Botulinum Toxin Injection for the Treatment of Third, Fourth, and Sixth Nerve Palsy: A Meta-Analysis.

The efficacy of botulinum toxin injection for the treatment of third, fourth, and sixth nerve palsy was evaluated. PubMed, Scopus, EMBASE, Web of Science, and Google Scholar databases were searched. Data about the duration of palsy (acute vs chronic), cause of the palsy, type of toxin used, mean dose, and other background characteristics were collected. Outcome variables were success rate (defined by alleviation of diplopia or reduction in eye deviation) and standardized mean difference of prism diopter and abduction deficit before and after injection. The Joanna Briggs Institute checklist was implemented for the risk of bias assessment. The analysis included 38 articles, comprising 643 patients. The overall treatment success rate in acute and chronic nerve palsy was 79% and 33%, respectively. The success rate was not significantly different between different subgroups of age, type of botulinum toxin, pre-injection prism diopter, etiology of the palsy, duration of follow-up, and mean dose of botulinum toxin injection. However, in both acute and chronic palsy, diabetes etiology was accompanied by the highest success rate. Overall symptomatic response to botulinum injection was 84% (95% CI: 67% to 96%), whereas functional response was observed in 64% (95% CI: 47% to 79%) of the patients. The odds ratio for the success rate of treatment of palsies with botulinum toxin versus expectant management was 2.67 (95% CI: 1.12 to 6.36) for acute palsy and 0.87 (95% CI: 0.17 to 4.42) for chronic palsy. Botulinum toxin can be used for the treatment of acute third, fourth, and sixth nerve palsy, especially in patients with acute palsy and more severe tropia. [J Pediatr Ophthalmol Strabismus. 2024;61(3):160-171.].

Bilateral sixth nerve palsy with subdural hematoma: a unique presentation of B12 deficiency.

Vitamin B12 is inextricably associated with the development and maintenance of neuronal functions. It is classically associated with subacute combined degeneration and peripheral neuropathy; however, cranial neuropathy is uncommon. We observed the rarest neurological manifestation of B12 deficiency. A 12 months infant had history of lethargy, irritability, anorexia, paleness, vomiting, and neurodevelopmental delay for 2 months. He also developed inattention and altered sleep pattern. His mother noticed bilateral inward rotation of both eyes. On examination, the infant had bilateral lateral rectus palsy. The infant was found to have anemia (7.7g/dL) and severe B12 deficiency (74pg/mL). On MRI, there was cerebral atrophy, subdural hematoma (SDH) and wide cisternal spaces and sulci. On supplementation with cobalamin, he improved clinically though mild restriction of lateral gaze on the left side persists. Follow up MRI showed significant improvement in cerebral atrophy with resolution of SDH. To date, such clinical presentation of B12 deficiency has never been reported. The authors suggest B12 supplementation for at risk population esp at antenatal stage and lactating mothers in national programs. The treatment of this condition should be initiated early to prevent long term sequelae.

Isolated Sixth Nerve Palsies in a Child With Familial Hemophagocytic Lymphohistiocytosis Type 2.

ABSTRACT: A previously healthy 2-year-old boy presented with a left sixth cranial nerve palsy. There was a family history of multiple sclerosis and optic neuritis. Neuroimaging showed multiple foci of T2/FLAIR hyperintense signal abnormality in both cerebral hemispheres and in the brainstem. The initial diagnosis was suspicious for demyelinating disease. However, there was no clinical improvement after a course of corticosteroids, and there was no change in his follow-up MRI. He later developed bilateral sixth nerve palsies, with esotropia addressed with bilateral medial rectus botulinum toxin injections. A brain biopsy was planned. However, his 3-month-old sister was separately admitted for fever and pancytopenia. She had markedly elevated ferritin, D-dimer, triglycerides, sIL-2R, CXCL9, and IL-18 and low fibrinogen. Her bone marrow biopsy showed hemophagocytosis. Genetic testing of both siblings revealed biallelic mutations in the PRF1 locus. The final diagnosis of familial hemophagocytic lymphohistiocytosis Type 2 was made. Both siblings underwent chemotherapy. The boy's sixth nerve palsies and MRI abnormalities resolved. Both siblings then went on to undergo bone marrow transplant.

Isolated Abducens Nerve Palsy After Herpes Zoster Ophthalmicus: A Case Report.

Aim: The purpose of this study was to demonstrate a case of herpes zoster in the patient. Methods: Case report. Results: Herpes zoster ophthalmicus is a rare but well-known cause of CN VI palsy that affects an elderly patient due to a reduction in the immunity to the Varicella Zoster Virus (VZV). We reported a case of herpes zoster in our patient, a 67-year-old Javanese female who presented with a VI nerve palsy within 1 week after the vesicular rash. Our patient received Valacyclovir, Gabapentin, and steroid treatment, then responded quite well to the combination of these therapies without side effects as the goals were to diminish acute and chronic pain, fasten the healing of the skin and nerve, and reduce the chances of dissemination. Based on studies, systemic antivirals should be given in all cases of HZO to minimize complications and steroids should not be given without antiviral therapy so as not to increase viral replication. Conclusions: As a complication of HZO, ophthalmoplegia may have various origins. We reported a case of sixth nerve palsy in HZO. Abbreviations: HZO = herpes zoster ophthalmicus, VZV = varicella-zoster virus, CN = Cranial Nerve.

Bilaterally recurrent benign abducens nerve palsy in a child.

Benign abducens nerve palsy with recurrent episodes in children is rare. In most cases, there are two episodes, the same eye is affected, and recovery is spontaneous. We present a patient with multiple episodes in both eyes, including bilateral simultaneous involvement, who was treated with botulinum toxin.

Early reversible leukoencephalopathy and unilateral sixth cranial nerve palsy in mild COVID-19 infection.

OBJECTIVES: To provide new insights into neurological manifestations of COVID-19. We describe a patient with mild COVID-19 associated with diplopia from right sixth cranial nerve palsy and early diffuse leukoencephalopathy, successfully treated with intravenous methylprednisolone. METHODS: The patient was evaluated for diplopia that occurred 1 day after the onset of fever, myalgia, and headache. A complete neurological workup, including neurological examination, cerebrospinal fluid (CSF) analysis with viral polymerase chain reaction (PCR), serum autoimmune encephalitis, and anti-nerve antibodies and brain magnetic resonance imaging (MRI), was performed. RESULTS: Clinical examination revealed incomplete right sixth cranial nerve palsy. Brain MRI showed diffuse confluent fluid-attenuated inversion recovery (FLAIR) hyperintense white matter abnormalities, while CSF analysis showed mild hyperproteinorrachia (61 mg/dL) without pleocytosis. The patients were treated with high-dose intravenous methylprednisolone with rapid improvement of neurological symptoms and resolution of CSF and MRI abnormalities. DISCUSSION: Our report shows that COVID-19 may predominantly present with neurological symptoms; furthermore, it argues the notion of leukoencephalopathy as a typical feature of a severe case of the disease. Mechanisms underpinning neurological symptoms in COVID-19 still need to be elucidated; nonetheless, early recognition and prompt management may ensure their improvement or even complete recovery and are therefore recommended.

Isolated sixth nerve palsy as an initial presentation of primary angiitis of the central nervous system.

BACKGROUND: Primary angiitis of the central nervous system (PACNS) is a newly-emerging disease, and it is known that early diagnosis with treatment is important for the improvement of prognosis. CASE DESCRIPTION: Here, we report the case of a previously healthy 13-year-old girl who presented with right eye abduction failure, attributed to isolated right sixth nerve palsy, as the initial symptom of PACNS. Magnetic resonance angiography (MRA) showed stenosis in the distal portion of the right internal carotid artery, and delay alternating with nutation for tailored excitation (DANTE)-prepared contrast-enhanced magnetic resonance imaging confirmed vasculitis at the same site. The patient was subsequently treated with three courses of pulse corticosteroid therapy (methylprednisolone intravenously 30 mg/kg/day for three consecutive days). Diplopia completely resolved within 3 months after three course of steroid pulse therapy, and when taking 10 mg PSL daily. Follow-up MRA confirmed complete resolution of the arterial narrowing, and no relapse was observed after 2 months of steroid cessation. DISCUSSION: This case report illustrates an unusual presentation of PACNS with isolated sixth nerve palsy. PACNS was thought to cause insults on a single cranial nerve either through local spread of inflammation or hypoxic-ischemic insults on the nerve root due to involvement of feeding microvessels. The decision to perform imaging studies in cases of isolated sixth nerve palsy remains controversial because of the possibility of spontaneous recovery. Our case supports the existing literature that recommends that even an isolated symptom of unilateral abducens nerve palsy requires timely imaging studies.

Two cases of benign abducens nerve palsy in children and their long-term follow-up.

Our aim was to explore the clinical characteristics and diagnostic methods of benign abducens nerve palsy in children. The clinical and laboratory characteristics, treatment approach, and prognosis of two children with benign abducens nerve palsy were retrospectively evaluated. The main clinical symptoms of the two children were limited binocular movement accompanied by double vision, and the positive physical signs were limited binocular abduction accompanied by diplopia. No abnormalities were found in laboratory examinations or in imaging of the head, chest, and abdomen. Both children were treated with B vitamins, methylprednisolone, and gamma globulin, and the clinical symptoms disappeared within 3 months of starting treatment. The cause of benign abducens nerve palsy in children is unknown, but may be related to immune factors. In the two cases presented here, the patients recovered after treatment with immunomodulators.

Acute Sixth Nerve Palsy and Retinal Hemorrhages as the Presenting Features of Acute Lymphoblastic Leukemia.

ABSTRACT: A 36-year-old apparently healthy man presented with acute onset of diplopia. Examination demonstrated left sixth nerve palsy with 3 retinal hemorrhages noted in one eye. Gadolinium-enhanced high-resolution skull base MRI revealed left sixth nerve enhancement involving the cisternal segment. Complete blood count, cerebrospinal fluid analysis, bone marrow biopsy, and flow cytometry confirmed acute T-cell lymphoblastic leukemia with central nervous system involvement. This case demonstrates the value of high-resolution MRI in the evaluation of cranial nerve palsy in young adults and also emphasizes the importance of systemic work up in these cases, particularly when retinal findings are present.

Analysis of Clinical Data from the Third, Fourth, or Sixth Cranial Nerve Palsy and Diplopia Patients Treated with Ijintanggagambang in a Korean Medicine Clinic: A Retrospective Observational Study.

Objective: The clinical course of the third, fourth, and sixth cranial nerve palsies varies according to etiology and onset. The effects of Ijintanggagambang in Korean patients with cranial nerve palsy and paralytic diplopia were assessed. Design: This is a retrospective observational study. Settings: The study was conducted in a Korean Medicine clinic in Seoul, Korea. Subjects: Subjects were 569 patients with cranial nerve palsy and diplopia who received Ijintanggagambang in 2009-2018. Interventions: The patients received herbal decoction, Ijintanggagambang, for 4 weeks. Main outcome measures: The baseline characteristics, including onset, etiology, type of paralysis, and deviation angle, were collected. Patients whose diplopia resolved were classified as completely recovered. Potential factors affecting the clinical effectiveness of Ijintanggagambang for this condition were explored. The rate and duration of complete recovery were narratively analyzed and compared with previous reports. Results: Sixth cranial nerve palsy was the most common type of paralysis (n = 311, 55%) and undetermined origin was the most frequent etiology (n = 281, 49%). The complete recovery rate was higher in patients who started treatment within 12 weeks of onset (95%, 503/532) than in those who started treatment later (19%, 7/37). In 532 patients who started treatment within 12 weeks of onset, the complete recovery rate of patients with vascular origin (98%, 122/124), other diseases (97%, 94/97), and undetermined etiology (96%, 252/263) was statistically high compared with those of traumatic origin (73%, 35/48, p < 0.05). The average treatment duration in the complete recovery group (n = 510) was 9.3 weeks. The treatment duration was correlated with the increase of deviation angle in all three types of cranial nerve palsies. Conclusions: Sixth cranial nerve palsy and undetermined etiology were common. There is an association between recovery of diplopia and the administration of Ijintanggagambang when started within 12 weeks of onset. Results of the study need to be interpreted cautiously due to the limited nature of narrative retrospective analysis.

Botulinum toxin A in the early treatment of sixth nerve palsy in type 2 diabetes.

Purpose: Our study aims at evaluating the efficacy and safety of botulinum toxin A in the early treatment of sixth nerve palsy in type 2 diabetic patients. Methods: This study is a prospective and interventional clinical case series of patients presenting with acute onset of sixth cranial nerve palsy, who received injection botulinum toxin A. Results: Thirty-one cases were included in the study. 58% of the study subjects had incomplete palsy at presentation (abduction deficit -1 to -3) and 42% had complete palsy (-4 and -5). The median dosage of injection was 5 U (range 3--6 U). The median follow-up period is 2 months. The P value shows that there is statistically significant improvement in head turn, ocular deviation in primary position, and improvement in abduction between baseline and 1 week (P-value <0.001), 1 month (P-value <0.001) and 2 month (P-value <0.001) postinjection follow-up visits. 90.3% of patients had full resolution of symptoms in the last follow-up visit. 83.9% of patients were successfully treated. Conclusion: Early injection of botulinum toxin A in select patients with acquired sixth nerve palsy due to diabetes is a safe and efficient treatment option in alleviating symptoms, restoring function and quality of life and reducing need for surgical interventions in future.

Herpes zoster involving the abducens and vagus nerves without typical skin rash: A case report and literature review.

RATIONALE: Herpes zoster is characterized by unilateral vesicular eruption and it most often affects the trigeminal nerve. We would like to report a rare case of abducens and vagus nerves palsy caused by varicella zoster virus (VZV) without the typical vesicular rash. PATIENT CONCERNS: A 71-year-old woman presented with diplopia. Three days previously, she had experienced sore throat and hoarseness. DIAGNOSIS: At presentation, the prism cover test revealed esotropia of 10 prism diopters at primary gaze, and abduction was restricted in the right eye. No vesicular rash was observed on the patient's face, and magnetic resonance imaging of the brain showed no pathology. Flexible fiberoptic laryngoscopy revealed multiple ulcerations on the right side of the larynx-from the epiglottis to the arytenoid. After 1 day of hospitalization, a diffuse skin rash occurred on the patient's trunk, and polymerase chain reaction for VZV DNA was positive at the skin lesion. The patient was diagnosed as having herpes zoster associated with vagus and sixth nerve palsy. INTERVENTION AND OUTCOMES: She received famciclovir at a dose of 500 mg 3 times daily for 7 days and coadministered methylprednisolone. At the 4-month follow-up, her diplopia and eye movement had resolved completely. LESSONS: In patients with abducens nerve palsy without typical vesicular lesion, herpes zoster may not be detected early. In that case, systemic examination is very important for diagnosing herpes zoster.

Typhoid fever with isolated left lateral rectus palsy.

A 17-year-old young woman presented to Patan Hospital, Kathmandu, Nepal, with high-grade fever and headache for 4 days and non-projectile vomiting for 1 day. She also had blurred vision with dizziness on and off. There was no abnormal physical finding. Enteric fever was suspected, and she was empirically started on azithromycin (20 mg/kg) for 7 days. She became afebrile after 2 days and was followed up in 7 days with diplopia since 5 days. At this time, the blood culture was positive for Salmonella serovar typhi. On examination, there was isolated left lateral rectus palsy which accounted for her diplopia. Methylprednisolone (1 mg/kg) was prescribed which was tapered over 1 month and gradually her diplopia subsided. We hypothesise that vasculitic change in the blood vessel supplying the left abducens nerve could be causing the diplopia.

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.