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.
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.
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.
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.
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
• 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.
Sunday, May 16, 2010
1. possible association of seminoma and demyelination disorder
2. dural av fistula lesions identified by stepwise progression and involvement of conus, angiography can miss it
3. Rabies case of Weinshenker-- rabies is increasing in bat population, catch the bat, give everyone a shot even if they don't have a bite, only have a week or so to get a shot
4. NMO CSF may be positive with negative serum studies, but is rare. Antibody arises in blood and leaks into CSF, does not get produced in CSF. Could be a question of CSF is cleaner with less noise of other antibodies in blood interfering with test.
5. Persistent black holes at onset is a good sign of non-ADEM; rarely if ever seen all enhancing lesions with ADEM more common to see none of lesions enhance.
2. Occurs post infection, infection may include VZV, EBV, HSV 6, measles, influenza
3. Acutely, all lesions enhance rather than being of different ages (MAY occur)
4. Pathologically perivenous inflammation with very little tissue or axonal destruction
5. Hurst's hemorrhaghic leuokoencephalitis is sometimes considered as part of spectrum of ADEM, with severe course, may be fatal, hemorrhage may be petechial, with pathological and MRI diagnosis and severe demyelination
6. Marburg's MS -- severe and unrelenting MS even within one year. Otto Marburg, 1906
7. Tumefactive MS--may be monophasic course or develop into MS, typical or otherwise
8. Balo's concentric sclerosis with concentric rings of demyelination alternating with remyelination, described 1927, variable course, more common in Southeast Asia, high level if inducible nitrous oxide synthase similar to hypoxia.
9. Isolated optic neuritis without MS--half may not progress to MS without associated MS lesions
10 CRION chronic relapsing inflammatory optic neuritis disease is restricted to optic nerves
11. NMO spectrum disease with isolated and recurrent optic neuritis
For above, treatment algorithm is five days of solumedrol, then plasma exchange (at Mayo Clinic) then cytoxan.
Saturday, May 15, 2010
2. NMO may have a central cord syndrome
3. Initial functinal score and a central lesion on MRI are predictors at outcome, as is systemic disease or NMO at outcome.
4. Paraneoplastic case with CRMP 5 in a 42 year old man with positive vep, cigar shaped faintly enhanicng lesions improved with removal of papillary thyroid cancer. One radiographic sign not well known is owl eye sign with 2 "eyes" suggests cancer or paraneoplastic.
5. Cord compression can produce abnormal signal mimicking transverse myelitis clue check axials, and clinically symptoms did not progress over 3 weeks. Signet ring pattern of enhancing signal is c/w compression
6. Case zoster leading to myelitis indistinguishable from NMO by MRI abnormalities. Infections that cause acute myelopathy include: Schistosomiasis (esp in Mideasterners), rabies virus, TB, lyme, syphilis, HSV, VZV, West Nile Virus, dengue, polio, coxsackie and Echovirus, actinomyces, blastomyces, >50 % none found, MAY HAVE OCB's
7. 71 yo woman with recurrent TM after 6 months, then paratonic spasms, TPO antibodies, letm, was NMO
8. ADEM can be NMO positive and turn out to be NMO
Summary- conclusions Algorithm: 1) is it compressive (subtle types included such as lipomatosis, spondylosis) 2) is it really a myelopathy (parasagittal meningioma, CIDP) 3) is it an acute presentation of a metabolic disorder (eg. B12 deficient patient exposed to nitrous oxide) 4) Is image quality and timing adequate? (too early, too late) 5) Is it functional?
* An MRI at any time showing dissemination in space (DIS) and showing 1 or more asymptomatic lesions enhancing and nonenhancing thus meeting criteria for dissemination in time (DIT) is sufficient to diagnose MS
* An MRI showing DIS but without enhancing lesions, or with all lesions enhancing (thus no DIT), would require a new MRI to demonstrate additional lesions
* An MRI at any time showing lesions but not DIT or DIS requires new MRI's
One DIS criterion: need one or more asymptomatic lesions in 2 of 4 locations considered characteristic for MS: juxtacortical (JC), periventricular (PV), infratentorial (IT), and spinal cord (SC).
Two DIT criteria: 1) presence of one or more enhancing and nonenhancing lesions irrespective of the time of the scan and 2) presence of a new T2 and/or Gd+ lesion compared to a previous scan, irrespective of the time of the scan
The above apply only to those with CIS, ie symptomatic patients.
Nocturia multiple NGB
increased energy requirements to move-- due to spasticity, balance
lots of drugs that contribute to fatigue
low vitamin levels, b12, D
temperature effects especially perimenstrual
effects of interferons. Try Naprelan, the long acting naprosyn, treximet,or pentoxifylline to prevent AE's before injections.
2. always get urology exam to look at pelvic floor after you have gotten PVR
3. Phasic spasms are treated differently than tonic spasms or restless legs, try levitiracetam
4. check ferritin, not just in restless legs patients along with vitamin D, thyroid
5. fampridine flattens decay curve of temperature effects, fatigue
6. Vyvanse given for fatigue and cognitive slowing-- works. hypertension uncommon but works
7. 4 AP the more truncal and postural instability, the likelier to respond to 4 AP
8. Hold 4 AP if you have a fever, uti, sepsis due to risk of seizure
9. aceto L carnitine double effect of amantadine on fatigue, 2 nice studies, 1-2 grams bid buy bronson's vitamins online cheap, may even be able to go off provigil or amphetamines
10. tizanidine occassionally causes formed visual hallucinations not always require stopping drug, eg. "Indian shaman visiting her, like having a doctor at home"
11. aerosolized ethyl chloride anesthetizes skin is best for injection pain.
12. Neuropathic sensations after sensory myelitis, MS "hug" (aka anaconda sign), sharp burning rhythmic oscillating pain after defecation and sexual intercourse ("real neurologists do "heads and tails"). tried levitiracetam, it helped, think of phasic spasticity and saw dramatic benefit. Thoracic squeezing continued clonazepam helped a little. Used belladonna and opiate suprettes (b & o supp) completetely resolved defecation spasms.
13. trigeminal neuralgia-- refractory-- suboccipital decompression first, then rhizotomy or gamma knife. What are you decommpressing? Decompress but also scrape and cut trigeminal root. Decompression works better when done as first procedure.
14. Causalgia on end of hand-- use topical compounded agents rather than systemic agents if topical and superficial-- compound almost any drug GBN, mexilitene/clonidine/lidocaine
15. Gait mechanics--swing limb advance is key causes toe drag, falling. Medicare now pays for many walk aid and similar devices (fes- functional electrical stimulators). prevent falls, decrease energy utilization
16. poor hip thrust due to weak iliopsoas, clonus, tonic and phasic spasticity, tight gastroc,
17. genu encurvatrum (hyperextension of knee during standing) cure with AFO. Dorsiflexion causes flexion of joint above.
18. Edema-- everyone with weakness has it. huge factor needs to be addressed buy at discountsurgicalstockings.com cheaply get 8-12 mm Hg "like a bilge pump" start at 15-20. ten dollars a pair. leg is lighter and movement is aided not carrying a gallon of water in each leg.
19. AFO pearls-- single piece (no articulation) is good for flail or dead foot. Hinged or articulated brace are preferred more like normal movement only works if patient has some control. FES is taking over for many. (Bioness or walkaid)
20. Walkers-- use all wheel or all rolling walkers not ones with "skis" likes U step walker because it has adjustable tension on wheel so patient cannot festinate and has laser light can pattern gait cycle
21. Pelvic obiquity hurts-- hip, gluteal girdle, takes energy, puts pressure on stance leg, AFO cures, also cures knee hyperextension. If single piece need to tell orthotist how many degrees of dorsiflexion (easier with articulated brace) start 5-7 degrees dorsiflexion with single piece
22. Some people with ballet foot needs to start with botox before AFO for it to work
23. Do 6 minute walk as well as 25 foot walk to test
24. Bone loss in men and women--at demarcation of EDSS of 4 and beyond. Get dexa scans every few years check femur hip and spine
25. Vitamin D goal is 60-80 not lower level
26. Dysautonomia in limbs (pain, cold, purple, edema) responds to ciolostazol (pletal) 50 bid or 100 bid affects platelets and relaxes smooth muscle. May work in Asa resistant strokes too. Viagra may also work for this, help acrocyanosis
27. baclofen less sedating than tizanidine,need to monitor lft's. Zanaflex is less sedating than tizanidine. May use at night.
28. hypertensive crisis may occur if stop tizanidine suddenly its an alpha two agonist big rebound effect
29. Dantrolene last choice can be hepatotoxic need to check, different mechanism, not gaba B or alpha 2 but works on sarcoplasmic reticulum it works sometimes.
30. Benzodiazepines are drug of choice for phasic spasticity usually clonazepam, some valium, and others GBN, levitiracetam
31. Botox for focal spasticity especially tight heel cords before bracing
32. Intrathecal baclofen can be dramatic-- use in patients you really know well and can trust to do adjustments for nine months realistic expectations are key.
33. Constipation--pay attention to fluid intake, physical activity, pelvic spasticity (benefit from antispasticity drugs or enemas), drugs that constipate, bulking agents, softeners, mild osmotics esp magnesium, avoid harsh laxatives, dulcolax or glycerin suppositories. Enemese plus has both glycerol, docusate (softening) and benzicaine for pain.
34. Bladder dysfunction ubiquitous even in pediatrics 100 %. Bladder stores to do need 2 things need. To store need competent sphincter annd relaxed detrusor, and to void need reflexive detrusor and ability to relax sphhincter. Detrusor hyperreflexia with closed sphincter is commonest type of neurogenic bladder. Symptoms are frequency, urgency, urge leaking, and nocturia. Dyssynergia of detrusor 2 types. Both DSD have tight sphincter. One has detrusor hyperreflexia, urgency, frequency and nocturia, other detrusor areflexia. This occurs with longstanding disease and leads to high post void residuals.Take history and get a post void residual and if its high send to urologist.If PVR is less than 100 treat, if its greater > 150 send to urologist. Couuld try relaxation, double void, triple void, vibrator, drugs like Cardura BEFORE intermittent catheterisation. Patch has 70 % reduction of side effects. Gel nique new rub on form of oxybutynin. Imipramine for enuresis. Alpha one agonism ( helps tighten sphincter). If can't get urine out use alpha blocker, such as flomax. These are sphincter drugs not bladder drugs. DDAVP most effective drug for nocturia. Only .1 to .4 at night to reduce urine and decrease voiding. Don't use in daytime. If have headache and confused, check sodium (hyponatremia). Catheters hurt urethra. Chronic-- consider suprapubic. Bricker procedure or ileoostomy effective. (diversion procedures)
35. intimacyinstitute.com and tootimid.com are 2 online sites to discuss sex
36. Eros clitoral device helps sensation, lubrication, threshold to orgasm its 400 dollars or so. Eroscillator is wall powered three speeds. Wall powered is better need high intensity to get thresholds. Libigel is hormone therapy for women not yet approved.
Sunday, May 09, 2010
glioma (don't biopsy these patients deteriorate over weeks to months not days)
Monday, April 26, 2010
• For each statement, please circle the one number that best describes your degree of limitation.
• Please answer all questions even if some seem rather similar to others, or seem irrelevant to you.
• If you cannot walk at all, please tick this box.
In the past two weeks, how much has your MS ... Not at all
Quite a bit
1. Limited your ability to walk? 1 2 3 4 5
2. Limited your ability to run? 1 2 3 4 5
3. Limited your ability to climb up and down stairs? 1 2 3 4 5
4. Made standing when doing things more difficult? 1 2 3 4 5
5. Limited your balance when standing or walking? 1 2 3 4 5
6. Limited how far you are able to walk? 1 2 3 4 5
7. Increased the effort needed for you to walk? 1 2 3 4 5
8. Made it necessary for you to use support when walking indoors (e.g., holding on to furniture, using a stick, etc.)? 1 2 3 4 5
9. Made it necessary for you to use support when walking outdoors (e.g., using a stick, a frame, etc.)? 1
2 3 4 5
10. Slowed down your walking? 1 2 3 4 5
11. Affected how smoothly you walk? 1 2 3 4 5
12. Made you concentrate on your walking? 1 2 3 4 5
Please check that you have circled ONE number for EACH question
© 2000 Neurological Outcome Measures Unit.