Friday, March 13, 2015
Sunday, March 08, 2015
Bowel incontinence in MS occurs in two principal situations…(1) an augmented gastrocolic reflex (colonic motility with gastric distention) with postprandial urgency (may or may not sense the colonic movements) and (2) reflex bowel emptying when the rectum becomes full.
Getting the bowel to empty regularly and predictably is the best prevention for reflexive incontinence. Using a pad is important for smaller episodes and confidence. Carrying a change of underclothes/pants is important.
First, parous women may have pelvic floor abnormalities which increase the likelihood of incompetence of the sphincter and urology or gynecology should evaluate.
Second, most medications with anticholinergic actions depress the forcefulness of the reflexes and help to manage urgency.
I don't find a low residue diet helpful. The most helpful is regular BMs. We call this "a bowel regimen." It is similar to what is used for constipation.
History should include the number of BMs. If this is infrequent due to constipation, then augmentation with PEG is used in the dose which regularly will produce a daily DM (1/2-2 doses a day).
To assure regular emptying, each AM they are instructed to have a hot drink for breakfast, preferably coffee, and go to bathroom to have a BM after. They are to use a glycerin suppository for stimulation if it does not occur in a timely fashion. If this is not routinely successful, a Dulcolax suppository can be used.
Those with frequent episodes usually require pharmacotherapy to impair the reflex oxybutynin, hyoscyamine typically. A strong gastrocolic reflex may require using the bathroom on a schedule multiple times a day postprandially.
For those with really aggressive hypermotility and more watery stool situations, cholestyramine is the best strategy, and finding the right dose usually greatly improves the frequency. Loperamide usually is helpful only in the most severe diarrheal cases, but sometimes helps.
GI evaluation is often fruitless. After a colonoscopy patients are usually told there is nothing to do. However, bloody or painful stools, or severe constipation or diarrhea, should have GI review.
Tuesday, December 02, 2014
Thursday, November 13, 2014
Tuesday, November 04, 2014
Of 71 patients in MS clinic given dalfampridine, 5 had a history either of trigeminal neuralgia (TN) or altered facial sensation. One with altered facial sensation developed TN after starting dalfampridine x 18 months. Pain subsided when dalfampridine was stopped. Three other patients had marked worsening of TN after starting dalfampridine, became refractory to medicinal treatment, and in one case required surgery for pain control
Moral- use dalfampridine with caution in patients with preexisting TN.
response to a letter to editor.
Teriflunamide is the active ingredient of leflunomide.
Published literature has about 100 pregnancies with accidental exposure. There were 56 live births from 64 women with an average of 3 weeks of postconception leflunomide exposure, of which 95 % underwent rapid elimination. Three of 56 (5.4 %) had major structural defects , 47 % had 3 or more minor structural anomalies, and 35.7 % were delivered preterm. Exposed infants were significantly smaller at birth and postnatally.
Recommendation is that a woman on teriflunomide desiring pregnancy should stop medication untila safe leflunomide level is reached either by natural elimination (approximately two years) or a rapdi elimination procedure.
based on Langer Gould AM. The pill x 2: what every woman with multiple sclerosis should know. Neurology 2014; 82: 654-655
Monday, October 27, 2014
1. Mechanism is drug acts of S1P3 receptor as agonist, reducing the tight junction between the endothelial cells of the retinal capillaries. Fluid accumulates in outer plexiform layer and the inner nuclear layer resulting in swelling of the Muller cells of retina.
2. OCT is recommended at baseline, 3,6, months and then annually. LATE onset ME (>12 mo) HAS BEEN REPORTED
3. Risk is increased in diabetic, h/o uveitis, undergoing surgery eg. cataracts
4. Treatment is stopping drug; anti-inflammatory medications can be used
5. The BRB (blood retinal barrier) , located in the retinal pigmented epithelium and retinal capillaries, can also be injured by VEGF, angiotensin 2thiazolidinediones (rosiglitazones, pioglitazeones), taxanes (docetaxol, paclitaxel), tamoxifen, niacin, and interferons. Ocular drugs can cause ME including PG analogues (latanoprost, bimatoprost, travopost), epinephrine, beta blockers (timolol, betaxolol) and mechanical factors such as vitreomacular traction
6. ME was more common in MS patients with previous optic neuritis
7. Proposed mechanism is focal intraretinal microglial activation and inflammation resulting in retinal neuronal and axonal injury AND breakdown of the BRB, which may occur in conjunction with breakdown of the blood brain barrier.
8. Risk of ME is dose dependent; in pivotal trials the risk on the 1.25 dose was 1- 1.6 %; among those on the 0.5 mg dose it ranged from 0-0.5 %,
9. Age > 41 is an additional risk factor.
10. Clinical presentation can include reduced vision, contrast sensitivity, and altered color vision; occasionally metmorphopsia or micropsia, or relative or absolute scotoma. Diagnosis without OCT can be made from dilated fundus exam with slit lamp or contact lens; findings include elevation of retinal, intraretinal cysts as an altered light reflex esp. with green light, and late fluorescein leakage.
Wednesday, June 04, 2014
2. No sex preponderance in ADEM. Also, although it occurs most in children, adults of any age can ge the disease.
3. Measles vaccine associated ADEM is 10-20 / 100,000 whereas ADEM after measles encephalitis is 100 per 100,000.
4. Upper respiratory infections (URI's) with fever occur in 50-75% of cases.
5. Children present with fever and headaches, adults with motor and sensory deficits.
6. Bilateral optic neuritis appears to be associated with chicken pox and has a less polysymptomatic course.
7. 12.5 % of kids , and 37-58% of adults may have OCB's, these often are transient.
8. apl AB syndrome may mimic ADEM in kids
9. Flareups while tapering medication eg. steroids should be regarded as flare ups of the initial monophasic courese (multiphasic disseminated encephalomyelitis or MDEM) not as MS which is the chief dDx of ADEM
10. Authors propose pulse iv steroids for 3-5 days, followed by prolonged oral prednisone taper over 3-6 weeks. Second line is plasma exchange, third line is immunosupression, cyclophosphamide or mitoxantrone.
Monday, June 02, 2014
Types of memory loss in ms
Social emotional function
Mspt Rudick has iPad based testing self administered
Patients self report of symptoms correlate except for cognition have anosognosia
Social cognition measures WMO nonexistent
Std tests for research discount individual need for test
Miscellany Consortium 2014
1) T2 much better than flair in post fossa
2) Black holes can resolve sometimes; these are "active black holes"
3) Enhancement doesn't equal active lesions; consider eg. whether used image delay, whether received recent steroids, gad dose, fluctuating enhancement
4) Uspio may be better? Need 24 hour delay to image. Stay positive longer than gado
Pathology types and MRI pearls
type 1 associated with macrophages
Type 2 associated with complement deposition and antibodies
Type 3 associated with apoptosis
type 4 associated with mitochondrial injury
Patterns one and 2 sharp border; ring enhancing often is macrophages full of iron patterns; also hypointesne rims; Ring on afc correlates with hypo intense rings but not with gad ring enhancement
Pattern 3 mixed border, no enhancement
Late progression compartmentaluzed inflamm with no gado enhancement
Includes meningeal inflammation = sub pial and slow progression older lesions these are hard to see even with 8t machines
Some disease is due to mitochondrial activation with oxidative injury
Dir wasn't correlated with path till 2012
Patterns of enhancement diffuse modular ring enhancing
1, Adc maps ms v abscess/tumor dark ring arc pattern V.Isointense ring pattern
2. Rapid shifts of adc typical ms not abscess/tumor
3. Ring enhancement and rim enhancement and response to plasmapheresis and steroids with type one and two
4. Nmo brain lesions in two and three
Concept of heterogeneity across patients and homogeneity within patients key
Also different bio markers
Saturday, May 17, 2014
Thursday, April 17, 2014
Monday, January 06, 2014
Saturday, August 10, 2013
Thursday, July 04, 2013
Neurology 2013; 80"1529-33.
1. Current therapy related risk is 0.81 % but varies widely among countries. It still is current therapy in many parts of Europe with different protocols in different countries.
2. Therapy related leukemia is specifically acute promyelocytic leukemia (the "other" PML). This may be due to preferential attachment to DNA breaks at the PML gene site locus.
3. Genetic variants of dna repair genes BRCA 2 (rs1801406) and XRCC5 (rs207906) and detoxification enzyme CYP384(rs2740574) may predispose to apml. Combinations of first two lead to 50 fold increase in risk of MTX associated leukemia in MS patients.
4. Early MTX cardiotoxicity is associated with a rare ABC transporter genotype leading to increased intracellular MTX levels.
5. aPML is aggressive and often fatal within hours or days if NOT recognized, but a very treatable form of leukemia if recognized and diagnosed promptly. 80 % curable with all trans retinoic acid and arsenic trioxide together with anthracycline chemotherapy, which is true also for MTX related forms.
6. Presentations of aPML: bruising, petechiae, anemia, thrombocytopenia, infections related to neutropenia and immune dysfunction, lymphadenopathy and splenomegaly, and systemic symptoms including fever and weight loss. Leukocyte nadir occurs 10-14 days after treatment and returns after 21 days, monitoring is crucial.
7. Other tests that hav potential value in assessing include blood smear, aPTT, fibronogen, d-dimer, LDH, and bone marrow biopsy.
8. aPML may occur up to five years after therapy so vigilance in surveillance is indicated.
Monday, June 17, 2013
Sunday, February 10, 2013
Patients in literature (42) were generally managed with discontinuation and PLEX/IA. 17 patients had contrast enhancement at time of discontinuation (early PML-IRIS) and 20 developed it later(late PML-IRIS). load All patients developed IRIS. Among early IRIS patients, JC virus load increased tenfold, among late IRIS patients, load increased lesthan two fold. All patients had worsening EDSS after discontinuation of natalizumab, but early IRIS patients did far worse. Mortality was about the same in early IRIS and late IRIS groups 20-30 %, slightly worse in early group. Corticosteroid therapy was associated with better EDSS outcome/score.
Conclusion: PLEX may accelerate IRIS, corticosteroids may be beneficial and may require a larger study to confirm.
there are also 2 forms of IRIS in HIV literature
there is no effect of prior immunosuppression
mefloquine and mirtazepine did not seem to help although this was not purpose of study
adjuvant steroids help another iris like syndrome, TB meningitis in HIV negative patients that helps survival.
Friday, October 05, 2012
Fox et al. CONFIRM investigators. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. NEJM 2012; 367: 1087-1097.
DEFINE 1234 patients were randomized and received at least one dose of meds (BG 12 , 240 bid, BG 12 240 tid, or placebo), about 400 per group. Primary endpoint was number with relapse at 2 years. Secondary endpoints were ANNUALIZED RELAPSE RATE, TIME TO CONFIRMED PROGRESSION OF DISABILITY, AND MRI FINDINGS.
Results favored BG-12. Percent with relapses were 27 and 26 % in two BG 12 groups and 46 % with placebo, p<.001 for both. ARR was .17, .19, and .36 again favoring BG 12. Percent with confirmed disability was 16 %, 18 %, and 27 % respectively favoring BG 12. MRI was also better.
Patient selection: age 18-55, EDSS ranging from 0-5, one relapse clinically or by MRI in period before entry into study. 198 sites in 28 countries participated with 1:`1:1 randomization. Baseline characteristics were similar in patients. Patients could switch therapy if they completed 48 weeks of study or developed confirmed worse disability.Half in MRI study. 78 % completed study with similar rates of withdrawal in the 3 groups. Time to first relapse was 37 weeks (placebo), 87 and 91 weeks in 2 BG 12 groups.
Safety: key events were nausea, vomiting, abdominal pain, pruritus, flushing, and PROTEINURIA ( 12 %). 3 % had elevated LFT's esp first six months.
1430 patients were randomized, and patient 18-55, EDSS 0-5, one relapse or MRI change before initiation into study. 1:1:1:1 groups including bid and tid BG 12, placebo and glatiramer. Study went 96 weeks. Primary endpoint was ARR, secondary endpoints were (in an MRI subcohort) new and enlarging lesions, enlarging T1 black holes, proportion of patients with relapse, and proportion with disability progression at two years. Dropout rates were higher in placebo group.
ARR was 0.22, 0.2 and 0.44 favoring BG12 against placebo, and rate was .29 for glatiramer.
Study was not powered to compare BG 12 and glatiramer. Disability was not affected significantly in any group at 24 weeks. All three non placebo groups had better outcome on MRI for new T1 black holes, number of new and enlarging lesions, and gado enhancing lesions.
Exciting data. CANNOT compare BG 12 and glatiramer. Define but not Confirm showed benefit for disability. Both studies showed benefit on relapse rates, and MRI although MRI was subgroup analysis in both studies.
Saturday, September 29, 2012
Saturday, September 08, 2012
Cochrane analysis of placebo controlled trials 1995-2012. 5 trials, 3082 patients. IFN did not reduce disability progression, there was small decrease in relapses, cognition not studied. More treated than placebo patients dropped out. Conclusion: Only use IFN in selected patients with active disease to reduce risk of disabling superimposed relapses.
Comment (blogger). If patients are relapsing they have RRMS. SPMS is diagnosed and differentiated from RRMS as an art form.
Tuesday, September 04, 2012
Sunday, September 02, 2012
Tuesday, May 15, 2012
Methadone Dolophine® Opiate agonist / pain control, narcotic dependence
Tizanidine Zanaflex® Muscle relaxant
Wednesday, April 11, 2012
Saturday, February 11, 2012
Strong evidence suggest relapses can be triggered by infections, the postpartum period and stressful life events. Hormone fertility treatment may trigger relapses.
Disease progression may occur due to stressful life events,radiotherapy to the head, low levels of physical activity and low vitamin D levels. Smoking affects disease progression clinically and by MRI. TNF inhibitors induce exacerbation. GCF colony stimulator factor for stem cells induces worsening in 4/10 patients. Add on statin to Betaseron may trigger relapses, larger trial is underway.
Vaccinations against influenza, tetanus and hepatitis B appear safe as are surgery, general and epidural anesthesia, and physical trauma.
Associations with lower relapses include pregnancy, exclusive breastfeeding, sunlight and higher vitamin D exposure.
Childbirth does not increase relapse rate. Protective effect of ETOH remains to be confirmed.
Thursday, February 09, 2012
Thursday, December 01, 2011
Tuesday, November 29, 2011
Natalizumab vs interferon beta 1a in relapsing-remitting multiple sclerosis: a head-to-head retrospective study; Lanzillo R, Quarantelli M, Bonavita S, Ventrella G, Lus G, Vacca G, Prinster A, Orefice G, Tedeschi G, Brescia Morra V; Acta Neurologica Scandinavica (Nov 2011)
Background - No head-to-head study has been performed yet to assess whether natalizumab is more effective than classical immunomodulators in multiple sclerosis (MS). Aim - To retrospectively compare the efficacy of natalizumab vs IFN beta 1a SC (44 μg; Rebif(®) ) on clinical and radiological findings in two matched cohorts of patients with MS. Patients and methods - We retrospectively enrolled two cohorts of 42 patients (F/M: 35/7) with relapsing-remitting multiple sclerosis treated with natalizumab or IFN beta 1a for at least 12 consecutive months. Outcome measures were annualized relapse rate (ARR), changes in expanded disability status scale (EDSS) score, and number of contrast-enhancing lesions (CELs) at magnetic resonance imaging (MRI). Results - In both groups, the ARR in the 12 months of treatment was lower than in the 12 months before therapy (0.24 vs 1.50 in natalizumab-treated group, P < 0.0000; 0.55 vs 1.10 in IFN beta 1a-treated group, P = 0.0006), being the effect of natalizumab significantly stronger (P = 0.0125). EDSS reduction was significantly different between the two groups in favor of natalizumab (P = 0.0018). The frequency and number of CELs per patient were decreased in both groups. In the second year, the treatment affected ARR and EDSS progression in the two groups of patients similarly to the first year, whereas number of CELs decreased more significantly in natalizumab group (P = 0.008). Conclusions - After 12 and 24 months of therapy, natalizumab was more effective than IFN beta 1a SC on both disease activity and disability progression. Prospective head-to-head studies would be helpful to further evaluate the differences observed in the MRI outcomes.
Sunday, June 12, 2011
Study adding Tysabri to glatiramer-- safety trial. Results showed increased natalizumab antibodies, but safe otherwise. Efficacy was much better in combination group than in the GA alone group re MRI. 110 patients were randomized, half got GA + placebo, others GA + NAT. Took patients with active disease year before entry.
Bottom line-- idea of using steroids in any scenario for Nabs is based on dubious evidence.
Authors analyzed 35 patients with PML related to natalizumab. 25 survived. Survivors had lower age and EDSS on mean, and shorter time to diagnosis of PML. 86 % had unilobar or multilobar disease on initial PML brain MRI, whereas 70 percent of fatal cases has widespread disease on MRI. Disability scores (Karnofsky scale) among survivors was highly variable. 16/36/48 % respectively had mild, moderate or severe disability.
Almost all patients withdrawn from natalizumab got IRIS and were treated with i-c corticosteroids, in addition to plasma pheresis to removed natalizumab. They also received mirtazepine or mefloquine due to in vitro studies showing an effect on replication.
Tables show much less nonfatal PML in US v. Europe. Rate of nonfatal to fatal PML was, US: 3:8 in Europe 22:2. This is not discussed but I wonder if more nonfatal PML slips through cracks in US and is either not diagnosed or reported.
Posterior fossa PML was rare. Most patients had enhancing lesions.
Saturday, June 11, 2011
339 African American MS patients and 342 controls were compared. MS patients had lower vitamin D levels than controls, but the lower levels did not affect disease severity. The differences were explained by geography and climate, as well as ancestry.
Authors review >2500 relapses and find only 7 with relapse with EDSS >6 that did not recover. 2 of those were on interferons at the time. Two had a presentation of tumefactive MS. They concluded that the fear of sudden irreversible disability should not affect treatment decisions.
Monday, April 25, 2011
zoster myelitis-- history of shingles
paraneoplastic-- history of cancer
infective-helminth-- prior "Wells" syndrome, with eosiniphilia
cord AVM- history of worsening with Vasalva, singing, defecation, also check blood sensitive sequences and MRA cord
Sjogren's-- controversial, check CSF NMO as well as serum
B12 deficiency-- posterior cord
copper deficiency-- also posterior cord
stroke-- can affect almost any part of cord
multiple sclerosis/transverse myelitis-- check brain MRI
GBS/CIDP-- may be difficult to differentiate clinically, check nerve roots for radiculitis on MRI
CMV radiculitis -- in immunocompromised
Sunday, April 03, 2011
Thursday, January 06, 2011
Sunday, November 07, 2010
The MS-STAT trial: a phase II trial of high-dose simvastatin for secondary progressive multiple sclerosis: baseline trial profile; Chataway J, Anderson V, Chan D, Frost C, Hunter K, Kallis C, Greenwood J, Schuerer N, Alsanousi A, Nicholas R; Journal of Neurology, Neurosurgery, & Psychiatry (JNNP Online) 81 (11), e55 (Nov 2010)
Background Therapeutic options for secondary progressive MS (SPMS) are very limited. Simvastatin is an attractive drug with potentially anti-inflammatory (e.g., reducing leukocyte migration) and neuro-protective effects (e.g., up-regulation of the major cell survival protein bcl-2), in addition to being well tolerated. In trials of early stage MS it is undergoing trials as a single agent or in combination therapy with standard disease modifying treatments. This is the first trial in SPMS. Trial Overview Double-blinded/placebo-controlled (1:1) with 80 mg of simvastatin. Two-year follow-up. Entry EDSS 4.0-6.5. Brain atrophy rate as determined from T1-weighted volumetric MRI using the brain boundary shift integral is the primary outcome measure. Secondary outcomes include disability scores, neuropsychological assessments and immunological profiling. Results 408 patients were referred, 203 screen failures, 140/140 patients were randomised. Age 52 years (range 35-65), 68% female, MS duration 21 years (8) with a secondary progressive phase of 13 years (7). Median EDSS 6.0 (IQR 0.5). MSFC 10 m walk/s 23.6 (25.6); Nine-hole peg test/s 34.6 (13.2); PASAT/60 35.3 (14.2). MSIS-29ver 2.0 scores: physical 49/80 (11), psychological 20/36 (8), total 69/116 (14). All data as mean (SD) unless stated. Conclusion This trial is fully recruited and will report in late 2011. ClinicalTrials.gov, number NCT00647348.
Sunday, August 15, 2010
1. Terminology: D2 = ergocalciferol is obtained from vegetables and oral supplements. D3= cholecalciferol is obtained from UVB sunlight, oily fish and some fortified foods such as milk and bread. 25 (OH) D= calidiol, contains D2 and D3. 1,25 (OH)2D= calcitriol and is converted in kidney and other tissues by the one alpha hydroxylase gene.
2. Deficiency is caused by lack of exposure to sunlight, dietary deficiency or malabsorption. Measuring calcidiol is best measurement of body stores of 25 (OH) D total vitamin D and is best test for deficiency, whereas 25 (OH) D D2 and D3 is useful for monitoring to detect noncompliance, or malabsorption. In general the D content of food is low, and D levels come from sunlight and supplements.
3. 1,25 (OH)D can be falsely normal in vitamin D deficient patients due to hyperparathyroidism and thus should not be measured.
4. Reference ranges may vary based on geographic location, season, ethnic background, age.
5. Vitamin D toxicity has never been reported with a level less than 80, and usually requires over 140. Fear of toxicity is overblown. This is because calcitriol, the renal 1,25 OH D, feedbacks directly limiting its production via 24 hydroxylase gene. Calcitriol also feeds back on the PTH gene. The alternative result is inert metabolites of Vit D, including 24,25 calcidiol and 1,24,25 calcitriol.
6. Used but not clinically validated for severe Vitamin D Deficiency: loading dose of 50,000 weekly for 2-3 months, or tiw for one month. A minimum total dose of 600,000 iu predicts increasing the level to normal (>30). A lower dose is used for moderate deficiency. Maintenance of 800-2000 iu is needed to prevent slideback.
7. Powder D3 does NOT clog feeding tubes unlike D2.
Tuesday, August 10, 2010
Motor cortex stimulation for intractable neuropathic facial pain related to multiple sclerosis; Tanei T, Kajita Y, Wakabayashi T; Neurologia Medico-Chirurgica (Tokyo) 50 (7), 604-7 (2010)
A 33-year-old man presented with ongoing severe right facial pain and sensory disturbances caused by multiple sclerosis (MS). Neuroimaging demonstrated demyelinating lesions in the right dorsal pons and medulla oblongata. The pain was refractory to carbamazepine at 800 mg/day, gabapentin at 1800 mg/day, morphine at 30 mg/day, amitriptyline at 60 mg/day, and diazepam at 4 mg/day, along with twice-monthly ketamine (60 mg) drip infusions. The patient underwent motor cortex stimulation (MCS), resulting in>60% pain relief, reduction in the required doses of pain medications, and discontinuation of ketamine administration. MCS is effective for MS-related neuropathic facial pain.
Tuesday, July 20, 2010
Schröder A, Lee DH, Hellwig K, Lukas C, Linker RA, Gold R; Archives of Neurology (Jul 2010)OBJECTIVE: To describe a case of successful clinical management of natalizumab-associated progressive multifocal leukoencephalopathy (PML) and immune reconstitution syndrome (IRIS) in a patient with multiple sclerosis. DESIGN: Case report. SETTING: University hospital. Patient A 41-year-old woman with relapsing-remitting multiple sclerosis developed PML after 29 natalizumab infusions. INTERVENTIONS: Immediate plasma exchange was combined for removal of natalizumab with application of mefloquine and mirtazapine to limit viral replication and oligodendrocyte infection. A subsequent IRIS was treated with glucocorticosteroids. RESULTS: After 3 months of treatment, cerebrospinal fluid tested negative for JC virus. There was a favorable outcome, and the Expanded Disability Status Scale score remained stable at 3.5 compared with before PML. CONCLUSIONS: In the setting of early diagnosis and consequent treatment, natalizumab-associated PML can be well managed in some cases. This situation differs from the course of PML in other conditions, eg, after the application of depleting monoclonal antibodies, in which irreversible cellular effects are associated with very high mortality.
Friday, July 02, 2010
Contains tests with alternate forms and test-retest capability.
Processing speed/Working memory
Symbol Digit Modality Test (SDMT) equally good as PASAT as standalone
Learning and Memory
Brief Visuospatia Memory Test- Revised
D- Kefs Sorting Test- sorting cards, Trails, Tower, Design Fluency, Stroop
Visual perception/Spatial Processing
Judgment of Line Orientation
Verbal Fluency (COWAT)
Non Macfims-- office assessment
1 trial PASAT
Trails (public domain)
Mental control (days forward, backwards, serial 7's)
Cancellation test (public domain)
list learning, 10 common, easy, unrelated words, 3 trials, 20 minute delay with recognition trials (yes/no)
5-10 pictures use for each patient
COWAT equivalents (CFL, PRW, FAS)
semantic category fluency
Motor coordination/processing speed:
9 hole peg
SDMT written and oral (public domain)
Multiple sclerosis neuropsychological questionnaire (Benedikt et al., 2004)
15 items, MSNQ
Thursday, July 01, 2010
Consensus for definition of b-MS is those who are fully functional after ten years. Different systems are used to classify patients. Authors defined as EDSS < 3 after 15 years of disease duration.
Authors used Rao BRB and added Stroop test, using a cutoff as 2 SD's below Italian normals. Patients with 3 or more test failures were classified as cognitively impaired. Tests included SRT, SPART (spatial recall, 10/36 cutoff), PASAT, SDMT, WLG, Stroop.
Authors followed patients at a mean of five years, using "still benign" measure. Disability was EDSS>4, or increase of 1.5 if starting EDSS was zero, or increase of >1 point if starting EDSS was > 1 confirmed at six months. 31.8 percent of patients with "b-MS" were impaired at baseline cognitively. Additional 16 % failed one test and 19 % failed 2 cognitive tests at baseline. At followup, 43 % had EDSS progression of one or more points, confirmed. 18 % became "no longer benign," or "NLB." NLB subjects had more relapses during followup period, but not in year before, and related to male gender and number of tests failed. Also baseline T1 lesion volume was predictive.
Benedict RHB, Fazekas F. Beningn or not benign MS: a role for routine neuropsychological assessment? Neurology 2009; 73: 494-495. Authors mention BRB and MacFims, each having alternate forms that permit repeat testing every 2-3 years.
Wednesday, June 30, 2010
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
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.