A practical approach to diagnosing adult onset leukodystrophies

Ahmed, Rm M.; Murphy, Elaine; Davagnanam, Indran; Parton, Matt; Schott, Jonathan M.; Mummery, C.J.; Rohrer, Jonathan D.; Lachmann, Robin; Houlden, Henry; Fox, Nick C.; Chataway, Jeremy

doi:10.1136/jnnp-2013-305888

Cited by 88 publications

(70 citation statements)

References 71 publications

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“…I was hoping for a white matter case, perhaps mitochondrial encephalopathy with lactic acidosis and stroke-like episodes, vanishing white matter disease or a leukodystrophy1—but it's not to be! This is about an 83-year-old gentleman who presented to the emergency department and was a bit confused, had a normal CT head scan, then died within 3 weeks.…”

Section: Discussion By Dr Jeremy Chatawaymentioning

confidence: 99%

Clinicopathological case: rapid cognitive decline in an older man

et al. 2016

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Section: Discussion By Dr Jeremy Chatawaymentioning

confidence: 99%

Clinicopathological case: rapid cognitive decline in an older man

et al. 2016

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“…A recent review addressing the approach to diagnosing adult onset leukodystrophy suggests the diagnostic yield of biopsy is up to 78% with management being altered in 63% of cases. 5 This case highlights the diagnostic (and potential therapeutic) importance of early consideration of brain biopsy in patients with rapidly progressive atypical neurological syndromes including cognitive decline. Figure 1 Brain magnetic resonance imaging (MRI) at presentation (A-C), with coronal (A) and axial (B) T2-weighted sequences demonstrating extensive white matter hyperintensity with no associated mass effect.…”

Section: Discussionmentioning

confidence: 99%

Lymphomatosis Cerebri: A Treatable Cause of Rapidly Progressive Dementia

Samani

Davagnanam²,

Cockerell

et al. 2015

J Neurol Neurosurg Psychiatry

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We describe a case of lymphomatosis cerebri (LC), an extremely rare variant of Primary Central Nervous System Lymphoma (PCNSL) characterised by diffuse infiltration of brain parenchyma by a non-cohesive mass of malignant lymphocytes.A 50 year-old lady presented with rapidly progressive cognitive decline. Neuropsychometric testing showed global cognitive deficits with magnetic resonance imaging of the brain showing diffuse T2-weighted white matter hyperintensity. Initial impression included metachromatic leukodystrophy however after a series of normal investigations, and clinicoradiological deterioration, a decision was made to proceed to brain biopsy which showed LC. Following chemoradiotherapy she regained the ability to ambulate independently and her cognitive state improved.PCNSL typically presents as discrete gadolinium-enhancing T2 hyperintense lesions. Very rarely it presents as LC, usually manifest as rapidly progressive cognitive decline and leukoencepahlopathy. Complete remission of LC has been achieved with steroid use followed by radiotherapy, cisplatin or methotrexate. Although there are many causes of rapidly progressive leukoencephalopathy, rapid progression of structural change, perhaps combined with new foci of enhancement, should prompt thoughts of an underlying neoplastic process and the need for biopsy. This case highlights the diagnostic (and potential therapeutic) importance of early consideration of brain biopsy in patients with rapidly progressive atypical neurological syndromes

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“…Further phenocopies of HSP are leukodystrophies like Krabbe disease, metachromatic leukodystrophy (MLD), vanishing white matter disease, Alexander disease, cerebrotendinous xanthomatosis, hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS), adult polyglucosan body disease, and the adrenomyeloneuropathy (AMN) variant of X-linked adrenoleukodystrophy (X-ALD) [ 69 ]. With adult onset especially AMN, Krabbe disease and Alexander disease present with prominent spasticity (Table 16.5 ) [ 5 ].…”

Section: Leukodystrophiesmentioning

confidence: 99%

Genetics of Hereditary Spastic Paraplegias (HSP)

Schüle¹,

Schöls²

2015

Movement Disorder Genetics

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Hereditary spastic paraplegias (HSP) are a group of degenerative disorders of the spinal cord that lead to a progressive spastic gait disturbance marked by lower limb spasticity and weakness. Genetically, HSPs are among the most heterogeneous Mendelian diseases and can be inherited following autosomal dominant, autosomal recessive, and X-chromosomal modes of inheritance. More than 80 genes and gene loci have been identifi ed so far and require next-generation sequencing approaches for comprehensive genetic testing. In this chapter we discuss clinical aspects of HSP including differential diagnostics, typical presentation of common HSPs, limitations of genotype-phenotype correlation, and overlap with genetic disorders that cause progressive spasticity but are not categorized as HSPlike spastic ataxias, slow variants of amyotrophic lateral sclerosis, spastic variants of peripheral neuropathies, and adult-onset variants of leukodystrophies. In consideration of the complexity of this fi eld, we propose an algorithm for a time-and costeffi cient strategy for genetic diagnostics in HSP.

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A practical approach to diagnosing adult onset leukodystrophies

Cited by 88 publications

References 71 publications

Clinicopathological case: rapid cognitive decline in an older man

Clinicopathological case: rapid cognitive decline in an older man

Lymphomatosis Cerebri: A Treatable Cause of Rapidly Progressive Dementia

Genetics of Hereditary Spastic Paraplegias (HSP)

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