MyMedR

Non-invasive electromyography as a disease biomarker: Are we only scratching the surface?

Shahrizaila N

Clin Neurophysiol, 2021 03;132(3):808-809.

PMID: 33558128 DOI: 10.1016/j.clinph.2021.01.008

Bickerstaff brainstem encephalitis and Fisher syndrome: anti-GQ1b antibody syndrome

Shahrizaila N, Yuki N

J Neurol Neurosurg Psychiatry, 2013 May;84(5):576-83.

PMID: 22984203 DOI: 10.1136/jnnp-2012-302824

In the 1950s, Bickerstaff and Fisher independently described cases with a unique presentation of ophthalmoplegia and ataxia. The neurological features were typically preceded by an antecedent infection and the majority of patients made a spontaneous recovery. In the cases with Bickerstaff brainstem encephalitis, there was associated altered consciousness and in some, hyperreflexia, in support of a central pathology whereas in Fisher syndrome, patients were areflexic in keeping with a peripheral aetiology. However, both authors recognised certain similarities to Guillain-Barré syndrome such as the presence of peripheral neuropathy and cerebrospinal fluid albuminocytological dissociation. The discovery of immunoglobulin G anti-GQ1b antibodies in patients with Fisher syndrome and later in Bickerstaff brainstem encephalitis was crucial in providing the necessary evidence to conclude that both conditions were in fact part of the same spectrum of disease by virtue of their common clinical and immunological profiles. Following this, other neurological presentations that share anti-GQ1b antibodies emerged in the literature. These include acute ophthalmoparesis and acute ataxic neuropathy, which represent the less extensive spectrum of the disease whereas pharyngeal-cervical-brachial weakness and Fisher syndrome overlap with Guillain-Barré syndrome represent the more extensive end of the spectrum. The conditions can be referred to as the 'anti-GQ1b antibody syndrome'. In this review, we look back at the historical descriptions and describe how our understanding of Fisher syndrome and Bickerstaff brainstem encephalitis has evolved from their initial descriptions more than half a century ago.

Antiganglioside antibodies in Guillain-Barré syndrome and its related conditions

Shahrizaila N, Yuki N

Expert Rev Neurother, 2011 Sep;11(9):1305-13.

PMID: 21864076 DOI: 10.1586/ern.11.114

Guillain-Barré syndrome (GBS) is typically classified into two major subtypes: acute inflammatory demyelinating neuropathy and acute motor axonal neuropathy. Its most recognizable variant is Fisher syndrome. The last two decades have seen considerable advances in our understanding of GBS. Of note, various autoantibodies against ganglioside antigens have been identified and found to have significant associations with the axonal forms of GBS and Fisher syndrome. In this article, we discuss the different clinical presentations in GBS and the role of antiganglioside antibodies in their underlying pathogenesis. We also discuss the impact that antiganglioside antibodies have had in the development of experimental models and treatment modalities in GBS.

The role of immunotherapy in Guillain-Barré syndrome: understanding the mechanism of action

Shahrizaila N, Yuki N

Expert Opin Pharmacother, 2011 Jul;12(10):1551-60.

PMID: 21473704 DOI: 10.1517/14656566.2011.564160

Guillain-Barré syndrome (GBS) is the most frequent cause of acute flaccid paralysis and, despite treatment, there continues to be an associated mortality and severe disability ranging from 9 to 17%. This article reviews the rationale behind the existing immunotherapy in GBS and discusses the future direction that work in this area should follow.

Fulltext Guillain-barré syndrome animal model: the first proof of molecular mimicry in human autoimmune disorder

Shahrizaila N, Yuki N

J Biomed Biotechnol, 2011;2011:829129.

PMID: 21197269 DOI: 10.1155/2011/829129

Molecular mimicry between self and microbial components has been proposed as the pathogenic mechanism of autoimmune diseases, and this hypothesis is proven in Guillain-Barré syndrome. Guillain-Barré syndrome, the most frequent cause of acute neuromuscular paralysis, sometimes occurs after Campylobacter jejuni enteritis. Gangliosides are predominantly cell-surface glycolipids highly expressed in nervous tissue, whilst lipo-oligosaccharides are major components of the Gram-negative bacterium C. jejuni outer membrane. IgG autoantibodies to GM1 ganglioside were found in the sera from patients with Guillain-Barré syndrome. Molecular mimicry was demonstrated between GM1 and lipo-oligosaccharide of C. jejuni isolated from the patients. Disease models by sensitization of rabbits with GM1 and C. jejuni lipo-oligosaccharide were established. Guillain-Barré syndrome provided the first verification that an autoimmune disease is triggered by molecular mimicry. Its disease models are helpful to further understand the molecular pathogenesis as well as to develop new treatments in Guillain-Barré syndrome.

Fulltext Biomarkers of 'acute-onset' chronic inflammatory demyelinating polyneuropathy

Miura Y, Shahrizaila N, Yuki N

Brain, 2015 Mar;138(Pt 3):e335.

PMID: 25183714 DOI: 10.1093/brain/awu252

Delayed facial palsy in Miller Fisher syndrome

Tan CY, Yuki N, Shahrizaila N

J Neurol Sci, 2015 Nov 15;358(1-2):409-12.

PMID: 26277343 DOI: 10.1016/j.jns.2015.08.009

Miller Fisher syndrome is characterised by the triad of ophthalmoplegia, ataxia and areflexia. However, facial palsy can occur during the course of the illness although development of facial palsy when other cardinal signs of Miller Fisher syndrome have reached nadir or improving, is unusual. This delayed appearance of facial palsy can be easily overlooked by the treating clinician. Here, we report four patients with Miller Fisher syndrome and delayed-onset facial palsy. We discuss the possible underlying reasons behind the delay in facial palsy.

Guillain-Barré syndrome

Shahrizaila N, Lehmann HC, Kuwabara S

Lancet, 2021 03 27;397(10280):1214-1228.

PMID: 33647239 DOI: 10.1016/S0140-6736(21)00517-1

Guillain-Barré syndrome is the most common cause of acute flaccid paralysis worldwide. Most patients present with an antecedent illness, most commonly upper respiratory tract infection, before the onset of progressive motor weakness. Several microorganisms have been associated with Guillain-Barré syndrome, most notably Campylobacter jejuni, Zika virus, and in 2020, the severe acute respiratory syndrome coronavirus 2. In C jejuni-related Guillain-Barré syndrome, there is good evidence to support an autoantibody-mediated immune process that is triggered by molecular mimicry between structural components of peripheral nerves and the microorganism. Making a diagnosis of so-called classical Guillain-Barré syndrome is straightforward; however, the existing diagnostic criteria have limitations and can result in some variants of the syndrome being missed. Most patients with Guillain-Barré syndrome do well with immunotherapy, but a substantial proportion are left with disability, and death can occur. Results from the International Guillain-Barré Syndrome Outcome Study suggest that geographical variations exist in Guillain-Barré syndrome, including insufficient access to immunotherapy in low-income countries. There is a need to provide improved access to treatment for all patients with Guillain-Barré syndrome, and to develop effective disease-modifying therapies that can limit the extent of nerve injury. Clinical trials are currently underway to investigate some of the potential therapeutic candidates, including complement inhibitors, which, together with emerging data from large international collaborative studies on the syndrome, will contribute substantially to understanding the many facets of this disease.

Zika virus infection and Guillain-Barré syndrome: a review focused on clinical and electrophysiological subtypes

Uncini A, Shahrizaila N, Kuwabara S

J Neurol Neurosurg Psychiatry, 2017 03;88(3):266-271.

PMID: 27799296 DOI: 10.1136/jnnp-2016-314310

In 2016, we have seen a rapid emergence of Zika virus-associated Guillain-Barré syndrome (GBS) since its first description in a French-Polynesian patient in 2014. Current evidence estimates the incidence of GBS at 24 cases per 100 000 persons infected by Zika virus. This will result in a sharp rise in the number of GBS cases worldwide with the anticipated global spread of Zika virus. A better understanding of the pathogenesis of Zika-associated GBS is crucial to prepare us for the current epidemic. In this review, we evaluate the existing literature on GBS in association with Zika and other flavivirus to better define its clinical subtypes and electrophysiological characteristics, demonstrating a demyelinating subtype of GBS in most cases. We also recommend measures that will help reduce the gaps in knowledge that currently exist.

Clinical Characteristics, Pain, and Quality of Life Experiences of Trigeminal Neuralgia in a Multi-Ethnic Asian Cohort

Tan CY, Shahrizaila N, Goh KJ

J Oral Facial Pain Headache, 2017 10 27;31(4):e15-e20.

PMID: 29073667 DOI: 10.11607/ofph.1793

AIMS: To describe the clinical characteristics of trigeminal neuralgia (TN) in a multi-ethnic Malaysian population and to relate them to standardized measures of pain severity, anxiety, depression, and quality of life (QoL).

METHODS: Patients fulfilling the International Headache Society (IHS) criteria for TN were prospectively interviewed for their demographic and clinical data. Pain intensity was rated with a visual analog scale (VAS), anxiety and depression were determined by the Hospital Anxiety and Depression Scale (HADS), and QoL was assessed by the Short-Form 36 (SF-36) questionnaire. Chi-square, Mann-Whitney U, and Spearman correlation tests were used to test for differences considering a significance level of P < .05.

RESULTS: Of the 75 included patients, 52 (69.3%) were women with a mean ± standard deviation (SD) onset age of 52.0 ± 12.7 years, and 57.3% were Chinese, 24.0% Malay, and 18.7% Indian. Pain was more common on the right side (69.3%) and in the maxillary and mandibular divisions. VAS scores for pain at its worst were higher in anxious/borderline anxious patients compared to non-anxious patients (89.5 ± 15.9 vs 80.9 ± 17.2, respectively; P < .05), and VAS scores for pain at its least were higher in depressed/borderline depressed subjects compared to non-depressed subjects (38.4 ± 25.8 vs 23.0 ± 19.2, respectively; P < .05). Chinese patients had lower VAS scores for pain at its least compared to Indian patients (19.7 ± 16.1 vs 39.9 ± 24.7; P < .01). TN patients scored lower in all eight domains of the SF-36 compared to the general population. Indian patients had lower scores in role limitations due to physical health (8.9 ± 23.2 vs 49.4 ± 43.8; P < .01) and social function (56.3 ± 13.6 vs 76.5 ± 23.6; P < .01) than Chinese patients, and Malay patients had lower mental health scores compared to Chinese patients (59.1 ± 19.5 vs 73.0 ± 21.0; P < .01).

CONCLUSION: Clinical characteristics of TN patients were similar to those of other populations. There were differences in pain ratings and QoL between TN patients of different ethnicities, as well as between those with anxiety and depression.

Nerve ultrasound: Unravelling the different patterns of nerve enlargement in CIDP subtypes

Tan CY, Liu M, Shahrizaila N

Clin Neurophysiol Pract, 2023;8:226-227.

PMID: 38152242 DOI: 10.1016/j.cnp.2023.11.003

Acute flaccid paralysis with chronic cough

Chai CH, Yuki N, Nor HM, Goh KJ, Shahrizaila N

Pract Neurol, 2012 Oct;12(5):328-31.

PMID: 22976064 DOI: 10.1136/practneurol-2011-000205

Successful treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) in systemic lupus erythematosus (SLE) with oral cyclophosphamide

Jasmin R, Sockalingam S, Shahrizaila N, Cheah TE, Zain AA, Goh KJ

Lupus, 2012 Sep;21(10):1119-23.

PMID: 22433918 DOI: 10.1177/0961203312440346

Peripheral neuropathy is a known manifestation of systemic lupus erythematosus. However, the association of primary autoimmune inflammatory neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP) with SLE is uncommon. We report a 26-year-old man who simultaneously presented with severe CIDP and photosensitive rash, but was unresponsive to intravenous immunoglobulin infusion and continued to progress. He was found to have underlying SLE and improved with combined corticosteroid and immunosuppressive therapy with oral cyclophosphamide. CIDP with underlying SLE may be more resistant to conventional therapy with IVIG, requiring the addition of other immunosuppressive agents.

Serial nerve conduction studies provide insight into the pathophysiology of Guillain-Barré and Fisher syndromes

Shahrizaila N, Goh KJ, Kokubun N, Abdullah S, Yuki N

J Neurol Sci, 2011 Oct 15;309(1-2):26-30.

PMID: 21849173 DOI: 10.1016/j.jns.2011.07.042

The electrodiagnosis of Guillain-Barré syndrome (GBS) can be broadly divided into acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). Fisher syndrome (FS) is a variant of GBS, although the underlying neuropathy of FS has yet to be established. Serial nerve conduction studies (NCS) can provide further insight into the likely pathophysiology by further subtyping of GBS and FS. We present a patient with an initial diagnosis of AIDP in whom repeated NCS revealed the AMAN variant. This led us to investigate serial NCS in five patients with GBS, FS and FS/GBS overlap presenting over a period of a year. Three patients with AIDP showed a gradual increase in distal motor latencies during the acute phase of illness. NCS of two patients with FS and FS/GBS overlap showed no demyelinating features suggesting underlying axonal neuropathy in this group of patients. The importance of serial NCS in establishing the underlying pattern of neuropathy in GBS and FS is further emphasized in this study. Larger studies incorporating serial NCS are required to confirm the observations seen in our case series especially when pathological studies are often not justified in this group of patients.

Two sets of nerve conduction studies may suffice in reaching a reliable electrodiagnosis in Guillain-Barré syndrome

Shahrizaila N, Goh KJ, Abdullah S, Kuppusamy R, Yuki N

Clin Neurophysiol, 2013 Jul;124(7):1456-9.

PMID: 23395599 DOI: 10.1016/j.clinph.2012.12.047

Recent studies have advocated the use of serial nerve conduction studies (NCS) in the electrodiagnosis of Guillain-Barré syndrome (GBS). The current study aims to elucidate when and how frequent NCS can be performed to reflect the disease pathophysiology.

Relationship between ultrasonographic nerve morphology and severity of diabetic sensorimotor polyneuropathy

Arumugam T, Razali SN, Vethakkan SR, Rozalli FI, Shahrizaila N

Eur J Neurol, 2016 Feb;23(2):354-60.

PMID: 26498575 DOI: 10.1111/ene.12836

In the current study, the aim was to characterize the nerve ultrasound cross-sectional areas (CSAs) of type 2 diabetic patients with diabetic sensorimotor polyneuropathy (DSP) of different severities.

Anti-GQ1b antibody syndrome: anti-ganglioside complex reactivity determines clinical spectrum

Fukami Y, Wong AH, Funakoshi K, Safri AY, Shahrizaila N, Yuki N

Eur J Neurol, 2016 Feb;23(2):320-6.

PMID: 26176883 DOI: 10.1111/ene.12769

Anti-GQ1b antibodies have been found in patients with Miller Fisher syndrome as well as its related conditions. Our aim was to identify the mechanism by which autoantibodies produce various clinical presentations in 'anti-GQ1b antibody syndrome'.

The utility of Guillain-Barré syndrome prognostic models in Malaysian patients

Tan CY, Razali SNO, Goh KJ, Shahrizaila N

J Peripher Nerv Syst, 2019 06;24(2):168-173.

PMID: 31001904 DOI: 10.1111/jns.12320

Guillain-Barré syndrome (GBS) is an acute immune-mediated neuropathy that has variable disease course and outcome. The Erasmus GBS outcome score (EGOS), modified EGOS (mEGOS), and Erasmus GBS respiratory insufficiency score (EGRIS) are prognostic models designed to predict the functional outcome of GBS patients at 6 months (EGOS and mEGOS) and the need for mechanical ventilation within a week of admission (EGRIS). The models were primarily developed in the Dutch GBS population, and thus the usefulness of these models in other GBS cohorts is less clear. In the current study, we aimed to validate mEGOS, EGOS, and EGRIS in Malaysian GBS patients. A total of 107 patients with GBS and its variants were consecutively recruited. Patients with GBS and Miller Fisher syndrome (MFS) were analysed separately. In the GBS cohort, high mEGOS and EGOS scores were significantly correlated with poor outcome at 6 months (mEGOS on admission: r = .381, P = .005; mEGOS at day 7 of admission: r = .507, P

Fulltext Determining the Utility of the Guillain-Barré Syndrome Classification Criteria

Tan CY, Razali SNO, Goh KJ, Shahrizaila N

J Clin Neurol, 2021 Apr;17(2):273-282.

PMID: 33835749 DOI: 10.3988/jcn.2021.17.2.273

BACKGROUND AND PURPOSE: Several variants of Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS) exist, but their frequencies vary in different populations and do not always meet the inclusion criteria of the existing diagnostic criteria. However, the GBS classification criteria by Wakerley and colleagues recognize and define the clinical characteristics of each variant. We applied these criteria to a GBS and MFS cohort with the aim of determining their utility.

METHODS: Consecutive GBS and MFS patients presenting to our center between 2010 and 2020 were analyzed. The clinical characteristics, electrophysiological data, and antiganglioside antibody profiles of the patients were utilized in determining the clinical classification.

RESULTS: This study classified 132 patients with GBS and its related disorders according to the new classification criteria as follows: 64 (48.5%) as classic GBS, 2 (1.5%) as pharyngeal-cervical-brachial (PCB) variant, 7 (5.3%) as paraparetic GBS, 29 (22%) as classic MFS, 3 (2.3%) as acute ophthalmoparesis, 2 (1.5%) as acute ataxic neuropathy, 2 (1.5%) as Bickerstaff brainstem encephalitis (BBE), 17 (12.9%) as GBS/MFS overlap, 4 (3%) as GBS/BBE overlap, 1 (0.8%) as MFS/PCB overlap, and 1 (0.8%) as polyneuritis cranialis. The electrodiagnosis was demyelinating in 55% of classic GBS patients but unclassified in 79% of classic MFS patients. Anti-GM1, anti-GD1a, anti-GalNAc-GD1a, and anti-GD1b IgG ganglioside antibodies were more commonly detected in the axonal GBS subtype, whereas the anti-GQ1b and anti-GT1a IgG ganglioside antibodies were more common in classic MFS and its subtypes.

CONCLUSIONS: Most of the patients in the present cohort met the criteria of either classic GBS or MFS, but variants were seen in one-third of patients. These findings support the need to recognize variants of both syndromes in order to achieve a more-complete case ascertainment in GBS.

Complement regulatory proteins (CD46, 55 and 59) expressed on Schwann cells: immune targets in demyelinating neuropathies?

Miyaji K, Paul F, Shahrizaila N, Umapathi T, Yuki N

J Neuroimmunol, 2014 Nov 15;276(1-2):172-4.

PMID: 25156074 DOI: 10.1016/j.jneuroim.2014.08.004

Given their localization and important role in regulating complement, complement regulatory proteins may act as target antigens and their antibodies as biomarkers in demyelinating neuropathies. We investigated the binding of autoantibodies to complement regulatory proteins (CD46, 55 and 59) in demyelinating diseases. In 42 acute inflammatory demyelinating polyneuropathy, 23 chronic inflammatory demyelinating polyneuropathy, 13 acute motor axonal neuropathy, 71 multiple sclerosis, and 19 neuromyelitis optica patients as well as 55 healthy controls, we were unable to detect significant titers of antibodies to CD46, CD55 and CD59. These autoantibodies are unlikely to be biomarkers in acute and chronic inflammatory demyelinating polyneuropathies.

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