Unilateral Vision Loss as the Only Presenting Symptom of Type 2 Foster Kennedy Syndrome.

A 38-year-old woman who presented with painless vision loss in the left eye over the course of 1 week was investigated at a tertiary neuro-ophthalmology clinic. She was otherwise asymptomatic with no reported headaches, focal neurological deficits, anosmia, or behavioural changes. Bilateral optic disc oedema was identified on examination. Neuroimaging and then resection and histopathological evaluation demonstrated a meningothelial meningioma centred on the left sphenoid ridge. The left optic disc later became atrophic. We have therefore described a case of type 2 Foster Kennedy syndrome with unilateral vision loss as the only initial manifestation.

Functional characterization of variants of unknown significance in a spinocerebellar ataxia patient using an unsupervised machine learning pipeline.

CAG-expanded ATXN7 has been previously defined in the pathogenesis of spinocerebellar ataxia type 7 (SCA7), a polyglutamine expansion autosomal dominant cerebellar ataxia. Pathology in SCA7 occurs as a result of a CAG triplet repeat expansion in excess of 37 in the first exon of ATXN7, which encodes ataxin-7. SCA7 presents clinically with spinocerebellar ataxia and cone-rod dystrophy. Here, we present a novel spinocerebellar ataxia variant occurring in a patient with mutations in both ATXN7 and TOP1MT, which encodes mitochondrial topoisomerase I (top1mt). Using machine-guided, unbiased microscopy image analysis, we demonstrate alterations in ataxin-7 subcellular localization, and through high-fidelity measurements of cellular respiration, bioenergetic defects in association with top1mt mutations. We identify ataxin-7 Q35P and top1mt R111W as deleterious mutations, potentially contributing to disease states. We recapitulate our mutations through Drosophila genetic models. Our work provides important insight into the cellular biology of ataxin-7 and top1mt and offers insight into the pathogenesis of spinocerebellar ataxia applicable to multiple subtypes of the illness. Moreover, our study demonstrates an effective pipeline for the characterization of previously unreported genetic variants at the level of cell biology.

Superior Oblique Myokymia Presumed Due to Large Posterior Fossa Arteriovenous Malformation.

A 26-year-old female presented with a complaint of intermittent oscillopsia and binocular vertical diplopia for the past 5 years. Over the past several months, she had noticed intermittent pulsatile tinnitus. She was otherwise healthy with no previous history of trauma and had no other visual or neurologic complaints. In Neuro-ophthalmology clinic, she was found to have 20/15 vision in both eyes with full ocular motility. There was a small exophoria in primary position and small esophoria in downgaze. Her slit lamp and fundus examinations were normal. During the assessment, the left eye was noted to undergo high-frequency, small amplitude incyclotorsional oscillations for a few seconds at a time (Video 1 in the supplementary material), which she was able to provoke by looking down. The diagnosis of superior oblique myokymia was made, and an MRI/MRA of the brain was requested.

Involvement of the intracranial circulation in giant cell arteritis.

OBJECTIVE: Giant cell arteritis (GCA) is the most common primary vasculitis affecting the elderly population. GCA preferentially involves the extracranial branches of the carotid artery; intracranial vasculitis is thought to be a rare occurrence. This study determined the prevalence of intracranial vasculitis in a large series of patients evaluated for GCA and describes the clinical presentation of such cases. DESIGN: Retrospective chart review using a prospective database. When possible, subjects underwent high-resolution 3T contrast-enhanced magnetic resonance imaging (MRI) and MR angiography (MRA) of the scalp and intracranial arteries. PARTICIPANTS: Patients presenting with suspected GCA between January 2015 and December 2018. Four additional, non-database cases of GCA with intracranial involvement are also described. RESULTS: Of 197 patients, 168 had a contrast-enhanced MRI of the head and 51 had imaging findings suggestive of vasculitis. Five patients showed probable or definitive involvement of both the anterior and posterior intracranial circulation with isolated posterior intracranial circulation involvement in one additional patient. One of these patients showed evidence of acute posterior circulation ischemia and presented with vertigo but no evidence of ischemic optic neuropathy or ophthalmic artery enhancement. Of the 51 patients, 14 had abnormal enhancement of the ophthalmic arteries, including 1 with arteritic ischemic anterior optic neuropathy and vertebral arteritis and 1 patient with involvement of the internal carotid and posterior cerebral arteries but no reported vision changes. CONCLUSION: Although uncommon, clinicians should be aware that GCA can directly involve the intracranial circulation with both the anterior and posterior circulation affected in most of our cases.

Relative Afferent Pupillary Defect with Normal Vision: Unique Localisation to the Contralateral Brachium of the Superior Colliculus.

A relative afferent pupillary defect (RAPD) is a very important clinical finding in neuro-ophthalmology, and is almost always accompanied by other signs of afferent visual pathway dysfunction including visual field defect, decreased acuity and abnormal colour vision. We present a case of isolated RAPD and describe the anatomic localisation of the lesion with a review of the literature for similar cases.

The expanded endoscopic endonasal approach for suprasellar meningiomas: long-term outcomes in a single-center series of 27 patients.

BACKGROUND: The endoscopic endonasal approach (EEA) has become increasingly employed in the treatment of suprasellar meningiomas. These tumors often cause visual symptoms due to compression of the anterior visual pathway. We aimed to examine long-term visual outcomes after EEA for optic nerve decompression and resection of suprasellar meningioma at our center, and to identify preoperative factors predictive of postoperative visual improvement. METHODS: We performed a retrospective cohort study on 27 patients who underwent the EEA for resection of meningiomas extending into the suprasellar cistern and decompression of anterior visual pathway between January 1, 2005, and March 1, 2019. RESULTS: We treated 8 male and 19 female patients, with a mean follow-up of 7.6 years. The mean age of our patients at initial presentation was 60.1 years. Eighteen patients (66.7%) presented with visual acuity deficits, and 12 (44.4%) patients presented with visual field deficits. Postoperatively, 11 patients had improved visual acuity, 6 had stable visual acuity, and 1 patient had slow and progressive decline of visual acuity; 5 patients had improved visual field, 6 had stable visual field, and 1 patient had slow and progressive decline in visual field. Patients less likely to have postoperative improvement of visual acuity were those with longer than 6-month duration of visual symptoms (P = 0.024*) as well as patients with the presence of a relative afferent pupillary defect (RAPD) (P = 0.023*). CONCLUSION: The EEA can achieve good visual outcomes in patients harboring suprasellar meningiomas. Symptom duration of less than 6 months and lack of a RAPD were positive predictors of postoperative visual acuity.

An evaluation of genetic causes and environmental risks for bilateral optic atrophy.

PURPOSE: To assess the clinical utility of next-generation sequencing (NGS) for the diagnosis of patients with optic atrophy (OA). DESIGN: Retrospective cohort study. METHODS: 97 patients were referred to the McMaster University Medical Center (Hamilton, Ontario) for evaluation of bilateral OA. All patients were sent for NGS including a 22 nuclear gene panel and/or complete mitochondrial DNA (mtDNA) sequencing. Positive genetic test results and abnormal vibration sensation were compared in patients +/- environmental exposures or a family history. RESULTS: 19/94 (20.2%) had a positive nuclear variant, of which 15/19 (78.9%) were in the OPA1 gene. No positive mtDNA variants were identified. The detection of a positive genetic variant was significantly different in patients who reported excessive ethanol use, but not in patients who smoke (0/19 (0%) vs. 19/78 (24.4%), P = 0.0164 and 4/22 (18.2%) vs. 15/74 (20.3%), P = 0.829, respectively). Patients with a positive family history were more likely to have a positive genetic variant compared to patients with a negative family history (P = 0.0112). There were significantly more excessive drinkers with an abnormal vibration sensation (P = 0.026), and with a similar trend in smokers (P = 0.074). CONCLUSIONS: All positive genetic variants were identified in nuclear genes. We identified a potential independent pathophysiological link between a history of excessive ethanol consumption and bilateral OA. Further investigations should evaluate and identify potential environmental risk factors for OA.

Neural network and logistic regression diagnostic prediction models for giant cell arteritis: development and validation.

PURPOSE: To develop and validate neural network (NN) vs logistic regression (LR) diagnostic prediction models in patients with suspected giant cell arteritis (GCA). Design: Multicenter retrospective chart review. METHODS: An audit of consecutive patients undergoing temporal artery biopsy (TABx) for suspected GCA was conducted at 14 international medical centers. The outcome variable was biopsy-proven GCA. The predictor variables were age, gender, headache, clinical temporal artery abnormality, jaw claudication, vision loss, diplopia, erythrocyte sedimentation rate, C-reactive protein, and platelet level. The data were divided into three groups to train, validate, and test the models. The NN model with the lowest false-negative rate was chosen. Internal and external validations were performed. RESULTS: Of 1,833 patients who underwent TABx, there was complete information on 1,201 patients, 300 (25%) of whom had a positive TABx. On multivariable LR age, platelets, jaw claudication, vision loss, log C-reactive protein, log erythrocyte sedimentation rate, headache, and clinical temporal artery abnormality were statistically significant predictors of a positive TABx (P≤0.05). The area under the receiver operating characteristic curve/Hosmer-Lemeshow P for LR was 0.867 (95% CI, 0.794, 0.917)/0.119 vs NN 0.860 (95% CI, 0.786, 0.911)/0.805, with no statistically significant difference of the area under the curves (P=0.316). The misclassification rate/false-negative rate of LR was 20.6%/47.5% vs 18.1%/30.5% for NN. Missing data analysis did not change the results. CONCLUSION: Statistical models can aid in the triage of patients with suspected GCA. Misclassification remains a concern, but cutoff values for 95% and 99% sensitivities are provided (https://goo.gl/THCnuU).

The 20/20 patient who can't read.

To understand how reading can be disrupted in patients with good acuity, it is important to realize the complexities that underlie this task, which normally seems so effortless. The process of reading is an interplay among vision, eye movements, attention, and linguistic processing, and impairments in any of these functions can result in reduced reading efficiency. The goal of this review is to provide a systematic review of these functions that can help clinicians generate a logical and useful differential diagnosis of impaired reading in the patient with 20/20 vision.

Incidence, morbidity, and mortality of Terson syndrome in Hamilton, Ontario.

OBJECTIVE: Evaluate the incidence, neurologic morbidity, and mortality of patients with Terson syndrome. METHODS: Consecutive patients admitted to the Hamilton General Hospital from May 2012 to May 2013 with a diagnosis of spontaneous subarachnoid hemorrhage (SAH) were recruited. Funduscopic examinations were performed under pharmacological mydriasis. Outcome measures included: (1) the presence or absence of Terson syndrome; (2) The Glasgow Coma Scale (GCS), Hunt and Hess scale (H&H), and SAH Fisher score upon admission to the hospital; (3) the modified Rankin score upon discharge; and (4) and all-cause mortality. RESULTS: Forty-six patients were included and 10 had Terson syndrome (21%). The median H&H, GCS, and Fisher scores were 4, 6.5, and 4.0 for patients with Terson syndrome vs. 2, 14, and 3 for patients without Terson syndrome (p=0.0032, 0.0052, and 0.031), respectively. The median Rankin score was 6 for patients with Terson syndrome vs. 3.5 for patients without Terson syndrome (p=0.0019). The odds of all-cause mortality with Terson syndrome vs. no Terson syndrome was 12: 1 (95% confidence interval 2.33-61.7), p =0.003. Only four of the 10 patients with Terson syndrome survived. CONCLUSIONS: Based on this study, approximately one-fifth of patients admitted to the hospital with a spontaneous SAH could have Terson syndrome. Patients with Terson syndrome have significantly worse GCS and H&H scores upon admission to the hospital, lower modified Rankin scores upon discharge, and greater mortality. Thus, Terson syndrome is not rare among patients with SAH and carries a worse prognosis.

Peroxisomal D-bifunctional protein deficiency: three adults diagnosed by whole-exome sequencing.

OBJECTIVE: To determine the causative genetic lesion in 3 adult siblings with a slowly progressive, juvenile-onset phenotype comprising cerebellar atrophy and ataxia, intellectual decline, hearing loss, hypogonadism, hyperreflexia, a demyelinating sensorimotor neuropathy, and (in 2 of 3 probands) supratentorial white matter changes, in whom numerous prior investigations were nondiagnostic. METHODS: The patients' initial clinical assessment included history and physical examination, cranial MRI, and nerve conduction studies. We performed whole-exome sequencing of all 3 probands, followed by variant annotation and selection of rare, shared, recessive coding changes to identify the gene responsible. We next performed a panel of peroxisomal investigations in blood and cultured fibroblasts, including assessment of D-bifunctional protein (DBP) stability and activity by immunoblot and enzymologic methods, respectively. RESULTS: Exome sequencing identified compound heterozygous mutations in HSD17B4, encoding peroxisomal DBP, in all 3 probands. Both identified mutations alter a conserved residue within the active site of DBP's enoyl-CoA hydratase domain. Routine peroxisomal screening tests, including very long-chain fatty acids and phytanic acid, were normal. DBP enzymatic activity was markedly reduced. CONCLUSION: Exome sequencing provides a powerful and elegant tool in the specific diagnosis of "mild" or "atypical" neurometabolic disorders. Given the broad differential diagnosis and the absence of detectable biochemical abnormalities in blood, molecular testing of HSD17B4 should be considered as a first-line investigation in patients with compatible features.

Hypertensive Retinopathy in Takayasu Arteritis.

A 26-year-old woman presented with painless vision loss secondary to hypertensive retinopathy in the setting of Takayasu arteritis and renal artery stenosis.