title: Adults with a history of illicit amphetamine use exhibit abnormal substantia nigra morphology and parkinsonism.
abstract: BACKGROUND
  The sonographic appearance of the substantia nigra is abnormally bright and enlarged (hyperechogenic) in young adults with a history of illicit stimulant use. The abnormality is a risk factor for Parkinson's disease. The aim of the current study was to identify the type of illicit stimulant drug associated with substantia nigra hyperechogenicity and to determine if individuals with a history of illicit stimulant use exhibit clinical signs of parkinsonism. We hypothesised that use of amphetamines (primarily methamphetamine) is associated with substantia nigra hyperechogenicity and clinical signs of parkinsonism.
  
  
  METHODS
  The area of echogenic signal in the substantia nigra was measured in abstinent human amphetamine users (n = 27; 33 ± 8 years) and in three control groups comprising a) 'ecstasy' users (n = 19; 23 ± 3 years), b) cannabis users (n = 30; 26 ± 8 years), and c) non-drug users (n = 37; 25 ± 7 years). A subset of subjects (n = 55) also underwent a neurological examination comprising the third and fifth part of the Unified Parkinson's Disease Rating Scale.
  
  
  RESULTS
  Area of substantia nigra echogenicity was significantly larger in the amphetamine group (0.276 ± 0.080 cm(2)) than in the control groups (0.200 ± 0.075, 0.190 ± 0.049, 0.191 ± 0.055 cm(2), respectively; P < 0.002). The score on the clinical rating scale was also significantly higher in the amphetamine group (8.4 ± 8.1) than in pooled controls (3.3 ± 2.8; P = 0.002).
  
  
  CONCLUSIONS
  Illicit use of amphetamines is associated with abnormal substantia nigra morphology and subtle clinical signs of parkinsonism. The results support epidemiological findings linking use of amphetamines, particularly methamphetamine, with increased risk of developing Parkinson's disease later in life.
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, GPO Box 2471, Adelaide, SA 5001, Australia. Electronic address: gabrielle.todd@unisa.edu.au.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Todd
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, GPO Box 2471, Adelaide, SA 5001, Australia. Electronic address: verity.pearson-dennett@mymail.unisa.edu.au.
authors.forename: Verity
authors.initials: V
authors.lastname: Pearson-Dennett
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, GPO Box 2471, Adelaide, SA 5001, Australia; Department of Neurology, Flinders Medical Centre, Flinders Drive, Bedford Park, SA 5042, Australia; Human Physiology, Medical School, Flinders University, GPO Box 2100, Adelaide, SA 5001, Australia. Electronic address: Robert.Wilcox@health.sa.gov.au.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wilcox
authors.affiliation: School of Health Sciences, University of South Australia, GPO Box 2471, Adelaide, SA 5001, Australia. Electronic address: chamt010@mymail.unisa.edu.au.
authors.forename: Minh T
authors.initials: MT
authors.lastname: Chau
authors.affiliation: School of Health Sciences, University of South Australia, GPO Box 2471, Adelaide, SA 5001, Australia. Electronic address: kerry.thoirs@unisa.edu.au.
authors.forename: Kerry
authors.initials: K
authors.lastname: Thoirs
authors.affiliation: School of Health Sciences, University of South Australia, GPO Box 2471, Adelaide, SA 5001, Australia. Electronic address: dominic.thewlis@unisa.edu.au.
authors.forename: Dominic
authors.initials: D
authors.lastname: Thewlis
authors.affiliation: Centre for Neuroscience of Speech, 550 Swanston Street, Parkville, The University of Melbourne, VIC 3010, Australia; Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, Eberhard Karls Universidad Tübingen, Germany. Electronic address: vogela@unimelb.edu.au.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Vogel
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, GPO Box 2471, Adelaide, SA 5001, Australia. Electronic address: jason.white@unisa.edu.au.
authors.forename: Jason M
authors.initials: JM
authors.lastname: White
mesh_terms: D000293:Adolescent; D000328:Adult; D000662:Amphetamines / Q000009:adverse effects*; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020734:Parkinsonian Disorders / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D012307:Risk Factors; D013378:Substantia Nigra / Q000473:pathology*; D017585:Ultrasonography, Doppler, Transcranial; D055815:Young Adult
chemical_list: D000662:Amphetamines; D000697:Central Nervous System Stimulants
keywords: Amphetamine; Methamphetamine; Parkinsonism; Substantia nigra; Transcranial ultrasound