsWe retrospectively reviewed all cases of NPC-related sixth nerve palsy receiving botulinum toxin injection in the Hong Kong Eye Hospital between January 2009 and January 2016. Only cases with diplopia for at least 6 months; and failed a trial of Fresnel prism therapy were recruited. We excluded cases with prior strabismus surgery and multiple cranial nerve palsies. Patients were offered botulinum toxin injection as primary treatment for their strabismus and were given further injections or offered surgery if diplopia persisted. Success with botulinum toxin was defined as a final distant orthophoria of <15 PD in primary gaze, no diplopia in primary position, and no head turn, as measured 6 months after the last injection, without requiring a second treatment.ResultsA total of 25 patients were included in the study. All patients received concurrent chemo-radiotherapy for NPC. There was a statistically significant reduction in the mean deviation at distant after the last injection compared to that at presentation (P<0.001, Wilcoxin signed rank test). Overall, 7 patients (28%) achieved clinical success and 15 patients (64%) remained diplopia-free by repeated botulinum toxin injections alone. Nine patients went on to receive definitive surgery and all achieved good ocular alignment after surgery. Transient ptosis or vertical deviation was seen in 7 patients, which resolved within 3 months and no serious complications arose from the treatment in our series.ConclusionsBotulinum toxin injection is a relatively less-invasive alternative to surgery that can be done under a topical anesthesia setting, which improves patient's quality of life via reduction in diplopia. It is a recommendable initial option in patients with chronic nerve palsies who may have higher risks associated with strabismus surgery.

Characterization of bipolar disorder patient-specific induced pluripotent stem cells from a family reveals neurodevelopmental and mRNA expression abnormalities.

Bipolar disorder (BD) is a common neuropsychiatric disorder characterized by chronic recurrent episodes of depression and mania. Despite evidence for high heritability of BD, little is known about its underlying pathophysiology. To develop new tools for investigating the molecular and cellular basis of BD, we applied a family-based paradigm to derive and characterize a set of 12 induced pluripotent stem cell (iPSC) lines from a quartet consisting of two BD-affected brothers and their two unaffected parents. Initially, no significant phenotypic differences were observed between iPSCs derived from the different family members. However, upon directed neural differentiation, we observed that CXCR4 (CXC chemokine receptor-4) expressing central nervous system (CNS) neural progenitor cells (NPCs) from both BD patients compared with their unaffected parents exhibited multiple phenotypic differences at the level of neurogenesis and expression of genes critical for neuroplasticity, including WNT pathway components and ion channel subunits. Treatment of the CXCR4(+) NPCs with a pharmacological inhibitor of glycogen synthase kinase 3, a known regulator of WNT signaling, was found to rescue a progenitor proliferation deficit in the BD patient NPCs. Taken together, these studies provide new cellular tools for dissecting the pathophysiology of BD and evidence for dysregulation of key pathways involved in neurodevelopment and neuroplasticity. Future generation of additional iPSCs following a family-based paradigm for modeling complex neuropsychiatric disorders in conjunction with in-depth phenotyping holds promise for providing insights into the pathophysiological substrates of BD and is likely to inform the development of targeted therapeutics for its treatment and ideally prevention.

Surgical outcome of single-staged three horizontal muscles squint surgery for extra-large angle exotropia.

PURPOSE: To report the surgical outcomes of 24 patients undergoing single-staged three horizontal muscles squint surgery for extra-large angle exotropia. PATIENTS AND METHODS: Prospective case series of 24 consecutive patients with primary exotropia>60 prism diopters (PD) at distant and underwent single-staged three horizontal muscles squint surgery from 2003 to 2006. Surgery consisted of bilateral lateral rectus recession of 9.0 mm for 50 PD exotropic correction. For every 5 PD remaining angle exceeding 50 PD, we additionally performed 1.0 mm of unilateral medial rectus resection. The mean follow-up period was 15.8 months (range 6.0-38.0 months; SD 9.5 months). RESULTS: The mean age at surgery was 31.2 years old (range 7-78 years old, SD 18.2 years old). The mean distant preoperative deviation was 71.3 PD (range 60-85 PD, SD 7.7 PD). No limitation of eye movement or diplopia was found. The success rate was higher in the intermittent group (88.2%) than the constant group (42.9%) (P=0.02) and in cases with preoperative deviation of <80 PD (84.2%) compared with those with deviation>or=80 PD (40.0%) (P=0.042). CONCLUSION: Measurement of preoperative deviation and the surgery for extra-large angle exotropia made management of this condition difficult. Single-staged three horizontal muscles squint surgery can be one of the options. Further researches on management of exotropia of >80 PD are warranted.

Residual torticollis in patients after strabismus surgery for congenital superior oblique palsy.

AIM: To study postoperative residual vertical deviation and abnormal head posture (AHP) after surgical treatment for congenital superior oblique palsy (SOP). METHOD: Children with both SOP and AHP who underwent extraocular muscle surgery for correction of AHP were recruited. The patients received complete ophthalmic and orthopaedic examinations. Residual AHP was classified according to severity of face turn, head tilt and chin elevation. RESULTS: Thirty-two children with mean age at operation of 82.6 months were recruited, with mean follow-up of 37.9 months. Of these children, 65.6% had a postoperative vertical deviation of less than three prism dioptres. In addition, 34.4% patients had resolved (0 degrees ), 34.4% had mild (1 degrees -10 degrees ), and 31.3% had significant residual torticollis (>10 degrees ). Of the patients with significant residual torticollis, 33.3% had ocular causes. The mean age at operation for the patients with residual torticollis (95.9 months) was older than those without torticollis (79.9 months) (p = 0.018). Residual torticollis was found to be related to sternocleidomastoid muscle tightness (p = 0.013). CONCLUSION: The success rate for eliminating significant AHP after strabismus surgery for patients with congenital SOP was 68.8%. Early surgery was associated with a better outcome. Association was also found between sternocleidomastoid tightness and AHP. A multidisciplinary approach is recommended in the management of torticollis as ophthalmic and orthopaedic comorbidities can coexist.