Australia and New Zealand Association of Neurologists,Annual Scientific Meeting, 2006 Abstracts

Platform Presenters

306: A prospective study of critical illness polyneuropathy

in childhood

Monique M. Ryan, Iain Horrocks, Stephen Williams, Seiki

Abe, Jonathan Gillis, Robert A. Ouvrier; The Children’s

Hospital at Westmead

Background: Critical illness polyneuropathy (CIP) iswell recognised in adults and causes muscle weaknessand wasting with failure to wean from ventilatory sup-port. Childhood CIP is relatively poorly characterised.We undertook a prospective clinical and neurophysiologi-cal study of critically ill children in order to determine thefrequency, nature and severity of neuropathy in suchpatients.

Methods: All children receiving ventilatory support for72 h or more in the Paediatric Intensive Care Unit of theChildren’s’ Hospital at Westmead were eligible for inclu-sion if there was no pre-existing neuropathy or myopathy.Data recorded included patient demographics, clinical find-ings including those suggestive of infection and/or organfailure, medications received, biochemical and haemato-logic investigations. A standardised electromyographic(EMG), and nerve conduction study (NCS) study protocolwas undertaken within 3 days of study enrollment andweekly thereafter whilst the studies remained abnormalor the child remained in PICU.

Results: 25 patients were studied. Nerve conductionstudies showed a mixed sensory and motor axonal neurop-athy consistent with CIP in fifteen children. Abnormalitieson NCS were associated with areflexia and loss of proximalmuscle strength. NCS parameters remained abnormal onrepeat studies in most cases.

Conclusion: CIP is common in critically ill children andmay be a significant cause of persisting neurologic morbid-ity in patients requiring ICU management.

doi:10.1016/j.jocn.2007.02.012

307: Prevalence of LRRK2 mutations in Australians with

Parkinson’s Disease

Julia Stevens a, Yue Huang a, Himesha Vandenbona b,Glenda M. Halliday a, George Mellick c, Frank

Mastaglia d, John Kwok e, Carolyn M. Sue b; a Prince of

Wales Medical Research Institute and University of New

South Wales; b Royal North Shore Hospital and

University of Sydney; c University of Queensland;d Queen Elizabeth II Medical Centre; e Garvan Institute

of Medical Research and University of New South Wales

Background: Mutations in the leucine-rich repeat kinase2 (LRRK2) gene can cause familial and sporadic Parkin-son’s disease (PD). Population frequencies for these muta-tions have been determined for European, North Americanand Asian populations. Australian population frequenciesfor LRRK2 mutations are currently unknown.

Aim: To determine the prevalence of the two most com-mon LRRK2 gene mutations (G2019S and R1441G/C/H)in a cohort of Australian patients with PD.

Methods: We performed PCR/RFLP based genetic anal-ysis for the two most common mutations in the LRRK2gene (G2019S and R1441G/C/H) in 420 Australianpatients with PD who consented to DNA donation forresearch purposes (207 from New South Wales, 108 Wes-tern Australia, and 105 Queensland). We confirmed thepresence of mutations using direct sequence analysis.

Results: Five cases carrying LRRK2 gene mutationswere identified. Four had the G2019S mutation (1.2%,two cases with positive family history) and one patientwas thought to have the R1441G mutation (2%, positivefamily history). Direct sequencing demonstrated that thisresult actually represented a novel A1442P mutation. Ageof PD onset and clinical features of these LRRK2 genemutation carriers did not differ compared with non-muta-tion carriers.

Conclusions: Our results demonstrate that mutations inthe LRRK2 gene are present in at least 1.2% of Australianpatients with PD. Genetic screening for this mutation

doi:10.1016/j.jocn.2007.02.011

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Journal of Clinical Neuroscience 14 (2007) 1009–1040

should be considered in patients with PD even in theabsence of a positive family history.

doi:10.1016/j.jocn.2007.02.013

308: Olfactory stem cells can be used as cell model for

neurological disease

Sarah L. Campbell a, Alan Mackay-Sim b, David

Veivers c, Carolyn M. Sue c; a Kolling Institute ofMedical Research; b Griffith University; c Royal North

Shore Hospital and University of Sydney

Background: The investigation of neurological diseasein vitro is best performed using neurological tissue. How-ever, it is impractical to obtain neurological tissue fromaffected individuals during life. Olfactory stem cell (OSC)cultures can be established from biopsies of the olfactorymucosa during life. Stem cells from these cultures formneurospheres that can be differentiated into neuronal cells.

Purpose: To determine whether OSC cultures can beused as a cell model for neurological disease.

Methods: We cultured OSCs from an olfactory biopsy ofa patient with MELAS A3243G. Mutational load wasmanipulated by culturing in GFGS (selective) media. Weused PCR/RFLP analysis to quantitate mutational loads.Cells with high and low mutational loads were induced toform neurospheres, then differentiated into neurons. Bio-chemical function (ATP and lactate production) was mea-sured using standard laboratory methods. Cells werestained for betatubulin III (early neuronal marker). 2D-gel electrophoresis was performed on protein isolated fromharvested neurons.

Results: PCR/RFLP analysis showed that the MELASA3243G mutational load of OSCs was reduced from 80%to 40% after GFGS selection. Biochemical functionimproved with the reduction in mutational load. Histolog-ical staining confirmed that the cells were differentiated intoneurons. Analysis of the 2D-gels of protein isolated fromneurons with 80% and 40% mutational load showed anovel spot in the cells with 40% mutational load, represent-ing a change in protein synthesis that may underlie the bio-chemical improvement and mutational shift.

Conclusions: OSCs can be differentiated down the neuro-nal path and used for detecting differences in biochemicalfunction and protein expression. This method could beused to investigate biochemical and protein changes in cellsfrom patients with many types of neurological disease.

doi:10.1016/j.jocn.2007.02.014

309: Postural orthostatic tachycardia syndrome (POTS) an

under recognized disorder

Jeyaraj D. Pandian, Kaye Dalton, Robert D. Henderson,Pamela McCombe; Royal Brisbane and Women’s Hospital

Postural orthostatic tachycardia syndrome (POTS), is aclinical syndrome of orthostatic intolerance characterisedby excessive tachycardia and symptoms of cerebral hypop-erfusion on standing.

Purpose: To report our results of the clinical symptom-atology, autonomic testing and outcome in patients withPOTS.

Methods: We have studied 16 subjects who met the cri-teria for diagnosis of POTS. Ten of these patients con-sented to be interviewed using a validated autonomicsymptom questionnaire (including two mother-daughterpairs). Heart rate (HR) responses to deep breathing (DB)and the Valsalva manoeuvre were measured using ColinBP – 508 machine. Tilt studies were performed for 10 min-utes to 80 degree of head up tilting. Outcome was classifiedusing recognised criteria.

Results: The mean age of 10 subjects was 24.9 ± 6.8years, 6 were female. The mean duration of symptomswas 70.7 months (range 3–228). The common presentingorthostatic symptoms were light headedness (100%), palpi-tation (90%), pallor (90%), weakness (80%), and clammyskin (80%). The other common symptoms were non-ortho-static (90%), secretomotor (90%), and gastrointestinal(60%). The autonomic symptoms were precipitated byexertion (70%) prolonged standing (60%), and exposureto heat (30%). The mean HR increment during Tilt studywas 51.7 ± 14.3 bpm. The mean duration of follow-upwas 8.9 months (range 1–16). Only 5 patients were func-tioning normally at the follow-up visit.

Conclusions: POTS is an under recognised but persistentautonomic disorder in young patients with a variety ofsymptoms and variable outcome. Some patients may havea family history of POTS.

doi:10.1016/j.jocn.2007.02.015

310: The spectrum of autonomic failure associated with

Sjogren’s syndrome

Judith M Spies; Royal Prince Alfred Hospital and The

University of Sydney

Introduction: Sensory peripheral neuropathy is a fre-quent complication of Sjogren’s syndrome. Autonomicdysfunction of varying severity ranging from mild distalhypohidrosis to acute pandysautonomia is also seen. Neu-rological presentation often precedes the recognition ofSjogren’s syndrome.

Case 1: A 50-year-old male presented in November 2004with a 4 day history of diarrhoea followed by severe ortho-static lightheadedness, postprandial bloating and photopho-bia. Investigation revealed severe panautonomic failure.Neurological examination was otherwise normal with noclinical or electrophysiological evidence of somatic periphe-ral neuropathy. Subsequent blood tests were consistent withprimary Sjogren’s syndrome. Orthostatic hypotension and

1010 Abstracts / Journal of Clinical Neuroscience 14 (2007) 1009–1040