Skip to main content

Advertisement

SpringerLink
Log in

Neuropsychological and neuroimaging characteristics of classical superficial siderosis

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Objective

To define the neuropsychological and neuroimaging characteristics of classical infratentorial superficial siderosis (iSS), a rare but disabling disorder defined by hemosiderin deposition affecting the superficial layers of the cerebellum, brainstem and spinal cord, usually associated with a slowly progressive neurological syndrome of deafness, ataxia and myelopathy.

Methods

We present the detailed neuropsychological and neuroimaging findings in 16 patients with iSS (mean age 57 years; 6 female).

Results

Cognitive impairment was present in 8/16 (50%) of patients: executive dysfunction was the most prevalent (44%), followed by impairment of visual recognition memory (27%); other cognitive domains were largely spared. Disease symptom duration was significantly correlated with the number of cognitive domains impaired (r = 0.59, p = 0.011). Mood disorders were also common (anxiety 62%, depression 38%, both 69%) but not associated with disease symptom duration. MRI findings revealed siderosis was not only in infratentorial brain regions, but also in characteristic widespread symmetrical supratentorial brain regions, independent of disease duration and degree of cognitive impairment. The presence of small vessel disease markers was very low and did not account for the cognitive impairment observed.

Conclusion

Neuropsychological disturbances are common in iSS and need to be routinely investigated. The lack of association between the anatomical extent of hemosiderin and cognitive impairment or disease duration suggests that hemosiderin itself is not directly neurotoxic. Additional biomarkers of iSS disease severity and progression are needed for future research and clinical trials.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Fig. 1
Fig. 2

Similar content being viewed by others

Availability of data and materials

Anonymized data supporting the findings of this study will be made available to appropriately qualified investigators on request.

References

  1. Wilson D, Chatterjee F, Farmer SF, Rudge P, McCarron MO, Cowley P et al (2017) Infratentorial superficial siderosis: classification, diagnostic criteria, and rational investigation pathway. Ann Neurol 81:333–343

    Article  CAS  Google Scholar 

  2. Fearnley JM, Stevens JM, Rudge P (1995) Superficial siderosis of the central nervous system. Brain 118(Pt 4):1051–1066

    Article  Google Scholar 

  3. Koeppen AH, Borke RC (1991) Experimental superficial siderosis of the central nervous system. I. Morphological observations. J Neuropathol Exp Neurol 50(5):579–594

    Article  CAS  Google Scholar 

  4. Hamill RC (1908) Report of a case of melanosis of the brain, cord and meninges. J Nerv Ment Dis 35:594

    Article  Google Scholar 

  5. van Harskamp NJ, Rudge P, Cipolotti L (2005) Cognitive and social impairments in patients with superficial siderosis. Brain 128:1082–1092

    Article  Google Scholar 

  6. Uttner I, Tumani H, Arnim C, Brettschneider J (2009) Cognitive impairment in superficial siderosis of the central nervous system: a case report. Cerebellum 8:61–63

    Article  Google Scholar 

  7. Dubessy AL, Ursu R, Maillet D, Augier A, Le Guilloux J, Carpentier AF et al (2012) Superficial siderosis of the central nervous system: a rare cause of dementia with therapeutic consequences. Age Ageing 41:275–277

    Article  Google Scholar 

  8. Gawryluk JR, Ritchie LJ, Sicz G, Kilgour AR, Schmidt BJ (2017) Case report: a comprehensive neuropsychological assessment of a case of superficial siderosis. Arch Clin Neuropsychol 32:483–490

    Article  Google Scholar 

  9. Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R et al (2013) Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol 12:822–838

    Article  Google Scholar 

  10. Gregoire SM, Chaudhary UJ, Brown MM, Yousry TA, Kallis C, Jäger HR et al (2009) The Microbleed Anatomical Rating Scale (MARS): reliability of a tool to map brain microbleeds. Neurology 73(21):1759–1766

    Article  CAS  Google Scholar 

  11. Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA (1987) MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. Am J Roentgenol 149(2):351–356

    Article  CAS  Google Scholar 

  12. Harper L, Barkhof F, Fox NC, Schott JM (2015) Using visual rating to diagnose dementia: a critical evaluation of MRI atrophy scales. J Neurol Neurosurg Psychiatry 86(11):1225–1233

    Article  Google Scholar 

  13. Nelson H, Willison J (1982) National adult reading test (NART) Windsor. Nelson Publishing Company, Canada

    Google Scholar 

  14. Wechsler D (1997) WAIS-III administration and scoring manual. The Psychological Corporation, San Antonio

    Google Scholar 

  15. Zigmond AS, Snaith RP (1983) The hospital anxiety and depression scale. Acta Psychiatr Scand 67:361–370

    Article  CAS  Google Scholar 

  16. Lovibond PF, Lovibond SH (1995) The structure of negative emotional states: Comparison of the Depression Anxiety Stress Scales (DASS) with the Beck Depression and Anxiety Inventories. Behav Res Ther 33:335–343

    Article  CAS  Google Scholar 

  17. Warrington EK (1984) Recognition Memory Test. NFER Nelson Publishing Co., Ltd, Windsor

    Google Scholar 

  18. Coughlan, A. K., & Hollows, S. E. (1985). The adult memory and information processing battery (amipb): Test manual. AK Coughlin, Psychology Department, St James' Hospital

  19. Warrington EK (1997) The graded naming test: a restandardisation. Neuropsychol Rehabil 7(2):143–146

    Article  Google Scholar 

  20. Oldfield RC, Wingfield A (1965) Response latencies in naming objects. Q J Exp Psychol. https://doi.org/10.1080/17470216508416445

    Article  PubMed  Google Scholar 

  21. Warrington EK, James M (1990) The visual object and space perception battery. Thames Valley Test Company, Bury St Edmunds

    Google Scholar 

  22. Trennary MR, Crossen B, DeBoe J, Leber WR (1989) Stroop Neuropsychological Screening Test (SNST). Psychological Assessment Resources, Odessa

    Google Scholar 

  23. Burgess PW, Shallice T (1997) The Hayling and Brixton tests. Thames Valley Test Company Limited, Bury St Edmunds

    Google Scholar 

  24. Nelson HE (1976) A modified card sorting test sensitive to frontal lobe defects. Cortex. https://doi.org/10.1016/S0010-9452(76)80035-4

    Article  PubMed  Google Scholar 

  25. MacPherson SE, Wagner GP, Murphy P, Bozzali M, Cipolotti L, Shallice T (2014) Bringing the cognitive estimation task into the 21st century: normative data on two new parallel forms. PLoS ONE 9(3):e92554

    Article  Google Scholar 

  26. Tombaugh TN, Kozak J, Rees L (1999) Normative data stratified by age and education for two measures of verbal fluency: FAS and animal naming. Arch Clin Neuropsychol 14(2):167–177

    CAS  PubMed  Google Scholar 

  27. Smith A (1985) The Symbol Digit Modalities Test (SDMT) Manual, Revised. Western Psychological Services, Los Angeles

    Google Scholar 

  28. Army Individual Test Battery (1944) Manual of directions and scoring. War Department, DC: Adjutant General’s Office, Washington

    Google Scholar 

  29. Willison JR, Warrington EK (1992) Cognitive retardation in a patient with preservation of psychomotor speed. Behav Neurol 1992(5):113–116

    Article  Google Scholar 

  30. Banerjee G, Summers M, Chan E, Wilson D, Charidimou A, Cipolotti L et al (2018) Domain-specific characterisation of early cognitive impairment following spontaneous intracerebral haemorrhage. J Neurol Sci 391:25–30

    Article  Google Scholar 

  31. Bellebaum C, Daum I (2007) Cerebellar involvement in executive control. Cerebellum 6(3):184–192

    Article  Google Scholar 

  32. Mega MS, Cummings JL (1994) Frontal-subcortical circuits and neuropsychiatric disorders. J Neuropsychiatry Clin Neurosci 6(4):358–370

    Article  CAS  Google Scholar 

  33. MacPherson SE, Bozzali M, Cipolotti L, Dolan RJ, Rees JH, Shallice T (2008) Effect of frontal lobe lesions on the recollection and familiarity components of recognition memory. Neuropsychologia 46:3124–3132

    Article  Google Scholar 

  34. Matsumae M, Kuroda K, Yatsushiro S, Hirayama A, Hayashi N, Takizawa K et al (2019) Changing the currently held concept of cerebrospinal fluid dynamics based on shared findings of cerebrospinal fluid motion in the cranial cavity using various types of magnetic resonance imaging techniques. Neurol Med Chir 59(4):133

    Article  Google Scholar 

  35. Fotiadis P, van Rooden S, van der Grond J, Schultz A, Martinez-Ramirez S, Auriel E et al (2016) Cortical atrophy in patients with cerebral amyloid angiopathy: a case-control study. Lancet Neurol 15(8):811–819

    Article  Google Scholar 

  36. Schmahmann JD, Sherman JC (1998) The cerebellar cognitive affective syndrome. Brain 121(Pt 4):561–579

    Article  Google Scholar 

  37. Sexton CE, Mackay CE, Ebmeier KP (2013) A systematic review and meta-analysis of magnetic resonance imaging studies in late-life depression. Am J Geriatr Psychiatry 21(2):184–195

    Article  Google Scholar 

Download references

Funding

This work was undertaken at UCLH/UCL, which received a proportion of funding from Department of Health’s National Institute for Health Research Biomedical Research Centre’s funding scheme.

Author information

Authors and Affiliations

  1. Department of Neuropsychology, National Hospital for Neurology and Neurosurgery, Queen Square, Box 37, London, WC1N 3BG, UK

    Edgar Chan, Natasja van Harskamp & Lisa Cipolotti

  2. Department of Brain Repair and Rehabilitation, Stroke Research Centre, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Russell Square House, London, UK

    Edgar Chan, Yezen Sammaraiee, Gargi Banerjee, Andreas Flores Martin, Natallia Kharytaniuk, Lisa Cipolotti & David J. Werring

  3. National Hospital for Neurology and Neurosurgery, Queen Square, London, UK

    Simon Farmer, Peter Cowley & Parag Sayal

  4. Department of Haematology, University College London, London, UK

    Perla Eleftheriou & John Porter

Authors
  1. Edgar Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yezen Sammaraiee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gargi Banerjee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andreas Flores Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Simon Farmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Peter Cowley
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Parag Sayal
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Natallia Kharytaniuk
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Perla Eleftheriou
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. John Porter
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Natasja van Harskamp
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Lisa Cipolotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. David J. Werring
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Edgar Chan.

Ethics declarations

Conflicts of interest

The authors declare no competing interests.

Ethical approval

This study included anonymised data collected as part of standard care, in accordance with a Service Evaluation Agreement approved by the local Research Ethics Committee (National Hospital for Neurology and Neurosurgery).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chan, E., Sammaraiee, Y., Banerjee, G. et al. Neuropsychological and neuroimaging characteristics of classical superficial siderosis. J Neurol 268, 4238–4247 (2021). https://doi.org/10.1007/s00415-021-10548-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-021-10548-z

Keywords

Search

Navigation