Saturday, March 28, 2015

pearls on vaccines in MS patients

1.  Standard guidelines indicate use of a killed and not inactivated vaccine v. influenzae is safe, but it should not be given during a relapse.
2.  Response to vaccines is high in standard therapies, but two new oral vaccines have a slightly lower response:  teriflunomide in the 14 mg dose is effective in only 76 %  of one particular strain (v.about 90 %)
3.  Fingolimod was effective in only 54 % with weakness v. certain strains such as California strain.  However the incidence of influenza was comparable in patients and controls in this 2015 study published in Neurology.

Imaging characteristics of NMO-SD esp in brain; update

Kim et al.  MRI characteristics of neuromyelitis optica spectrum disorder: an international update.Neurology 2015; 84: 1165-1173
While the findings below are not considered pathognomonic, and do not even construe the "main" elements of the disease, they can be considered imaging pearls for NMO that may help differentiate it from  MS.
1.  Up to 46 % have involvement of the area postrema, which has been postulated as the port of entry in the CNS
2.  Callosal lesions occur in NMO SD but rather than being ovoid,  perpendicular, "Dawson's fingers" as in MS, have unique characteristics.  They are more likely periependymal, following the ependymal lining; they may be edematous and heterogenous forming a "marbled pattern,"; and may involve the whole thickness of the splenium in an "arch bridge " pattern. Clinical symptoms of callosal lesions have not been well described.
3.  Lesions involving the corticospinal tracts, unilateral or bilateral, that may be contigious and longitudinally extensive may occur, curiously, since the area is not rich in aquaphorin 4 receptor.
4.  Contrast enhancement in a marginated, subtle, multiple "cloudlike" pattern may appear.
5.  Optic nerve involvement tends to be more posterior, to involve chiasm and be bilateral
6. On MRS, myo-inositol is reduced compared to NAA in MS

More on risk of PML Annals article

The only published data on indices that I am aware of, is in the Annals publication ("Anti–JC Virus Antibody Levels in Serum or Plasma Further Define Risk of Natalizumab-Associated Progressive Multifocal Leukoencephalopathy", ANN NEUROL 2014;76:802–812). A couple of quotes that may be relevant to this discussion are pasted below. If anyone has information on PML in 'low titer positives' (index <0.9), I would appreciate receiving it. The official Biogen website, that gives updates on PML cases (, accessed today) has this to say: "As of Mar 3, 2015, there are 278 natalizumab-treated MS PML patients with pre-PML samples collected at least 6 months prior to PML diagnosis. Of these 278 patients, 275 (99%) tested anti-JCV antibody positive prior to diagnosis and 3 (1%) tested anti-JCV antibody negative." However, there is no information on PML in low-positives.

Quotes from Annals article:

"Using the predicted probabilities from the combined data sets, PML risk estimates were generated for anti-JCV antibody index thresholds of 0.9 to 1.5 (Table 2). For anti-JCV antibody–positive patients with no prior immunosuppressant use and an anti-JCV antibody index at or below thresholds of 0.9 to 1.5, the risk of PML was approximately 0.1 per 1,000 patients during the first 2 years of natalizumab treatment, and it ranged from 0.3 to 1.3 per 1,000 patients from month 25 to 48 and from month 49 to 72. For patients with no prior immunosuppressant use and an anti-JCV antibody index > 1.5, the risk of PML was approximately 1 per 1,000 patients during the first 2 years of natalizumab treatment, and ranged from 8.1 to 8.5 per 1,000 patients from month 25 to 48 and from month 49 to 72.
Twenty-five natalizumab-treated MS patients with no prior immunosuppressant use who developed PML had at least 2 pre-PML samples. For 24 of these patients (96%), all samples had an anti-JCV antibody index- > 0.9, and for 21 of 25 patients (84%), all samples had an anti-JCV antibody index > 1.5 (Fig 5). In 1 patient, 3 of 4 available samples had an anti-JCV antibody index- 0.9, 2 of which were collected within 12 months of PML diagnosis."

Friday, March 13, 2015

PLEX for central demyelination

Magana SM, Keegan M, Weinshenker BG, et al.,Beneficial plasma exchange response in central nervous sytem inflammatory demyelination.  Arch Neurol 2011; 68: 870-878
Authors from Mayo Clinic reviewed clinical documentation for PLEX for 153 patients in inflammatory CNS demyelination seen over 2 year period.  Diagnoses included NMOSD, probable or definite MS, monophasic ON, ADEM, shorrt segment TM, and CIS.
Ninety patients (59%) showed moderate or substantial clinical improvement at six months. 
Patients with preserve deep tendon reflexes had a fourfold chance of positive response to PLEX
Plex responders had a shorter median diseae duration but not affected by gender, EDSS at time of initial attack, or time from index event to initiation of PLEX.
Most patients responded quickly, with a median response noted byt he third exchange.  A small subset,six percent, responded late by day 60.  Patients with RRMS had highest PLEX response of any of diagnostic categories (75 %, p<.008).  Progressive MS patients had a lower response rate (30 %).
Radiographic features associated with response were ring enhancement of lesions(82 v. 54 % response for non ring enhancement) and mass effect (75 % v. 50 % for non masss effect MRI's).These two patterns had four fold and three fold,respecctive increased chance of respone over patients lacking these features.
NMO serologic status was not important in this study for PLEX response.
see also Llufriu , Castillo J, Blanco Y, Neurology 2009; 73:949=953 for another clinical trial supportig use of PLEX is certain patients with MS.
Also note that the average EDSS of the patients in this study, both responders and nonresponders was 8.

Sunday, March 08, 2015

Bowel regiment in MS

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.