Undefined Disorder Research Articles

In vivo Mechanisms of Antibody-Mediated Neurological Disorders: Animal Models and Potential Implications.

Over the last two decades, the discovery of antibodies directed against neuronal surface antigens (NSA-Abs) in patients with different forms of encephalitis has provided a basis for immunotherapies in previously undefined disorders. Nevertheless, despite the circumstantial clinical evidence of the pathogenic role of these antibodies in classical autoimmune encephalitis, specific criteria need to be applied in order to establish the autoimmune nature of a disease. A growing number of studies have begun to provide proof of the pathogenicity of NSA-Abs and insights into their pathogenic mechanisms through passive transfer or, more rarely, through active immunization animal models. Moreover, the increasing evidence that NSA-Abs in the maternal circulation can reach the fetal brain parenchyma during gestation, causing long-term effects, has led to models of antibody-induced neurodevelopmental disorders. This review summarizes different methodological approaches and the results of the animal models of N-methyl-d-aspartate receptor (NMDAR), leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein 2 (CASPR2), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) antibody-mediated disorders and discuss the results and the limitations. We also summarize recent experiments that demonstrate that maternal antibodies to NMDAR and CASPR2 can alter development in the offspring with potential lifelong susceptibility to neurological or psychiatric disorders.

Non-celiac gluten/wheat sensitivity (NCGS)-acurrently undefined disorder without validated diagnostic criteria and of unknown prevalence: Position statement of the task force on food allergy of the German Society of Allergology and Clinical Immunology (DGAKI).

Within the last decade, non-celiac gluten/wheat sensitivity (NCGS) has been increasingly discussed not only in the media but also among medical specialties. The existence and the possible triggers of NCGS are controversial. Three international expert meetings which proposed recommendations for NCGS were not independently organized and only partially transparent regarding potential conflicts of interest of the participants. The present position statement reflects the following aspects about NCGS from an allergist’s and nutritionist’s point of view: (A) Validated diagnostic criteria and/or reliable biomarkers are still required. Currently, this condition is frequently self-diagnosed, of unknown prevalence and non-validated etiology. (B) Gluten has not been reliably identified as an elicitor of NCGS because of high nocebo and placebo effects. Double-blind, placebo-controlled provocation tests are of limited value for the diagnosis of NCGS and should be performed in a modified manner (changed relation of placebo and active substance). (C) Several confounders hamper the assessment of subjective symptoms during gluten-reduced or gluten-free diets. Depending on the selection of food items, e.g., an increased vegetable intake with soluble fibers, diets may induce physiological digestive effects and can modify gastrointestinal transit times independent from the avoidance of gluten. (D) A gluten-free diet is mandatory in celiac disease based on scientific evidence. However, a medically unjustified avoidance of gluten may bear potential disadvantages and risks. (E) Due to a lack of diagnostic criteria, a thorough differential diagnostic work-up is recommended when NCGS is suspected. This includes a careful patient history together with a food-intake and symptom diary, if necessary an allergy diagnostic workup and a reliable exclusion of celiac disease. We recommend such a structured procedure since a medically proven diagnosis is required before considering the avoidance of gluten.

Isolation of live Borrelia burgdorferi sensu lato spirochaetes from patients with undefined disorders and symptoms not typical for Lyme borreliosis

Lyme borreliosis is a multisystem disorder with a diverse spectrum of clinical manifestations, caused by spirochaetes of the Borrelia burgdorferi sensu lato complex. It is an infectious disease that can be successfully cured by antibiotic therapy in the early stages; however, the possibility of the appearance of persistent signs and symptoms of disease following antibiotic treatment is recognized. It is known that Lyme borreliosis mimics multiple diseases that were never proven to have a spirochaete aetiology. Using complete modified Kelly–Pettenkofer medium we succeeded in cultivating live B. burgdorferi sensu lato spirochaetes from samples taken from people who suffered from undefined disorders, had symptoms not typical for Lyme borreliosis, but who had undergone antibiotic treatment due to a suspicion of having Lyme disease even though they were seronegative. We report the first recovery of live B. burgdorferi sensu stricto from residents of southeastern USA and the first successful cultivation of live Borrelia bissettii-like strain from residents of North America. Our results support the fact that B. bissettii is responsible for human Lyme borreliosis worldwide along with B. burgdorferi s.s. The involvement of new spirochaete species in Lyme borreliosis changes the understanding and recognition of clinical manifestations of this disease.

Candida, Food Discipline and the Dietary Taming of Uncertainty

Discourses of nutritional health are strongly associated with illness, and have recently been linked to the prevalence and management of chronic undefined disorders. Using the case of Candida—a yeast-related disorder of vague symptomatology—I explore the role of food in the narratives of twenty-four people living with Candida. As Candida remains a speculative illness within the boundaries of biomedical science, it is relevant to critically explore the often-focal role of food in the management of this condition, and to consider the range of personal, social and cultural motivations at work in its dietary regulation. Taking up Foucault's theory of docility, I trace the ways in which dietary practices can be understood as normalizing the Candidad-body by helping to create a sense of certainty and control in the persistent face of illness ambiguity. In drawing on Foucault's later work, I move beyond illness dieting as solely a disciplinary regime and explore the ways in which dietary regime can also be conceptualized as a practice in the care of the self, fostering a heightened, often-changing sense of self. While Candida dieting practices will never fully operate separate from the pervasive discourses of nutritional science, they can offer productive possibilities in the regulation and maintenance of an illness not fully recognized by biomedical science.

Women's undefined disorders--a challenge for clinical communication.

Patients presenting illness without disease are common in general practice. A clinical communicative method was developed in order to clarify women's 'undefined' disorders. Outcomes from this approach registered from 122 audiotaped consultations were qualitatively analysed, in order to explore potential conditions and premises constituting the phenomena labelled as undefined. Knowledge produced by female patients was applied for transformation of the undefined nature of the problem into various levels of medical understanding. Gender-specific illness-promotive mechanisms were identified, as well as certain communicative dilemmas distorting symptom presentation into undefinedness. Relevant medical management was also suggested.

The nosology of genetic peripheral neuropathies in Swedish children.

103 consecutive childhood cases of genetic peripheral neuropathies of heredodegenerative background were collected from Gothenburg from 1973 to 1980. From this series, 63 hereditary motor and sensory neuropathies (HMSN) were distinguished: 31 cases of demyelinating and remyelinating HMSN (HMSN I), 21 (18 families) with an autosomal dominant and 10 with sporadic mode of inheritance and unaffected parents; and 32 cases of neuronal-axonal types (HMSN II), 27 of whom (25 families) had at least one affected, if asymptomatic, parent. In one family, both parents were neurologically and neurophysiologically completely normal. Three cases of uncharacteristic HSN were diagnosed. Among 37 cases with a combined degenerative encephalopathy/myelopathy and a peripheral neuropathy, nine had hereditary spastic paraplegia, six had heredoataxias (three of the Friedreich type), nine had lysosomal storage diseases (five of the Krabbe type), seven had other known inborn metabolic errors and six had biochemically undefined disorders. Progressive neuropathies are important manifestations of a large variety of genetically determined heredodegenerative neurological disorders of infancy and childhood. For classification of HMSN, clinical and neurophysiological examinations are necessary for the index case and for both parents as well.