Friday, 29 May 2015

Headache, hmm?

Neurol Sci. 2015 May;36(Supplement 1):75-78.

Headache in multiple sclerosis and autoimmune disorders.

La Mantia L, Prone V.

The headache may be considered among the neuropathic pain syndromes of multiple sclerosis (MS). Several studies have showed that it is more frequent in MS patients than in controls or general population. Headache may occur at the pre-symptomatic phase, at clinical onset and during the course of the disease. Tension-type headache and migraine without aura are the most common primary headaches reported in MS patients. The disease-modifying therapies, such as interferons, may cause or exacerbate headache, although the new available treatments do not seem to increase the risk of pain. Pharmacological and not pharmacological approach may be considered in selected patients to prevent the risk of headache, ameliorate quality of life and increase the adherence to treatment.

Are headaches simply a nuisance, bad luck or an imprecation of divine punishment? It's a disease with 100% penetrance in the human population. 

The association between headache and MS ranges anywhere between 4 and 69% (the wide reported ranges are due to differences in study design, participants etc.) but it's still higher than in the control groups (by more than 50%).

The most commonly reported headaches according to this article are:
  • Tension-type headache - a dull ache across your forehead, or on the sides and back of your head
  • Migraine without aura - usually one-sided (but not always) throbbing headache associated with light sensitivity, noise sensitivity, nausea, irritability etc. 
They even report that there is a correlation with the type of MS - migraine is more commonly reported in RRMS, while tension type headaches are more frequent in progressive MS. 

Headache at onset of MS is considered a 'minor' symptom with frequencies of 1.6-28.5%, and wait for it...has also been reported in 'asymptomatic MS' or the so-called radiologically isolated syndrome/RIS.

What about the pathology? 

Headache during an attack of MS appears more likely if there is brain stem involvement, particularly a lesion in the periaqueductal gray matter (PAG) with migraine-like headaches.

What about DMTs?

Interferon-beta (IFN) has had more reports of headache than placebo, and to a smaller extent so has Copaxone, but not the newer drugs (natalizumab, fingolimod, tecfidera, teriflunomide).

So should we opt to scan people presenting with a migraine/tension type headache who also happen to be of the female gender? 

Over 50% of people with brain tumours experience headaches at some stage, but even here it's not considered routine practice...

ClinicSpeak: benign MS is a misnomer

Should we stop using the term benign MS? #ClinicSpeak #MSBlog #MSResearch

"The study below on benign MS illustrates a point that we have made many times before; benign MS is a very difficult call. A significant proportion of benign MSers have cognitive impairment and associated fatigue, depression and anxiety. Therefore is it correct to simply call someone as having benign disease based on the EDSS, when the EDSS is not a very good way of capturing the impact of MS early on? To diagnose someone as having benign MS is very difficult; it can only be done retrospectively after you have had the disease for 15 years or longer. Even after  waiting 15 years to diagnose MS the majority of people with benign disease will end up acquiring disability over time."

"The good news is that most of what we know about benign MS comes from natural history studies and with new and emerging treatments and treatment strategies (treat-2-target of NEDA) the proportion of MSers with benign disease will increase. It is our treatment aim to make everyone with MS have benign disease."

Epub: Gajofatto et al. Benign multiple sclerosis: physical and cognitive impairment follow distinct evolutions. Acta Neurol Scand. 2015 May 26. doi: 10.1111/ane.12442.

BACKGROUND: Benign multiple sclerosis (BMS) definitions rely on physical disability level but do not account sufficiently for cognitive impairment which, however, is not rare.

OBJECTIVE: To study the evolution of physical disability and cognitive performance of a group of MSers with BMS followed at an University Hospital Multiple Sclerosis Center.

METHODS: A consecutive sample of 24 BMS cases (diagnosis according to 2005 McDonald's criteria, relapsing-remitting course, disease duration ≥10 years, and expanded disability status scale [EDSS] score ≤2.0) and 13 sex- and age-matched non-BMS patients differing from BMS cases for having EDSS score 2.5-5.5 were included. Main outcome measures were as follows: (i) baseline and 5-year follow-up cognitive impairment defined as failure of at least two tests of the administered neuropsychological battery; (ii) EDSS score worsening defined as confirmed increase ≥1 point (or 0.5 point if baseline EDSS score = 5.5).

RESULTS: At inclusion, BMS subjects were 41 ± 8 years old and had median EDSS score 1.5 (range 0-2), while non-BMS patients were 46 ± 8 years old and had median EDSS score 3.0 (2.5-5.5). At baseline 16% of patients in both groups were cognitively impaired. After 5 years, EDSS score worsened in 8% of BMS and 46% of non-BMS patients (P = 0.008), while the proportion of cognitively impaired subjects increased to 25% in both groups.

CONCLUSIONS: MSers with BMS had better physical disability outcome at 5 years compared to non-BMS cases. However, cognitive impairment frequency and decline over time appeared similar. Neuropsychological assessment is essential in MSers with BMS given the distinct pathways followed by disease progression in cognitive and physical domains.

Dr Giles does Diagnosis

MS Society Press Release: World MS Day - Diagnosis Story

Survey reveals many people are misdiagnosed and
live in uncertainty for years before MS diagnosis

·        1 in 4 people with MS misdiagnosed with having a trapped nerve
·        1 in 10 people with MS told they'd had a stroke
·        39% of people with MS left waiting a year or more for diagnosis

DrGiles said in a comment
"This is important data; we need timely accurate diagnosis of MS. It is important also to consider the other side of the coin - those people who are given an incorrect diagnosis of MS, often from over-interpretation of non-specific MRI changes. Any push for faster diagnosis tends to risk over-diagnosis. At least one person has died from DMD complication and was found to not have MS.

You can watch Dr Giles making the surprise Diagnosis of Simon Donald on film.

Simon is one of the founders of an Comic called Viz and is currently a stand-up comic and was helping some people making a film about MS, when things went as he says "proper tits up"-Excuse the language.

Dr.Giles picked up Simon's MS that he didn't know he had, 
No scans, just knowledge!

Asthma and MS...Little effect on the disease course

Manouchehrinia A, Edwards LJ, Roshanisefat H, Tench CR, Constantinescu CS.Multiple sclerosis course and clinical outcomes in patients with comorbid asthma: a survey study.
BMJ Open. 2015 May 20;5(5):e007806. doi: 10.1136/bmjopen-2015-007806.

OBJECTIVE:To determine if comorbid asthma is associated with accumulation of multiple sclerosis (MS)-related impairment and disability.
METHOD:We sent a comprehensive questionnaire to a cohort of patients with MS and examined the association between comorbid asthma and reaching Expanded Disability Status Scale (EDSS) scores 4.0 and 6.0. Multiple Sclerosis Impact Scale (MSIS-29) scores were compared between patients with MS with and without comorbid asthma.
RESULTS:680 patients participated in our study of whom 88 (12.9%) had comorbid asthma. There was no difference in the prevalence of asthma between our MS cohort and the England general population (OR: 0.89, 95% CI 0.68 to 1.17). We did not observe a significant association between having asthma and the risk of reaching EDSS scores 4.0 and 6.0 (HR: 1.29, 95% CI 0.93 to 1.77, and HR: 1.33, 95% CI 0.93 to 1.89, respectively) after controlling for confounders. Patients with MS with asthma reported higher level of psychological impairments (coefficient: 2.29, 95% CI 0.1 to 4.49).
CONCLUSIONS:Asthma is a prevalent condition among patients with MS and it may contribute to the psychological impairment in MS. Although we did not observe significant association between comorbid asthma and physical disability in MS, it seems that the two conditions influence one another.

The aim of many immunologists is the drive a Th1/Th17 response towards a Th2 response. It is thought that Asthma is associated with a Th2 biased response. So what is the influence of having asthma and MS. Will a Th2-Asthma response slow MS. 

Well the answer is no, not that much. Most EAE experiments are not done for long enough for proper B cell responses to develop, so it is considered that a Th2 response should be desirable in two legged EAE (If you ask people to describe MS they tell you about EAE). However, it probable that both Th1 and Th2/B responses are undesirable and so far studies aimed at driving Th2 (B cell  promoting) responses in MS have yet to show the promise of that hoped.

This is the basis of the many studies, trying to give MSers parasitic worms, in the hope that it drives a TH2 responses such as in the TRIOMS (Germany) trial. The HINT (USA) and WIRMS (UK) trials should have been finished by now.  Do we know that has happened?