Topoisomerase 3α Is Required for Decatenation and Segregation of Human mtDNA.

How mtDNA replication is terminated and the newly formed genomes are separated remain unknown. We here demonstrate that the mitochondrial isoform of topoisomerase 3α (Top3α) fulfills this function, acting independently of its nuclear role as a component of the Holliday junction-resolving BLM-Top3α-RMI1-RMI2 (BTR) complex. Our data indicate that mtDNA replication termination occurs via a hemicatenane formed at the origin of H-strand replication and that Top3α is essential for resolving this structure. Decatenation is a prerequisite for separation of the segregating unit of mtDNA, the nucleoid, within the mitochondrial network. The importance of this process is highlighted in a patient with mitochondrial disease caused by biallelic pathogenic variants in TOP3A, characterized by muscle-restricted mtDNA deletions and chronic progressive external ophthalmoplegia (CPEO) plus syndrome. Our work establishes Top3α as an essential component of the mtDNA replication machinery and as the first component of the mtDNA separation machinery.

Structural insight and characterization of human Twinkle helicase in mitochondrial disease.

Twinkle is the mammalian helicase vital for replication and integrity of mitochondrial DNA. Over 90 Twinkle helicase disease variants have been linked to progressive external ophthalmoplegia and ataxia neuropathies among other mitochondrial diseases. Despite the biological and clinical importance, Twinkle represents the only remaining component of the human minimal mitochondrial replisome that has yet to be structurally characterized. Here, we present 3-dimensional structures of human Twinkle W315L. Employing cryo-electron microscopy (cryo-EM), we characterize the oligomeric assemblies of human full-length Twinkle W315L, define its multimeric interface, and map clinical variants associated with Twinkle in inherited mitochondrial disease. Cryo-EM, crosslinking-mass spectrometry, and molecular dynamics simulations provide insight into the dynamic movement and molecular consequences of the W315L clinical variant. Collectively, this ensemble of structures outlines a framework for studying Twinkle function in mitochondrial DNA replication and associated disease states.

Uraemic brainstem encephalopathy mimicking ocular myasthenia: a case report.

BACKGROUND: Uraemia causes a generalised encephalopathy as its most common neurological complication. Isolated brainstem uraemic encephalopathy is rare. We report a case of fatigable ptosis and complex ophthalmoplegia in brainstem uraemic encephalopathy. CASE PRESENTATION: A 22-year-old Sri Lankan man with end stage renal failure presented with acute onset diplopia and drooping of eyelids progressively worsening over one week. The patient had not complied with the prescribed renal replacement therapy which was planned to be initiated 5 months previously. On examination, his Glasgow coma scale score was 15/15, He had a fatigable asymmetrical bilateral ptosis. The ice-pack test was negative. There was a complex ophthalmoplegia with bilateral abduction failure and elevation failure of the right eye. The diplopia did not worsen with prolonged stare. The rest of the neurological examination was normal. Serum creatinine on admission was 21.81 mg/dl. The repetitive nerve stimulation did not show a decremental pattern. Magnetic resonance imaging (MRI) of the brain demonstrated diffuse midbrain and pontine oedema with T2 weighted/FLAIR hyperintensities. The patient was haemodialyzed on alternate days and his neurological deficits completely resolved by the end of the second week of dialysis. The follow up brain MRI done two weeks later demonstrated marked improvement of the brainstem oedema with residual T2 weighted/FLAIR hyperintensities in the midbrain. CONCLUSIONS: Uraemia may rarely cause an isolated brainstem encephalopathy mimicking ocular myasthenia, which resolves with correction of the uraemia.

A controlled clinical study on efficacy and safety of periocular triamcinolone acetonide injection for treating ocular myasthenia gravis.

OBJECTIVE: To evaluate the efficacy and safety of peribulbar triamcinolone acetonide injection for treating ocular myasthenia gravis (OMG), with a comparison of traditional oral drug therapy. METHODS: A total of 22 patients with OMG who received periocular triamcinolone acetonide injection (initially 20 mg weekly, then once per month later if symptoms were improved) from July 2019 to July 2022 were evaluated by a comparison of symptom degree before and after treatment. Adverse reactions were also monitored during the period of treatment. The period of follow-up was more than 6 months. Additionally, a comparison of the treatment efficacy between this periocular injection and traditional oral administration was performed in OMG patients. RESULTS: After 4 weeks of treatment, the degree of ptosis in OMG patients decreased to -3.00 ± 0.69, compared to the value (-0.86 ± 1.32) before treatment. The degree of ophthalmoplegia also decreased from 3.12 ± 0.72 to 0.86 ± 0.88 (P < 0.001) after treatment. The achievement rates of minimal manifestations status (MMS)for ptosis and ophthalmoplegia after 4 week-treatment were 86.3% and 75%, respectively, while they were 50% and 30% in patients with traditional oral administration. There was statistically significant difference only in MMS (rather than symptom relief rate and generalization conversion rate) between two groups. No serious complications (except for intraorbital hematoma) were found in OMG patients during the treatment period. CONCLUSION: Repeated peribulbar injection of triamcinolone acetonide can effectively alleviate the initial symptoms of OMG patients. However, the evaluation of its long-term efficacy is still needed. CLINICAL TRIAL REGISTRY: This study has been clinically registered by Chinese Clinical Trial Registry (ChiCTR), first trial registration date:05/07/2019, registration number: ChiCTR1900024285.

Endoscopic transorbital decompression for traumatic superior orbital fissure syndrome: from cadaveric study to clinical application.

PURPOSE: The endoscopic endonasal approach (EEA) is a minimally invasive and promising modality for treating traumatic superior orbital fissure (SOF) syndrome (tSOFS). Recently, the endoscopic transorbital approach (ETOA) has been considered an alternative method for reaching the anterolateral skull base. This study accessed the practicality of using the ETOA to treat SOF decompression using both cadaveric dissection and clinical application. METHODS: Bilateral anatomic dissections were performed on four adult cadaveric heads using the ETOA and EEA to address SOF decompression. The ETOA procedure for SOF decompression is described, and the extent of SOF decompression was compared between the ETOA and EEA. The clinical feasibility of the ETOA for treating SOF decompression was performed in two patients diagnosed with tSOFS. RESULTS: ETOA allowed for decompression over the lateral aspect of the SOF, from the meningo-orbital band superolaterally to the maxillary strut inferomedially. By contrast, the EEA allowed for decompression over the medial aspect of the SOF, from the lateral opticocarotid recess superiorly to the maxillary strut inferiorly. In both patients treated using the ETOA and SOF decompression, the severity of ophthalmoplegia got obvious improvement. CONCLUSIONS: Based on the cadaveric findings, ETOA provided a feasible access pathway for SOF decompression with reliable outcomes, and our patients confirmed the clinical efficacy of the ETOA for managing tSOFS.

[Wernicke encephalopathy : a neuro-ophthalmological side effect of bariatric surgery]. / L'encéphalopathie de Gayet-Wernicke : une complication neuro-ophtalmologique de la chirurgie bariatrique.

Due to an increase in the worldwide prevalence of obesity and the efficiency of bariatric surgery, this procedure is more often performed. Besides its benefits, it has also disadvantages and may be the cause of nutritional deficiencies. Thiamin deficiency is particularly important to diagnose and to treat early as it can lead to major sequelae and even to death. Wernicke's encephalopathy is the most frequent presentation associating confusion, ataxia, ophtalmoplegia and nystagmus. The full triad is not usually observed, which may lead to sub-diagnosis of this affection. The diagnosis is clinical, biological and radiologic thanks to the brain MRI. Intravenous thiamin supplementation therapy must be administered as fast as possible in order to avoid long-term damages. In the ophthalmological field, the potential sequelae are ophthalmoplegia, nystagmus and optic neuropathy. Therapeutics for nystagmus are pharmacological, surgical and/or optical. We illustrate this condition with a case report of an 18-year-old man developing Wernicke's encephalopathy as early as six weeks after a sleeve gastrectomy.

Suite à une augmentation de la prévalence de l'obésité dans le monde et à l'efficacité de la chirurgie bariatrique, cette technique est pratiquée de plus en plus fréquemment. Malgré ses avantages, elle n'est pas sans risque et peut être responsable de déficits nutritionnels multiples. Le déficit en vitamine B1 ou thiamine est particulièrement important à connaître et, à rapidement diagnostiquer en raison des nombreuses séquelles invalidantes, voire le décès du patient, dont il peut être responsable. Le tableau classique est l'encéphalopathie de Gayet-Wernicke associant confusion, ataxie et troubles oculomoteurs. Néanmoins, il n'est pas toujours complet, ce qui participe au sous-diagnostic de cette pathologie. Le diagnostic est clinique, biologique et/ou radiologique grâce à l'IRM cérébrale. La supplémentation vitaminique intraveineuse doit être instaurée le plus rapidement possible afin d'éviter des séquelles à long terme. D'un point de vue ophtalmologique, les séquelles potentielles sont les ophtalmoplégies, les nystagmus et les neuropathies optiques. Les thérapies envisageables du nystagmus, outre la supplémentation en thiamine en aigu, sont pharmacologiques, chirurgicales et/ou optiques. Nous illustrons cette pathologie par un cas clinique d'encéphalopathie de Gayet-Wernicke dès la 6ème semaine post-opératoire d'une chirurgie bariatrique de type «sleeve¼ chez un patient de 18 ans.

Painful Diplopia as an Initial Presentation of VEXAS Syndrome.

This is a case report describing an unusual presentation of acute painful diplopia that led to the diagnosis of VEXAS syndrome. VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is an adult-onset monogenic auto-inflammatory disease due to somatic UBA1 gene mutation in haematopoietic progenitor cells. Our patient was a 67-year-old diabetic male who presented with painful eye movements associated with diplopia, left periorbital pain and swelling. Imaging revealed an inflammatory process involving multiple intra- and extra-orbital structures. The patient improved initially with a short course of intravenous steroids. However, two months later he re-presented with right facial swelling. Bone marrow biopsy demonstrated UBA1 gene mutation supporting the diagnosis of VEXAS syndrome. This case highlights a unique ocular presentation of VEXAS.

Recurrent Third Nerve Paresis with Migraine: A Case Report and Review of the Literature.

Ophthalmoplegic migraine (OM), first described by Charcot in 1870, is a disorder characterised by recurrent episodes of migraine associated with ophthalmoplegia. It has been extensively described in children and is rarer in adults. Commonly, the third nerve is affected with pupillary involvement and, more rarely, the fourth or the sixth nerve. OM is now believed to be an inflammatory demyelinating neuropathy. However, in the largest series of OM so far, by Lal et al. it most commonly involved the sixth nerve, started with a crescendo migraine and was accompanied by no enhancement of the cranial nerves. This has led to a rethink about the role of migraine, in the pathogenesis of OM. We describe a 14-year-old boy, with a 10-year history of intermittent headache followed by drooping of right eyelid and diplopia. The current episode started with a migrainous headache, which increased in severity over 3 days, followed by right third nerve paresis with pupillary involvement. Contrast-enhanced magnetic resonance imaging (MRI) of the brain with contrast showed nodular thickening at the root entry zone of the right oculomotor nerve with bright enhancement. The child responded to oral prednisolone, which was tapered over a month. Migraine prophylaxis with propranolol was concurrently added. His repeat MRI brain showed complete disappearance of enhancement of the lesion at 1 year.

Evaluation of Patients with Painful Ophthalmoplegia for Benign and Secondary Etiologies.

This study aims to establish the final definite etiology among patients with long-term follow-up for painful ophthalmoplegia. The data of 44 cases (16 females, 28 females) were examined. In the first diagnosis, subjects were scanned in terms of benign and secondary etiologies. Clinical and radiological follow-up results of patients were recorded. During the follow-up period, data on clinical outcomes (relapse or progression), treatment responses, and final diagnoses were evaluated In total, 49 episodes of painful ophthalmoplegia (44 patients) were evaluated. Secondary etiologies were identified in 21 patients benign/secondary tumours causes in 10, inflammatory in 1, infectious in 3, vascular in 3, demyelinating disease in 1, autoimmune in 2, drug-related cause in 1. 23 patients with benign etiologies; 11 had Tolosa-Hunt syndrome (THS), 2 had Recurrent Painful Ophthalmoplegic Neuropathy (RPON), and 10 had diabetic ophthalmoparesis (DO). 7 of 11 patients with THS met the International Classification Headache Disorders 3rd edition (ICHD-3 beta) criteria, 4 were with a normal MRI, and 1 had a recurrence. 9 of 10 patients with benign/secondary tumours causes were malignant, and 7 died due to disease progression during the treatment process. One of ten patient was followed with diabetic ophthalmoparesis and was diagnosed with cavernous sinus involvement of B-cell lymphoma as a result of clinical progression during follow-up. Painful ophthalmoplegia is a complex clinical condition with a broad differential diagnosis with malignant and benign etiologies. A detailed clinical examination, imaging, and long-term follow-up are essential for accurate diagnosis and treatment management.

Heterozygous p.Y955C mutation in DNA polymerase γ leads to alterations in bioenergetics, complex I subunit expression, and mtDNA replication.

In human cells, ATP is generated using oxidative phosphorylation machinery, which is inoperable without proteins encoded by mitochondrial DNA (mtDNA). The DNA polymerase gamma (Polγ) repairs and replicates the multicopy mtDNA genome in concert with additional factors. The Polγ catalytic subunit is encoded by the POLG gene, and mutations in this gene cause mtDNA genome instability and disease. Barriers to studying the molecular effects of disease mutations include scarcity of patient samples and a lack of available mutant models; therefore, we developed a human SJCRH30 myoblast cell line model with the most common autosomal dominant POLG mutation, c.2864A>G/p.Y955C, as individuals with this mutation can present with progressive skeletal muscle weakness. Using on-target sequencing, we detected a 50% conversion frequency of the mutation, confirming heterozygous Y955C substitution. We found mutated cells grew slowly in a glucose-containing medium and had reduced mitochondrial bioenergetics compared with the parental cell line. Furthermore, growing Y955C cells in a galactose-containing medium to obligate mitochondrial function enhanced these bioenergetic deficits. Also, we show complex I NDUFB8 and ND3 protein levels were decreased in the mutant cell line, and the maintenance of mtDNA was severely impaired (i.e., lower copy number, fewer nucleoids, and an accumulation of Y955C-specific replication intermediates). Finally, we show the mutant cells have increased sensitivity to the mitochondrial toxicant 2'-3'-dideoxycytidine. We expect this POLG Y955C cell line to be a robust system to identify new mitochondrial toxicants and therapeutics to treat mitochondrial dysfunction.

Nothnagel Syndrome.

The internist Hermann Nothnagel (1841-1905) took a special interest in the cerebellum. In an early experimental study on rabbits conducted in 1876, he demonstrated the involvement of the vermis in the pathophysiology of motor ataxia. Between 1879 and 1889, he reported four cases of tectal tumors that clinically manifested with bilateral ophthalmoplegia and unilateral gait ataxia, culminating in the Cerebellar Classic highlighted here. Nothnagel attributed this clinical syndrome to lesions of the colliculi ("quadrigeminal bodies") and compression of the nuclei of the third cranial nerves, but also left open the possibility of the involvement of neighboring structures, such as the cerebellar vermis. Today, the ataxic component of Nothnagel syndrome is explained by a dorsal midbrain abnormality of either neoplastic or vascular origin, involving the superior cerebellar peduncles, besides the oculomotor nerves.

Single internal carotid cavernous sinus aneurysm presented as bilateral painful ophthalmoplegia: a case report.

BACKGROUND: Intracranial aneurysms are the most common vascular cause of painful ophthalmoplegia. Symptoms include retro-orbital pain, diplopia, ophthalmoplegia, trigeminal neuropathy, or a combination of these. Most single aneurysms cause ipsilateral, painful ophthalmoplegia. Here, we report the first, to our knowledge, case of bilateral painful ophthalmoplegia possibly caused by an aneurysm of the cavernous segment of the left internal carotid artery. CASE PRESENTATION: A 62-year-old male patient presented with headache and bilateral ptosis. Laboratory tests revealed hypopituitary function. Computerized tomography angiography showed a large aneurysm in the cavernous sinus segment of the left internal carotid artery. Aneurysm embolization was performed in the Nerve Interventional Department. Four months after surgery, the patient's symptoms returned to normal. CONCLUSIONS: This case suggests that patients with bilateral painful ophthalmoplegia should be screened for aneurysms using computed tomography angiography or magnetic resonance angiography immediately.

A case report on recurrent alternating Tolosa-Hunt syndrome due to bacterial sphenoid sinusitis: rediscussing the diagnostic terminology and classification.

BACKGROUND: Tolosa-Hunt syndrome (THS) is characterized by painful ophthalmoplegia caused by idiopathic granulomatous inflammation involving the cavernous sinus region. Patients respond well to steroid therapy. THS is included in the differential diagnosis of cavernous sinus syndrome, so it is important to fully exclude other lesions in this area before treatment, otherwise steroid treatment may lead to fatal outcomes. Here we describe a patient who initially presented with symptoms that simulated THS symptoms and developed recurrent alternating painful ophthalmoplegia during follow-up, and the patient was finally diagnosed with cavernous sinusitis caused by bacterial sphenoid sinusitis. CASE PRESENTATION: A 34-year-old woman presented with left painful ophthalmoplegia. Magnetic resonance imaging (MRI) revealed abnormal signals in the left cavernous sinus area, and these abnormal signals were suspected to be THS. After steroid treatment, the patient obtained pain relief and had complete recovery of her ophthalmoplegia. However, right painful ophthalmoplegia appeared during the follow-up period. MRI showed obvious inflammatory signals in the right cavernous sinus and right sphenoid sinus. Then nasal sinus puncture and aspiration culture were performed, and the results showed a coagulase-negative staphylococcus infection. After antibiotic treatment with vancomycin, the painful ophthalmoplegia completely resolved, and the neurological examination and MRI returned to normal. CONCLUSION: Some other causes of painful ophthalmoplegia also fulfill the diagnostic criteria for THS in the International Classification of Headache Disorders third edition (ICHD-3) and respond well to steroid therapy. Early diagnosis of THS may be harmful to patients, and clinicians should exercise great caution when dealing with similar cases without a biopsy. Using "cavernous sinus syndrome" instead of "Tolosa-Hunt syndrome" as a diagnostic category may provide a better clinical thinking for etiological diagnosis.

Clinical characteristics and prognosis of temporary miller fisher syndrome following COVID-19 vaccination: a systematic review of case studies.

BACKGROUND: Miller Fisher syndrome (MFS) is a subtype of Guillain-Barré syndrome (GBS) which is characterized by the three components of ophthalmoplegia, ataxia, and areflexia. Some studies reported MFS as an adverse effect of the COVID-19 vaccination. We aimed to have a detailed evaluation on demographic, clinical, and para-clinical characteristics of subjects with MFS after receiving COVID-19 vaccines. MATERIALS AND METHODS: A thorough search strategy was designed, and PubMed, Web of Science, and Embase were searched to find relevant articles. Each screening step was done by twice, and in case of disagreement, another author was consulted. Data on different characteristics of the patients and types of the vaccines were extracted. The risk of bias of the studies was assessed using Joanna Briggs Institute (JBI) tools. RESULTS: In this study, 15 patients were identified from 15 case studies. The median age of the patients was 64, ranging from 24 to 84 years. Ten patients (66.6%) were men and Pfizer made up 46.7% of the injected vaccines. The median time from vaccination to symptoms onset was 14 days and varied from 7 to 35 days. Furthermore,14 patients had ocular signs, and 78.3% (11/14) of ocular manifestations were bilateral. Among neurological conditions, other than MFS triad, facial weakness or facial nerve palsy was the most frequently reported side effect that was in seven (46.7%) subjects. Intravenous immunoglobulin (IVIg) was the most frequently used treatment (13/15, 86.7%). Six patients received 0.4 g/kg and the four had 2 g/kg. Patients stayed at the hospital from five to 51 days. No fatal outcomes were reported. Finally, 40.0% (4/15) of patients completely recovered, and the rest experienced improvement. CONCLUSION: MFS after COVID-19 immunization has favorable outcomes and good prognosis. However, long interval from disease presentation to treatment in some studies indicates that more attention should be paid to MFS as the adverse effect of the vaccination. Due to the challenging diagnosis, MFS must be considered in list of the differential diagnosis in patients with a history of recent COVID-19 vaccination and any of the ocular complaints, ataxia, or loss of reflexes, specially for male patients in their 60s and 70s.

Pontine stroke in a patient with Chronic Progressive External Ophthalmoplegia (CPEO): a case report.

BACKGROUND: Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial disease with slowly progressive bilateral ptosis and symmetric ophthalmoplegia due to a genetic mutation that results in defective oxidative phosphorylation. Common genes that are implicated in CPEO include POLG, RRM2B, ANT1 and PEO1/TWNK. Here, we report a case of a patient diagnosed with CPEO caused by a novel mutation in PEO/TWNK after suffering a right pontine stroke. CASE PRESENTATION: A 70-year-old man with history of chronic progressive bilateral ptosis and ophthalmoplegia, as well as similar ocular symptoms in his father and grandfather, presented with acute onset of right hemifacial weakness and dysarthria. Brain MRI revealed an acute ischemic stroke in the right dorsal pons. The patient did not experience diplopia due to severe baseline ophthalmoplegia. Creatine kinase was elevated to 6,080 U/L upon admission and normalized over the course of one week; electromyography revealed a myopathic process. Genetic testing revealed a novel mutation c.1510G > A (p. Ala504Thr) in a pathogenic "hot spot" of the C10ORF2 gene (TWNK/PEO1), which is associated with CPEO. The mutation appears to be deleterious using several pathogenicity prediction tools. CONCLUSIONS: This case report describes a patient with late-onset CPEO caused by a novel, likely pathogenic, mutation in the TWNK gene. Although the patient presented with a pontine stroke, it manifested with solely new onset facial palsy, as he had a severe underlying ophthalmoplegia secondary to his CPEO.

Macrocytosis in Mitochondrial DNA Deletion Syndromes.

Large single mitochondrial DNA (mtDNA) deletion syndrome is a rare inborn error of metabolism with variable heteroplasmy levels and clinical phenotype among affected individuals. Chronic progressive external ophthalmoplegia (CPEO) is the most common phenotype in adults with this form of mitochondrial disease [J Intern Med. 2020;287(6):592-608 and Biomed Rep. 2016;4(3):259-62]. The common CPEO clinical manifestations are ptosis and ophthalmoplegia. More variable phenotypic manifestations of CPEO (CPEO plus) include involvement of the peripheral nervous system and myopathy. Here, we describe a 62-year-old female with CPEO and the major mtDNA deletion present at 40% heteroplasmy, who had a coexistent previously undescribed CPEO phenotypic feature of persistent unexplained macrocytosis without anemia. Building on this case, we reviewed other major mtDNA deletion cases seen in our Adult Metabolic Diseases Clinic (AMDC) at the University of British Columbia, Vancouver, Canada, from 2016 to 2022. The major mtDNA deletion cases (n = 26) were compared with mtDNA missense variants identified in the clinic over the same period who acted as the comparison group (n = 16). Of these, the most frequent diagnosis was maternally inherited diabetes and deafness and mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes. Ten out of 26 (38%) of mtDNA deletion patients had macrocytosis with elevated mean corpuscular volume (MCV), median (interquartile range) of 108 fL (102-114 fL). Seven of the patients with macrocytosis had no pertinent etiology. None of the comparison group had macrocytosis. There was a significant difference (p = 0.000) between the MCV and MCH in the mtDNA deletion group compared to the comparison group. This communication sheds light on the association of macrocytosis with the mtDNA deletion syndrome. It would be of great interest to determine if the association is found in other mitochondrial disease clinic populations.

Ocular motility disorders following coronavirus disease-19 vaccination.

PURPOSE: To describe clinical manifestations and short-term prognosis of ocular motility disorders following coronavirus disease-2019 (COVID-19) vaccination. METHODS: Ocular motility disorders were diagnosed by clinical assessment, high-resolution magnetic resonance imaging, and laboratory testing. Clinical manifestations, short-term prognosis, and rate of complete recovery were analyzed. RESULTS: Sixty-three patients (37 males, 26 females) with a mean age of 61.6 ± 13.3 years (range, 22-81 years) were included in this study. Among 61 applicable patients with sufficient information regarding medical histories, 38 (62.3%) had one or more significant underlying past medical histories including vasculopathic risk factors. The interval between initial symptoms and vaccination was 8.6 ± 8.2 (range, 0-28) days. Forty-two (66.7%), 14 (22.2%), and 7 (11.1%) patients developed symptoms after the first, second, and third vaccinations, respectively. One case of internuclear ophthalmoplegia, 52 cases of cranial nerve palsy, two cases of myasthenia gravis, six cases of orbital diseases (such as myositis, thyroid eye disease, and IgG-related orbital myopathy), and two cases of comitant vertical strabismus with acute onset diplopia were found. Among 42 patients with follow-up data (duration: 62.1 ± 40.3 days), complete improvement, partial improvement, no improvement, and exacerbation were shown in 20, 15, 3, and 4 patients, respectively. CONCLUSION: This study provided various clinical features of ocular motility disorders following COVID-19 vaccination. The majority of cases had a mild clinical course while some cases showed a progressive nature. Close follow-up and further studies are needed to elucidate the underlying mechanisms and long-term prognosis.

Sphenoid sinus mucocele causing ptosis with pupil-spared ophthalmoplegia: a hint on carotid artery doppler ultrasound.

OBJECTIVE: Sphenoid sinuses mucocele (SSM) is an uncommon cause of orbital apex syndrome (OAS). Diagnosis of neurological complications in SSM might be delayed when the expansion of mucocele beyond the sinuses is not evident in conventional sinuses imaging. METHODS: We present a case of a 76-years old man with spared-pupil ophthalmoplegia associated with ptosis caused by a unilateral left SSM in which internal carotid artery Doppler ultrasound showed distal sub-occlusion waves pattern. RESULTS: Sinus occupation was noted in the magnetic resonance imaging (MRI) and was further evaluated in computed tomography (CT) scan and MR angiography. Nor CT or MR angiography showed clear evidence of neighboring structures compression. Doppler ultrasound of internal carotid showed high-resistance waveforms and decreased wave velocities helping diagnosis. Structures compression was confirmed intra-operatively and the patient was discharged asymptomatic after sphenoid sinus drainage. CONCLUSION: In this first report of carotid Doppler ultrasound findings in a patient with a neurological presentation of a sphenoid sinus mucocele, a high-resistance waveform of the internal carotid may help differentiate uncomplicated sinusitis from invasive mucocele.

Odontogenic Lemierre's syndrome with septic superior ophthalmic vein and cavernous sinus thrombophlebitis complicated by blindness and ophthalmoplegia.

Lemierre's syndrome is a triad consisting of oropharyngeal infection, internal jugular vein thrombophlebitis, and systemic embolisation typically involving lung and brain. Orbital involvement in this life-threatening condition is rare but potentially blinding and may be an indicator of intracranial involvement. We describe a case of odontogenic Lemierre's syndrome complicated by extensive orbital and intracranial septic venous thrombosis, with optic and cranial neuropathy resulting in monocular blindness and ophthalmoplegia. A multidisciplinary approach with abscess drainage, antibiotic and antithrombotic therapy, and close radiological monitoring was critical for preserving contralateral vision and neurological function.

Acute unilateral vision loss and bilateral cerebral infarction following cosmetic filler injection.

The current case report describes acute unilateral vision loss and bilateral cerebral infarction as devastating complications following cosmetic injection of hyaluronic acid to the nasal bridge in a 34-year-old female. The patient reported the onset of sudden eye pain, headache, and vision loss in her right eye. At the initial visit to the hospital, the patient had no light perception in the right eye. Examinations revealed marked ptosis and complete ophthalmoplegia with no proptosis. At the time of the patient's hospital evaluation, computed tomography, and magnetic resonance imaging were ordered. Few mottled materials (denser than blood) were observed in the cavernous sinus with a density of 106 Hounsfield units (HU), yet no air was depicted in the cavernous sinus. MRI scan revealed multiple areas of bilateral intracranial infarcts. Although cosmetic injection of hyaluronic acid has been documented as a safe procedure, vision loss remains one of the most feared complications.