Wednesday, June 04, 2014

ADEM pearls

old paper, useful insights
Menge T, Hemmer B, Nessler S et al  Acute disseminated encephalomyelitis: an update. Arch Neurol 2005; 62: 1673-1680
1.  Consider a temporal relationship to a vaccine or infection.  If vaccine, especially MMR, also polio and European tick borne encephalitis vaccination. Many organisms are related, but temporal relationship is almost always within 3 months.  Average latency however is 4-13 days.

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

Alochol protective against MS

Hedstrom AK, Hillert J, Olsson T et al.  Alcohol as a modifiable lifestyle factor affecting multiple sclerosis risk.  Jama Neurology 2014; 71: 300-305.
2 case control studies were combined looking at , in first, 745 cases and 1761 controls; and in the second 58 74 cases and 5246 controls.  There was a dose dependent inverse association between alocho consumption and risk of developing MS in both sexes.  Women with high etoh consumption had an odds ratio of 0.6, and men, 0.5 in EIMS, and was 0.7 in both sexes in GEMS.  Moreover the detrimental effect of smoking was higher among nondrinkers. 

antiMOG seronegative NMO

Kitley J, Waters P, Woodhall M, et al. Neuromyelitis optica spectrum disorders with aquaphorin-4 and Myelin-oligodendrocyte glycoprotein antibodies: a comparative study.
see Levy M. Does aquaphorin-4-seronegative neuromyelitis optica exist? (editorial) JAMA Neurology 2014; 71:271-2.
Authors of both studies ferret out a subtype of seronegative NMO that is actually yet another disease.   Anti MOG positve patients with clinical features of NMO have a slightly different phenotype with features of ADEM also.  This group encompasses young males with severe episodes with better recoveries that are more likely to be monophasic, sometimes with simultaneous or rapidly sequential optic neuritis and transverse myelitis.. AntiMOG patients also had more conus involvement on spine MRI and more involvement of deep gray nuclei on brain MRI.  There were no patients with both anti MOG and anti AQU4 antibodies.  anti MOG antibodies are available at Neuroimmunology Testing Service, Oxford, England for 30 pounds).  "n" of the study was 10 aq-4 patients and 9 MOG AB patients. 
More clinical information:  4/9 anti MOG and 6/20 AQU$ AB patients had ON as initial invoolvement or part of ; anti MOG had more bilateral ON involvement (75 v. 33 %); both had severe ON when it did happen.  12/20 AQU$ 4 and 9/9 antiMOG had spinal cord involvement initially; Transverse myelitis differed with more bladder involvement in anti MOG patients as iniital symptom (33 v. 0 %) and more late sphincter disturbance in NMO ab patients.  Brain MRI was more likley to be ADEM like in MOG ab patients (44 %) v. 0 % in NMO. 

cog research tidbit on ms

Types of memory loss in ms

Meta memory

Cognitive fatigue

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


misc adverse effects tysabri and fingolimod




Bulbous pemphigoid

Liver crisis

Treatment withdrawal a

Relapse on discontinuation



adverse effects tysabri and fingolimod misc




Bulbous pemphigoid

Liver crisis

Treatment withdrawal a

Relapse on discontinuation



MS Consortium notes 2014 on pathology of MS

Miscellany Consortium 2014


MRI pearls


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


MRI correlates


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

Differential diagnosis: 

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