In October, the European Lupus Meeting was held in Venice. Professor Shoenfeld and I were asked to give the opening lectures at the conference. My talk was on “The Challenges of 2020”.
As far as Hughes Syndrome is concerned, there are still major challenges – the best anticoagulant, what to think when the tests are negative yet the clinical features strongly point to the diagnosis, and the screening for ‘sticky blood’ in pregnancy – to name but three.
Another ‘challenge’ concerns the causes (and treatment) of ‘funny turns’ in Hughes Syndrome – the topic of this month’s ‘patient of the month’.
Patient of the Month
Mrs L.B., aged 47, was admitted to hospital having had 3 seizures. They were witnessed by her daughter, who was with her, and who felt that they were epileptic.
Mrs L.B’s past history was complicated. She had been diagnosed several years earlier with Hughes Syndrome, having had a collection of symptoms including headaches, slurred speech, sleep disturbance and ‘funny turns’. During these episodes, she would develop ‘the shakes’ with movements of the hands and feet, muscle contractions and a feeling of ‘not being there’. Between episodes, she was reasonably well, though still complaining of fatigue and occasional severe headaches.
The diagnosis of Hughes Syndrome had been made some 10 years earlier, when investigations showed a deep vein thrombosis and positive aPL tests. She had been taking warfarin for 6 months following the DVT, but then stopped, and was now on low dose aspirin (irregularly).
In the family history, her mother and one sister had lupus, and an aunt was diagnosis with M.S.
On admission to hospital, Mrs L.B. developed a shaking attack – originally thought to be a rigor – secondary to infection. The urine test did in fact show a slight infection but blood cultures were negative.
During the course of her admission, she suffered several similar episodes. On those occasions, the movements appeared more ‘epileptic’ in the opinion of the neurologist.
A new set of investigations showed a normal MRI brain scan. However, an EEG (electro-encephalogram) showed prominent abnormal epileptic waves, including discharges from the temporal lobe of the brain. Her tests for ‘sticky blood’ (aPL tests) were positive.
During one of her turns, an interesting observation was made. She was given oxygen via an oxygen mask, with marked improvement. She was finally started on heparin injections with a view to starting warfarin. Success!
What is this patient teaching us?
A patient recently contacted NHS Choices website, asking why the many brain symptoms, such as mini-strokes, were always attributed to brain clots – especially as patients such as her had normal brain MRI.
I thought she had a fair point : my own view is that cerebral blood sludging is a more likely explanation than full blown clotting – for 2 main reasons: firstly, the normal MRI in so many cases, and secondly, the often full and dramatic resolution of the symptoms with warfarin or heparin.
The other lesson from Mrs L.B. is the importance of seizures in Hughes Syndrome.
Some 30 years ago, my registrar, Dr Charles Mackworth-Young and I wrote a paper suggesting that in lupus patients seizures were more common in those lupus patients with positive aPL tests. (1)
Since then, there have been many reports of the association. Two of my own cases stick in my memory.
The first was an American Diplomat’s wife who had mild lupus, but with severe epilepsy, the latter requiring up to 6 anti-epileptic drugs a day. Whilst in London, she developed a DVT (yes, she turned out to be aPL positive), was started on warfarin – with dramatic reduction in the frequency of fits. (2)
The second was a family tree of one of my Hughes Syndrome patients. She was an EEG technician by profession. During her training, she EEG tested 4 of her brothers and sisters. All 4 had abnormal EEG’s : temporal lobe epilepsy! (3)
The colleague who has contributed the most to this subject is my friend Dr Rolando Cimaz from Milan. In one study, he found that an amazing 20% of teenagers with idiopathic (not due to trauma etc.) epilepsy were aPL positive. (4)
Coincidence! Today I received this month’s volume of the journal LUPUS. The first article was an outstanding review entitled “Hughes Syndrome and epilepsy”, from the excellent research group in the American University Medical Centre, Beirut, Lebanon. (5)
As newer imaging techniques showing blood flow, oxygen uptake, and so on, are developed, we will certainly learn more about the mechanisms of brain manifestations of Hughes Syndrome.
Mackworth-Young C & Hughes GRV Epilepsy : an early symptom of SLE J.Neurol Neurosurg Psychiatry 1985 48: 185
2. Hughes GRV. Understanding Hughes Syndrome Springer. ISBN 978-1-84800-375-0 (Case 3 : Diplomatic epilepsy)
3. Hughes GRV. Hughes Syndrome/APS. 30 years on. LUPUS 2014 23: 400-406
4. Cimaz Review. Cimaz R, Meroni P, Shoenfeld Y. Epilepsy as part of SLE and systemic antiphospholipid syndrome (Hughes Syndrome). LUPUS 2006 15: 191-197
5. Noureldine MHA et al. Hughes Syndrome and Epilepsy : when to test for antiphospholipid antibodies? LUPUS 2016 25: 1397-1411
Professor Graham R V Hughes MD FRCP