Long latency reflexes of the median nerves in healthy adults.

INTRODUCTION/AIMS: Long latency reflexes (LLRs) are late responses in nerve conduction studies seen after peripheral nerve stimulation during submaximal muscle contraction. They follow a short latency reflex, also known as the H reflex, and are thought to involve transcortical pathways, providing a measure of proximal nerve and central conduction. For this reason, they have been evaluated in several central nervous system diseases, but reference values are not widely published and are mostly based on old studies with very small numbers of participants. Therefore, in this work we aim to provide comprehensive reference values for LLR testing. METHODS: LLRs were tested in a cohort of 100 healthy participants, testing the median nerve bilaterally. RESULTS: Mean latencies for short latency reflex (SLR), LLR1, LLR2, and LLR3 were 27.00, 38.50, 47.60, and 67.34 milliseconds, respectively. The allowable side-to-side difference was approximately 3 to 4 milliseconds. No significant sex-related differences were seen. Height correlated moderately with the SLR latency, but only weakly with LLR1, LLR2, and LLR3. DISCUSSION: This work provides normal LLR values for comparison with future studies in disease. The technique used may allow for improved evaluation of central nervous system or proximal peripheral nerve disorders.

Optimizing the technique for eliciting antidromic sural and superficial fibular sensory nerve action potentials.

INTRODUCTION/AIMS: Lower limb sensory nerve action potentials are an important component of nerve conduction studies. Most testing of the sural and superficial fibular nerves involves antidromic techniques above the ankle, which result in a falsely unobtainable response in 2%-6% of healthy people. Cadaver, surgical, and more recent ultrasound series suggest this may relate to the site of fascia penetration of the nerve, and it is hypothesized that a modified technique may be more likely to produce reliable responses and reduce false-negative errors. METHODS: This article evaluates a variety of recording distances for both nerves in 100 healthy controls, including varying recording electrode positions and techniques, to provide the optimal electrodiagnostic information in healthy control subjects. RESULTS: Shorter stimulation distances produce higher-amplitude responses but become confounded by increasing stimulation artifact at very short distances, with the best balance found at around 10 cm. In both sural and superficial fibular nerves, amplitude increases by approximately 10%/cm compared with the standard 14 cm distance. The Daube superficial fibular technique produced a higher amplitude than the Izzo Intermediate technique (by 22.46%, p < .001). The calculated upper limit of normal for side-to-side variation in amplitude was around 50% in the sural nerve but over 70% in the superficial fibular nerve. DISCUSSION: It is proposed that the 10 cm recording distance for both nerves is optimal, with minimal false-negatives and a higher amplitude elicited than with existing techniques.

Contraction-Induced H Reflexes of the Upper and Lower Limbs in Healthy Adults.

PURPOSE: Contraction-induced H reflexes are a late neurophysiologic response elicited with submaximal nerve stimulation during isometric muscle contraction. Mediated by spinal pathways, like other H reflexes, their use has remained somewhat limited despite a long history of development dating back to the original description by Hoffman. There is a paucity of data on normal reference ranges, which this article aims to add to. METHODS: Contraction-induced H reflexes were elicited from the first dorsal interosseous, flexor carpi radialis, and tibialis anterior bilaterally in 100 healthy volunteers. Reference values, including side-to-side variation, were calculated. Pearson test and multiple regression were used to evaluate the relationship of H-reflex latency to height, age, and sex of participants. RESULTS: The mean onset latencies of 28.00, 17.44, and 31.10 ms were seen for first dorsal interosseous, flexor carpi radialis, and tibialis anterior muscles, respectively. The calculated allowable side-to-side latency difference in individual participants was 3 to 4 ms. A correlation to participant height was seen. CONCLUSIONS: This work provides normal reference values of contraction-induced H reflexes to three muscles, including allowable side-to-side variation. The latter suggests that bilateral testing evaluating for asymmetry within an individual is likely to be optimally sensitive. The relationship to height is also confirmed.

Early Electrophysiology in Suspected Acute Guillain-Barré Syndrome: A Prospective Study of Comprehensive Testing.

PURPOSE: Electrophysiologic changes in early Guillain-Barré Syndrome (GBS) can be nondiagnostic. Improved testing paradigms may improve hyperacute treatment. METHODS: This work prospectively evaluated consecutive patients admitted to a metropolitan teaching hospital in Melbourne, Australia, with suspected acute GBS. We performed extensive neurophysiology at three different time points. Novel tests, including cutaneous silent periods, long latency reflexes, and contraction-induced H reflexes, were assessed. RESULTS: Twenty-three participants were studied, including 13 cases of acute GBS. In total, 69% of acute cases of GBS were accurately diagnosed on the first nerve conduction study using published neurophysiologic criteria, with serial studies rarely altering the GBS subtype classification. Antidromic and orthodromic upper limb sensory studies were diagnostically equivalent. A sural sparing pattern was seen in 77% of cases of GBS at the first test. Long latency reflexes and contraction-induced H reflexes testing were abnormal in most participants but were limited by muscle weakness in some. Cutaneous silent periods testing was unobtainable in approximately 50% of cases because of weakness and did not discriminate from mimic disorders. CONCLUSIONS: Abnormalities of long latency reflexes and contraction-induced H reflexes may be helpful where initial electrophysiology is nondiagnostic but are nonspecific. Cutaneous silent periods testing seems of limited value. Comprehensive testing provides diagnostic certainty in most cases of GBS from the very first study.

Chronic mimics of myasthenia gravis: a retrospective case series.

Myasthenia gravis often presents a diagnostic challenge and may be misdiagnosed, particularly in seronegative disease with active symptoms. We retrospectively evaluated 61 patients following the introduction of single fibre electromyography at our service, and identified 8 mimics which had been inappropriately diagnosed and treated as refractory myasthenia gravis. 6 of these were seronegative, but two had positive acetylcholine receptor (AChR) antibodies. The final diagnoses included one case each of chronic progressive external ophthalmoplegia, chronic ptosis, oculopharyngeal muscular dystrophy, and an undifferentiated disorder suspicious for either a mitochondrial cytopathy or low-grade myositis. Four were diagnosed with functional neurological disorder, one of which had a superimposed thyroid myopathy and orbitopathy. We found the average duration of misdiagnosis was 9 years (SD±5.2, median 11 years), and patients were often exposed to years of unnecessary treatment. All patients had received anticholinesterase therapy, three had immunotherapy, and three surgical interventions were performed including two thymectomies. We found myasthenic mimics should be suspected in disease that is static and treatment refractory, and functional mimics in disease with frequent flares. Thorough neurophysiologic assessment is important, particularly when making a diagnosis of seronegative myasthenia gravis.

COVID-19 Vaccine Status, Intent, Hesitancy, and Disease-Related Beliefs in People with Multiple Sclerosis.

BACKGROUND: People with multiple sclerosis (MS) are susceptible to severe COVID-19 outcomes. They were included as a priority group for the Australian COVID-19 vaccine roll-out in early 2021. However, vaccine hesitancy remains a complex barrier to vaccination in this population group, which may be partly related to disease relapse concerns following COVID-19 vaccination. This study examined the COVID-19 vaccination status, intent, hesitancy, and disease-related beliefs in people with MS. METHODS: An online survey was conducted with people with MS receiving care at two Australian health services between September and October 2021. It collected sociodemographic and disease-specific characteristics and responses to validated scales that assessed vaccine hesitancy and general and MS-related vaccine beliefs. RESULTS: Of the 281 participants [mean age 47.7 (SD 12.8) years; 75.8% females], most (82.9%) had received at least one COVID-19 vaccine dose. Younger participants were less likely to be vaccinated, as were those within 1-5 years of disease duration. After controlling for age, disease duration was not associated with vaccination status. Unvaccinated participants were more likely to report less willingness to receive the COVID-19 vaccine, higher vaccine complacency and lower vaccine confidence, greater MS-related vaccine complacency, and higher MS and treatment interaction concerns. CONCLUSIONS: People with MS reported a high vaccination rate, despite general and MS-specific COVID-19 vaccine concerns. Greater MS-specific concerns were reported by those who indicated that their MS was not well-controlled and their MS impacted their daily activities. By understanding the factors that influence vaccine hesitancy and their interplay with MS disease course and treatment concerns, this can inform tailored interventions and educational messages to address these concerns in people with MS. Clinicians, governments, and community organisations are key partners in delivering these interventions and messages, as ongoing booster doses are needed for this vulnerable population.

RFC1 in an Australasian neurological disease cohort: extending the genetic heterogeneity and implications for diagnostics.

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome is a progressive, generally late-onset, neurological disorder associated with biallelic pentanucleotide expansions in Intron 2 of the RFC1 gene. The locus exhibits substantial genetic variability, with multiple pathogenic and benign pentanucleotide repeat alleles previously identified. To determine the contribution of pathogenic RFC1 expansions to neurological disease within an Australasian cohort and further investigate the heterogeneity exhibited at the locus, a combination of flanking and repeat-primed PCR was used to screen a cohort of 242 Australasian patients with neurological disease. Patients whose data indicated large gaps within expanded alleles following repeat-primed PCR, underwent targeted long-read sequencing to identify novel repeat motifs at the locus. To increase diagnostic yield, additional probes at the RFC1 repeat region were incorporated into the PathWest diagnostic laboratory targeted neurological disease gene panel to enable first-pass screening of the locus for all samples tested on the panel. Within the Australasian cohort, we detected known pathogenic biallelic expansions in 15.3% (n = 37) of patients. Thirty indicated biallelic AAGGG expansions, two had biallelic 'Maori alleles' [(AAAGG)exp(AAGGG)exp], two samples were compound heterozygous for the Maori allele and an AAGGG expansion, two samples had biallelic ACAGG expansions and one sample was compound heterozygous for the ACAGG and AAGGG expansions. Forty-five samples tested indicated the presence of biallelic expansions not known to be pathogenic. A large proportion (84%) showed complex interrupted patterns following repeat-primed PCR, suggesting that these expansions are likely to be comprised of more than one repeat motif, including previously unknown repeats. Using targeted long-read sequencing, we identified three novel repeat motifs in expanded alleles. Here, we also show that short-read sequencing can be used to reliably screen for the presence or absence of biallelic RFC1 expansions in all samples tested using the PathWest targeted neurological disease gene panel. Our results show that RFC1 pathogenic expansions make a substantial contribution to neurological disease in the Australasian population and further extend the heterogeneity of the locus. To accommodate the increased complexity, we outline a multi-step workflow utilizing both targeted short- and long-read sequencing to achieve a definitive genotype and provide accurate diagnoses for patients.

Serious Underlying Medical Conditions and COVID-19 Vaccine Hesitancy: A Large Cross-Sectional Analysis from Australia.

As COVID-19 vaccinations became available and were proven effective in preventing serious infection, uptake amongst individuals varied, including in medically vulnerable populations. This cross-sectional multi-site study examined vaccine uptake, hesitancy, and explanatory factors amongst people with serious and/or chronic health conditions, including the impact of underlying disease on attitudes to vaccination. A 42-item survey was distributed to people with cancer, diabetes, or multiple sclerosis across ten Australian health services from 30 June to 5 October 2021. The survey evaluated sociodemographic and disease-related characteristics and incorporated three validated scales measuring vaccine hesitancy and vaccine-related beliefs generally and specific to their disease: the Oxford COVID-19 Vaccine Hesitancy Scale, the Oxford COVID-19 Vaccine Confidence and Complacency Scale and the Disease Influenced Vaccine Acceptance Scale-Six. Among 4683 participants (2548 [54.4%] female, 2108 [45.0%] male, 27 [0.6%] other; mean [SD] age, 60.6 [13.3] years; 3560 [76.0%] cancer, 842 [18.0%] diabetes, and 281 [6.0%] multiple sclerosis), 3813 (81.5%) self-reported having at least one COVID-19 vaccine. Unvaccinated status was associated with younger age, female sex, lower education and income, English as a second language, and residence in regional areas. Unvaccinated participants were more likely to report greater vaccine hesitancy and more negative perceptions toward vaccines. Disease-related vaccine concerns were associated with unvaccinated status and hesitancy, including greater complacency about COVID-19 infection, and concerns relating to vaccine efficacy and impact on their disease and/or treatment. This highlights the need to develop targeted strategies and education about COVID-19 vaccination to support medically vulnerable populations and health professionals.

Calculated Decisions: HINTS for stroke in acute vestibular syndrome.

The HINTS score identifies potential stroke in patients with acute vestibular syndrome.

Current concepts in multiple sclerosis therapy.

Over the past 20 years, the available therapies for multiple sclerosis have expanded exponentially. With several more agents likely to be approved for public funding in Australia in the next 12 months on top of the existing multitude of Australian Pharmaceutical Benefits Scheme-subsidized therapies, the choice is becoming even more complex. This review summarizes the current state of available therapies and anticipates likely future directions, including an important focus on contemporary symptom management. For each agent, the major trials, side effects, and clinical utility are summarized, with a particular focus on the Australian experience of these therapies. It is hoped this review provides an up-to-date reference of the exciting current state of multiple sclerosis therapy.