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.

Objective. Neuropathic pain is a common presenting complaint of patients with peripheral neuropathy (PN) and is considered one of the most disabling neuropathic symptoms, with detrimental effects on patients’ quality of life (QoL). The aim of this review was to overview the current literature that focuses on QoL in painful PN of various aetiologies. We sought to clarify the direct effect of pain and its treatment on patients’ QoL.Methodology. A systematic computer-based literature search was conducted using the PubMed database to search for papers on QoL in painful PN. Information was extracted regarding prevalence, demographics, and response to treatment where relevant.Results. We identified 66 articles eligible for inclusion. The vast majority of studies (n=47) focused on patients with diabetic PN. Other aetiologies of painful PN where QoL has been studied to date include gluten, immune-mediated, HIV, chemotherapy-induced, and chronic idiopathic axonal polyneuropathy. Pharmacological treatment is the mainstay in managing pain and has a direct positive and independent effect on the overall QoL. Other nonpharmacological approaches can also be of benefit, either alone or as adjuvant treatments, and are discussed.Conclusion. The findings demonstrate that QoL is impaired in painful PN and should not be neglected in clinical practice. Patients’ pain management and subsequent impact on QoL should routinely be assessed and monitored.

Amyotrophic lateral sclerosis (ALS) is a universally fatal neurodegenerative disease. ALS is determined by gene-environment interactions and improved understanding of these interactions may lead to effective personalised medicine. The role of physical exercise in the development of ALS is currently controversial. First, we dissected the exercise-ALS relationship in a series of two-sample Mendelian randomisation (MR) experiments. Next we tested for enrichment of ALS genetic risk within exercise-associated transcriptome changes. Finally, we applied a validated physical activity questionnaire in a small cohort of genetically selected ALS patients. We present MR evidence supporting a causal relationship between genetic liability to frequent and strenuous leisure-time exercise and ALS using a liberal instrument (multiplicative random effects IVW, p=0.01). Transcriptomic analysis revealed that genes with altered expression in response to acute exercise are enriched with known ALS risk genes (permutation test, p=0.013) including C9ORF72, and with ALS-associated rare variants of uncertain significance. Questionnaire evidence revealed that age of onset is inversely proportional to historical physical activity for C9ORF72-ALS (Cox proportional hazards model, Wald test p=0.007, likelihood ratio test p=0.01, concordance=74%) but not for non-C9ORF72-ALS. Variability in average physical activity was lower in C9ORF72-ALS compared to both non-C9ORF72-ALS (F-test, p=0.002) and neurologically normal controls (F-test, p=0.049) which is consistent with a homogeneous effect of physical activity in all C9ORF72-ALS patients. Our MR approach suggests a positive causal relationship between ALS and physical exercise. Exercise is likely to cause motor neuron injury only in patients with a risk-genotype. Consistent with this we have shown that ALS risk genes are activated in response to exercise. In particular, we propose that G4C2-repeat expansion of C9ORF72 predisposes to exercise-induced ALS. We acknowledge support from the Wellcome Trust (JCK, 216596/Z/19/Z), NIHR (PJS, NF-SI-0617-10077; IS-BRC-1215-20017) and NIH (MPS, CEGS 5P50HG00773504, 1P50HL083800, 1R01HL101388, 1R01-HL122939, S10OD025212, P30DK116074, and UM1HG009442).

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).

Objective: The aim of this systematic review was to explore the relationship between coeliac disease (CD) and headache. The objectives were to establish the prevalence of each entity amongst the other, to explore the role of gluten free diet (GFD), and to describe the imaging findings in those affected by headaches associated with CD. Methodology: A systematic computer-based literature search was conducted on the PubMed database. Information regarding study type, population size, the age group included, prevalence of CD amongst those with headache and vice versa, imaging results, the nature of headache, and response to GFD. Results: In total, 40 articles published between 1987 and 2017 qualified for inclusion in this review. The mean pooled prevalence of headache amongst those with CD was 26% (95% CI 19.5–33.9%) in adult populations and 18.3% (95% CI 10.4–30.2%) in paediatric populations. The headaches are most often migraine-like. In children with idiopathic headache, the prevalence of CD is 2.4% (95% CI 1.5–3.7%), whereas data for adult populations is presently unavailable. Brain imaging can be normal, although, cerebral calcifications on CT, white matter abnormalities on MRI and deranged regional cerebral blood flow on SPECT can be present. GFD appears to be an effective management for headache in the context of CD, leading to total resolution of headaches in up to 75% of patients. Conclusions: There is an increased prevalence of CD amongst idiopathic headache and vice versa. Therefore, patients with headache of unknown origin should be screened for CD, as such patients may symptomatically benefit from a GFD.

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.