A wet bank holiday. An ‘indoors’ day. Shopping? No. Go to watch Charlton Athletic (my wife’s favourite team)? Neither of us keen to get wet and cold. So, an April blog.
An interesting paper was published recently in the journal Rheumatology. In a collaborative study from eight centres in Italy, 959 lupus patients were divided into two groups – those who had suffered neuropsychiatric involvements and those without.
The two groups were then compared to assess whether any clinical or laboratory features cropped up more frequently in those with neurological involvement.
The findings were largely negative, but with one striking exception: antiphospholipid antibodies (aPL) were strongly associated (p<0.0001). Not surprisingly, stroke, in particular, correlated strongly.1
Over the years many groups, including my own team, have studied the effects of different antibodies on the brain. A number have had the spotlight on them, but hopes that they would prove diagnostically useful in diseases such as lupus have proved short-lived.
In 1983, the description of the antiphospholipid syndrome – related to, but separate from lupus, highlighted the importance of cerebral disease as a feature of the syndrome.2 As the years have gone by, the clinical links between APS/Hughes syndrome and the world of neurology have become stronger and stronger.
Not surprising therefore that those patients with lupus who are aPL positive (about 30-35%) have been found to have more neurological disease.
Clinically, these observations have important implications for the treatment of lupus.
When a patient is admitted to hospital with ‘cerebral lupus’, treatment is, rightly, aggressive, usually with steroids and immunosuppressive drugs. But what about the role of aPL and clotting?
In the parallel world of APS, the introduction of treatment (such as heparin) in patients with neuropsychiatric illness can be very, very striking, as in the following case of the month …
Case of the Month: ‘A weekend drama’
Mrs DP, a 54 year old nurse working in a GP group practice, was admitted to London Bridge hospital by the cardiologists with angina and a suspected heart attack. She had suffered from shortness of breath and chest pain for several months, and on admission, the tests showed possible myocarditis.
However, the picture became more complicated.
She had complained of increasingly severe headaches, ‘behaviour difficulties’ and very peculiar ‘seizures’. The level of consciousness fluctuated. A brain MRI showed 8-9 small ‘dots’ but nothing more widespread. Among the other tests run by the cardiologist was a blood test for aPL.
Positive.
So, late on Friday afternoon, I was asked to see the patient, as a possible case of APS. Certainly the odd cerebral and cardiac features could fit. So too could the MRI. She also had skin livedo (‘corned beef skin’). The GPs in her workplace confirmed the complexity of this patient’s history.
We decided to start her immediately on heparin – (low molecular weight ‘Fragmin’ by injection twice daily).
On Sunday morning the cardiologist called me at home. The patient was well, sitting up in bed with a cup of tea and chatting to her family!
Over the next few days the story became clearer. The patient, an excellent historian, recalled a lifetime tendency to headache and migraine, worse over the past year, worsening memory loss and bout of confusion, odd seizures, many witnessed by her husband, and slowly worsening chest pains and shortness of breath.
Now all better! In the words of one colleague: ‘a life-changing diagnosis’.
What is this patient teaching us?
Many lessons. Firstly, that Hughes syndrome can and does affect the brain.3 I passionately believe that one day the syndrome will be recognised as an important chapter in the neurology textbook.
Secondly, that despite the severity and the long history in this patient’s case, the response to anticoagulation can be immediate.
Thirdly, the syndrome of ‘sticky blood’ can deprive other organs of oxygen – in this patient’s case both the heart and the skin (livedo) were also clinically affected.
Finally, where next? As few weeks longer on heparin then almost certainly on to warfarin, with an INR in the high 3 range.
And we will be testing her relatives, a number of who have histories of seizures and migraine.
References
1. Govoni et al. Factors and comorbidities associated with first neuropsychiatric event in systemic lupus erythematosus: does a risk profile exist? A large multicentre retrospective cross-sectional study on 959 Italian patients. Rheumatology 2012 51: 157-168
2. Hughes GRV. Thrombosis, abortion, cerebral disease and the lupus anticoagulant. British Medical Journal 1983 287: 1088-9
3. Hughes GRV. Understanding Hughes syndrome: case studies for patients. Springer ISBN 978-1-84800-375-0
GP who does not agree with Prof Hughes.
Been to see Prof Khamashta...
Rheumatoid and Hughes
