Radiological isolated syndrome

NEUROLOGY 2009;72:800-805

criteria above

44 patients

mean time for those converting to CDMS was 5.4 years

30 percent converted to CDMS, the majority 8/11 with CSF positive bands. The band positive group also had 10/11 with radiographic progression

the biggest risk factor is gad positive MRI lesions

depression scales other scales for PD, AD and MS

http://www.mhsfopcls.com/downloads/ger_dep_scl.pdf Geriatric Depression scale

 

 

http://www.ibogaine.desk.nl/graphics/3639b1c_23.pdf  Beck Depression inventory- pref in Parkinson's disease

 

http://healthnet.umassmed.edu/mhealth/ZungSelfRatedDepressionScale.pdf  Zung SRDS

 

Other scales

http://www.nysaaaa.org/Caregiver_Forum/CaregiverForumErieHandout09.pdf caregiver burden assessment

 

http://www.nationalmssociety.org/for-professionals/researchers/clinical-study-measures/mfis/index.aspx

MFIS with link to MSQLI (Connie is this different than MSQOL and how?)

 

http://www.nationalmssociety.org/for-professionals/researchers/clinical-study-measures/index.aspx

link to links to many clinical tools in MS research

 

http://www.mdvu.org/library/ratingscales/pd/updrs.pdf  updrs and scwab (parkinson;s)

 

http://www.alegent.com/documents/Sleep_eval.pdf berlin and epworth sleep questionnaire

 

http://www.hospitalmedicine.org/geriresource/toolbox/pdfs/clock_drawing_test.pdf clock drawing and mini cog (= 3 word recall)

 

http://www.hospitalmedicine.org/geriresource/toolbox/pdfs/instrumental_activities.pdf Instrumental activities of daily livving (IADL)

http://www.hospitalmedicine.org/geriresource/toolbox/pdfs/phys_selfmain.pdf physical self maintenance scale

 

http://www.hospitalmedicine.org/geriresource/toolbox/pdfs/function_status_questionnai.pdf (last page is functional activities questionnaire)

 

http://www.hospitalmedicine.org/geriresource/toolbox/pdfs/painscales.pdf pain scale

 

http://www.mocatest.org/  Moca-- has links for multiple languages

 

http://www.neurotransmitter.net/alzheimerscales.html   link to MANY Alz assessment tools, behavior and otherwise a few linked below

 

http://strokecenter.org/trials/scales/blessed_dementia.html blessed dementia scale

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

MSQOL link

http://www.nationalmssociety.org/for-professionals/researchers/clinical-study-measures/msqol-54/download.aspx?id=261

More studies of cognitive dysfunction in MS

Prakash RS, Snook EM, Lewis JM, Motl RW, Kramer AF. Cognitive impairments in relapsing-remitting multiple sclerosis: a meta-analysis. Multiple Sclerosis 2008; 00: 1-12.

Used 57 studies with 3891 participants with 755 "effect sizes"
Cognitive deficits are reported in broad domains of memory, attention, executive function, and verbal fluency. One report suggested by subtype that PPMS had more problem with executive control, whereas RRMS had more significant memory related dysfunction.

"With exception of motor functioning and mood status, most effect sizes were in the moderate range" MS patients had more trouble with nonverbal than verbal intellectual deficits.
Attention-- most abnormal was selective / focused attention with SDMT, TMT, Stroop word and color reading more than measures of working memory and short term storage. Categories also included processing speed (abnormal), sustained attention/vigilance, executive control, short term storage capacity.

Memory and learning-- categories
verbal immediate recall
verbal delayed recall* key item that was abnormal among subcategories
verbal recognition-- not enough data, item eventually dropped.
visual immediate recall
visual delayed recall, visual recognition

All other categories were medium

Verbal function- normal
categories-- verbal fluency were more impaired than comprehension, verbal expression and discourse.
Other factors-- age > 40 was very important, females more than males. Education, disease duration, and EDSS not important EXCEPT for memory and learning

Motor tests
grooved pegboard, finger tapping, nine hole peg test

Paper 2: Chiaravalottti ND, DeLuca J. Cognitive impairment in multiple sclerosis. Lancet Neurol 2008; 7: 1139-51. review paper. Emphasizes processing speed, attention, executive function and long term memory. Refers to minimal assessment battery (see Benedict RH, Cookfair D , Gavett, R et al. Validity of the minimal assessment of cognitive function in MS. J Int Neuropsychol Soc 2006; 12:549-558. Also refers to re internet based testing, Younes M, Hill J Quinles J, Kilfuss M et al. Internet based cognitive testing in multiple sclerosis. Multiple Sclerosis 2007; 13: 1011-19.
Adds assessment of rudimentary oral motor function, since most tests are done orally.See Arnett et al. JINS 2008; 14: 454-462.

Objective, structured, standardised assessment of functional activity, designed by OT, resulted in executive functions performance test (Baum et al., Cognitive performance in senile dementia of the Alzheimer's type: the kitchen task assessment. Am J Occ Ther 1993; 47; 431-436) found correlation to cognition (Kalmar et al. Neuropsychology 2008; 22: 442-449) whereas subjective assessment of cognitive function correlates with emotional distress. Functional deficits are common including housework, driving, cooking, using public transportation.

Beatty et al. found five variables correlate with 49 % of variance in employment status in MS , 3 of which are cognitive (J Neurol Rehab 1995; 9: 167-173). Benedict found poor cognitiion especially on processing efficiency, verbal memory and executive function predicted vocational status (op cit).

Neuropscch screening test key: Benedict RH , Zivadinov R. Reliability and validty of neuropsychological screening and assessment strategies in MS J Neurol 2007; May 254: s 2 1122-1125.
Amato MP et al. The Rao's BRB and Stroop Test ; nornative values with age, education and gender corrections in an Italian population. Mult Scler. Dec 2006 12: 787-793.
Parmenter BA. Screening for cognitive impairment in multiple sclerosis using the Symbol Digit Modalities Test. Mult Scler Jan 2007 13: 52-57.


Components of BRB-- SRT
10/36 spatial recall test
SDMT
PASAT
Word list generation (20 minutes)

MACFIMS-- takes 90 minutes
COWAS
JLO
CVLT 2d edition
Brief visuospatial memory test
SDMT
PASAT
Delis-Kaplan executive function system scoring test

MS Cognitive Impairment

Possible Panel for Study

MSQOL
Beck or Hamilton Depression Scale
Fatigue Impact Scale
Cognition
Med list
Sexual dysfunction

Test Batteries
*Rao's BRB Brief Repeatable Battery (Neurology 1991; 41:685-691)
Above plus Stroop Color Word Test
MS Neuropsychological Screening Questionnaire
Minimal Assessment of cognitive function in MS

Individual tests
PASAT
Symbol Digit Modalities Test (adapted for use in MS)
California Verbal Learning Test
Brief Visuospatial Memory Test (revised)
Delis-Kaplan Executive Function Symptom, Sorting Test
Controlled Oral Word Association Test
Judgment of Line Orientation Test
Auditory Consonant Trigrams
WCST
Trails A/B
WMS Revised
Rey COmplex Figure
EDSS


Published studies
Aricept Christodoulou et al. CNS Drugs 2008; 22:87-97 and J Neurol Sci 2006; 245: 127-136.
Avonex-- benefit after two years see Fischer et al. Ann Neurol 2000; 48:885-892.
Betaseron-- small group study Barak et al. Eur Neurol 2002
Copaxone-- open label ext trial (Schwid et al. J Neurol Sci 2007) suggestive of benefit
COGIMUS (Cog in MS) Italian study prospective Italian study with cognition measured annually using BRB and Stroop

Post optic neuritis (Nilsson P, Rorsman I, Larrson EM, Norving B, Sandberg-Wollheim M. Cognitive dysfunction 24-31 years after isolated optic neuritis. Multiple Sclerosis 2008; 14:913-918. was case ascertainment study of 110 individuals, 86 of whom consented to followup 22 who did not have MS and who were alive underwent further testing. Most common abnormalities were WCST (exec function) and Trails A (attention) and Rey Figure. Less affected, BNT, verbal learning, verbal memory or verbal comprehension (Token Test). There was not much correlation with MRI findings.

Sources for MS Cognitive Screens

Computerized testing
Wilken JA, Kane R, Sullivan CL et al. The utility of computerized neuropsychological assessment in patients with relapsing-remitting multiple sclerosis. Mult Scler. 2003;9:119-127.

brief screening
Parmenter BA, Weinstock-Guttman B, Garg N, Munschauer F, Benedict RHB. Screening for cognitive impairment in MS using the Symbol Digit Modalities Test. Mult Scler 2007; 13:52-57.

also see
Benedict RHB, Cox D, Thompson LL, Foley FW, Weinstock-Guttman B, Munschauer F . Reliable screening for neuropsychological impairment in MS. Mult Scler 2004; 10: 675-678.

Suggest use of above with concurrent measures for depression and fatigue for minimal cost.

Once cognitive impairment is identified, can then use other measures to follow it These include The Brief Repeatable Neuropsychological Battery for MS (BRNB) see Rao SM. A Manual for the BRNB in MS. New York, National MS Society, 1991.

Or, The Minimal Assessment of Cognitive Function in MS (MACFIMS). JINS 200612: 549-558.

Former has more non English assessments

Purpose to detect worsening MS or non benign MS.

Possible Journal Club article: Portaccio E. et al. Neuropsychological and MRI measures predict short term evolution in benign MS. Neurology 2009; 73:498-503.

PML A Stochastic event before brain infection

per Dr Joe Berger's talk at AAN. A number of necessary events must occur

1. 80 % of individuals are infected with JC virus, virtually all by age 20.

2. Latent primary viral infection must occur, involving spleen, kidney, bone marrow, tonsil, oropharyngeal lymph nodes and other tissues. Controversial whether it is latent in brain. Virus appears incapable of replicating in brain. Must have receptor to allow virus to bind.

3. Infected cell must have NF 1X to allow virus to replicate

4. 98 base pair tandem repeat within nucleus probably within B cells must allow insertion to allow replication of virus within brain (b cells must activate)

5. Failure of immunosuppression in periphery and allow detectable JC virus in blood (see IgG antibody in blood suggesting its reactivated infection)

6. Periodic reexpression of JC virus in PBMC

7. Entry of JC virus into brain and allowance of productive oligodendrocyte function

8. Failure of immunoregulatory function in the brain

Natalizumab-- may cause release of B cells and ciruculate, premature and mature B cells and increased transcription factors resulting in a productive infection. Decreased immunosurveillance in brain. JC toxic circulating t lymphocytes are important. Also loss dendritic cells responsible for antigen presentation.

Rebif site reaction

Memantine transiently worsens MS

Villoslada P et al. Memantine induces reversible neurologic impairment in patients with MS.
30 patients underwent a one year randomized crossover trial with 30 mg memantine. Patients had poor cognitive scores and MS . The trial was halted after 9 patients due to blurred vision, fatigue, headache, increased muscle weakness, trouble walking/gait. Symptoms only occurred at maximum dose.

Early MRI in ON" Risk for disability

Swanton et al. Neurology 2009; 72: 542-550. (Queen's Square)
106/143 patients reached scheduled five year followup after being diagnosed with ON. 100 were evaluated clinically. At median 6 years, 48 % converted to CDMS 52 % did not. At baseline, the presence and number of spinal cord lesions and new T2 lesions at followup (odds ratio, respectively of 3.3, 1.94, 7.12) predicted higher disability. Also Gd+ lesions and number of infratentotial lesions at baseline were predictive.

Many factors were not predictive including age, gender, baseline EDSS, spectros/MTR measures, NOT baseline lesion number although lesion load at 5 years and increase from baseline was predictive.

ACT trial negative

Cohen et al. Neurology 2009: 72:535-541.

There were 313 subjects, no benefit of adding IVMP or MTX to interferon beta one alpha. Trend to less NABs. It was safe and well tolerated. There was a trend to benefit in the IVMP group.