Fundoscopy use in neurology departments and the utility of smartphone photography: a prospective prevalence and crossover diagnostic accuracy study amongst neurology inpatients.

BACKGROUND AND PURPOSE: Although fundoscopy is a crucial part of the neurological examination, it is challenging, under-utilized and unreliably performed. The aim was to determine the prevalence of fundus pathology amongst neurology inpatients and the diagnostic accuracy of current fundoscopy practice compared with systematic screening with smartphone fundoscopy (SF) and portable non-mydriatic fundus photography (NMFP). METHODS: This was a prospective cross-sectional surveillance and diagnostic accuracy study on adult patients admitted under neurology in an Australian hospital. Inpatients were randomized to initial NMFP (RetinaVue 100, Welch Allyn) or SF (D-EYE) followed by a crossover to the alternative modality. Images were graded by neurology doctors, using telemedicine consensus neuro-ophthalmology NMFP grading as the reference standard. Feasibility parameters included ease, comfort and speed. RESULTS: Of 79 enrolled patients, 14.1% had neurologically relevant pathology (seven, disc pallor; one, hypertensive retinopathy; three, disc swelling). The neurology team performed direct ophthalmoscopy in 6.6% of cases and missed all abnormalities. SF had a sensitivity of 30%-40% compared with NMFP (45.5%); however, it had a lower rate of screening failure (1% vs. 13%, p < 0.001), a shorter examination time (1.10 vs. 2.25 min, p < 0.001) and a slightly higher patient comfort rating (9.2 vs. 8/10, p < 0.001). CONCLUSION: Our study demonstrates a clinically significant prevalence of fundus pathology amongst neurology inpatients which was missed by current fundoscopy practices. Portable NMFP screening appears more accurate than SF, whilst both are diagnostically superior to routine fundoscopic practice, feasible and well tolerated by patients.

High Degree of Genetic Heterogeneity for Hereditary Cerebellar Ataxias in Australia.

Genetic testing strategies such as next-generation sequencing (NGS) panels and whole genome sequencing (WGS) can be applied to the hereditary cerebellar ataxias (HCAs), but their exact role in the diagnostic pathway is unclear. We aim to determine the yield from genetic testing strategies and the genetic and phenotypic spectrum of HCA in Australia by analysing real-world data. We performed a retrospective review on 87 HCA cases referred to the Neurogenetics Clinic at the Royal North Shore Hospital, Sydney, Australia. Probands underwent triplet repeat expansion testing; those that tested negative had NGS-targeted panels and WGS testing when available. In our sample, 58.6% were male (51/87), with an average age at onset of 37.1 years. Individuals with sequencing variants had a prolonged duration of illness compared to those with a triplet repeat expansion. The detection rate in probands for routine repeat expansion panels was 13.8% (11/80). NGS-targeted panels yielded a further 11 individuals (11/32, 34.4%), with WGS yielding 1 more diagnosis (1/3, 33.3%). NGS panels and WGS improved the overall diagnostic rate to 28.8% (23/80) in 14 known HCA loci. The genetic findings included novel variants in ANO10, CACNA1A, PRKCG and SPG7. Our findings highlight the genetic heterogeneity of HCAs and support the use of NGS approaches for individuals who were negative on repeat expansion testing. In comparison to repeat disorders, individuals with sequencing variants may have a prolonged duration of illness, consistent with slower progression of disease.

"Peering at the Tip of the Nose" as a Sign of Thalamic Haemorrhage.

A 76-year-old female presented with sudden onset of left hemiplegia and hemianaesthesia. Examination revealed tonic downward deviation of both eyes and esodeviation of the left eye, with no upgaze beyond midline and mild abduction deficits bilaterally. Bilateral ptosis was seen, reflecting partial levator dehiscence compounded by pseudoptosis due to the depressed position of the eyes. "Peering at the tip of the nose" sign, reflecting acute downward and esodeviation of the eyes, is highly suggestive of thalamic haemorrhage. It is thought to reflect damage to the mesodiencephalic junction, which contains structures important for vertical gaze and vergence. Awareness of this sign may assist clinicians with the correct anatomical localisation of stroke in patients who present with thalamic haemorrhage.

Use of Whole-Genome Sequencing for Mitochondrial Disease Diagnosis.

BACKGROUND AND OBJECTIVES: Mitochondrial diseases (MDs) are the commonest group of heritable metabolic disorders. Phenotypic diversity can make molecular diagnosis challenging, and causative genetic variants may reside in either mitochondrial or nuclear DNA. A single comprehensive genetic diagnostic test would be highly useful and transform the field. We applied whole-genome sequencing (WGS) to evaluate the variant detection rate and diagnostic capacity of this technology with a view to simplifying and improving the MD diagnostic pathway. METHODS: Adult patients presenting to a specialist MD clinic in Sydney, Australia, were recruited to the study if they satisfied clinical MD (Nijmegen) criteria. WGS was performed on blood DNA, followed by clinical genetic analysis for known pathogenic MD-associated variants and MD mimics. RESULTS: Of the 242 consecutive patients recruited, 62 participants had "definite," 108 had "probable," and 72 had "possible" MD classification by the Nijmegen criteria. Disease-causing variants were identified for 130 participants, regardless of the location of the causative genetic variants, giving an overall diagnostic rate of 53.7% (130 of 242). Identification of causative genetic variants informed precise treatment, restored reproductive confidence, and optimized clinical management of MD. DISCUSSION: Comprehensive bigenomic sequencing accurately detects causative genetic variants in affected MD patients, simplifying diagnosis, enabling early treatment, and informing the risk of genetic transmission.

Functional neurological disorders in outpatient practice: An Australian cohort.

Functional disorders are defined as neurological symptoms without causative organic pathology identified. They are a diverse and often neglected group of disorders. The aim of this was to determine the incidence and outcome of functional neurological disorders in an Australian neurology practice. Over a 17month period, all patients presenting to a single outpatient neurology service were evaluated to determine the incidence and outcome of these disorders. A total of 884 patients were assessed and of these, 137 had a final diagnosis of functional neurological illness, equating to an incidence of 15% of all patients seen. Functional disorders were the third most common presentation overall. Patients with functional disorders were younger, more likely to be female and had a higher rate of current psychiatric comorbidity compared to other neurology patients. Sensory symptoms were the most common manifestation (48%) followed by limb weakness (37%) and psychogenic non-epileptic seizures (14%). Outcome information was available for 49% of patients at an average of 3months follow-up. 45% had some improvement in their symptoms, 43% had static symptoms and 12% had worsening of symptoms. This study confirms the high incidence of functional disorders in outpatient neurology practice. Early improvement was seen in a substantial proportion of patients and is influenced by duration of symptoms.

Beyond what the eye can see.

A 45-year-old woman presented with acute sequential optic neuropathy resulting in bilateral complete blindness. No significant visual recovery occurred. Past medical history was relevant for severe preeclampsia with resultant renal failure, diabetes mellitus, and sudden bilateral hearing loss when she was 38 years old. There was a family history of diabetes mellitus in her mother. Testing for common causes of bilateral optic neuropathy did not reveal a diagnosis for her illness. The maternal and personal history of diabetes and deafness prompted testing for mitochondrial disease. The 3 primary mitochondrial DNA mutations responsible for Leber hereditary optic neuropathy were absent, but the patient was subsequently found to have a disease causing mitochondrial DNA mutation, m.13513G>A. The case illustrates the importance of early testing for mitochondrial disease and demonstrates that Leber hereditary optic neuropathy-like presentations may be missed if testing is limited to the 3 primary mutations.

Rhabdoid meningioma presenting with subependymal and diffuse meningeal involvement but no mass lesion.

Rhabdoid meningiomas are rare, aggressive tumours of the meninges that have a generally poor prognosis. We report a 49-year-old man with a background history of sarcoidosis who presented with nausea and vomiting. Imaging showed generalised leptomeningeal and subependymal enhancement suggestive of chronic meningitis. He had multiple lumbar punctures and a brain biopsy, none of which led to a pathological diagnosis. He died within months, and a postmortem examination was performed. At this stage, a diagnosis of rhabdoid meningioma was made. The clinical and radiological presentation of rhabdoid meningioma as a diffuse leptomeningeal process without a mass lesion is unique. All other published cases of rhabdoid meningioma have been of a discrete lesion. This highlights the importance of a tissue diagnosis in patients where the imaging is non-specific. A brief review of rhabdoid meningioma follows.

Echocardiography in the detection of cardioembolism in a stroke population.

Both transthoracic (TTE) and transoesophageal (TOE) echocardiography are used routinely to investigate ischaemic stroke. We retrospectively assessed the incidence of abnormalities on TTE/TOE and whether an abnormal TTE/TOE result could have been predicted on the basis of ancillary tests and clinical cardiological examination. Data from 428 patients were analysed. The diagnostic yield of TTE was 12%. For TOE there was a diagnostic yield of 40% in tests actually performed. Overall, echocardiography altered management in 5% of patients. A significant correlation was found between clinical cardiac disease, stroke subtype and the diagnostic yield of TTE. We conclude that the vast majority of abnormal findings occur in patients who already have clinical evidence of cardiac disease. This suggests that the use of these tests should not be "routine", but determined on an individual patient basis.