523693 research-article2014
MSJ0010.1177/1352458514523693Multiple Sclerosis JournalD’Anna et al.
MULTIPLE SCLEROSIS MSJ JOURNAL
Case Report
The contribution of assessing cognitive impairment in radiologically-isolated syndrome (RIS): a single case report follow-up study
Multiple Sclerosis Journal 2014, Vol. 20(14) 1912–1915 © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1352458514523693 msj.sagepub.com
L D’Anna, S Lorenzut, A Perelli, B Zanchettin, M Valente and GL Gigli
Abstract Radiologically-isolated syndrome (RIS) is a recently-defined entity, described as the incidental discovery of lesions suggestive of multiple sclerosis (MS) on brain magnetic resonance imaging (MRI) scans demonstrating dissemination in space (DIS) without symptom expression and with a normal neurological examination. Recent studies demonstrate that RIS patients present similar features of cognitive impairment as MS patients. We describe a case of a RIS patient in whom investigating cognitive functions was a useful tool for diagnostic and therapeutic decisions. Keywords Brain lesions, case study, cognitive impairment, early treatment, multiple sclerosis, neuropsychological testing, radiologically-isolated syndrome Date received: 8 December 2013; accepted: 12 January 2014
Introduction In 2009, Okuda et al.1 introduced the term ‘radiologically isolated syndrome’ (RIS) to describe subjects whom show incidental brain magnetic resonance imaging (MRI) white matter lesions that are suggestive of multiple sclerosis (MS) and whom fulfill the Barkhof criteria for dissemination in space (DIS), with a normal neurological examination and no medical history consistent with MS. Cognitive impairment (CI) is a core feature of MS, affecting up to 70% of patients from the earliest stage of the disease, and may also represent a sensitive marker of brain damage.2 Recently, the similarity of the cognitive profile between MS and RIS became noteworthy.3 This case report aims to explore disease management and therapeutic issues in RIS by employing detailed neuropsychological examinations that can provide a better characterization of these asymptomatic subjects.
Case report A 47-year-old female patient was admitted to the Multiple Sclerosis Center, University of Udine, Italy after undergoing a MRI brain scan for recent onset of a headache. The patient was a right-handed woman with 13 years of schooling, a bank employee with an unremarkable prior medical
history, with the exception of recent onset of headache treated with Nonsteroidal anti-inflammatory drugs (NSAIDs). No previous history of alcohol nor substance abuse, prior psychiatric nor neurological disease were reported. Her family history was negative for any neurological or autoimmune disease. The MRI scan with T2-weighted images showed multiple periventricular, juxtacortical, infratentorial and cervical white matter hyperintense lesions; fulfilling the criteria for DIS, but not the criteria for dissemination in time (DIT)4 (Figure 1(a)). General and neurological examinations were unremarkable. Her autoimmune antibodies and viral profile test results were negative. Cerebrospinal fluid (CSF) analysis revealed the presence of oligoclonal bands and an Immunoglobulin G (IgG) Index of 3.32. Visual evoked potentials test (VEP) showed prolonged latency of P100 waves, bilaterally. Multiple Sclerosis Center, Neurology Clinic, University of Udine Medical School, Italy. Corresponding author: Lucio D’Anna, Neurology, University of Udine Medical School, Santa Maria della Misericordia University Hospital, Piazza Santa Maria della Misericordia, 33100 Udine, Italy. Email: [email protected]
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D’Anna et al.
Figure 1. (a) Brain and cervical cord MRI scan showing multiple periventricular (Dawson’s fingers), juxtacortical, infratentorial and cervical white matter hyperintense lesions; NPS examinations with (b) Trial Making Test B and (c) Rey Figure Copy Test, performed at baseline and after 1 year. MRI: magnetic resonance imaging; NPS: neuropsychological
The patient reported moderate memory impairment for the past 2 years, especially within short-term memory, and reported mild difficulties in executive functions. These deficits, with insidious onset, had a progressive course and remained a substantial mild source of handicap in her everyday working life. At baseline, the neuropsychological (NPS) examinations revealed a mild deficit in semantic language fluency and a mild deficit in visual-spatial abilities on Rey figure copy (either first copy or recall figure test). The patient was discharged with the diagnosis of RIS. After 6 and 12 months, her MRI scans and neurological examinations were unchanged. NPS testing performed after 1 year (Table 1) revealed moderate deficits in short-term memory on Corsi’s Test and in sustained attention/concentration, on the Trial-Making Test B (Figure 1(b)), Cognitive Estimation Task, Wisconsin Card-Sorting Test and on the Stroop Color Word Interference Test. She performed the Rey Figure Copy Test even worse (Figure 1(c)). On the basis of these results, we shared with the patient the decision to introduce an off-label interferon beta 1-a treatment once weekly. After 1 year, the patient presented double vision with internuclear ophthalmoplegia and a MRI
scan detected two new enhancing infratentorial and periventricular lesions, fulfilling the diagnostic criteria for MS.4
Discussion RIS is a recently-defined entity, described as the incidental discovery of lesions suggestive of MS upon brain MRI scans, demonstrating DIS without symptom expression and with a normal neurological examination.1 About 30% of RIS patients will experience MS during their 3-year follow-up.5 Information-processing speed, working memory, attention and executive functions have the most frequent cognitive impairments in MS patients, and have a great negative impact on health-related quality of life and on employment of these patients.3 Cognitive impairment is also an important factor in determining employment status in MS patients.6 Some existing randomized controlled trials indicate that interferon IFN β-1b and IFN β-1a are associated with modest cognitive improvement in patients with MS.7 Recent papers demonstrate that RIS patients could present the same cognitive profile as MS and clinically-isolated
1914
Multiple Sclerosis Journal 20(14)
Table 1. NPS examinations performed at baseline evaluation and 1-year follow-up evaluation. Cognitive domains and test
(Correct score) Baseline evaluation
(Correct score) 1-yr follow-up evaluation
Qualitative assessment
Spatial orientation Temporal orientation Language NAME (Novelli et al., 1986) Phonological Fluency (Carlesimo et al., 1995) Semantic Fluency (Novelli et al., 1986) Reading Writing Intelligence Raven’s Coloured Progressive Matrices (SPM38) (Spinnler and Tognoni, 1987) Short-term memory Short Spatial Memory Corsi’s Test (Orsini et al., 1987) Short Verbal Memory Digit Span Forward (Orsini et al., 1987) Working memory Digit Span Backward (qualitative) Verbal long memory Rey’s 15-word Test (Carlesimo et al., 1995) Immediate recall Delayed recall Story Recall (Novelli et al., 1995) Executive functions Attention matrices (Spinnler and Tognoni, 1987) Trial-making Test (Giovagnoli et al., 1996) TMT-A TMT-B Cognitive Estimation Task Error scores
5/5 5/5
5/5 5/5
(30.75/32)
(30.75)
Adequate Adequate Adequate
(27.9)
(33.3)
Adequate
(39)
(39)
Adequate
(31/48)
(34/48)
Adequate Adequate Adequate
(6)
(3.75)
Small deficit (down)
(5.5)
(5.75)
Adequate
4
5
(43.1) (10.5) (15.5/28)
(52.5) (11) (13/28)
(48.75/60)
(42.75/60)
(65’’) (80’’)
(80’’) Interrupted
(11.2 = 45° percentile)
Bizarreness scores
(2 = 70° percentile)
(18.2 = 95–100° percentile) (4 = 90° percentile)
Wisconsin Card Sorting Test, Modified (Nelson, 1976; Caffarra et al., 2004) Number of categories
1/6
0
Number of perseverative errors
(14.5)
0
(40.5) (18.5)
(41.5) (10.5)
Stroop Color Word Interference Test (Barbarotto et al., 1998) Fair condition Incongruous condition
Adequate Adequate Adequate Adequate Borderline (down) Adequate Down Compromise (down) Compromise (down) Compromise (down) Compromise (down) Adequate Compromise (down) (Continued)
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D’Anna et al. Table 1. (Continued) Cognitive domains and test
(Correct score) Baseline evaluation
Apraxia, perception and visual-constructional ability Poppelreuter-Ghent’s overlapping figure test (72/72) Shape Copy (9.3/12) (Carlesimo et al., 1995) Immediate recall (25/36) Delayed recall (10.25/36)
(Correct score) 1-yr follow-up evaluation
Qualitative assessment
(72/72) (9.3/12)
Adequate Adequate
(25/36) (19.25/36)
Compromise Adequate (improvement)
NPS: neuropsychological; TMT: Trial-making Test; Name: denomination.
syndrome (CIS) patients,2 and that cognitive impairment is a pejorative marker in converting to MS. This raises the question of the definition of neurological asymptomaticity and disability related to cognition, and its possible negative impact on employment and quality of life in RIS patients, too. Cognitive impairment influences the working capacity of MS patients and it could also affect RIS patients’ ability to work. This case report emphasizes the importance of investigating cognitive functions, in order to better identify some RIS patients suggestive of MS whom could benefit from earlier treatment with disease modifying drugs (DMDs). Based on our case report, we believe that the early identification and case-by-case decision to treat the best RIS patient subgroup could contribute to preserve their brain integrity and to reduce their risk of disease progression. NPS examination provides a better characterization of these ‘asymptomatic’ subjects, and it could be potentially useful for diagnostic and therapeutic decisions. Conflict of interest None declared.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
References 1. Okuda DT, Mowry EM, Beheshtian A et al. Incidental MRI anomalies suggestive of multiple sclerosis. The radiologically isolated syndrome. Neurology 2009; 800–805. 2. Lebrun C, Blanc F, Brassat D et al. Cognitive function in radiologically isolated syndrome. Mult Scler 2010;16: 919– 925. 3. Langdon DW. Cognition in multiple sclerosis. Curr Opin Neurol 2011; 24: 244–249. 4. Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald Criteria. Ann Neurol 2011; 69: 292–302. 5. Okuda DT, Mowry EM, Cree BA et al. Asymptomatic spinal cord lesions predict disease progression in radiologically isolated syndrome. Neurology 2011; 76: 686–692. 6. Rao SM, Leo GJ, Ellington L et al. Cognitive dysfunction in multiple sclerosis. Impact on employment and social functioning. Neurology 1991; 41: 692–696. 7. Amato MP, Langdon D, Montalban X et al. Treatment of cognitive impairment in multiple sclerosis: Position paper. J Neurol 2012; 260:1452–1468.
MSJ0010.1177/1352458514523693Multiple Sclerosis JournalD’Anna et al.
MULTIPLE SCLEROSIS MSJ JOURNAL
Case Report
The contribution of assessing cognitive impairment in radiologically-isolated syndrome (RIS): a single case report follow-up study
Multiple Sclerosis Journal 2014, Vol. 20(14) 1912–1915 © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1352458514523693 msj.sagepub.com
L D’Anna, S Lorenzut, A Perelli, B Zanchettin, M Valente and GL Gigli
Abstract Radiologically-isolated syndrome (RIS) is a recently-defined entity, described as the incidental discovery of lesions suggestive of multiple sclerosis (MS) on brain magnetic resonance imaging (MRI) scans demonstrating dissemination in space (DIS) without symptom expression and with a normal neurological examination. Recent studies demonstrate that RIS patients present similar features of cognitive impairment as MS patients. We describe a case of a RIS patient in whom investigating cognitive functions was a useful tool for diagnostic and therapeutic decisions. Keywords Brain lesions, case study, cognitive impairment, early treatment, multiple sclerosis, neuropsychological testing, radiologically-isolated syndrome Date received: 8 December 2013; accepted: 12 January 2014
Introduction In 2009, Okuda et al.1 introduced the term ‘radiologically isolated syndrome’ (RIS) to describe subjects whom show incidental brain magnetic resonance imaging (MRI) white matter lesions that are suggestive of multiple sclerosis (MS) and whom fulfill the Barkhof criteria for dissemination in space (DIS), with a normal neurological examination and no medical history consistent with MS. Cognitive impairment (CI) is a core feature of MS, affecting up to 70% of patients from the earliest stage of the disease, and may also represent a sensitive marker of brain damage.2 Recently, the similarity of the cognitive profile between MS and RIS became noteworthy.3 This case report aims to explore disease management and therapeutic issues in RIS by employing detailed neuropsychological examinations that can provide a better characterization of these asymptomatic subjects.
Case report A 47-year-old female patient was admitted to the Multiple Sclerosis Center, University of Udine, Italy after undergoing a MRI brain scan for recent onset of a headache. The patient was a right-handed woman with 13 years of schooling, a bank employee with an unremarkable prior medical
history, with the exception of recent onset of headache treated with Nonsteroidal anti-inflammatory drugs (NSAIDs). No previous history of alcohol nor substance abuse, prior psychiatric nor neurological disease were reported. Her family history was negative for any neurological or autoimmune disease. The MRI scan with T2-weighted images showed multiple periventricular, juxtacortical, infratentorial and cervical white matter hyperintense lesions; fulfilling the criteria for DIS, but not the criteria for dissemination in time (DIT)4 (Figure 1(a)). General and neurological examinations were unremarkable. Her autoimmune antibodies and viral profile test results were negative. Cerebrospinal fluid (CSF) analysis revealed the presence of oligoclonal bands and an Immunoglobulin G (IgG) Index of 3.32. Visual evoked potentials test (VEP) showed prolonged latency of P100 waves, bilaterally. Multiple Sclerosis Center, Neurology Clinic, University of Udine Medical School, Italy. Corresponding author: Lucio D’Anna, Neurology, University of Udine Medical School, Santa Maria della Misericordia University Hospital, Piazza Santa Maria della Misericordia, 33100 Udine, Italy. Email: [email protected]
1913
D’Anna et al.
Figure 1. (a) Brain and cervical cord MRI scan showing multiple periventricular (Dawson’s fingers), juxtacortical, infratentorial and cervical white matter hyperintense lesions; NPS examinations with (b) Trial Making Test B and (c) Rey Figure Copy Test, performed at baseline and after 1 year. MRI: magnetic resonance imaging; NPS: neuropsychological
The patient reported moderate memory impairment for the past 2 years, especially within short-term memory, and reported mild difficulties in executive functions. These deficits, with insidious onset, had a progressive course and remained a substantial mild source of handicap in her everyday working life. At baseline, the neuropsychological (NPS) examinations revealed a mild deficit in semantic language fluency and a mild deficit in visual-spatial abilities on Rey figure copy (either first copy or recall figure test). The patient was discharged with the diagnosis of RIS. After 6 and 12 months, her MRI scans and neurological examinations were unchanged. NPS testing performed after 1 year (Table 1) revealed moderate deficits in short-term memory on Corsi’s Test and in sustained attention/concentration, on the Trial-Making Test B (Figure 1(b)), Cognitive Estimation Task, Wisconsin Card-Sorting Test and on the Stroop Color Word Interference Test. She performed the Rey Figure Copy Test even worse (Figure 1(c)). On the basis of these results, we shared with the patient the decision to introduce an off-label interferon beta 1-a treatment once weekly. After 1 year, the patient presented double vision with internuclear ophthalmoplegia and a MRI
scan detected two new enhancing infratentorial and periventricular lesions, fulfilling the diagnostic criteria for MS.4
Discussion RIS is a recently-defined entity, described as the incidental discovery of lesions suggestive of MS upon brain MRI scans, demonstrating DIS without symptom expression and with a normal neurological examination.1 About 30% of RIS patients will experience MS during their 3-year follow-up.5 Information-processing speed, working memory, attention and executive functions have the most frequent cognitive impairments in MS patients, and have a great negative impact on health-related quality of life and on employment of these patients.3 Cognitive impairment is also an important factor in determining employment status in MS patients.6 Some existing randomized controlled trials indicate that interferon IFN β-1b and IFN β-1a are associated with modest cognitive improvement in patients with MS.7 Recent papers demonstrate that RIS patients could present the same cognitive profile as MS and clinically-isolated
1914
Multiple Sclerosis Journal 20(14)
Table 1. NPS examinations performed at baseline evaluation and 1-year follow-up evaluation. Cognitive domains and test
(Correct score) Baseline evaluation
(Correct score) 1-yr follow-up evaluation
Qualitative assessment
Spatial orientation Temporal orientation Language NAME (Novelli et al., 1986) Phonological Fluency (Carlesimo et al., 1995) Semantic Fluency (Novelli et al., 1986) Reading Writing Intelligence Raven’s Coloured Progressive Matrices (SPM38) (Spinnler and Tognoni, 1987) Short-term memory Short Spatial Memory Corsi’s Test (Orsini et al., 1987) Short Verbal Memory Digit Span Forward (Orsini et al., 1987) Working memory Digit Span Backward (qualitative) Verbal long memory Rey’s 15-word Test (Carlesimo et al., 1995) Immediate recall Delayed recall Story Recall (Novelli et al., 1995) Executive functions Attention matrices (Spinnler and Tognoni, 1987) Trial-making Test (Giovagnoli et al., 1996) TMT-A TMT-B Cognitive Estimation Task Error scores
5/5 5/5
5/5 5/5
(30.75/32)
(30.75)
Adequate Adequate Adequate
(27.9)
(33.3)
Adequate
(39)
(39)
Adequate
(31/48)
(34/48)
Adequate Adequate Adequate
(6)
(3.75)
Small deficit (down)
(5.5)
(5.75)
Adequate
4
5
(43.1) (10.5) (15.5/28)
(52.5) (11) (13/28)
(48.75/60)
(42.75/60)
(65’’) (80’’)
(80’’) Interrupted
(11.2 = 45° percentile)
Bizarreness scores
(2 = 70° percentile)
(18.2 = 95–100° percentile) (4 = 90° percentile)
Wisconsin Card Sorting Test, Modified (Nelson, 1976; Caffarra et al., 2004) Number of categories
1/6
0
Number of perseverative errors
(14.5)
0
(40.5) (18.5)
(41.5) (10.5)
Stroop Color Word Interference Test (Barbarotto et al., 1998) Fair condition Incongruous condition
Adequate Adequate Adequate Adequate Borderline (down) Adequate Down Compromise (down) Compromise (down) Compromise (down) Compromise (down) Adequate Compromise (down) (Continued)
1915
D’Anna et al. Table 1. (Continued) Cognitive domains and test
(Correct score) Baseline evaluation
Apraxia, perception and visual-constructional ability Poppelreuter-Ghent’s overlapping figure test (72/72) Shape Copy (9.3/12) (Carlesimo et al., 1995) Immediate recall (25/36) Delayed recall (10.25/36)
(Correct score) 1-yr follow-up evaluation
Qualitative assessment
(72/72) (9.3/12)
Adequate Adequate
(25/36) (19.25/36)
Compromise Adequate (improvement)
NPS: neuropsychological; TMT: Trial-making Test; Name: denomination.
syndrome (CIS) patients,2 and that cognitive impairment is a pejorative marker in converting to MS. This raises the question of the definition of neurological asymptomaticity and disability related to cognition, and its possible negative impact on employment and quality of life in RIS patients, too. Cognitive impairment influences the working capacity of MS patients and it could also affect RIS patients’ ability to work. This case report emphasizes the importance of investigating cognitive functions, in order to better identify some RIS patients suggestive of MS whom could benefit from earlier treatment with disease modifying drugs (DMDs). Based on our case report, we believe that the early identification and case-by-case decision to treat the best RIS patient subgroup could contribute to preserve their brain integrity and to reduce their risk of disease progression. NPS examination provides a better characterization of these ‘asymptomatic’ subjects, and it could be potentially useful for diagnostic and therapeutic decisions. Conflict of interest None declared.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
References 1. Okuda DT, Mowry EM, Beheshtian A et al. Incidental MRI anomalies suggestive of multiple sclerosis. The radiologically isolated syndrome. Neurology 2009; 800–805. 2. Lebrun C, Blanc F, Brassat D et al. Cognitive function in radiologically isolated syndrome. Mult Scler 2010;16: 919– 925. 3. Langdon DW. Cognition in multiple sclerosis. Curr Opin Neurol 2011; 24: 244–249. 4. Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald Criteria. Ann Neurol 2011; 69: 292–302. 5. Okuda DT, Mowry EM, Cree BA et al. Asymptomatic spinal cord lesions predict disease progression in radiologically isolated syndrome. Neurology 2011; 76: 686–692. 6. Rao SM, Leo GJ, Ellington L et al. Cognitive dysfunction in multiple sclerosis. Impact on employment and social functioning. Neurology 1991; 41: 692–696. 7. Amato MP, Langdon D, Montalban X et al. Treatment of cognitive impairment in multiple sclerosis: Position paper. J Neurol 2012; 260:1452–1468.
