Do you have high blood pressure?

Barts-MS rose-tinted-odometer  ★ ★ ★ ★ ★

Who knows their current blood pressure?

If you have MS you should know your blood pressure, your BMI (body mass index), your lipid status and whether or not you have impaired glucose tolerance or diabetes. In other words, all pwMS should have an annual health check outside of their MS clinic appointment to be screened for comorbidities. We know that pwMS have a higher chance of developing comorbidities that speed up worsening disability. This is why the holistic management of MS is so important. Preventing the development of comorbidities is part of our treatment strategy to maximise the lifelong brain health of someone with MS. Even if we can’t prevent you developing a comorbid disease then aggressively managing comorbidities will help improve MS outcomes. 

The substudy of the SPRINT hypertension trial (see below) shows that targeting a systolic BP of less than 120 mm Hg, compared with less than 140 mm Hg, was associated with a smaller increase in cerebral white matter lesion volume. This raises the question that if you have MS and are hypertensive should you be lowering your systolic blood pressure to less than 120 mm Hg or less than 140 mm Hg? I would suggest the former. Preventing new hypertension-related white matter lesions must be part of the treatment target for people with MS. It also makes it easier to interpret the annual monitoring MRI; we don’t want to escalate your DMT based on new vascular lesions. 

Please note that pwMS who have one of four comorbidities (smoking, hypertension, diabetes or dyslipidaemia) do much worse than pwMS with no comorbidities. On average, pwMS with comorbidities need to use a walking stick 6 years earlier than pwMS who don’t have comorbidities. This 6-year difference in disability outcomes is bigger than the treatment effect of interferon-beta. 

If you don’t know what your blood pressure it please make a point to see your family doctor or pharmacist or you can purchase or borrow a self-administered BP machine to check your own BP on a regular basis. This should be part of your MS self-management. 

SPRINT MIND Investigators for the SPRINT Research Group. Association of Intensive vs Standard Blood Pressure Control With Cerebral White Matter Lesions. JAMA. 2019 Aug 13;322(6):524-534. doi: 10.1001/jama.2019.10551.

IMPORTANCE: The effect of intensive blood pressure lowering on brain health remains uncertain.

OBJECTIVE: To evaluate the association of intensive blood pressure treatment with cerebral white matter lesion and brain volumes.

DESIGN, SETTING, AND PARTICIPANTS: A substudy of a multicenter randomized clinical trial of hypertensive adults 50 years or older without a history of diabetes or stroke at 27 sites in the United States. Randomization began on November 8, 2010. The overall trial was stopped early because of benefit for its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. Brain magnetic resonance imaging (MRI) was performed on a subset of participants at baseline (n = 670) and at 4 years of follow-up (n = 449); final follow-up date was July 1, 2016.

INTERVENTIONS: Participants were randomized to a systolic blood pressure (SBP) goal of either less than 120 mm Hg (intensive treatment, n = 355) or less than 140 mm Hg (standard treatment, n = 315).

MAIN OUTCOMES AND MEASURES: The primary outcome was change in total white matter lesion volume from baseline. Change in total brain volume was a secondary outcome.

RESULTS: Among 670 recruited patients who had baseline MRI (mean age, 67.3 [SD, 8.2] years; 40.4% women), 449 (67.0%) completed the follow-up MRI at a median of 3.97 years after randomization, after a median intervention period of 3.40 years. In the intensive treatment group, based on a robust linear mixed model, mean white matter lesion volume increased from 4.57 to 5.49 cm3 (difference, 0.92 cm3 [95% CI, 0.69 to 1.14]) vs an increase from 4.40 to 5.85 cm3 (difference, 1.45 cm3 [95% CI, 1.21 to 1.70]) in the standard treatment group (between-group difference in change, -0.54 cm3 [95% CI, -0.87 to -0.20]). Mean total brain volume decreased from 1134.5 to 1104.0 cm3 (difference, -30.6 cm3 [95% CI, -32.3 to -28.8]) in the intensive treatment group vs a decrease from 1134.0 to 1107.1 cm3 (difference, -26.9 cm3 [95% CI, 24.8 to 28.8]) in the standard treatment group (between-group difference in change, -3.7 cm3 [95% CI, -6.3 to -1.1]).

CONCLUSIONS AND RELEVANCE: Among hypertensive adults, targeting an SBP of less than 120 mm Hg, compared with less than 140 mm Hg, was significantly associated with a smaller increase in cerebral white matter lesion volume and a greater decrease in total brain volume, although the differences were small.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01206062.

CoI: multiple

What is end-organ damage?

Help! How do I manage progressive brain atrophy in a patient who is NEDA-3?

End-organ damage is a catch-all phrase for the degeneration of the brain; it occurs as part of the ageing process that some consider pathological and others as a normal fact of life. I have hinted that I consider it both because end-organ damage is potentially modifiable via lifestyle modifications and pharmacological interventions. If it was a normal process it should not be modifiable. How can you be more normal than normal? Making ageing a disease also has political ramifications, for example, it will almost certainly incentivise Pharma to develop treatments for ageing.

In MS end-organ damage is massively accelerated by the MS disease process itself, i.e. inflammation and demyelination, and from delayed downstream processes triggered by inflammation, for example, energy failure, microglial activation, ongoing inflammation driven by antibodies, possible slow viral infection and its consequences and comorbidities. It is clear that all people with MS will have end-organ damage, but what can we do about it? To be honest, apart from early treatment to prevent damage, we haven’t got an evidence base about how to manage this problem in MS.

As an example, I saw a patient earlier this week. He has relapsing-remitting MS diagnosed in the mid-2000s and started on interferon-beta (Avonex). He also has type 1 diabetes which he developed when he was 14 years of age, 8 years before he was diagnosed with MS. His diabetes was poorly controlled initially but is now well controlled on an insulin pump. He has renal (proteinuria), eye (retinopathy) and hypertension as complications of his diabetes. His hypertension is controlled on medication. He has been relapse-free and his MRI has not shown any obvious new lesions over the last 6 years; i.e. he is NEDA-3. He does not smoke, but he drinks between 3 and 4 units of alcohol per day. He was referred to me because he is sick and tired of injecting himself with interferon and he has heard of a new drug called ocrelizumab. He wants to be switched to it because is more efficacious and only give every 6 months. His treating neurologist said no, hence his referral to me for a second opinion.

When I went through his history it is clear he has had no relapses in the last 6 years and is fully functional and working full-time. I reviewed his MRIs and I agree he has no new lesions over the last 6 years, but he has developed quite profound and progressive brain atrophy over this timeframe; he is definitely not NEDA-4. What do I do?

Do I switch him from interferon-beta to ocrelizumab? Or do I leave him on Avonex, which is doing its job and rendering him NEDA-3?

If I do switch him to ocrelizumab, will it normalise his brain volume loss? Will he become NEDA-4?

What is causing his brain volume loss? MS, hypertension, diabetes, alcohol or something else?

Do I tell him about his gross brain atrophy, which he is blissfully unaware of?

Do I offer him a formal cognitive assessment to see if he has cognitive impairments? If he has a cognitive assessment and they come back abnormal, which they are likely to, how do I tell him? Will knowing he cognitively impaired affect his management?

Do I offer him a lumbar puncture to measure his spinal fluid neurofilament levels?

Do I recommend any add-on off-label treatments that may help?

Or do I just take the easy option and send him back to his neurologist with a recommendation to leave things as is?

Can I suggest we debate these issues over the next few days and I can then potentially do a live webinar on the issue of end-organ damage and how to handle the problem of progressive brain volume loss on DMTs when you are NEDA-3.

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