Wednesday, June 30, 2010

Cortical lesions and atrophy associated with cognitive impairment in RRMS

Calabrese M, Agosta F, Rinaldi F, et al. (last author Filippi).  Arch Neurol 2009; 66:1144-1150.

Authors studied 70 patients with multiple sclerosis and 22 normal controls .  They used the Rao BRB and used a cutoff of 2 SD's below mean on at least one test of, version A of BRB to define cognitive impairment.  They also looked at T2 lesion volume, contrast enahncing lesion number, cortical lesions using double inversion recovery sequences, volume, and normalized grey matter volume.  Finding was that T2 lesion number and enahncing lesions were not important, but that cortical lesions, cortical and brain volume and gray matter involvement predicted cognitive impairment. 

Tests used in BRB were"  SRT and delayed recall, spatial and delayed recall (10/36 cutoff), PASAT 3 and SDMT, and word list generation.  See Camp et al, Brain, 1999 for normative values. (see article anyway). 

24 patients were listed as cognitively impaired.  The rate of impairment was, for SRT delayed, 12.9%; PASAT and word generation 10 %, SDMT 8.6 %, EDSS also predicted. 

Authors discussed the "cognitive impairment index" as discussed in Brain article above.  This is a continuous variable obtained by a grading system applied to each patient's score on each test, depending on number of SD's below mean normal.  Grade 0 means index was above mean for normal controls.  Grade 1 was given for mean to 1 SD below normal.  Grade 2 was 1-2 SD's  below normal.  Grade 3 was given for more than 3 standard deviations below.  The results for all tests were added to give an overlal measure of cognitive dysfunction.

Authors discussed that the CL (cortical lesion) number and volume correlated with CI index score, and deficits in attention, concentration, speed of processing, and memory. 

Saturday, June 26, 2010

Neuropsychological effects of interferons

Fischer JS, Priore RL, Jacobs LD et al.  Neuropsychological effects of interferon B-1a in relapsing multiple sclerosis.  Neurology 2000; 48: 885- 892.

Study looked specifically at Avonex to 166 patients 104 weeks apart.  The neuropsych battery was divided into Set A (information processing and learning/memory) ,  Set B ( visuospatial and problem solving), and Set C (verbal abilities and attention span).  Avonex benefitted A set, with a trend in B set and no effect on C.  Secondary analysis showed a treatment effect on time to worsening with PASAT. 

Subject selection-- disease duration at least one year, at least 2 relapsed in 3 years, and EDSS 1-3.5 inclusive.  age 18-55. Study was placebo controlled.  Actual tests used were , for Set A, signnificant group, CalCap Sequential reaction time (information processing), Ruff Figural Fluency Test error ratio, and CVLT Trials 1-5 (total).

Set B tests were WMS-R Visual Memory Span (forward), WCST perseverative responses, visual search number of trials, TOL % planning time. 

Set C tests were WAIS-R information, and digit span forward.

Secondary outcomes were RFFT error ratios, RFFT unique designs, CVLT trials 1-5 (total), PASAT processing . 

Results-- on set A, the CVLT test was most important.  On Set B, Tower of London was most important.  Set C was negative tests.  In secondary outcomes, slopes were correct direction in all variables, RFFT appeared significant, and  practice effects were noted in all groups. 

Authors contrast to 2 other studies of cognition with treatment for MS.  One was a copaxone study (Weinstein et al, Arch Neurol, 1999) which was negative, and one was for Betaseron, that showed an effect for visual memory  (Pliskin et al, Neurology, 1996).  However, neither of those was as good of a study. 

MIMS Study for Novantrone in MS

Hartung H-P et al.  Mitoxantrone in progressive multiple sclerosis: a placebo controlled, double blind randomised multicentre trial.  The Lancet 2002; 360: 2018-2025.

194 patients with worsening RRMS or SPMS were given MTX or placebo  q 3 months for 24 months (5 mg/meter squared).  at end, the treated group had a benefit in five clinical primary outcome measures:  change in EDSS, change in ambulation index, adjusted total number of treated relapses, time to first treated relapse, and change in standard neurological status. 

Shortened version of PASAT is effective discriminant in MS

Solari A, Motta A, Radice D, Mendozzi L.  A shortened version of the PASAT 3 is feasible.Multiple Sclerosis 2007

Authors studied PASAT in 105 persons with multiple sclerosis and controls using PASAT 3 regular and shorrtened version.  They used the first 20 items.  The first 20, 30 and 50 items of the PASAT 3 retained discriminant value for MS

Notes study did not norm for age (highly sensitive) or practice effect (important). 

Note:  A review of the PASAT Tombaughh TN Arch Clin Neuropsychol 2006; 21:53-76.

Effect of copaxone on fatigue in MS

Metz IM, Patten B, Archibald CJ et al.,The effect of immunomodulatory treatment on multiple sclerossi fatigue.  JNNP 20 04; 75: 1045-7. 

In Calgary 218 MS clinic studied patients with initially comparable levels of fatigue who were treated with glatiramer (copaxone) v. interferons using fatigue impact scale.  2x as many started on copaxone and 2x as many reported greater reductions in fatigue.  This was true for all MS patients and RRMS patients.  The difference affected total FIS, the physical and cognitive subscale but not the social subscale.  The authors used one SD as the cutoff. 

Cognitive dysfunction in patients with CIS or newly diagnosed MS

Glanz BI, Holland CM, Gauthier SA et al.  Multiple Sclerosis 2007; 13:   senior author Howard Weiner BWH

Authors studied 92 patients with CIS/new MS and fouund 49 % impaired on one or more tests of the battery.  There was not correlation with MRI measures of disease including T2 lesion volume, NAWM, grey matter volume or brain parenchymal fraction.

Tests given were Rao's brief repeatable battery including SRT, 10/36 Spatial Recall test, SDMT, PASAT, COWAT, CES Depression Scale.  PASAT, SDMT, and SRT were the clear tests that showed abnormalities in MS v healthy controls. 

Authors contrast their results to Achiron and Barak (JNNP 2003) who found visual learning and recall , COWAT and SDMT to be most abnormal tests.  Other studies were Feinstein (Brain, 1992; 115: 1403-15) and Callanan MM et al (Warrington) Brain 1989; 112: 361-74.   

Wednesday, June 16, 2010

main references for Zamboni procedure for MS

• Zamboni P, Menegatti E, Salvi F, et al. Intracranial venous haemodynamics in multiple sclerosis. Curr Neurovasc Res 2007;4:252–258.

• Zamboni P, Galeotti R, Salvi F, et al. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2009;80:392–399.

• Zamboni P, Galeotti R, Salvi F, et al. Endovascular treatment of chronic cerebrospinal venous insufficiency: A prospective open-label study. J Vasc Surg 2009; 50:1348–1358.