Intraarterial Thrombolytic Treatment for Visual Deficits Caused by Hyaluronic Acid Filler: Efficacy, Safety, and Prognostic Factors.

BACKGROUND: The benefits of intraarterial thrombolytic treatment (IATT) in reversing hyaluronic acid (HA)-related visual deficits remain unclear. This study aimed to report a 5-year experience in the treatment of visual deficits resulting from HA embolization by IATT in a tertiary medical center. METHODS: From December of 2015 to June of 2021, the medical records of consecutive patients with HA-related visual deficits who underwent IATT were reviewed retrospectively. The demographics, clinical features, imaging data, treatment details, and follow-up results of the patients were analyzed. RESULTS: A total of 72 consecutive patients were analyzed, including five men (6.9%) men and 67 women (3.1%), aged 29.3 ± 7.6 years (range, 17 to 50 years). Thirty-two patients (44.4%) showed preserved visual acuity, and 40 (55.6%) exhibited no light perception on admission. Ocular motility disorders were detected in 63 patients (87.5%), ptosis was detected in 61 patients (84.7%), and facial skin changes were detected in 54 patients (75%). The technical success rate of IATT was 100%, with successful recanalization of the occlusive artery. No procedure-related complications were detected, and all skin injuries, ptosis, and ocular motility disorders were healed. Improved visual acuity was detected in 26 cases (36.1%). In the binary logistic regression model, only preoperative preserved visual acuity was independently associated with a good outcome. CONCLUSIONS: IATT for selective patients with HA-related visual deficits is efficient and safe. Preoperative preserved visual acuity was independently associated with a good outcome after IATT. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Botulinum Toxin A Injection for Convergence Insufficiency.

PURPOSE: To evaluate the effects of botulinum toxin A injection in one or both lateral rectus muscles in patients with convergence insufficiency previously managed with non-surgical and/or surgical options other than botulinum toxin A injection. METHODS: All patients with symptomatic convergence insufficiency treated with botulinum toxin A injection to one or both lateral rectus muscles from 2013 to 2018 at the Department of Ophthalmology, Rigshospitalet-Glostrup, Copenhagen University Hospital were retrospectively reviewed. All patients had near symptoms and were previously treated with a combination of convergence exercises, prisms, and/or surgery. Patients with previous botulinum toxin A injection in an extraocular muscle were excluded. Reading symptoms and deviation at near and distance were recorded at baseline and after 1 and 6 months. RESULTS: Twenty-three patients with convergence insufficiency were included (8 men and 15 women). Follow-up was conducted after a median of 47 days (interquartile range [IQR]: 31.5 to 72.5 days) and 174 days (IQR: 139 to 267 days). At baseline, median near angle of deviation was 18 PD of exophoria (IQR: 13 to 21 PD). The near deviation was reduced to 10 PD of exophoria (IQR: 7 to 17 PD) at first follow-up visit and 14 PD of exophoria (IQR: 12 to 18 PD) at last follow-up visit. Thirteen of 23 patients (57%) and 3 of 13 patients (23%) reported improvement in reading symptoms at first and last follow-up visit, respectively, compared to baseline. CONCLUSIONS: Botulinum toxin A injection may be useful in patients with convergence insufficiency. However, some patients may require repeated injections. [J Pediatr Ophthalmol Strabismus. 2023;60(2):108-113.].

Postinfectious SARS-CoV-2 Opsoclonus-Myoclonus-Ataxia Syndrome.

BACKGROUND: The opsoclonus-myoclonus-ataxia syndrome (OMAS) represents a pathophysiology and diagnostic challenge. Although the diverse etiologies likely share a common mechanism to generate ocular, trunk, and limb movements, the underlying cause may be a paraneoplastic syndrome, as the first sign of cancer, or may be a postinfectious complication, and thus, the outcome depends on identifying the trigger mechanism. A recent hypothesis suggests increased GABAA receptor sensitivity in the olivary-oculomotor vermis-fastigial nucleus-premotor saccade burst neuron circuit in the brainstem. Therefore, OMAS management will focus on immunosuppression and modulation of GABAA hypersensitivity with benzodiazepines. METHODS: We serially video recorded the eye movements at the bedside of 1 patient with SARS-CoV-2-specific Immunoglobulin G (IgG) serum antibodies, but twice-negative nasopharyngeal reverse transcription polymerase chain reaction (RT-PCR). We tested cerebrospinal fluid (CSF), serum, and nasopharyngeal samples. After brain MRI and chest, abdomen, and pelvis CT scans, we treated our patient with clonazepam and high-dose Solu-MEDROL, followed by a rituximab infusion after her formal eye movement analysis 10 days later. RESULTS: The recordings throughout her acute illness demonstrated different eye movement abnormalities. While on high-dose steroids and clonazepam, she initially had macrosaccadic oscillations, followed by brief ocular flutter during convergence the next day; after 10 days, she had bursts of opsoclonus during scotopic conditions with fixation block but otherwise normal eye movements. Concern for a suboptimal response to high-dose Solu-MEDROL motivated an infusion of rituximab, which induced remission. An investigation for a paraneoplastic etiology was negative. CSF testing showed elevated neuron-specific enolase. Serum IgG to Serum SARS-CoV2 IgG was elevated with negative RT-PCR nasopharyngeal testing. CONCLUSION: A recent simulation model of macrosaccadic oscillations and OMAS proposes a combined pathology of brainstem and cerebellar because of increased GABAA receptor sensitivity. In this case report, we report 1 patient with elevated CSF neuronal specific enolase, macrosaccadic oscillations, ocular flutter, and OMAS as a SARS-CoV-2 postinfectious complication. Opsoclonus emerged predominantly with fixation block and suppressed with fixation, providing support to modern theories on the mechanism responsible for these ocular oscillations involving cerebellar-brainstem pathogenesis.

Oftalmoplejía internuclear bilateral (WEBINO) en un paciente pediátrico con Lupus Eritematoso Sistémico / Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) in a pediatric patient with Systemic Lupus Erythematosus

Resumen El síndrome de WEBINO (wall-eyed bilateral internuclear ophthalmoplegia), se presenta por una lesión del tegmento pontino (incluye área pontina paramediana, fascículo longitudinal medial y núcleo del abducens). Presenta limitación bilateral en la aducción y exotropía en la posición de la mirada primaria, nistagmo del ojo que abduce e incapacidad para la convergencia. Reporte de caso: Presentamos el caso de una paciente de 14 años con antecedente de Lupus Eritematoso Sistémico que debutó con diplopía horizontal de inicio súbito. El diagnóstico de WEBINO fue clínico y asociado con hallazgos de lesión isquémico pontomesencefálica en Resonancia Nuclear Magnética y angioresonancia cerebral. Se administró tratamiento con Metilprednisolona y presentó resolución gradual de los síntomas, sin embargo una semana después falleció por criptococosis sistémica. Conclusiones: Hacer el diagnostico de WEBINO se hace desafiante por su rareza y por la precisión de su localización neuroanatómica. Se debe realizar una exploración detallada para definir la causa probable y establecer el tratamiento oportuno que favorezca el pronóstico neurológico.

Background: Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) is presented by a lesion of the pontine tegment (includes paramedian pontine area, medial longitudinal fascicle and nuclei of the abducens). It presents bilateral limitation in adduction and exotropia in the position of the primary gaze, abducting eye nystagmus and inability to converge. Case report: We present the case of a 14-year-old patient with a history of Systemic Lupus Erythematosus who debuted with sudden onset horizontal diplopia. WEBINO's diagnosis was clinical and associated with findings of ponto-mesencephalic ischemic injury in magnetic resonance imaging and magnetic resonance angiography. Treatment with Methylprednisolone was administered and she presented gradual resolution of the symptoms, however, one week later she died of systemic cryptococcosis. Conclusions: Making the WEBINO diagnosis is challenging due to its rarity and the precision of its neuroanatomical location. A detailed examination should be performed to define the probable cause and establish the appropriate treatment that favors the neurological prognosis.

Ophthalmologic manifestations in myasthenia gravis: presentation and prognosis.

We investigated the ophthalmologic manifestations and factors that influence outcomes in patients with myasthenia gravis (MG). We retrospectively analyzed the prevalence of neuro-ophthalmologic findings and clinical and outcome measures of 100 consecutive patients (53 males, 47 females), aged 55.7 ± 17.5 (range 15-85) years with an established diagnosis of MG. Forty-eight patients had purely ocular symptoms at the onset of disease (OMG) and 52 patients presented with generalized symptoms (GMG). Overall, 21 patients presented with extraocular muscle (EOM) weakness. Bilateral EOM weakness was seen in 12 patients, and unilateral EOM weakness was seen in nine patients. Diplopia responded partially to immunosuppressive treatments in 60% of patients with ophthalmoparesis. Twenty-five (52.1%) patients with ocular-onset MG converted to secondary GMG at a mean time of 14.5 months. Patients who developed secondary GMG were younger and had an earlier age of disease onset when compared with patients with pure OMG (p < 0.05). Patients with secondary GMG presented more frequently with ptosis and diplopia (72% vs. 28%) compared with patients with pure ocular MG who presented more frequently with isolated ptosis (66.7% vs. 33.3%) (p = 0.02). Remission and minimal manifestation status were achieved in 50 (79.3%) of all patients with a clinical follow-up ≥ 3 years. Poor outcome was associated with the presence of thymoma (p < 0.05). Myasthenic ophthalmoparesis is bilateral and heterogeneous and partly responds to treatment with immunotherapy. Younger patients with ptosis and diplopia at disease onset had an increased risk of secondary GMG. The presence of thymoma increases the risk for poor prognosis.

Isolated opsoclonus heralding neuromyelitis optica spectrum disorder.

Opsoclonus is an ocular motility disorder characterized by spontaneous, arrhythmic conjugate saccades of varying amplitude occurring in all directions of gaze without normal intersaccadic interval. Etiological spectrum of opsoclonus encompasses paraneoplastic and neoplastic conditions, infectious and para-infectious encephalitis, autoimmune, metabolic and toxic encephalopathies, drugs, motor neuron diseases, multiple sclerosis and rarely neuromyelitis optica spectrum disorder (NMOSD). Opsoclonus has never been reported as a presenting manifestation heralding NMOSD. We herein report a previously healthy 37-year-old Asian Indian woman who presented with oscillopsia and opsoclonus, followed, 12 h later, by right-sided hemiparesis, right-sided appendicular ataxia, and left-sided lower motor neuron type facial palsy and dysarthria. Brain magnetic resonance imaging revealed hyperintense lesions in brainstem and thalamus in T2-weighted and fluid attenuated inversion recovery-weighted images, quite suggestive of NMOSD. Serum and cerebrospinal fluid samples were positive for anti-aquaporin-4 antibodies, which clinched the diagnosis of seropositive NMOSD. After completion of a course of intravenous methylprednisolone 1 g/day for 5 days, her opsoclonus disappeared completely. There was significant improvement in her speech and weakness within the first week of therapy and no objective deficit after day 20 of admission. After one-and-a-half-year follow-up, the patient was maintaining well on rituximab as secondary prophylaxis without any further attack. Our case highlights that isolated opsoclonus can be the presenting feature of NMOSD.

A case of acquired Brown syndrome treated with adalimumab.

We present the case of a 4-year-old boy with acquired Brown syndrome of inflammatory origin. Without evidence of systemic inflammation, the disease typically resolves with oral steroids or nonsteroidal anti-inflammatory drugs. Refractory cases can be treated with local steroid injections or surgery. The present case of inflammatory Brown syndrome did not respond to conservative therapy, and parental concerns and wishes precluded more invasive treatments. Adalimumab was initiated and led to complete resolution of the disease.

Infratentorial immature teratoma of congenital origin can be associated with a 20-year survival outcome: a case report and review of literature.

BACKGROUND: Congenital intracranial tumors are very rare and account for less than 2% of all childhood brain tumors. Teratomas constitute about one third to one half of these, predominantly located midline in the supratentorial region. Posterior fossa location rarely occurs and, based on the cases reported in the literature, commonly has a poor prognosis. CASE PRESENTATION: A newborn female, diagnosed prenatally with hydrocephalus, is presented at birth with increasing head circumference and Parinaud's syndrome. Magnetic resonance imaging scans demonstrated a huge posterior fossa tumor with obstructive hydrocephalus. At surgery, through a suboccipital craniotomy, complete excision was achieved of a histological-proven immature teratoma. The infant received adjuvant chemotherapy for 1 year. She had normal neurological development and remained tumor-free through her 20-year follow-up. CONCLUSION: The authors report this rare case of congenital posterior fossa teratoma with long-term outcome, and the literature is reviewed.

Paraneoplastic syndrome - a rare but treatable cause of non-thyroid-related extraocular muscle enlargement.

Paraneoplastic syndrome is a rare but reversible cause of non-thyroid-related extraocular muscle enlargement. We present a 71-year-old lady with diplopia, restricted eye movements, suppressed thyroid-stimulating hormone and enlargement of all extraocular muscles while on thyroxine replacement for hypothyroidism. She had distant history of metastatic breast cancer treated with chemotherapy, surgical resection and tamoxifen. She had negative anti-thyroid autoantibodies and thyroid ultrasound was not consistent with autoimmune thyroid disease. Carcinoembryonic antigen and cancer antigens 15-3, 125 and 72-4 were elevated, and whole-body positron emission tomography-computed tomography showed avid liver, left adrenal and skeletal lesions, with liver biopsy confirming breast cancer recurrence. She received prednisone and chemotherapy (letrozole, palbociclib) and achieved normalisation of eye movements and reduction in her EOME at 9-month follow-up. Our case highlights the importance of exploring paraneoplastic syndrome as a treatable cause of EOME in a patient lacking features of thyroid orbitopathy and autoimmune thyroid disease.

Amyloid clearance defect in ApoE4 astrocytes is reversed by epigenetic correction of endosomal pH.

Endosomes have emerged as a central hub and pathogenic driver of Alzheimer's disease (AD). The earliest brain cytopathology in neurodegeneration, occurring decades before amyloid plaques and cognitive decline, is an expansion in the size and number of endosomal compartments. The strongest genetic risk factor for sporadic AD is the ε4 allele of Apolipoprotein E (ApoE4). Previous studies have shown that ApoE4 potentiates presymptomatic endosomal dysfunction and defective endocytic clearance of amyloid beta (Aß), although how these two pathways are linked at a cellular and mechanistic level has been unclear. Here, we show that aberrant endosomal acidification in ApoE4 astrocytes traps the low-density lipoprotein receptor-related protein (LRP1) within intracellular compartments, leading to loss of surface expression and Aß clearance. Pathological endosome acidification is caused by ε4 risk allele-selective down-regulation of the Na+/H+ exchanger isoform NHE6, which functions as a critical leak pathway for endosomal protons. In vivo, the NHE6 knockout (NHE6KO) mouse model showed elevated Aß in the brain, consistent with a causal effect. Increased nuclear translocation of histone deacetylase 4 (HDAC4) in ApoE4 astrocytes, compared with the nonpathogenic ApoE3 allele, suggested a mechanistic basis for transcriptional down-regulation of NHE6. HDAC inhibitors that restored NHE6 expression normalized ApoE4-specific defects in endosomal pH, LRP1 trafficking, and amyloid clearance. Thus, NHE6 is a downstream effector of ApoE4 and emerges as a promising therapeutic target in AD. These observations have prognostic implications for patients who have Christianson syndrome with loss of function mutations in NHE6 and exhibit prominent glial pathology and progressive hallmarks of neurodegeneration.

Orbital cysticercosis.

A young male patient presented to our ocular emergency department with chief complaints of progressive pain, redness, diplopia and a right-sided face turn. Ocular examination revealed severely restricted extraocular movements along with retinal folds in the left eye. Initial orbital ultrasound and CT findings were equivocal; however, serology favoured an infective cause. Considering the endemicity of the disease and equivocal investigation findings, a diagnosis of orbital cysticercosis with an atypical presentation was made. The patient was managed medically with a combination of oral albendazole and steroids over a period of 6 weeks to achieve optimal results.

Visual loss due to optic nerve infarction and central retinal artery occlusion after spine surgery in the prone position: A case report.

RATIONALE: Visual loss after spine surgery in the prone position is a serious complication. Several cases of central retinal artery occlusion with ophthalmoplegia after spine surgery have been reported in patients with ophthalmic arteries fed by the internal carotid artery (ICA) in a normal manner. PATIENT CONCERNS: A 74-year-old man developed visual loss after undergoing a spinal decompression and fusion operation in the prone position that lasted approximately 5 hours. DIAGNOSES: We detected an extremely rare case of visual loss due to optic nerve infarction and central retinal artery occlusion through fundoscopic examination, fluorescein angiogram, brain magnetic resonance imaging, and magnetic resonance angiography. The patient's visual loss may have been caused by compromised retrograde collateral circulation of the ophthalmic artery from branches of the external carotid artery in the presence of proximal ICA occlusion after a spinal operation in the prone position. INTERVENTIONS: To recover movement of the left extraocular muscles, the patient received intravenous injections of methylprednisolone for 3 days and then oral prednisolone for 6 days. OUTCOMES: Twenty days after the treatment, the motion of the left extraocular muscles was significantly improved. However, recovery from the left visual loss did not occur until 4 months after the operation. LESSONS: In high-risk patients with retrograde collateral circulation of the ophthalmic artery from the external carotid artery due to proximal ICA occlusion, various measures, including the use of a head fixator to provide a position completely free of direct compression of the head and face, should be considered to decrease the risk of postoperative visual loss.

Diphenhydramine for Acute Extrapyramidal Symptoms After Propofol Administration.

Extrapyramidal symptoms are an uncommon but well-recognized side effect after the administration of general anesthesia in patients without a significant neurologic history. Several case reports implicate propofol as the likely causative agent producing these symptoms, which include ballismus, dystonia, choreoathetosis, and opisthotonus. Currently, there is no clear consensus on first-line treatment of these symptoms. In each of the published cases, anticholinergic medications and benzodiazepines were central to initial management, although the speed and extent of symptom resolution were variable. Here we present a case of a 17-year-old boy with ulcerative colitis who presented with ballismus, torticollis, tongue thrusting, and oculogyric movements after colonoscopy under general anesthesia with propofol. The patient responded promptly to treatment with diphenhydramine. This is the first reported case in which diphenhydramine was successfully used as the primary treatment of severe extrapyramidal symptoms in a pediatric patient after propofol administration.

Parinaud's oculoglandular syndrome: A case report. / Síndrome oculoglandular de Parinaud: a propósito de un caso.

CLINICAL CASE: A 33-year old woman presents with unilateral granulomatous conjunctivitis, ipsilateral regional lymphadenopathy and fever. A Bartonella henselae infection is demonstrated by indirect immunofluorescence, and a diagnosis of a Parinaud's oculoglandular syndrome is established. Outcome after treatment with oral doxycycline is satisfactory. DISCUSSION: Parinaud's oculoglandular syndrome is the most frequent ocular manifestation of a Bartonella henselae infection.

[Use of botulinum toxin in strabismus]. / Zum Einsatz von Botulinumtoxin in der Strabologie.

Botulinum toxin can be a useful tool for treating acute sixth nerve palsy and excessive eye deviations due to unstable Graves' disease, when surgery is not yet possible. The diagnostic injection for estimation of possible postoperative double vision also makes sense. In convergence spasms, periocular botulinum toxin injections can be a therapeutic option. Botulinum toxin is not a first line option in infantile esotropia without binocularity or in adult horizontal strabismus. Side effects include ptosis and vertical deviations.

Internuclear ophthalmoplegia associated with anti-TNFα medication.

AIM: To describe the presentation of an internuclear ophthalmoplegia (INO) associated with the use of anti-tumor necrosis factor α (anti-TNFα) medication. METHODS: A case report of a woman, aged 27 years, who developed facial numbness, blurred vision, and diplopia on right gaze. She had a history of Crohn's disease, which was being treated by the anti-TNFα drug, adalimumab. On examination, a left INO was found. TREATMENT: The patient was prescribed a short course of corticosteroids and adalimumab treatment was discontinued. RESULTS: Magnetic resonance imaging demonstrated typical demyelinating lesions including one responsible for the INO. Following a short course of corticosteroids and the discontinuation of the adalimumab treatment, the INO resolved, resulting in a swift improvement of ocular motility over a 2-week period. CONCLUSION: Anti-TNFα therapies have been associated with the development of demyelinating diseases. The presentation of a brainstem syndrome in a patient on anti-TNFα therapy should lead to investigation for central nervous system demyelination and cessation of the medication.

Sustained improvement of reading symptoms following botulinum toxin A injection for convergence insufficiency.

INTRODUCTION: We evaluated the use of botulinum toxin A in adults with convergence insufficiency in whom prior treatment had failed. METHODS: We studied 8 patients (median age 36 years, range 17 to 77 years) with reading symptoms due to convergence insufficiency defined as an exodeviation greater at near, not exceeding 10 PD in the distance measured by prism and alternate cover test, and either convergence near point>6 cm or reduced fusional amplitudes. All patients were still symptomatic after prior treatment by convergence exercises (n=8), base-in prism glasses (n=5) or strabismus surgery (n=2). Five patients received injection of 5 IU botulinum toxin in 0.1 ml saline to one lateral rectus muscle, two received 2.5 IU, and one received 2.5 IU to both lateral rectus muscles. RESULTS: At 1 month post injection, all patients had an initial reduction of exodeviation from baseline (median 9 PD, p=0.008) at near, although 2 patients had a temporary intermittent esotropia in the distance with diplopia associated with difficulty driving. At 6 months, when the pharmacological effect of botulinum toxin had completely worn off, patients still maintained a small reduction of exodeviation (median 4 PD, p=0.3) at near. Reading symptoms improved in 7 of 8 patients at 1-month post injection, and in all patients at 6 months. Two patients had health-related quality of life assessed with the Adult Strabismus 20 Questionnaire, showing improved Reading Function scores at 6 months. Interestingly, 3 patients reported improved reading despite returning to the baseline angle at 6 months, and 2 of 4 with 12-month follow-up still reported improvement. CONCLUSIONS: In adult convergence insufficiency, botulinum toxin injection to a lateral rectus muscle improves reading symptoms beyond the duration of the pure pharmacological effect. Botulinum toxin injection may be useful in management of adult convergence insufficiency, although repeat injections may be needed.

An update on neuro-ophthalmology of multiple sclerosis: the visual system as a model to study multiple sclerosis.

PURPOSE OF REVIEW: The purpose of this review is to familiarize the reader with the landscape of current neuro-ophthalmology research in the field of multiple sclerosis and to highlight important findings, directions of future research and advances in the clinical management of visual and ocular motor manifestations of multiple sclerosis. RECENT FINDINGS: Research pertaining to the visual system in multiple sclerosis has identified new biomarkers of disease and is contributing to a better understanding of disease mechanisms. Progress has been made in the symptomatic management of visual manifestations of multiple sclerosis and visual outcome measures are now being included in clinical trials, with important quality of life ramifications. Perhaps the most prominent contribution from neuro-ophthalmology research in multiple sclerosis has been the establishment of the visual system as a model to study disease pathogenesis, and for the systematic, objective, and longitudinal detection and monitoring of protective and restorative neurotherapeutic strategies. The emergence of these sophisticated capabilities has been in large part due to the application of high speed, high definition, and objective methods for the elucidation of both the structure and function of visual system networks. SUMMARY: Advances in neuro-ophthalmology research in multiple sclerosis have led to the establishment of the visual system as a model to objectively study disease pathogenesis, and for the identification of novel neurotherapeutic capabilities. With the prospects of myelin repair and neuroprotective agents increasingly becoming recognized as achievable goals, the validation and utility of new visual outcome measures quantifying changes in axonal integrity, myelin protection, and repair will likely prove invaluable.