Dietary treatment of gluten neuropathy

We studied the effect of a gluten-free diet in patients with idiopathic sensorimotor axonal neuropathy and circulating antigliadin antibodies. Consecutive patients underwent baseline neurophysiological assessment and were offered a gluten-free diet. Those who went on the diet formed the intention-to-treat group and those who did not were the control group. Repeat neurophysiological assessment and subjective evaluation of neuropathy symptoms were performed at 1 year. A total of 35 patients participated in the study, with 25 patients going on the diet and 10 not doing so. There was a significant difference in the change of sural sensory action potentials (pre-defined primary endpoint), with evidence of improvement in the intention-to-treat group and deterioration in the control group. Subjective change in neuropathy symptoms also showed significant differences, with patients in the intention-to-treat group reporting improvement and those in the control group reporting deterioration. Gluten-free diet may thus be a useful therapeutic intervention for patients with gluten neuropathy.     

Myopathy associated with gluten sensitivity

Ataxia and peripheral neuropathy are the most common neurological manifestations of gluten sensitivity. Myopathy is a less common and poorly characterized additional neurological manifestation of gluten sensitivity. We present our experience with 13 patients who presented with symptoms and signs suggestive of a myopathy and in whom investigation led to the diagnosis of gluten sensitivity. Three of these patients had a neuropathy with or without ataxia in addition to the myopathy. The mean age at onset of the myopathic symptoms was 54 years. Ten patients had neurophysiological evidence of myopathy. Inflammatory myopathy was the most common finding on neuropathological examination. One patient had basophilic rimmed vacuoles suggestive of inclusion-body myositis. Six patients received immunosuppressive treatment in addition to starting on a gluten-free diet; five improved and one remained unchanged. Among seven patients not on immunosuppressive treatment, four showed clinical improvement of the myopathy with a gluten-free diet. The improvement was also associated with reduction or normalization of serum creatine kinase level. The myopathy progressed in one patient who refused the gluten-free diet. Myopathy may be another manifestation of gluten sensitivity and is likely to have an immune-mediated pathogenesis. A gluten-free diet may be a useful therapeutic intervention.     

Krabbe's disease presenting as a peripheral neuropathy

A 13-year-old female initially presented with scoliosis and pes cavus. Initial examination revealed distal lower extremity weakness and sensory loss, as well as greater auricular nerve hypertrophy. There was a Babinski sign on the right. Nerve conduction velocities were consistent with a demyelinating neuropathy. Four years after initial presentation she developed lower extremity spasticity and bilateral Babinski signs. Magnetic resonance imaging of the brain showed diffuse white matter disease. Laboratory evaluation revealed an abnormally low galactocerebroside beta-galactosidase level. Nerve biopsy demonstrated inclusions consisting of globoid clusters and evidence of demyelination. DNA analysis was used to identify mutations consistent with Krabbe's disease. Patients presenting with an atypical peripheral neuropathy should be evaluated for Krabbe's disease. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20: 1024–1028, 1997     

Non‐celiac gluten or wheat sensitivity: It's complicated!

In the last 30 years, non‐celiac gluten sensitivity (NCGS) has emerged as an intriguing and controversial topic in gastroenterology. The diagnosis of NCGS/NCWS requires a symptomatic reaction to gluten, or wheat‐containing food, and remission of symptoms with gluten or wheat challenge, in patients in whom celiac disease and wheat allergy have been excluded. There have been several randomized clinical trials (RCT) addressing this issue which have produced controversial results. In this issue of Neurogastroenterology and Motility, a double‐blind placebo‐controlled randomized trial in patients with suspected NCGS on GFD, did not reproduce symptoms after gluten intake compared to placebo. This mini‐review addresses outstanding issues related to the diagnosis of NCGS/NCWS as well as areas of interest for future studies that could explain, in part, the controversy in this area.     

The gluten connection: the association between schizophrenia and celiac disease

OBJECTIVE: Schizophrenia affects roughly 1% of the population and is considered one of the top 10 causes of disability worldwide. Given the immense cost to society, successful treatment options are imperative. Based on initial findings, gluten withdrawal may serve as a safe and economical alternative for the reduction of symptoms in a subset of patients. METHOD: A review of the literature relevant to the association between schizophrenia and celiac disease (gluten intolerance) was conducted. RESULTS: A drastic reduction, if not full remission, of schizophrenic symptoms after initiation of gluten withdrawal has been noted in a variety of studies. However, this occurs only in a subset of schizophrenic patients. CONCLUSION: Large-scale epidemiological studies and clinical trials are needed to confirm the association between gluten and schizophrenia, and address the underlying mechanisms by which this association occurs.     

Markers of gluten sensitivity and celiac disease in bipolar disorder

Dickerson F, Stallings C, Origoni A, Vaughan C, Khushalani S, Alaedini A, Yolken R. Markers of gluten sensitivity and celiac disease in bipolar disorder.
Bipolar Disord 2011: 13: 52–58. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S. Objectives: Increased immune sensitivity to dietary gluten proteins has been reported in schizophrenia but has not been studied in bipolar disorder. In this study, we examine the levels of antibody reactivity to gliadin, deamidated gliadin, and tissue transglutaminase (tTG) in individuals with bipolar disorder and compare these levels to those in individuals who do not have any history of psychiatric disorder. Methods: The sample of 275 individuals included 102 with bipolar disorder and 173 controls without a psychiatric disorder. Immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies to gliadin and tTG and IgG antibodies to deamidated gliadin were measured by enzyme immunoassay. Participants’ levels of antibodies to deamidated gliadin and tTG were classified based on the cutoffs for positivity that are predictive of celiac disease. Quantitative levels of antibodies were compared between groups employing regression models which were controlled for demographic variables. Results: Individuals with bipolar disorder had increased levels of IgG antibodies to gliadin compared with controls in multivariate analyses. We also found evidence of increased levels of antibodies to deamidated gliadin in the bipolar disorder population. The levels of IgA class antigliadin antibodies and antibodies to tTG did not differ significantly between groups. There was also not a significant difference between groups in the number of persons who were classified as having levels of antibodies to deamidated gliadin or tTG that are predictive of celiac disease. Conclusions: Individuals with bipolar disorder have increased levels of IgG antibodies to gliadin. However, such antibody increase is not accompanied by an elevation in IgA antibodies to gliadin or the celiac disease‐associated antibodies against deamidated gliadin and tTG. These results warrant further detailed examination of the molecular specificity and pattern of reactivity of the antibody response to gluten antigens in bipolar disorder.     

Celiac disease and alopecia areata in a child with Down's syndrome

According to recent reports in the literature, there seems to be an association between alopecia areata and celiac disease. The present author describes a 9‐year‐old girl with Down’s syndrome, and alopecia areata, and documented celiac disease, who displayed a normal growth of hair after a gluten‐free diet. Given the high prevalence of these two diseases in patients with Down’s syndrome, the present author recommends both serological screening for celiac disease in every individual with Down’s syndrome, and in particular, the inclusion of such screening in any diagnostic work‐up for alopecia areata.     

Multifocal motor neuropathy with high titers of anti‐MAG antibodies

Multifocal motor neuropathy (MMN) and anti‐myelin‐associated glycoprotein (anti‐MAG)‐associated neuropathy are clinically and electrophysiologically distinct entities. We describe a patient with characteristic features of both neuropathies, raising the possibility of an overlap syndrome. A 49‐year‐old patient reported a history of slowly progressive predominantly distal tetraparesis, with mild sensory deficits. Nerve conduction studies demonstrated persistent motor conduction blocks outside compression sites, typical of MMN. Laboratory findings revealed persistently high titers of anti‐MAG immunoglobulin Mλ (IgMλ) paraprotein in the context of a monoclonal gammapathy of unknown significance. Skin biopsy of distal lower limb revealed IgM positive terminal nerve perineurium deposits. This case suggests that the distinction between subtypes of chronic inflammatory neuropathies may not be as clear as initially thought, and that the pattern of pathogenicity of anti‐MAG antibodies may vary.     

Demyelinating peripheral neuropathy in Creutzfeldt-Jakob disease.

We describe 2 patients of Jewish Libyan descent, who presented with a clinical syndrome compatible with Creutzfeldt-Jakob disease and who were found to have a mutation of codon 200 in the prion protein. The patients developed symptoms and signs of peripheral nerve involvement diagnosed by electrodiagnostic and histopathological studies as demyelinating neuropathy. This may be a rare manifestation of Creutzfeldt-Jakob disease.     

GAD antibody‐associated neurological illness and its relationship to gluten sensitivity

Hadjivassiliou M, Aeschlimann D, Grünewald RA, Sanders DS, Sharrack B, Woodroofe N. GAD antibody associated neurological illness and its relationship to gluten sensitivity.
Acta Neurol Scand: 2011: 123: 175–180.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Background – The high prevalence of gluten sensitivity in patients with stiff‐person syndrome (SPS) lead us to investigate the relationship between gluten sensitivity and GAD‐antibody‐associated diseases. Methods – We used ELISA assays for anti‐GAD and for serological markers of gluten sensitivity. Patients were recruited from clinics based at the Royal Hallamshire hospital, Sheffield, UK. Patients with gluten sensitivity were followed up after the introduction of a gluten‐free diet and serological testing was repeated. Results – Six of seven (86%) patients with SPS were positive for anti‐GAD, mean titre 109 U/ml; This compared with 9/90 (11%) patients with idiopathic sporadic ataxia, mean titre 32 U/ml, 16/40 (40%) patients with gluten ataxia, mean titre 25 U/ml, and 6/10 patients with type 1 diabetes only, mean titre 8 U/ml. None of 32 patients with celiac disease only, and of 40 patients with genetic ataxia were positive for anti‐GAD. The titre of anti‐GAD reduced following the introduction of a gluten‐free diet in patients with SPS who had serological evidence of gluten sensitivity. The same was observed in patients with gluten ataxia and anti‐GAD antibodies. This was also associated with clinical improvement. Conclusion – These findings suggest a link between gluten sensitivity and GAD antibody‐associated diseases.     

Paroxysmal nonkinesigenic dystonia and celiac disease.

Celiac disease has been associated with ataxia and other neurological signs but has not been associated with paroxysmal nonkinesigenic dyskinesias (PNKD) to date. We present a child with biopsy-proven celiac disease and a movement disorder resembling PNKD since the age of 6 months. She had complete resolution of her neurological symptoms with introduction of a gluten-free diet. Because a susceptibility locus for celiac disease has been reported on 2q33 and studies in PNKD show linkage to 2q, this report suggests further genetic investigations around this locus may be useful. We also review the literature regarding the genetic susceptibility to PNKD and celiac disease.     

Effect of intravenous immunoglobulin on cerebellar ataxia and neuropathic pain associated with celiac disease

Background: Cerebellar syndrome and small fiber neuropathy may complicate celiac disease (CD) and may be resistant to a strict gluten‐free diet. Methods: Case series. Results: We report three patients with biopsy‐proven CD who developed cerebellar ataxia and neuropathic pain despite strict adherence to a gluten‐free diet. A small fiber neuropathy was suggested by skin biopsy findings in two patients. All patients’ symptoms, including small fiber neuropathy symptoms, responded to treatment with intravenous immunoglobulin (IVIG). Discontinuation of IVIG in two patients resulted in worsened ataxia that reversed after resumption of IVIG. Conclusion: Intravenous immunoglobulin may be effective in treating cerebellar ataxia and small fiber neuropathy associated with CD, suggesting an immune pathogenesis. Further prospective, controlled studies are necessary to determine the long‐term response to IVIG or other immunomodulation therapy.     

Chronic multifocal demyelinating neuropathy simulating motor neuron disease

We describe a patient with a chronic acquired predominantly motor polyneuropathy. His clinical picture initially led to a diagnosis of lower motor neuron form of amyotrophic lateral sclerosis. However electrophysiological examination revealed multifocal, prevalently proximal, conduction blocks at sites not prone to compression. Distinguishing this unusual polyneuropathy from motor neuron diseases is critical, since the former is a potentially, treatable disorder.

---

Sommario Viene descritto un paziente con polineuropatia cronica acquisita prevalentemente motoria, inizialmente diagnosticata come sclerosi laterale amiotrofica. L'esame elettrofisiologico ha evidenziato blocchi di conduzione prevalentemente prossimali in segmenti nervosi solitamente non soggetti a compressione. Distinguere questa inusuale polineuropatia dalle malattie del motoneurone è di fondamentale importanza sia per quanto riguarda la prognosi che la terapia.

     

Prevalence and predictors of peripheral neuropathy in nondiabetic children with chronic kidney disease

Introduction: This study sought to determine the prevalence and predictors of peripheral neuropathy in nondiabetic children with chronic kidney disease (CKD). Methods: Fifty‐one consecutive normally nourished children, 3–18 years of age, with CKD stages IV and V of nondiabetic etiology were enrolled from May to December 2012. Nerve conduction studies were performed in 50 children. Blood samples were analyzed for the biochemical parameters, trace elements, and micronutrients. Results: The prevalence of peripheral neuropathy in our cohort was 52% (95% confidence interval 37.65, 66.34). The majority (80.8%) of the children had axonal neuropathy, and 11.5% had demyelinating neuropathy. Isolated motor neuropathy was identified in 92.3% of the children, and sensorimotor neuropathy was identified in 7.6%. The significant risk factors associated with peripheral neuropathy were older age, low serum copper, and dialysis therapy. Discussion: Electrodiagnostic studies should be performed in children with CKD to assess for peripheral neuropathy for the purpose of optimizing medical care. Muscle Nerve 57 : 792–798, 2018     

Neurological abnormalities associated with celiac disease

Abstract Background Celiac disease (CD) is a gluten-sensitive enteropathy in genetically susceptible individuals. Anecdotal reports suggest that the nervous system might be affected in the disorder, but the severity and prevalence of such an involvement have not been systematically evaluated. Materials and methods Analysis of files of CD patients diagnosed between 1980 and 1999 for neurological abnormalities. Diagnosis of CD was based on the modified criteria of the European Society for Pediatric Gastroenterology and Nutrition. Results Of 148 CD patients, 18 (12%) had 21 neurological disorders that could not be attributed to any other condition including muscle abnormality (3), epilepsy (3), psychiatric disease (4), peripheral neuropathy (3), cerebrovascular disease (1), myelopathy (1) and Down syndrome (2). Other disorders probably unrelated to CD were present in 8 patients. Conclusion If this association is not coincidental, both the central and the peripheral nervous systems may be affected in CD by a spectrum of neurological disorders that are either the outcome of CD or share the same pathogenesis with the enteropathy.     

Autonomic and peripheral neuropathy in endstage liver disease and following liver transplantation

Severe chronic liver disease may be associated with a peripheral somatic and an autonomic neuropathy. There are only a limited number of reports on the incidence and features of these neuropathies. In addition the effects of liver transplantation on these neuropathies have not been well studied. We examined peripheral somatic and autonomic nerve function in 42 patients with endstage liver disease prior to transplantation and also examined the effect of liver transplantation on these neuropathies in 14 patients. Peripheral somatic neuropathy (93%) and autonomic neuropathy (50%) were common in patients with endstage liver disease and were more frequent than previously reported. Abnormalities improved in some patients after liver transplantation, particularly if there was return of normal hepatic function.