Some of use with a long history of Migraine turn out to have Hughes Syndrome/APS, Antiphospholipid syndrome, Sticky blood etc etc. Many of us have had a very difficult route to diagnosis! Professor Graham Hughes based at the London Lupus Centre, London Bridge Hospital, writes a monthly blog, this one contains so much about migraine I felt it relevant to put on here.
One of my children attended the National Migraine Centre with a view to sorting their migraines, they did turn out to have Hughes Syndrome, as does another child and also myself and other relatives. I found attending the Migraine Centre very useful for ruling lots of things out and helping us in the right direction. The rest was my own detective work with building rather an alarming but interesting family tree.
Professor Graham Hughes November 2014 Blog:
November is true to itself – rain and dark skies. Fireworks lasting for weeks – Lucy, our Schnauzer, frightened to go out alone.
A number of our London Lupus Centre team travelled to Boston to present papers and posters at the annual American College of Rheumatology meeting.
For me, two other meetings in November proved memorable. A Midlands GP meeting in Northampton/Wellingborough attracted 300 GPs - a good opportunity for me to spread the word about the impact of Hughes syndrome in general practice. The meeting was held in an aircraft hangar – a ‘first’ for me – stimulating and enjoyable.
The second was a one-day meeting in Barcelona, an international bringing together of colleagues working in the field of antibody testing. Specialised, but so, so important in the widespread testing of antibodies in medicine – including antiphospholipid antibodies in Hughes syndrome.
Finally, good news on the ‘awareness’ front. This year, the international journal LUPUS published a special edition (volume 23, no.12, 2014) on Hughes syndrome – selected articles following the 14th international congress on antiphospholipid antibodies, held in Brazil in 2013, an unforgettable meeting of like-minded experts, brought together by Drs Roger Levy and Yehuda Shoenfeld.
For those wishing to delve deeper into the science of the antiphospholipid syndrome, can I strongly recommend this publication: lup.sagepub.com/.
Patient of the month
A patient’s journey.
Mrs S.L., aged 53, was referred by herself. That is to say she had seen a number of specialists and no firm diagnosis or treatment had resulted.
As a teenager, she had regular migraines, bad enough to be referred by her GP to a neurologist. A diagnosis of migraine was made and a trial of anti-migraine drug followed.
In her early 20s, she developed ‘glandular fever’ – a sore throat with neck glands. This illness “knocked her out”. She became listless with aches and pains, fatigue and sleep disturbance. In addition, she developed a cold circulation, affecting both the hands and feet.
The headaches continued and she found that her balance wasn’t perfect.
She was investigated by her GP, but her blood tests were normal. On this occasion, she saw a different neurologist, who arranged a brain MRI. Normal.
A new problem appeared – she found that she was slightly short of breath – even on relatively moderate exercise. There was some chest discomfort. She was referred to a cardiologist who found, on cardiac echo, a slightly leaky heart valve. No special treatment needed.
All along, the headaches continued and life was made more difficult by her aches and pains. A diagnosis of ‘fibromyalgia’ was added. A new drug was tried –Tri-imipramine – but this made her mouth and eyes very dry and was stopped.
Then came the ‘Eureka’ moment. Her sister, Jill, who lived in Scotland, came to stay. Jill had been diagnosed recently with Hughes syndrome and was doing well on aspirin. The symptoms were similar.
Here we go ………. the internet!
Mrs S.L. and her husband did their homework. It all seemed to fit.
She went back to her GP who was excellent. He confirmed to knowing next to nothing of Hughes syndrome (“I only know that it is a cause of recurrent miscarriage”), but was prepared to learn.
Mrs S.L. was referred to our clinic at London Bridge Hospital. The blood tests (mercifully) were positive. I say “mercifully” because so often they can be ‘borderline’ or even ‘negative’ despite the clear history.
Mrs S.L. was started on baby aspirin – with some improvement – not one hundred percent, however. We next prescribed my ‘heparin trial’ – a 3-4 week course of low molecular weight heparin – a course of daily injections designed to assess any response to such anticoagulant therapy.
The result was spectacular. No headaches, brain ‘clearer’. And, interestingly, a disappearance of the chest pains.
One year later, on daily warfarin tablets, with an INR ratio of 3.5, the patient is back in this world. A clinical success!
What is this patient teaching us?
Firstly, Hughes syndrome (‘sluggish blood supply’) can affect many organs, notably the brain and the heart.
Secondly, these patients often gravitate from clinic to clinic, seemingly getting nowhere.
Thirdly, migraine is an important symptom of Hughes syndrome, something the world of neurology is now appreciating.
Fourthly, (and discussed in previous ‘blogs’), two other conditions are often associated with Hughes syndrome – Sjögren’s syndrome (dry eyes and aches and pains – ‘fibromyalgia’) and hypothyroidism (a ‘lazy’ thyroid).
Finally, in this patient, the tests were positive, helping the diagnosis. But they can be negative. Listen to the patient! The clinical diagnosis carries far more weight than the blood tests.
Professor Graham Hughes Lupus Centre
London Bridge Hospital thelondonlupuscentre.co.uk
ps Professor Graham Hughes 2010 talk: lupus (2010) 19, 555-556
Antiphospholipid syndrome, migraine and stroke
It IS over a quarter of a centut•y since the descrip-tion of the antiphospholipid (Hughes) syndrome (APS). 1 2 This pro-thrombotic condition, charactcr-izcd by the presence of antiphospholipid antibodies (aPL), results in an increased tendency to thrombo-sis and, in pregnancy, to recurrent miscarriage and other obstetric complications.
Strikingly, APS can ant•ct both veins and arteries, the latter leading, for exan»lc, to myocar-dial infarction and stroke.
Thc brain appears to be particularly susceptible to the syndrome, with its attendant thrombosis and ischacmia, the neurological presentations ranging from memory loss to Inovement disorders, from atyp-ical multiple sclerosis to epilepsy. Additionally, some or these clinical associates or aPL may well have been under-recognized until recently. Forexample. the asso-ciation with seizures (including temporal lobe epilepsy) first recognized in 1985,• may well be substantial - a recent report suggesting that 20% ofcases ofidiopa thic teenage epilepsy were linked to aPL, for example.
However, the two most important clinical neuro-logical manifestations of Hughes syndromc arc Inigraine and stroke.
Migraine, in all its forms, is arguably (he com-monest clinical Inanifcstation of the syndrolne. Many Hughes syndrome patients presenting with thrombosis, transient ischacmic attacks (TTAs) or stroke at, say, the age of 40, give a history of severe headaches, often migrainous, dating back to child-hood, Interestinglve there is often a familv history of niigrainc, and a number of large family cohorts embracin; migraine, APS and stroke are now being
Attempts at quantifying the prevalence of head-ache and migraine in Hughes syndrome (and in lupus) are limited by the well known diffculties in classification, 9 This is doubly important as the links with cognitive impairment, in both lupus and in patients with antiphospholipid antibodies need
Correspondence 10: Graham Hughes, Head, The London Lupus
Centre, London Bridge Hospital, London SEI 2PR. UK.
The AuthÆt(s), 2010. Reftnts and co.ukfptirralspetgissioc.s.nav
clarification. For example, in a recent study of cog-nitive impairment in lupus, and its relationship to headache, Whitelaw and Spangenberg concluded
'it is only APS (Hughes) syndrome which
has bccn documented to produce impaired cogni-tive function in lupus'.
The cause of the headache is uncertain.
Howcvcr, one of the most striking clinical observa-tions is the often complete disappearance of the headaches when anticoagulation with heparin or warfarin is started, say, for a peripheral thrombo-sis, or with heparin prophylaxis in pregnancy.
This observation has led to the use of a 2—3-week therapeutic trial of low-molecular-weight heparin in some cases of APS in which increasingly severe headaches are a feature.
Stroke is now internationally recognized as an important manifestation of Hughes syndrolne the severity ranging from small TIAS to catastro-
phic fatal cerebral infarction.
What is the relative contribution of Hughes syn-drome to the huge medical social and economic problem of stroke?
Published figures vary, ranging from 7% of all strokes I to 41 % in a major collaborative American stroke study. 3 The latter study has, however, been criticised for a number of shortcomings including the reliance on single aPL assesynents.
An important study from Rome found that in a younger population (under 45) a striking one in five
Of all strokes were associated with aPl_,
If such estimates are correct (and despite flaws in the standardization of aPL testing, clinical experi-ence suggests that they are), then here we have a large group of individuals who, with a silnple blood test, could be identified as being at risk of stroke and in wh01n preventative anti-aggregant or antic-oagulant treaunent could be instituted,
Furthermore, a greater awareness of the fact that even on warfarin anticoagulation, patients with APS ale at greater risk of thrombosis than from bleeding, would lead to more appropriate treatment.
The discovery of the antiphospholipid syndrome has opened up new avenues for research in medi-cine and in epidemiology.
Antiphospholipid syndrome. migraine ard stroke G Hüt,e;
Two such avenues concern migraine and stroke.
Firstly, the health econolnic implications of stroke arc well known. Thc British Government is currently running an important awareness campaign on stroke. Heightened awareness of the contribution of APS, especially in younger victims (e.g. under 45) could bring tangible benefits 10 the economic and medical burden of stroke
Secondly, a clinical link betwccn migraine and stroke has long been suspected. 17 Recently, Schurks and colleagues found that the risk or ischaemic stroke in patients with migraine was magnified by the combination of smoking and oral contraceptive use and that it was Inost apparent in women under
It mav be that the antiphospholipid syndrone
is a significant missing link
Hughes GRV. Thrombosis, abortion. cerebral disease and the lupus anticoagulant. BM./ 1983: 287: 1088 1099.
Harris EN, Gharavi AE, Asherson RA, el al. Cerebral infarction in systcmic lupus. Associauon with anticardiolipin antibodies. Clin Exp Rheumatol 1984; 2: 51
3 DP. Antiphospholipid (Hughes) syndrome: An Overview. In: Hughes Syndrome Anliphospholipid Syndrome 2nd ed. Ed.
Khamashta MA. Springer-Verlag (London), 2006; 9-2'
4 Hughes GRV. Migraine, memory loss and 'multiple sclerosis.' Neurological features ol' the antiphospholipid (Hughes) syndrome.
Med 2003; 79: 81-83
5 Mackworth.young CG, Hughes (_iRV. Epilepsy. an early symptom of systemic lupus erythematosus. J Neurol Neurosurg Psychiatry
1985; 48: 185.
6 Cimaz R, Meroni PL, Shoenfeld Y. Epilepsy as part of systemic lupus crythematosus and systemic antiphospholipid (Hughes) syn-