- Email: [email protected]
55.
2050
Abstracts / Journal of Clinical Neuroscience 21 (2014) 2033–2058
such as neurons are vulnerable to mtDNA depletion and can be used for assessing POLG related disease. http://dx.doi.org/10.1016/j.jocn.2014.06.066
53. Autoimmune encephalitides in a regional centre: Presentation and implications for management Linda Tjoa a, Emily Watson a, Martin Newman b, Mike Boggild a, Richard White a a b
Townsville Hospital, North Queensland, QLD, Australia Royal Brisbane and Womens Hospital, QLD, Australia
Autoimmune encephalitides (AIE) are increasingly recognised as the cause of a range of clinical presentations including confusional state, new onset psychosis and seizures. Early diagnosis and institution of appropriate immunotherapy are thought to improve clinical outcomes in these patients. We report the presentation and clinical outcomes of AIE diagnosed though a newly established regional neurology centre and consider implications for clinical practice. All patients with AIE seen through the centre in 2012–2013 were identified. Further cases were sought via statewide immunology reference laboratory records (for voltage-gated potassium channel [VGKC], NMDA and related antibody requests) from 2010–2013. Five AIE patients presenting in 2012–2013 were identified from centre records. No additional patients could be identified in the region covered from reference laboratory samples. Two ‘‘false positive’’ antibody results, both in 2012, were noted (cryptococcal meningitis and normal pressure hydrocephalus). The five patients presented initially to general physicians (n = 3) or psychiatrists (n = 2). In each case a clinical diagnosis of AIE and institution of appropriate immunotherapy occurred only following neurology consultation. Clinical presentations and outcomes will be presented. In a regional setting, patients with AIE are likely to present to non-neurologists. The absence of requests for and/or positive results for VGKC/NMDA in the 2 years preceding establishment of a viable neurology service in the region would suggest such patients were not diagnosed by non-neurologists with likely consequent morbidity. Education of psychiatrists, general, infectious diseases and intensive care unit physicians with regard to the clinical features of these rare disorders will be key to their early recognition and institution of appropriate management. http://dx.doi.org/10.1016/j.jocn.2014.06.067
54. Regulatory T cells in amyotrophic lateral sclerosis: A role for disease modulation? Parvathi Menon a, Fiona McKay b, Steve Schibeci b, David Booth c, Najwa Marmash b, Greg Parnell b, Graeme Stewart b, Steve Vucic a a
Department of Neurology, Westmead Hospital, University of Sydney, NSW, Australia b Department of Immunology, Westmead Hospital, NSW, Australia c Westmead Millineum Institute, University of Sydney, NSW, Australia Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective and progressive deterioration of cortical, brainstem, and spinal cord motor neurons. While the mechanisms underlying the development of neurodegeneration in ALS remain elusive, an immune response, dominated by T cells, is evident within the central nervous system (CNS) of ALS patients. Recent evidence suggests a role for regulatory T cells (Tregs) in neuroprotection, neurogenesis and in slowing of disease progression in animal models of ALS. Consequently, the immune response,
specifically changes in the Treg population, was assessed in the present ALS cohort for evidence of disease related changes. The frequency of naive (CD45RA+) and memory (CD45RO+) subsets of CD4+CD25hiCD127loFoxP3+ Tregs obtained by flow cytometry of peripheral blood mononuclear cells in ALS patients (n = 38) was compared with age-matched controls (n = 40). ALS patients underwent clinical assessment using the revised ALS functional rating scale (ALSFRS-R) and rate of disease progression was calculated from the duration of disease according to a previously reported formula in order to determine the correlation of Treg frequency with rate of disease progression. An elevated Treg response was noted in ALS patients when compared with controls with a higher proportion of naive Tregs in ALS (p = 0.037) as a percentage of all CD4 and a higher expression of the transcriptional controller of Tregs, FoxP3 (correlated with suppressive capacity) in memory Tregs in ALS (p = 0.036). These results are in agreement with findings in the early disease phase in the animal model in ALS. A significant inverse correlation between Treg frequency and rate of disease progression measured by ALSFRS-R (r = 0.3, p = 0.034) was also evident in the present study. We hypothesise that Tregs are elevated in an attempt to protect the neurons early in disease, but are overtaken by a neurotoxic T effector response later in disease, and that higher Treg levels slow disease progression. Future work will examine immune gene expression in this cohort and potential therapeutic strategies to increase Tregs in ALS. http://dx.doi.org/10.1016/j.jocn.2014.06.068
55. What gastrointestinal dysmotility issues are there in adult patients with mitochondrial disease? Christina Liang, Carolyn Sue Royal North Shore Hospital, St Leonards, NSW, Australia This study aimed to explore the characteristics and range of gastrointestinal (GI) motility problems in adult patients with mitochondrial disease. We retrospectively identified 30 patients with molecularly and/or biopsy-proven mitochondrial disease who during the course of their clinical work-up, had formal gastric and colonic transit studies. We reviewed their upper and lower GI symptoms over time, and compared these with their GI transit studies, nutrition level, diabetic status, and their response to various management options. Of the 30 patients, 12 had the m.3243 A>G mutation (six had mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes); three had other mitochondrial point mutations; two had polymerase gamma (POLG) mutations; two had mitochondrial neurogastrointestinal encephalopathy, five had chronic progressive external ophthalmoplegia, and six had multi-systemic manifestations. Upper and lower gastrointestinal segments were variably involved. Increasing fibre intake or stool softener was less effective than osmotic or stimulant laxatives, and bowel rest in severe cases. Fluctuation in GI motility may relate to exacerbations in other organ systems. Patients’ average body mass indices were low average, and caloric, vitamin and iron deficiencies may necessitate parenteral replacement. GI dysmotility is a common problem amongst patients with a range of mitochondrial conditions, with involvement of different segments of the gastrointestinal tract. Gastrointestinal dysmotility should be screened regularly in patients with suspected mitochondrial disease. Acute exacerbation of gastrointestinal dysmotility may relate to a generalised deterioration. Both oral and parenteral administration of caloric, vitamin and iron supplementation should be considered when these nutritional deficiencies are present. http://dx.doi.org/10.1016/j.jocn.2014.06.069
Abstracts / Journal of Clinical Neuroscience 21 (2014) 2033–2058
such as neurons are vulnerable to mtDNA depletion and can be used for assessing POLG related disease. http://dx.doi.org/10.1016/j.jocn.2014.06.066
53. Autoimmune encephalitides in a regional centre: Presentation and implications for management Linda Tjoa a, Emily Watson a, Martin Newman b, Mike Boggild a, Richard White a a b
Townsville Hospital, North Queensland, QLD, Australia Royal Brisbane and Womens Hospital, QLD, Australia
Autoimmune encephalitides (AIE) are increasingly recognised as the cause of a range of clinical presentations including confusional state, new onset psychosis and seizures. Early diagnosis and institution of appropriate immunotherapy are thought to improve clinical outcomes in these patients. We report the presentation and clinical outcomes of AIE diagnosed though a newly established regional neurology centre and consider implications for clinical practice. All patients with AIE seen through the centre in 2012–2013 were identified. Further cases were sought via statewide immunology reference laboratory records (for voltage-gated potassium channel [VGKC], NMDA and related antibody requests) from 2010–2013. Five AIE patients presenting in 2012–2013 were identified from centre records. No additional patients could be identified in the region covered from reference laboratory samples. Two ‘‘false positive’’ antibody results, both in 2012, were noted (cryptococcal meningitis and normal pressure hydrocephalus). The five patients presented initially to general physicians (n = 3) or psychiatrists (n = 2). In each case a clinical diagnosis of AIE and institution of appropriate immunotherapy occurred only following neurology consultation. Clinical presentations and outcomes will be presented. In a regional setting, patients with AIE are likely to present to non-neurologists. The absence of requests for and/or positive results for VGKC/NMDA in the 2 years preceding establishment of a viable neurology service in the region would suggest such patients were not diagnosed by non-neurologists with likely consequent morbidity. Education of psychiatrists, general, infectious diseases and intensive care unit physicians with regard to the clinical features of these rare disorders will be key to their early recognition and institution of appropriate management. http://dx.doi.org/10.1016/j.jocn.2014.06.067
54. Regulatory T cells in amyotrophic lateral sclerosis: A role for disease modulation? Parvathi Menon a, Fiona McKay b, Steve Schibeci b, David Booth c, Najwa Marmash b, Greg Parnell b, Graeme Stewart b, Steve Vucic a a
Department of Neurology, Westmead Hospital, University of Sydney, NSW, Australia b Department of Immunology, Westmead Hospital, NSW, Australia c Westmead Millineum Institute, University of Sydney, NSW, Australia Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective and progressive deterioration of cortical, brainstem, and spinal cord motor neurons. While the mechanisms underlying the development of neurodegeneration in ALS remain elusive, an immune response, dominated by T cells, is evident within the central nervous system (CNS) of ALS patients. Recent evidence suggests a role for regulatory T cells (Tregs) in neuroprotection, neurogenesis and in slowing of disease progression in animal models of ALS. Consequently, the immune response,
specifically changes in the Treg population, was assessed in the present ALS cohort for evidence of disease related changes. The frequency of naive (CD45RA+) and memory (CD45RO+) subsets of CD4+CD25hiCD127loFoxP3+ Tregs obtained by flow cytometry of peripheral blood mononuclear cells in ALS patients (n = 38) was compared with age-matched controls (n = 40). ALS patients underwent clinical assessment using the revised ALS functional rating scale (ALSFRS-R) and rate of disease progression was calculated from the duration of disease according to a previously reported formula in order to determine the correlation of Treg frequency with rate of disease progression. An elevated Treg response was noted in ALS patients when compared with controls with a higher proportion of naive Tregs in ALS (p = 0.037) as a percentage of all CD4 and a higher expression of the transcriptional controller of Tregs, FoxP3 (correlated with suppressive capacity) in memory Tregs in ALS (p = 0.036). These results are in agreement with findings in the early disease phase in the animal model in ALS. A significant inverse correlation between Treg frequency and rate of disease progression measured by ALSFRS-R (r = 0.3, p = 0.034) was also evident in the present study. We hypothesise that Tregs are elevated in an attempt to protect the neurons early in disease, but are overtaken by a neurotoxic T effector response later in disease, and that higher Treg levels slow disease progression. Future work will examine immune gene expression in this cohort and potential therapeutic strategies to increase Tregs in ALS. http://dx.doi.org/10.1016/j.jocn.2014.06.068
55. What gastrointestinal dysmotility issues are there in adult patients with mitochondrial disease? Christina Liang, Carolyn Sue Royal North Shore Hospital, St Leonards, NSW, Australia This study aimed to explore the characteristics and range of gastrointestinal (GI) motility problems in adult patients with mitochondrial disease. We retrospectively identified 30 patients with molecularly and/or biopsy-proven mitochondrial disease who during the course of their clinical work-up, had formal gastric and colonic transit studies. We reviewed their upper and lower GI symptoms over time, and compared these with their GI transit studies, nutrition level, diabetic status, and their response to various management options. Of the 30 patients, 12 had the m.3243 A>G mutation (six had mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes); three had other mitochondrial point mutations; two had polymerase gamma (POLG) mutations; two had mitochondrial neurogastrointestinal encephalopathy, five had chronic progressive external ophthalmoplegia, and six had multi-systemic manifestations. Upper and lower gastrointestinal segments were variably involved. Increasing fibre intake or stool softener was less effective than osmotic or stimulant laxatives, and bowel rest in severe cases. Fluctuation in GI motility may relate to exacerbations in other organ systems. Patients’ average body mass indices were low average, and caloric, vitamin and iron deficiencies may necessitate parenteral replacement. GI dysmotility is a common problem amongst patients with a range of mitochondrial conditions, with involvement of different segments of the gastrointestinal tract. Gastrointestinal dysmotility should be screened regularly in patients with suspected mitochondrial disease. Acute exacerbation of gastrointestinal dysmotility may relate to a generalised deterioration. Both oral and parenteral administration of caloric, vitamin and iron supplementation should be considered when these nutritional deficiencies are present. http://dx.doi.org/10.1016/j.jocn.2014.06.069