Australian and Newhttp://anp.sagepub.com/ Zealand Journal of Psychiatry
Metachromatic leukodystrophy presenting as bipolar disorder Dennis Velakoulis, Amy Ting, Toby Winton-Brown, Mark Walterfang and Frank Gaillard Aust N Z J Psychiatry published online 18 September 2014 DOI: 10.1177/0004867414550212 The online version of this article can be found at: http://anp.sagepub.com/content/early/2014/09/17/0004867414550212
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On behalf of:
The Royal Australian and New Zealand College of Psychiatrists
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550212 letter2014
ANP0010.1177/0004867414550212Australian & New Zealand Journal of PsychiatryVelakoulis et al.
Letter Australian & New Zealand Journal of Psychiatry 1–2
Letter
© The Royal Australian and New Zealand College of Psychiatrists 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav anp.sagepub.com
Metachromatic leukodystrophy presenting as bipolar disorder Dennis Velakoulis1,2, Amy Ting3, Toby Winton-Brown2, Mark Walterfang1,2 and Frank Gaillard3 1Melbourne
Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Melbourne, Australia 2Neuropsychiatry Unit, Royal Melbourne Hospital, Melbourne, Australia 3Department of Radiology, Royal Melbourne Hospital, Melbourne, Australia Corresponding author: Dennis Velakoulis, Neuropsychiatry Unit, Level 2, John Cade Building, Royal Melbourne Hospital, VIC 3050, Australia. Email: [email protected]
around the age of 25. The mental state examination revealed a fit looking, fatuous and disinhibited man. Cognitive assessment revealed memory and executive dysfunction. MRI revealed changes consistent with metachromatic leukodystrophy (Figure 1(b)–(d)). Subsequent testing identified elevated urinary sulphatides. Genetic testing revealed one mutation (c.459+1G>A) with the second yet to be identified.
Metachromatic leukodystrophy (MLD) is the commonest lysosomal storage disorder, with an autosomal recessive pattern of inheritance. A deficiency of the lysosomal enzyme arylsulfatase-A (cerebroside sulfatase) results in accumulation of sulfatides, myelin breakdown and widespread dysmyelination (Kumar et al., 2012). Infantile forms involve gait and movement problems, and mental deterioration. In adult MLD,
Figure 1. Typical imaging findings of MLD. (A) Non-contrast CT brain demonstrates confluent bilateral periventricular deep white matter hypodensity (arrows) which is hypointense on T1 imaging without contrast enhancement (B) and hyperintense on T2 imaging (D). The abnormality spares the subcortical U fibres (arrowheads, inset B, D). Spectroscopy trace (C) demonstrates elevated myo inositol, reduced N-acetylaspartate and increased lactate.
DOI: 10.1177/0004867414550212
To the Editor A 31-year-old man, John, presented with a history of depression with episodes of disinhibition. He had lost his job as a professional two years earlier and been provisionally diagnosed with bipolar disorder. There was a history of a head injury aged 17 without loss of consciousness or cognitive sequelae. A recent CT scan (Figure 1(a)) was reported by a radiologist as demonstrating frontal changes ‘consistent with a past head injury’. John was referred for neuropsychiatric assessment of his ‘head injury’ and mood changes. Following the head injury, John had completed high school, a university degree and progressed well through his profession. The history of cognitive decline and behavioural and mood changes had only commenced at Australian & New Zealand Journal of Psychiatry Downloaded from anp.sagepub.com at DALHOUSIE UNIV on November 10, 2014
2
ANZJP Correspondence
psychotic symptoms often precede progressive executive deficits, dementia, seizures, chorea or dystonia (Walterfang et al., 2009).
MR spectroscopy usually demonstrates decreased NAA (n-acetyl aspartate), elevated myo-inositol and occasionally elevated lactate (Figure 1(c)) (Scott 2009).
Imaging findings
Summary
Classic MRI findings include symmetric areas of high T2 signal within the periventricular and cerebellar white matter (Figure 1) that become confluent with disease progression. A frontal predominance is seen in late onset MLD (juvenile and adult forms), with signal abnormality progressing anterior to posterior (Scott, 2009). A ‘tigroid’ or ‘leopard skin’ appearance with radially oriented stripes of low signal intensity (normal white matter) within the diffuse symmetric T2 hyperintense white matter abnormality (areas of dysmyelination) has also been described (Van der Voorn, 2005).
John’s behavioural and affective changes, first diagnosed as a primary mood disorder, were then attributed to a head injury, supported by an abnormal CT. The case highlights two important principles: first, the importance of a detailed history, which revealed that the behavioural and cognitive changes had occurred years after the head injury, and second, the utility of MRI compared with non-contrast CT. Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References Kumar V, Abbas A and Aster J. (2012) Robbins and Cotran Pathologic Basis of Disease, 9th ed. Philadelphia: Elsevier. Scott W (2009) Magnetic Resonance Imaging of The Brain and Spine 4th ed. Philadelphia: Lippincott, Williams and Wilkins. Van der Voorn JP, Pouwels PJ, Kamphorst W, et al. (2005) Histopathologic correlates of radial stripes on MR images in lysosomal storage disorders. AJNR American Journal of Neuroradiology 26: 442–446. Walterfang M, Mocellin R, Velakoulis D. (2009) Neuropsychiatric aspects of metabolic and endocrine disorder. In: Sadock BJ, Sadock VA, and Ruiz P (eds.) Kaplan and Sadock Textbook of Psychiatry. 9th edition. Sydney: Wolters Kluwer / Lippincott Williams and Wilkins, pp. 592–618.
Australian & New Zealand Journal of Psychiatry Downloaded from anp.sagepub.com at DALHOUSIE UNIV on November 10, 2014
Metachromatic leukodystrophy presenting as bipolar disorder Dennis Velakoulis, Amy Ting, Toby Winton-Brown, Mark Walterfang and Frank Gaillard Aust N Z J Psychiatry published online 18 September 2014 DOI: 10.1177/0004867414550212 The online version of this article can be found at: http://anp.sagepub.com/content/early/2014/09/17/0004867414550212
Published by: http://www.sagepublications.com
On behalf of:
The Royal Australian and New Zealand College of Psychiatrists
Additional services and information for Australian and New Zealand Journal of Psychiatry can be found at: Email Alerts: http://anp.sagepub.com/cgi/alerts Subscriptions: http://anp.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav
>> OnlineFirst Version of Record - Sep 18, 2014 What is This?
Downloaded from anp.sagepub.com at DALHOUSIE UNIV on November 10, 2014
550212 letter2014
ANP0010.1177/0004867414550212Australian & New Zealand Journal of PsychiatryVelakoulis et al.
Letter Australian & New Zealand Journal of Psychiatry 1–2
Letter
© The Royal Australian and New Zealand College of Psychiatrists 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav anp.sagepub.com
Metachromatic leukodystrophy presenting as bipolar disorder Dennis Velakoulis1,2, Amy Ting3, Toby Winton-Brown2, Mark Walterfang1,2 and Frank Gaillard3 1Melbourne
Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Melbourne, Australia 2Neuropsychiatry Unit, Royal Melbourne Hospital, Melbourne, Australia 3Department of Radiology, Royal Melbourne Hospital, Melbourne, Australia Corresponding author: Dennis Velakoulis, Neuropsychiatry Unit, Level 2, John Cade Building, Royal Melbourne Hospital, VIC 3050, Australia. Email: [email protected]
around the age of 25. The mental state examination revealed a fit looking, fatuous and disinhibited man. Cognitive assessment revealed memory and executive dysfunction. MRI revealed changes consistent with metachromatic leukodystrophy (Figure 1(b)–(d)). Subsequent testing identified elevated urinary sulphatides. Genetic testing revealed one mutation (c.459+1G>A) with the second yet to be identified.
Metachromatic leukodystrophy (MLD) is the commonest lysosomal storage disorder, with an autosomal recessive pattern of inheritance. A deficiency of the lysosomal enzyme arylsulfatase-A (cerebroside sulfatase) results in accumulation of sulfatides, myelin breakdown and widespread dysmyelination (Kumar et al., 2012). Infantile forms involve gait and movement problems, and mental deterioration. In adult MLD,
Figure 1. Typical imaging findings of MLD. (A) Non-contrast CT brain demonstrates confluent bilateral periventricular deep white matter hypodensity (arrows) which is hypointense on T1 imaging without contrast enhancement (B) and hyperintense on T2 imaging (D). The abnormality spares the subcortical U fibres (arrowheads, inset B, D). Spectroscopy trace (C) demonstrates elevated myo inositol, reduced N-acetylaspartate and increased lactate.
DOI: 10.1177/0004867414550212
To the Editor A 31-year-old man, John, presented with a history of depression with episodes of disinhibition. He had lost his job as a professional two years earlier and been provisionally diagnosed with bipolar disorder. There was a history of a head injury aged 17 without loss of consciousness or cognitive sequelae. A recent CT scan (Figure 1(a)) was reported by a radiologist as demonstrating frontal changes ‘consistent with a past head injury’. John was referred for neuropsychiatric assessment of his ‘head injury’ and mood changes. Following the head injury, John had completed high school, a university degree and progressed well through his profession. The history of cognitive decline and behavioural and mood changes had only commenced at Australian & New Zealand Journal of Psychiatry Downloaded from anp.sagepub.com at DALHOUSIE UNIV on November 10, 2014
2
ANZJP Correspondence
psychotic symptoms often precede progressive executive deficits, dementia, seizures, chorea or dystonia (Walterfang et al., 2009).
MR spectroscopy usually demonstrates decreased NAA (n-acetyl aspartate), elevated myo-inositol and occasionally elevated lactate (Figure 1(c)) (Scott 2009).
Imaging findings
Summary
Classic MRI findings include symmetric areas of high T2 signal within the periventricular and cerebellar white matter (Figure 1) that become confluent with disease progression. A frontal predominance is seen in late onset MLD (juvenile and adult forms), with signal abnormality progressing anterior to posterior (Scott, 2009). A ‘tigroid’ or ‘leopard skin’ appearance with radially oriented stripes of low signal intensity (normal white matter) within the diffuse symmetric T2 hyperintense white matter abnormality (areas of dysmyelination) has also been described (Van der Voorn, 2005).
John’s behavioural and affective changes, first diagnosed as a primary mood disorder, were then attributed to a head injury, supported by an abnormal CT. The case highlights two important principles: first, the importance of a detailed history, which revealed that the behavioural and cognitive changes had occurred years after the head injury, and second, the utility of MRI compared with non-contrast CT. Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References Kumar V, Abbas A and Aster J. (2012) Robbins and Cotran Pathologic Basis of Disease, 9th ed. Philadelphia: Elsevier. Scott W (2009) Magnetic Resonance Imaging of The Brain and Spine 4th ed. Philadelphia: Lippincott, Williams and Wilkins. Van der Voorn JP, Pouwels PJ, Kamphorst W, et al. (2005) Histopathologic correlates of radial stripes on MR images in lysosomal storage disorders. AJNR American Journal of Neuroradiology 26: 442–446. Walterfang M, Mocellin R, Velakoulis D. (2009) Neuropsychiatric aspects of metabolic and endocrine disorder. In: Sadock BJ, Sadock VA, and Ruiz P (eds.) Kaplan and Sadock Textbook of Psychiatry. 9th edition. Sydney: Wolters Kluwer / Lippincott Williams and Wilkins, pp. 592–618.
Australian & New Zealand Journal of Psychiatry Downloaded from anp.sagepub.com at DALHOUSIE UNIV on November 10, 2014
