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Osmotic demyelination syndrome improving after immune-modulating treatment: Case report and literature review.
Kalampokini, S, Artemiadis, A, Zis, P, Hadjihannas, L, Parpas, G, Kyrri, A, Hadjigeorgiou, GM
Clinical neurology and neurosurgery. 2021;:106811
Abstract
BACKGROUND Osmotic demyelination syndrome (ODS), which embraces central pontine and extrapontine myelinolysis, is an uncommon neurological disorder that occurs due to plasma osmotic changes. CASE PRESENTATION We present the case of a 55-year-old man, who presented with severe hyponatremia due to repeated vomiting, antidepressant treatment and consumption of large amounts of water. Fifteen days after sodium correction, the patient showed fluctuation of vigilance, dysarthria and dysphagia, tremor, cogwheel rigidity, bilateral facial palsy, ophthalmoplegia and tetraparesis. A brain MRI scan revealed extrapontine and later on pontine myelinolysis. He received intravenous steroids and subsequently immunoglobulin. His status began to improve gradually after completion of immunoglobulin and at three month-follow-up had no neurological deficit. LITERATURE REVIEW A comprehensive literature search of all reported ODS cases that received immunoglobulin, steroids or plasmapheresis was conducted in the electronic databases PubMed and Web of science. CONCLUSIONS Improvement was seen in most cases that received immunoglobulin either during treatment or in the first days after treatment. With regard to steroids, although most cases reported improvement in the following months their effect on the outcome is unclear. Most cases treated with plasmapheresis reported favorable outcome at variable follow-up time. Immunoglobulin and steroids have immunomodulatory effects, which could contribute to promotion of myelin repair in ODS. Plasmapheresis has effects on the immune system beyond removing myelinotoxins from the circulation. More evidence is required to support their use in ODS. However, in view of the disease severity, these therapeutic choices should be considered in the clinical management of ODS.
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2.
The Neuropathology of Gluten-Related Neurological Disorders: A Systematic Review.
Rouvroye, MD, Zis, P, Van Dam, AM, Rozemuller, AJM, Bouma, G, Hadjivassiliou, M
Nutrients. 2020;12(3)
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Coeliac disease (CD) is an autoimmune disorder triggered by the ingestion of gluten in genetically susceptible individuals. A wide range of extraintestinal manifestations has been attributed to CD, changing the classic perception of a disease limited to the intestine, to a multisystem disorder. The aim of this study was to analyse the published neuropathology of confirmed cases of gluten-related neurological dysfunction to aid our understanding of the pathogenesis. CD can therefore manifest with dental problems, consequences of malabsorption, skin and neurological disorders. This study is a systematic review of thirty-two neurological disorder focused studies. Results show that: - the neuropathological findings in gluten-related neurological disorders are widespread and not limited to the cerebellum. - the pathology is immune mediated and not related to vitamin or trace elements deficiencies. - the pathophysiology of neurological damage in the context of gluten sensitivity has an immune mediated basis. - more gluten-related neurological disorders affected men (57%), which was even higher in the ataxia group (76%). - transglutaminase 6 antibodies might be helpful in the diagnostic workup of gluten-related neurological disorders. Authors conclude that the current evidence is suggestive of both humoral and cell-mediated immunological responses. Further research is required to investigate the underlying neuropathological mechanism by characterisation of the inflammatory cell infiltrate and identification of target epitopes.
Abstract
Gluten-related neurological disorders (GRND) represent a spectrum of neurological manifestations that are triggered by gluten. In coeliac disease, a T-cell mediated enteropathy is triggered by gluten in genetically predisposed individuals. The underlying pathological mechanism of the neurological dysfunction is not yet clear. The aim of this review is to collate existing neuropathological findings in GRND as a means of aiding the understanding of the pathophysiology. A systematic search of the Pubmed Database yielded 188 articles, of which 32 were included, containing 98 eligible cases with a description of pathological findings in GRND. In gluten ataxia, loss of Purkinje cells, atrophy, gliosis and astrocytosis were apparent, as well as diffuse lymphocytic infiltration and perivascular cuffing with lymphocytes. In patients with large-fiber neuropathy, nerve biopsies revealed axonopathy, loss of myelinated fibers and focal and perivascular infiltration by inflammatory cells. Inflammatory infiltrate was also observed in muscle in myopathy and in cerebrum of patients with encephalopathy and patients with epilepsy. Such changes were not seen in skin biopsies from patients with small fiber neuropathies. The findings from this systematic review suggest an immune mediated pathogenesis for GRND. Future research should focus on the characterization of the inflammatory cell infiltrates and identifying target epitopes.
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B12 as a Treatment for Peripheral Neuropathic Pain: A Systematic Review.
Julian, T, Syeed, R, Glascow, N, Angelopoulou, E, Zis, P
Nutrients. 2020;(8)
Abstract
Neuropathic pain describes a range of unpleasant sensations caused by a lesion or disease of the somatosensory nervous system. The sensations caused by neuropathic pain are debilitating and improved treatment regimens are sought in order to improve the quality of life of patients. One proposed treatment for neuropathic pain is vitamin B12, which is thought to alleviate pain by a number of mechanisms including promoting myelination, increasing nerve regeneration and decreasing ectopic nerve firing. In this paper, the evidence for B12 as a drug treatment for neuropathic pain is reviewed. Twenty four published articles were eligible for inclusion in this systematic review in which a range of treatment regimens were evaluated including both B12 monotherapy and B12 in combination with other vitamins or conventional treatments, such as gabapentinoids. Overall, this systematic review demonstrates that there is currently some evidence for the therapeutic effect of B12 in the treatment of post-herpetic neuralgia (level II evidence) and the treatment of painful peripheral neuropathy (level III evidence).
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The Role of Oxidative Stress in Peripheral Neuropathy.
Mallet, ML, Hadjivassiliou, M, Sarrigiannis, PG, Zis, P
Journal of molecular neuroscience : MN. 2020;(7):1009-1017
Abstract
Peripheral neuropathy (PN) is a common disease affecting about 5% of the general population after the age of 50. Causes of PN are numerous and include genetic, diabetes, alcohol, vitamin deficiencies, and gluten sensitivity among others. This systematic review aimed to study the association between oxidative stress and PN in an attempt to better understand PN pathogenesis. A computer-based, systematic search was conducted on the PubMed database, and ensuing data from included articles was analyzed and discussed in this review. Sixty-nine papers were eligible and were used for this review. Peripheral neuropathy is associated with an increase of reactive oxygen species and a decrease in endogenous antioxidants. Genetic predisposition to oxidative damage may be a factor. Antioxidant treatment is promising regarding treatment. Though further research is necessary to better understand the underlying mechanism, it is evident that oxidative stress is implicated in the pathogenesis of - or is at least systematically present in - PN.
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5.
Psychiatric Manifestations of Coeliac Disease, a Systematic Review and Meta-Analysis.
Clappison, E, Hadjivassiliou, M, Zis, P
Nutrients. 2020;(1)
Abstract
BACKGROUND Coeliac disease (CD) is increasingly prevalent and is associated with both gastrointestinal (GI) and extra-intestinal manifestations. Psychiatric disorders are amongst extra-intestinal manifestations proposed. The relationship between CD and such psychiatric disorders is not well recognised or understood. AIM: The aim of this systematic review and meta-analysis was to provide a greater understanding of the existing evidence and theories surrounding psychiatric manifestations of CD. METHODOLOGY An online literature search using PubMed was conducted, the prevalence data for both CD and psychiatric disorders was extracted from eligible articles. Meta analyses on odds ratios were also performed. RESULTS A total of 37 articles were included in this review. A significant increase in risk was detected for autistic spectrum disorder (OR 1.53, 95% CI 1.24-1.88, p < 0.0001), attention deficit hyperactivity disorder (OR 1.39, 95% CI 1.18-1.63, p < 0.0001), depression (OR 2.17, 95% CI 2.17-11.15, p < 0.0001), anxiety (OR 6.03, 95% CI 2.22-16.35, p < 0.0001), and eating disorders (OR 1.62, 95% CI 1.37-1.91, p < 0.00001) amongst the CD population compared to healthy controls. No significant differences were found for bipolar disorder (OR 2.35, 95% CI 2.29-19.21, p = 0.43) or schizophrenia (OR 0.46, 95% CI 0.02-10.18, p = 0.62). CONCLUSION CD is associated with an increased risk of depression, anxiety, eating disorders as well as ASD and ADHD. More research is required to investigate specific biological explanations as well as any effect of gluten free diet.
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Small fiber neuropathy in coeliac disease and gluten sensitivity.
Zis, P, Sarrigiannis, PG, Rao, DG, Sanders, DS, Hadjivassiliou, M
Postgraduate medicine. 2019;(7):496-500
Abstract
Objectives: The commonest types of peripheral neuropathy in the context of Coeliac Disease (CD) and gluten sensitivity (GS) are length-dependent symmetrical sensorimotor neuropathies and sensory ganglionopathies. In patients with such neuropathy, (gluten neuropathy), peripheral neuropathic pain is prevalent suggesting involvement of small fibers. The purpose of this report was to describe the clinical characteristics of patients with CD or GS and pure small fiber neuropathy (SFN). Methods: We reviewed the records of all patients that had been referred to the Gluten-Related Neurological Disorders clinic who had clinical and neurophysiological evidence of SFN. All patients had serological evidence of gluten sensitivity (GS) prior to commencing GFD. All patients were offered a duodenum biopsy. Patients with comorbidities that could cause SFN were excluded. Results: We identified 13 patients (9 males) with SFN and gluten sensitivity. Of 11 patients who underwent duodenal biopsy 10 had evidence of enteropathy (CD). Mean age at onset of pain was 53.5 ± 11.4 years (range 34-72) and mean age of CD/GS diagnosis was 50.8 ± 10.4 years (range 34-68). In 8 patients (61.5%) pain was the presenting feature. Neurophysiological assessment suggested a length-dependent small fiber neuropathy in 11 patients, whereas in 2, a non-length dependent pattern was identifying suggesting that the predominant pathology lies in the dorsal root ganglia. Conclusion: SFN can be a presenting feature of CD and GS and, therefore, screening for CD and GS should be included in the diagnostic workup of patients with idiopathic SFN.
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Alcohol-related peripheral neuropathy: a systematic review and meta-analysis.
Julian, T, Glascow, N, Syeed, R, Zis, P
Journal of neurology. 2019;(12):2907-2919
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Abstract
The primary aim of this systematic review was to establish the prevalence, character, and risk factors of peripheral neuropathy amongst chronic alcohol abusers and to identify the most appropriate management strategies. In this review, possible pathogenetic mechanisms are also discussed. A systematic, computer-based search was conducted using the PubMed database. Data regarding the above parameters were extracted. 87 articles were included in this review, 29 case-control studies, 52 prospective/retrospective cohort studies and 2 randomised control trials, 1 cross sectional study, and 3 population-based studies. The prevalence of peripheral neuropathy amongst chronic alcohol abusers is 46.3% (CI 35.7- 57.3%) when confirmed via nerve conduction studies. Alcohol-related peripheral neuropathy generally presents as a progressive, predominantly sensory axonal length-dependent neuropathy. The most important risk factor for alcohol-related peripheral neuropathy is the total lifetime dose of ethanol, although other risk factors have been identified including genetic, male gender, and type of alcohol consumed. At present, it is unclear what the pathogenetic mechanisms for the development of neuropathy amongst those who chronically abuse alcohol are, and therefore, it is unknown whether it is attributed to the direct toxic effects of ethanol or another currently unidentified factor. There is presently sparse data to support a particular management strategy in alcohol-related peripheral neuropathy, but the limited data available appears to support the use of vitamin supplementation, particularly of B-vitamin regimens inclusive of thiamine.
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Treatment of Neurological Manifestations of Gluten Sensitivity and Coeliac Disease.
Zis, P, Hadjivassiliou, M
Current treatment options in neurology. 2019;(3):10
Abstract
PURPOSE OF REVIEW The aim of this paper was to overview the current literature in order to establish the available treatment options for the neurological manifestations of gluten-related disorders (serologically confirmed gluten sensitivity and coeliac disease). RECENT FINDINGS A range of debilitating neurological manifestations is increasingly being recognized in patients with gluten sensitivity with and without enteropathy even in the absence of gastrointestinal symptoms. Ataxia is the commonest neurological manifestation, followed by peripheral neuropathy. Epilepsy, headache, encephalopathy, various movement disorders, cognitive impairment, and muscle disorders have also been linked to gluten sensitivity and coeliac disease and are discussed in this review. Strict gluten-free diet is an effective first-line treatment of the neurological manifestations of gluten-related disorders. Very few patients will require additional immunosuppressive treatment usually in the form of mycophenolate.
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9.
Gluten sensitivity and epilepsy: a systematic review.
Julian, T, Hadjivassiliou, M, Zis, P
Journal of neurology. 2019;(7):1557-1565
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Abstract
OBJECTIVE The aim of this systematic review was to establish the prevalence of epilepsy in patients with coeliac disease (CD) or gluten sensitivity (GS) and vice versa and to characterise the phenomenology of the epileptic syndromes that these patients present with. METHODOLOGY A systematic computer-based literature search was conducted on the PubMed database. Information regarding prevalence, demographics and epilepsy phenomenology was extracted. RESULTS Epilepsy is 1.8 times more prevalent in patients with CD, compared to the general population. CD is over 2 times more prevalent in patients with epilepsy compared to the general population. Further studies are necessary to assess the prevalence of GS in epilepsy. The data indicate that the prevalence of CD or GS is higher amongst particular epileptic presentations including in childhood partial epilepsy with occipital paroxysms, in adult patients with fixation off sensitivity (FOS) and in those with temporal lobe epilepsy (TLE) with hippocampal sclerosis. A particularly interesting presentation of epilepsy in the context of gluten-related disorders is a syndrome of coeliac disease, epilepsy and cerebral calcification (CEC syndrome) which is frequently described in the literature. Gluten-free diet (GFD) is effective in the management of epilepsy in 53% of cases, either reducing seizure frequency, enabling reduced doses of antiepileptic drugs or even stopping antiepileptic drugs. CONCLUSION Patients with epilepsy of unknown aetiology should be investigated for serological markers of gluten sensitivity as such patients may benefit from a GFD.
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Neuropathic Pain in Acute and Subacute Neuropathies: A Systematic Review.
Artemiadis, AK, Zis, P
Pain physician. 2018;(2):111-120
Abstract
BACKGROUND Neuropathic pain (NP) is a common symptom caused by lesions or diseases of the somatosensory nervous system. Acute/subacute peripheral neuropathies (APN) are rare, however can be particularly painful. OBJECTIVES The aim of this systematic review was to estimate the incidence of NP in APN and overview the various etiologies of such neuropathies. STUDY DESIGN Systematic review. SETTING Medline search. METHODS We hand-searched Medline for observational studies published between 1995 and 2017. RESULTS Our search strategy identified 1,400 papers. Of these, 70 met our inclusion criteria and were included in this review. Out of a total of 2,341 patients, 1,139 patients were diagnosed with NP (pooled incidence of NP 48.7%). In Guillain-Barré syndrome (GBS), the commonest cause of APN, the pooled estimate of NP was 34.8%. Other causes of painful APN include immune-mediated, vasculitic, metabolic, nutritional, toxic, paraneoplastic, and infectious. LIMITATIONS An important limitation was that GBS accounted for the majority of patients with APN, as such the calculated incidence reflected mainly this disease entity. Another important limitation was that very few studies targeted primarily NP. Thus, it is highly likely that observational studies reporting NP were missed. Finally there could always be a publication bias due to underreporting and gray literature. CONCLUSIONS NP is a cardinal manifestation of APN. The use of validated diagnostic tools and accepted diagnostic criteria of NP is recommended for both clinical and research purposes. KEY WORDS Neuropathic, pain, acute, subacute, neuropathy, polyneuropathy, frequency, incidence.
