Encephalitis lethargica affected a large number of people in the pandemic in the early 1900s (von Economo, 1930). Histological and biochemical data suggest that autoimmune mechanisms play an important role in this disorder and recently serum anti-basal ganglia antibodies (ABGA) have been detected in affected sporadic cases associated with evidence of recent streptococcal infection (Dale et al., 2004a). ABGA are also associated with other neuropsychiatric disorders including Sydenhams chorea, paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, Tourettes syndrome and obsessive compulsive disorder. The precise frequency, presentation, disease course, treatment response and causes of these disorders are still unknown. As ABGA are strongly associated with recent streptococcal infection, these disorders represent a potentially good model for the study of molecular mimicry and autoimmunity. The present study focussed on various aspects of this group of disorders. Profiling of group A streptococcus isolates from both patients with postulated post-streptococcal disorders of the CNS and controls was done which highlighted differences in virulence factors like M protein and superantigens between the two groups. Also in the present study we demonstrated the pathogenicity of anti-neuronal antibodies found in patients in both an in vivo and in vitro setting. An animal model of the disorders was produced by passive transfer of antibodies from patients which resulted in symptoms reminiscent of diseases like encephalitis lethargica and dystonia. An active immunization animal model using GABHS proteins and recombinant proteins (putative autoantigens) was also developed. Furthermore, the autoantibodies from patients and animal models were analysed on both neuronal and non-neuronal cells where they demonstrated to have a functional effect on cytotoxicity, apoptosis, calcium flux and enolase activity. N-methyl D-aspartate glutamate receptor and voltage gated potassium channel have been recently been implicated in a 16 range of neurological disorders, hence we also tested the patient sera for antibodies against these receptors and found a group of patients to be positive. In summary, EL and other ABGA-associated disorders are still an emerging entity, with major implications for neuropsychiatry. As auto-antibody mediated diseases respond to immunomodulatory therapy, identifying and defining the pathogenesis of these disorders is important so that patients can be appropriately treated.

An interwoven fiction piece representing four perspectives and its effects on self-awareness. The most effective way to blur the line of self in this structure is to braid the minds, voices, and stories, of each perspective. With a focal point where all the voices eventually drift to being the frame of the story, there will be a unique distance between the stories. This thesis explores the effects of different types of mental and physiological illnesses through fiction, highlighting the effect of perception on fact and the perspective of the mentally ill.