FEATURED ARTICLE OF THE WEEK

Diagnosis and classification of optic neuritis

There is no consensus regarding the classification of optic neuritis, and precise diagnostic criteria are not available. This reality means that the diagnosis of disorders that have optic neuritis as the first manifestation can be challenging. Accurate diagnosis of optic neuritis at presentation can facilitate the timely treatment of individuals with multiple sclerosis, neuromyelitis optica spectrum disorder, or myelin oligodendrocyte glycoprotein antibody-associated disease. Epidemiological data show that, cumulatively, optic neuritis is most frequently caused by many conditions other than multiple sclerosis. Worldwide, the cause and management of optic neuritis varies with geographical location, treatment availability, and ethnic background. We have developed diagnostic criteria for optic neuritis and a classification of optic neuritis subgroups. Our diagnostic criteria are based on clinical features that permit a diagnosis of possible optic neuritis; further paraclinical tests, utilising brain, orbital, and retinal imaging, together with antibody and other protein biomarker data, can lead to a diagnosis of definite optic neuritis. Paraclinical tests can also be applied retrospectively on stored samples and historical brain or retinal scans, which will be useful for future validation studies. Our criteria have the potential to reduce the risk of misdiagnosis, provide information on optic neuritis disease course that can guide future treatment trial design, and enable physicians to judge the likelihood of a need for long-term pharmacological management, which might differ according to optic neuritis subgroups.

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Diagnosis and management of progressive ataxia in adults

Progressive ataxia in adults can be difficult to diagnose, owing to its heterogeneity and the rarity of individual causes. Many patients remain undiagnosed (‘idiopathic’ ataxia). This paper provides suggested diagnostic pathways for the general neurologist, based on Ataxia UK’s guidelines for professionals. MR brain scanning can provide diagnostic clues, as well as identify ‘structural’ causes such as tumours and multiple sclerosis. Advances in molecular genetics, including the wider and cheaper availability of ‘next-generation sequencing’, have enabled clinicians to identify many more cases with a genetic cause. Finally, autoimmunity is probably an under-recognised cause of progressive ataxia: as well as patients with antigliadin antibodies there are smaller numbers with various antibodies, including some associated with cancer. There are a few treatable ataxias, but also symptomatic treatments to help people with the spectrum of complications that might accompany progressive ataxias. Multidisciplinary team involvement and allied health professionals’ input are critical to excellent patient care, including in the palliative phase. We can no longer justify a nihilistic approach to the management of ataxia.

Trigeminal neuralgia: a practical guide

Trigeminal neuralgia (TN) is a highly disabling disorder characterised by very severe, brief and electric shock like recurrent episodes of facial pain. New diagnostic criteria, which subclassify TN on the basis of presence of trigeminal neurovascular conflict or an underlying neurological disorder, should be used as they allow better characterisation of patients and help in decision-making regarding medical and surgical treatments. MR imaging, including high-resolution trigeminal sequences, should be performed as part of the diagnostic work-up. Carbamazepine and oxcarbazepine are drugs of first choice. Lamotrigine, gabapentin, pregabalin, botulinum toxin type A and baclofen can be used either alone or as add-on therapy. Surgery should be considered if the pain is poorly controlled or the medical treatments are poorly tolerated. Trigeminal microvascular decompression is the first-line surgery in patients with trigeminal neurovascular conflict while neuroablative surgical treatments can be offered if MR imaging does not show any neurovascular contact or where patients are considered too frail for microvascular decompression or do not wish to take the risk.

Diagnosis and management of functional neurological disorder

Functional neurological disorder (FND), previously regarded as a diagnosis of exclusion, is now a rule-in diagnosis with available treatments. This represents a major step toward destigmatizing the disorder, which was often doubted and deemed untreatable. FND is prevalent, generally affecting young and middle aged adults, and can cause severe disability in some individuals. An early diagnosis, with subsequent access to evidence based rehabilitative and/or psychological treatments, can promote recovery—albeit not all patients respond to currently available treatments. This review presents the latest advances in the use of validated rule-in examination signs to guide diagnosis, and the range of therapeutic approaches available to care for patients with FND. The article focuses on the two most frequently identified subtypes of FND: motor (weakness and/or movement disorders) and seizure type symptoms. Twenty two studies on motor and 27 studies on seizure type symptoms report high specificities of clinical signs (64-100%), and individual signs are reviewed. Rehabilitative interventions (physical and occupational therapy) are treatments of choice for functional motor symptoms, while psychotherapy is an emerging evidence based treatment across FND subtypes. The literature to date highlights heterogeneity in responses to treatment, underscoring that more research is needed to individualize treatments and develop novel interventions.

The “Noise” of Medicine

In this article, we use the term “noise” not to refer to the literal noise of a busy emergency department on a Saturday night, but rather, to refer to the statistical concept of “noise.” Specifically, we focus on “occasion noise,” which arises whenever the accurate responses to the same question vary with factors that are, from a logical point of view, irrelevant to the question asked. In an ideal world, the accuracy of medical diagnosis would not depend neither on how busy the emergency department is at the time of diagnosis, what the doctor had for breakfast, whether it was humid or not that day, what the previous patient’s diagnosis was, nor myriad other considerations not germane to the clinical scenario. Human performance, however, does perforce depend on many such irrelevant factors, although we are only vaguely aware of their impact. Sleep deprivation, for example, slows reaction time and induces “unstable and unpredictable patterns of behavior.” Thus, it is unsurprising that a high level of sleep deprivation is associated with nearly doubled rates of self-reported medical errors. 

Guillain-Barré or Guillain-Barré-Strohl syndrome: medical and non-medical reasons for omitting Andre Strohl from the eponym

The increasing incidence of Guillain-Barré syndrome (GBS) during the coronavirus disease 2019 pandemic prompts a discussion concerning the correct form of the eponym and the reasons for omitting André Strohl. André Strohl was born on March 20, 1887 in Poitiers in west-central France. Initially, Strohl began medical studies, later switching to mathematics, physics and chemistry. Afterwards, he returned to study medicine at the University of Paris and in 1913 defended his medical doctorate thesis. During World War I (WWI), Strohl served in the French army at his request and was assigned to perform radiological examinations. The military service did not suppress his scientific work, which was reflected in 1916 when he used a radiological imaging technique to locate a bullet in the body of a wounded person. In the same year, together with two neurologists working in the Sixth French Army neurological unit, Georges Guillain (1876–1961) and Jean-Alexandre Barré (1880–1967), he described one of the most recognized neurological syndromes in the history of neurology

Significance of Neuronal Autoantibodies in Comparison to Infectious Etiologies among Patients Presenting with Encephalitis in a Region with a High Prevalence of Infections

Prevalence of antibody mediated autoimmune encephalitis (AE) is reported to be comparable to infectious encephalitis in Western populations. We evaluated the frequency and significance of AE and neuronal autoantibodies in comparison to infectious etiologies among patients presenting with encephalitis in a South Asian population. Methods: Ninety nine consecutive patients with a clinical diagnosis of encephalitis/meningoencephalitis admitted to two of the largest tertiary care hospitals in Sri Lanka were studied. PCR and ELISA were used to screen viruses while Gram stain and culture were used to screen bacteria. Sera were tested for antibodies binding to primary embryonic rat hippocampal neuronal cultures and cell based assays for antibodies to NMDAR, LGI1, CASPR2, Contactin2, AMPAR, GABAAR, GABABR, aquaporin 4 and MOG. Results: Patient ages ranged from 1 month to 73 years (mean = 24.91; SD = 21.33) with a male: female ratio of 1.75:1. A viral etiology was identified in 27.3% and bacterial meningoencephalitis was diagnosed in 17.1%. Sera of nine patients had antibodies binding to live primary neurons, but only five had specific antibodies to CASPR2 (n = 1), NMDAR (n = 2) or GABABR antibodies (n = 2). Moreover, the patients with CASPR2 antibodies and NMDAR antibodies were also positive for dengue antibodies. Only the two patients with NMDAR antibodies had features and responses to immunotherapy consistent with AE. Conclusions: Identified infectious forms of meningoencephalitis (44.4%) greatly exceeded the occurrence of neuronal autoantibodies (9.1%) and AE (2%) in Sri Lanka, and this may be common in those regions where infections are prevalent.

Prevalence and correlates of carotid artery stenosis in a cohort of Sri Lankan ischaemic stroke patients

Large artery atherosclerotic disease is an important cause of stroke, accounting for 15–46% of ischaemic strokes in population-based studies. Therefore, current guidelines from west recommend urgent carotid imaging in all ischaemic strokes or transient ischaemic attacks and referral for carotid endarterectomy. However, the clinical features and epidemiology of stroke in Asians are different from those in Caucasians and therefore the applicability of these recommendations to Asians is controversial. Data on the prevalence of carotid artery stenosis (CAS) among South Asian stroke patients is limited. Therefore, we sought to determine the prevalence and associated factors of significant CAS in a cohort of Sri Lankan patients with ischaemic stroke.

Familial Multiple Sclerosis in a Mother and Son Pair: A Sri Lankan and a South Asian First

Multiple sclerosis (MS) is an immune-mediated demyelinating disorder involving the central nervous system (CNS). It is common amongst young females. Although the exact cause of MS is yet unknown, viral infections such as EBV, environmental factors, and autoimmune and genetic mechanisms involving HLA-DRB1 loci are implicated. Familial MS is reported from some geographic locations and ethnic groups but is thought to be rare in Asia. In this paper, we present both a Sri Lankan mother and her son, with clinically definite MS conforming to McDonald’s 2017 clinical and MAGNIMS 2016 radiological criteria. Both had oligoclonal bands in their CSF (OCB-IEF) with no serum bands indicating intrathecal production and were negative for AQP4 and MOG IgG
serology. Familial MS is more common among siblings, with sister-sister relationship having the highest rate. +e lowest relation was amongst father-son and mother-son pairs. Amongst siblings, the risk of MS is between 3.5% and 4.7%. Inherited factors rather than common environmental exposure influence susceptibility in such cases. To the best of our knowledge, MS occurring in a
mother-son pair has not been reported before either from Sri Lanka or South Asia.

Evolution of Evidence-Based Medicine in Stroke

The introduction and evolution of evidence-based stroke medicine has realized major advances in our knowledge about stroke, methods of medical research, and patient outcomes that continue to complement traditional individual patient care. It is humbling to recall the state of knowledge and scientific endeavour of our forebears who were unaware of what we know now and yet pursued the highest standards for evaluating and delivering effective stroke care. The science of stroke medicine has evolved from pathophysiological theory to empirical testing. Progress has been steady, despite inevitable disappointments and cul-de-sacs, and has occasionally been punctuated by sensational breakthroughs, such as the advent of reperfusion therapies guided by imaging.

Strokectomy for malignant middle cerebral artery infarction: experience and meta‐analysis of current evidence

Strokectomy means surgical excision of infarcted brain tissue post-stroke with preservation of skull integrity, distinguishing it from decompressive hemicraniectomy. Both can mitigate malignant middle cerebral artery (MCA) syndrome but evidence regarding strokectomy is sparse.

Autoimmune encephalitis in a South Asian population

Autoimmune encephalitis (AE) is now considered a main, potentially curable cause of encephalitis, but remains conspicuously underreported from South Asia. We studied the clinical characteristics in relation to their antibody status and outcomes of patients presenting with AE in Sri Lanka.

Stroke in Sri Lanka : How Can We Minimize the Burden?

The burden of stroke in Sri Lanka is high and steadily increasing. Accurate estimation of the burden is hampered by a paucity of epidemiological data. More neurologists, stroke units, facilities for modern treatments and multi-disciplinary rehabilitation services are urgently needed. Essential drugs for risk factor control and secondary prevention are available in many hospitals. Aggressive preventive strategies and promoting stroke awareness are the best ways to minimise the stroke burden in Sri Lanka.

Anterior interosseous nerve palsy caused by Parsonage-Turner syndrome

A 58-year-old man presented with difficulty in moving his left hand. Three weeks before this presentation, he had symptoms of an upper respiratory tract infection, which resolved spontaneously in several days. And 1 week after that, he experienced a severe stabbing pain in his entire left upper arm, which resolved in several days. At that time, he also developed difficulty in moving the thumb and index finger of his left hand.

Second intravenous immunoglobulin dose in patients with Guillain-Barré syndrome with poor prognosis (SID-GBS): a double-blind, randomised, placebo-controlled trial

Treatment with one standard dose (2 g/kg) of intravenous immunoglobulin is insufficient in a proportion of patients with severe Guillain-Barré syndrome. Worldwide, around 25% of patients severely affected with the syndrome are given a second intravenous immunoglobulin dose (SID), although it has not been proven effective. We aimed to investigate whether a SID is effective in patients with Guillain-Barré syndrome with a predicted poor outcome.

A rare mutation in the COLQ gene causing congenital myasthenic syndrome with remarkable improvement to fluoxetine: A case report

Congenital myasthenic syndromes (CMS) are genetically determined heterogenous disorders of neuromuscular transmission. We report a rare mutation of COLQ causing CMS in an Asian man that remarkably improved with fluoxetine. A 51-year-old Sri Lankan man with slowly progressive fatigable muscle weakness since eight years of age, presented with type 2 respiratory failure that required mechanical ventilation in the acute crisis and subsequent home-based non-invasive ventilation. His birth and family histories were unremarkable. On examination, he had limb girdle type of muscle weakness with fatigability and normal tendon reflexes with no ocular or bulbar involvement. DNA sequencing revealed a pathogenic homozygous mutation in COLQ gene: ENST00000383788.10:exon16:c.1228C>T:p.R410W, the first report in an Asian. Treatment with fluoxetine resulted in remarkable improvement and regain of muscle power and independence from assisted ventilation.

Effective treatment of osmotic demyelination syndrome with plasmapheresis: a case report and review of the literature

Rapid correction of hyponatraemia is associated with osmotic demyelination syndrome (ODS), which is a demyelinating disorder of the central nervous system (CNS). Brain adapts to chronic hyponatraemia by extracellular movement of osmotically active organic and inorganic particles. During rapid correction of hyponatraemia, organic osmolytes cannot re-enter the intracellular compartment as rapidly as ionic movement creating an osmotic disequilibrium. This causes shrinkage of brain cells including astrocytes and oligodendrocytes causing accelerated apoptosis leading to disruption of the blood brain barrier and demyelination. Consequently, symptoms related to pontine and extra-pontine demyelination typically occurs after two to six days of rapid sodium correction. Traditionally, established ODS is considered to be associated with a poor prognosis. Apart from supportive therapy, sodium re-lowering therapy has shown to be beneficial in the acute stage. However, successful outcome of chronic ODS is limited to a few case reports. Out of the experimental therapies, plasmapheresis alone or in combination with other treatment modalities has shown variable benefit. We report a case of complete clinical and radiological recovery of ODS with plasmapheresis, initiated twenty-two days after rapid sodium correction.

Acute Cerebrovascular Events With COVID-19 Infection

Coronavirus disease 2019 (COVID-19) has been associated with an increased incidence of thrombotic events, including stroke. However, characteristics and outcomes of COVID-19 patients with stroke are not well known. COVID-19 has been associated with an increased incidence of thrombotic events, including severe cerebrovascular events in young patients. However, some centers have reported a decline in acute cardiovascular and cerebrovascular cases and low rates of such events among hospitalized COVID-19 patients during the pandemic. We sought to summarize the characteristics and short-term outcomes of patients admitted to a large multi-hospital health system in New York City with acute cerebrovascular disease during the COVID-19 pandemic. We hypothesized that patients with stroke and confirmed SARS-CoV-2 infection would have fewer traditional vascular risk factors, poorer outcomes, and an embolic or cryptogenic stroke cause more commonly than those without confirmed infection.

Effects of Flickering Seizures on Road Drivers and Passengers

The road environment includes many factors that, due to the repetitions of light signals within a limited area of the field of vision, can cause discomfort and in some cases flickering seizures amongst drivers and passengers. These potentially dangerous factors may occur when driving along an open road and in tunnel. The authors develops an experimental program in order to deepen the main factors of the road environment able to trigger seizures due to the flickering effect and to provide useful indications for the designing and maintaining of roads that are safe for all types of user, including photosensitive subjects.