The art of and importance of diagnosis

If you have NMO you don’t want to be diagnosed as having MS. #MSBlog #MSResearch

“This study highlights how important it is to see an experienced clinician to get an accurate diagnosis. Neuromyelitis optica (NMO), or optico-spinal MS as it is called in Japan, often mimics MS when it presents. NMOers have optic neuritis and myelitis; these attacks are typically devastating with poor recovery, but not always. The treatment of NMO is very different to  that of MS; DMTs for MS typically make NMO worse. Therefore if you get the wrong diagnosis and the wrong treatment you will be in trouble.”

“Please note that when this survey was done one-third of MSers had died from NMO; this mortality is very high. With modern treatments, none of which are licensed the mortality is usually lower than; i.e. steroids and azathioprine or mycophenolate, if that fails most of us use rituximab. You may find it interesting that we have no licensed treatments for NMO. This is because it is an orphan disease; too uncommon for large trials. This however may be changing with several pharma companies interested in developing treatments for NMO. Why? Money; the prices that can be charged for orphan drugs in the developed world are eye bogglingly large so watch this space.”

“Another interesting observation about NMO is that despite it being a relapsing-remitting condition it is not associated with a secondary progressive phase of the disease. This tells us that SPMS must have ongoing pathology in addition to focal inflammatory events; in other words focal inflammatory events that recover are probably not the whole story when it comes to secondary progression. This is why it is so important to develop drugs that are neuroprotective in MS.”

Epub: Papais-Alvarenga et al. The impact of diagnostic criteria for neuromyelitis optica in patients with MS: a 10-year follow-up of the South Atlantic Project.Mult Scler. 2013 Aug.

BACKGROUND: It is recognized that there is a particular geographic and ethnic distribution of neuromyelitis optica (NMO) among Caucasian and non-Caucasian populations.

OBJECTIVE: To review the diagnoses of NMOers whom were enrolled in the South Atlantic Project, a Brazilian multiple sclerosis (MS) survey performed from 1995-1998, and to identify NMO and MS case frequencies.

METHODS: They reviewed the data from a 10-year follow-up of MSers. To apply the current diagnostic criteria, the neurologists were asked to collect clinical and laboratory data from the medical records of study MSers treated from 1999-2009.

RESULTS: The spectrum of inflammatory demyelinating disease in 322 MSers (67% white; 33% African-Brazilian) was: 49 (15%) with NMO; 14 (4%) with NMO syndromes; 10 (3%) with acute disseminated encephalomyelitis (ADEM); one isolated tumefactive brain lesion; 249 (77%) with MS (151 with relapsing-remitting MS (RRMS), 70 with secondary progressive MS (SPMS) and 27 with primary progressive MS (PPMS)). Disability was more severe in NMO and PPMS. One-third of the NMOers had died.

CONCLUSIONS: The frequency of NMO was 6.8% in São Paulo and 20.5% in Rio de Janeiro, and mainly seen in persons of African descent, which strengthens the hypothesis of there being an ethnic association of this disease. We recommend that epidemiological studies on MS that were performed previously be reviewed again, to ensure more accurate diagnoses.

Other posts of interest:
25 Aug 2013
Michael BD, Elsone L, Griffiths MJ, Faragher B, Borrow R, Solomon T, Jacob A. Post-acute serum eosinophil and neutrophil-associated cytokine/chemokine profile can distinguish between patients with neuromyelitis optica 
05 Sep 2013
BACKGROUND: Multiple sclerosis (MS) and neuromyelitis optica (NMO) occasionally have an extremely aggressive and debilitating disease course; however, its molecular basis is unknown. This study aimed to determine a 
27 Apr 2013
Storoni M, Davagnanam I, Radon M, Siddiqui A, Plant GT. Distinguishing Optic Neuritis in Neuromyelitis Optica Spectrum Disease From Multiple Sclerosis: A Novel Magnetic Resonance Imaging Scoring System.
07 Mar 2013
Background. Brain lesions are common in neuromyelitis optica spectrum disorder (NMOsd) and may resemble lesions of multiple sclerosis (MS). Objectives. To describe the imaging characteristics of supratentorial lesions in 
25 Jan 2013
RESULTS: The mean time interval between symptom onset and development of optic neuritis and myelitis was 39.9 months in neuromyelitis optica (NMO). About 40% of patients with limited NMO would have fulfilled the 
20 Mar 2013
Epub: Matthews et al. Distinction of seropositive NMO spectrum disorder and MS brain lesion distribution. Neurology. 2013 Mar 13. OBJECTIVE: Neuromyelitis optica and its spectrum disorder (NMOSD) can present similarly 
08 Aug 2013
Purpose: To compare the retinal layer thickness of eyes with optic neuritis (ON) and that of control eyes and ON eyes with and without neuromyelitis optica (NMO) or multiple sclerosis (MS). Methods: Horizontal and vertical 
26 Sep 2012
BACKGROUND: Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disease of the CNS in which a pathogenic role of anti-aquaporin-4 (AQP4) antibodies has been suggested. Although AQP4 is expressed in 
17 Aug 2012
BACKGROUND: The effective treatment of neuromyelitis optica (NMO) with rituximab has suggested an important role for B cells in NMO pathogenesis. OBJECTIVE: To explore the antibody-independent function of B cells in 
22 Nov 2012
METHODS: MTX (12 mg/m(2)) combined with methylprednisolone 1 g as three monthly courses followed by three quarterly courses was administered during an observational multicentre open study including 51 consecutive 
30 May 2012
Varrin-Doyer et al. Aquaporin-4-specific T cells in neuromyelitis optica exhibit a Th17 bias and recognize Clostridium ABC transporter. Annal Neurol. 25 MAY 2012. Objective: Aquaporin-4 (AQP4)-specific autoantibodies in 
18 Feb 2012
Kleiter et al. Failure of Natalizumab to Prevent Relapses in Neuromyelitis Optica.Arch Neurol. 2012 ;69:239-245. OBJECTIVE: To describe first experiences with the integrin inhibitor natalizumab, given to patients with 
14 Apr 2012
METHODS: A total of 190 women with NMOSD were enrolled from 7 referral hospitals in 4 countries. The investigators reviewed medical records and used a structured questionnaire to investigate gravidity (number of 
27 May 2012
There is little agreement amongst neuropathologists regarding the timing and nature of oligodendrocyte loss in MS. The oligodendrocyte is the cell that makes myelin or the insulation around nerve fibres. This review describes 
17 Oct 2012
Neuromyelitis optica (NMO) is a chronic inflammatory disease of the CNS that is mediated, in part, by a self-reactive Ab against the astrocyte aquaporin-4 (AQ4) protein. In the current study, we examined the possibility and the 
14 Aug 2012
Epub: Sinnecker et al. Distinct lesion morphology at 7-T MRI differentiates neuromyelitis optica from multiple sclerosis. Neurology. 2012 Aug 1. OBJECTIVE: To investigate distinct white matter and cortical gray matter 
09 Dec 2011
“There are lessons here for both neurologists and MS’ers. (1) It is important to make the correct diagnosis of MS before starting treatment. (2) Fingolimod is unlikely to be effective in NMO. (3) NMO is a separate disease entity; 

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.


  • If there is likely to be a second pathology involved in secondary progression, why the hype around alemtuzumab? Surely alemtuzumab will only alter the outlook on ms if inflammation (or it's consequences) is the major driving force behind progression.

    • My bet is that if you blitz inflammation in SPMS, or PPMS, you will eventually get burnt out MS. The damage that inflammation causes takes months to years to play out, which is why we only saw positive effects of IFNbeta at 5 years in the Barcelona PPMS study.

      The problem is that progressive trials are too short; but who will pay for a 5 year study? I suspect burnt out MS is more likely to occur in younger MSers; i.e. you will only see burnt out MS emerge before the ravages of accelerated, or early, ageing kick in. Inflammation unfortunately reduces your brain reserve and hence you will see age related changes that occur in everyone appear at an earlier age.

      If I could give Genzyme some advice I would recommend they partner with TEVA to test alemtuzumab in SPMS and PPMS as an induction therapy and to then add-on laquinimod as neuroprotection. Who knows the combination may work? I can't think of a better combination at present; alemtuzumab the most effective anti-inflammatory and laquinimod the oral with the best neuroprotection data.

      What are the chances of Genzyme and Teva collaborating? I suspect zero.

    • Re: "You commented on other post that your alem delayed SPMS in your treated patients, not prevented SPMS."

      That is correct; it can't prevent SPMS as the MSers who are treated are already in the SPMS phase. Can it flat line SPSMS? Not in the short-term; Alasdair Coles has already published on this. However, the follow-up of this group of MSers was short and some of them may flat line after many years; we simply do not know this. Despite this data it does not mean that SPMS is non-inflammatory. To the contrary there is a lot of ongoing inflammation in SPMS; this is why I am promoting combination therapies.

    • " it can't prevent SPMS as the MSers who are treated are already in the SPMS phase"…

      Can you explain please? If I had first attack now I am in SPMS?

    • Don't get him started on the brain shred…If you had first attack and were progressing you would be PPMS or relapsing progressive if you have relapsing remitting course and then go progressive then SPMS. Will some nerve tracts go afte one attack, it is possible.

  • Patients with NMO never become progressive?? Does that mean they recover completely from attacks?

    Then NMO is a better disease to have than MS

    • No NMOers acquire their disability in steps from relapses with poor recovery. MSers acquire their disability both ways; poor recovery from relapses in steps and relentless progression that characterises non-relapsing progressive MS (SPMS & PPMS).

  • On the subject of diagnosis I am not impressed with how I was diagnosed or the 'limited' questions I was asked by the neurology registrar at my examination during my relapse. I needed him to ask me more questions as this was my first relapse (relapse onset). I guess that comes with experience and I really wished I was examined by a consultant. I had no knowledge of MS or even neurology at this examination so I did not know some things that happened to me were important to let him know. I at the time did not see it relevant. He just kept saying 'anything else' I didn't know what he meant at the time I should of said 'like what, give me an example?'.

    I am sorry to moan on this blog about it.

    The procedure was that I got a phone call a few days after my MRI scan to say I had a brain swelling and could get my steroid prescription from the GP in a few days as it would be faxed over. Due to my relapse or anxiety I had short term memory loss and forgot to tell him some very very important things during this phone call.

    I went to the GP surgery to get the prescription and the nurse did a 'very quick' UTI dipstick test. The GP was the one that gave me a diagnosis of 'lesions on brain which may or may not be MS'. She seemed unhappy to give me this diagnosis and said she thought it should be the hospitals job. I completely agree with her. With what I know now about my condition I would of appreciated being asked to return to the hospital to discuss my MRI results,be re-examined, given a thorough UTI check at the hospital as I was taking oral steroids. I was returning to my parents home 200 miles away to recover. I know now from doing my own UTI checks at home results are not always immediate. It does make me think if I need oral steroids again I would like the UTI check done at the hospital.

    • I've had similar experiences with Senior Registras and a Consultant for serious comorbidities. One healthcare assistant followed me out of the consulting room and told me to wait until she got a specialist Nurse to see me as I needed to be examined. I've just had a similar experience for another life threatening illness. There seems to be an attitude problem and doctors can't be bothered to read patient's notes. This has happened to me many times. All the senior registras I saw in the '80s are now consultants in major hospitals and they were very caring. something has changed not for the better.

By Prof G



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