The brain is particularly susceptible in APS patients, and it can protest in a variety of ways, including:
Headache and migraine
One of the most common features of APS is recurrent headaches – often migrainous and sometimes accompanied by flashing lights, zigzag patterns, nausea and vomiting.
One recent study of 1,000 APS patients from Europe reported that migraine headaches occurred in up to 20% of people with APS.
With APS patients, migraines often start in the childhood or teenage years, then sometimes disappear only to return during the patient’s 30s and 40s. Migraines appear to be more prevalent in female patients with APS who also have lace-like rashes and arthritis. Other studies have suggested that APS headaches can be associated with a prior history of stroke.
There are indications that some migraine sufferers may have antiphospholipid antibodies (aPL) and that, once diagnosed with APS, the patient’s headaches and migraines often respond to treatment with aspirin and migraine treatments. If untreated, the migraines can become increasingly severe and frequent, sometimes resulting in hemiplegic migraines that can mimic a TIA or stroke.
Because of the increased risk of bleeding, blood-thinning treatment for headaches with warfarin is not recommended, especially in older patients. However, patients who have had to start warfarin because of a major blood clot often find that their headaches improve.
The exact cause of APS headaches remains unknown. One preliminary study has suggested that they could be the result of abnormal platelets (the smallest circulating blood cells) causing an imbalance of nerve signalling molecules that disrupt normal blood vessel function in the brain.
Dr Yu (Ray) Zuo, who is an Assistant Professor in the Division of Rheumatology at the Department of Internal Medicine, University of Michigan, has shared with us an article he has written on APS and headaches and has kindly written an introduction:
"My name is Ray Zuo. I’m an Assistant Professor and a rheumatology consultant at the University of Michigan in the USA. Apart from managing over 200 APS patients in my clinic, I’m also a physician-scientist with a research focus on the pathogenic role of neutrophil extracellular traps (NETs) and autoimmunity against NETs in various thromboinflammatory diseases such as APS and most recently, COVID-19.
While blood clots and pregnancy complications are well-known features of APS, in our daily clinical practice, APS is much more complex and represents a disease spectrum. Many APS patients have “non-traditional” manifestations, either alone or in addition to the well-known features such as blood clots. Among those, APS headache is frequently brought up by my patients. In this article, I discuss headaches associated with APS and strategies that may help you manage them."
You can read Dr Yu Zuo's article in full here.
Memory loss affects many people with APS, who often have difficulty thinking clearly and describe the sensation as ‘brain fog’.
Memory loss can range from mild, such as difficulty finding words and forgetfulness, to severe, when people slur their speech or forget well-travelled routes. Some patients taking warfarin because they have had a blood clot will often know when their INR has dropped and is too low as the ‘brain fog’ returns.
The cause of memory loss in APS patients can sometimes be a result of strokes and/or TIAs. Still, it is also possible that antiphospholipid antibodies can damage the brain without causing a stroke or TIA. Blood-thinning treatment with warfarin may be necessary for patients with memory loss due to having had multiple strokes, but warfarin is not used to treat ‘brain fog’ on its own because of the risks of bleeding.
There is an excellent guide to coping with brain fog published by Lupus UK.
Balance problems and dizziness are very common in APS patients, and some people complain of a constant feeling of giddiness. Naturally, this is dangerous and can lead to accidents.
In some cases, balance problems can come on suddenly and are often misdiagnosed as labyrinthitis, Ménière's disease or vertigo. Some patients are unnecessarily referred to Ear, Nose and Throat (ENT) units. It is also increasingly being recognised that various middle ear symptoms, particularly tinnitus (a ringing in the ears), can occur as a result of APS.
Seizures and spasms
Impaired circulation to parts of the brain can sometimes lead to seizures varying from epileptic seizures to jerks and spasms. A single fit or a series of epileptic seizures can occasionally be the first manifestation of APS, a subject that is being increasingly investigated.
Other involuntary convulsions caused by APS range from jerking movements (tics, twitches or spasms) to rare cases of chorea, historically referred to as St Vitus’ Dance, which is characterised by rapid, uncoordinated jerking movements affecting the face, feet and hands primarily. These abnormal movements often cease when anticoagulation treatment is started.
This is the most severe neurological symptom associated with APS. Strokes develop when a blood clot (known medically as a thrombosis) blocks the supply of blood to the brain. Unfortunately, it is the first sign of the condition for 13% of people with APS. The brain needs the oxygen and nutrients provided by blood to function correctly. If the supply of blood is restricted or stopped, brain cells begin to die, leading to brain damage, some degree of disability and possibly death.
Stroke is usually associated with the older population, but with APS, it usually occurs among young adults years earlier than would be expected. Approximately 1 in 6 cases of all young strokes (under the age of 50) are caused by APS.
A stroke is a serious medical emergency; if left untreated with anticoagulants, it can progress to multiple strokes and even cause death. Present evidence indicates that anticoagulation treatment can prevent further strokes in APS patients.
As of 2023, the latest Royal College of Physicians' National Stroke Guidelines includes a partial update of the 2016 edition, and now APS has its own section (5.16). This was developed in collaboration with the Scottish Intercollegiate Guidelines Network (SIGN) and the National Clinical Programme for Stroke, Ireland. The 2023 edition is endorsed for use in clinical practice by the Royal College of Physicians of London, SIGN and the Royal College of Physicians of Ireland.
For more information about strokes, how to recognise the symptoms, diagnosis and life after stroke, please visit the Stroke Association at: www.stroke.org.uk and Different Strokes' website: www.differentstrokes.co.uk - a charity set up for younger stroke patients.
In 2021, we collaborated with the charity, Different Strokes to produce a video in which our Medical Vice Chair, Professor Anisur Rahman, explains how antiphospholipid syndrome can cause strokes in younger people. You can watch it here.
Transient Ischemic Attacks (TIAs)
These are ‘mini strokes’ in which a blood clot causes a temporary reduction, or blockage, of the blood supply to the brain. The symptoms of a TIA are similar to a stroke but less severe and only last from between a few minutes to a few hours – hence ‘transient’ - and then completely disappear. TIAs are the first sign of APS in 7% of patients.
The symptoms can include a severe headache or migraine, temporary loss of sight, temporary loss of speech and weakness or numbness on one side of the body.
TIAs may be common in untreated APS patients, and if the patient continues to be untreated, there is a serious risk of stroke.
With a TIA, the blood clot on the brain spontaneously dissolves, and MRI and CT scans often show no permanent damage. However, you should never ignore a TIA because it indicates there is a serious problem, and you are at risk without preventative treatment – often as simple as taking 75mg aspirin daily.
A number of APS patients have bladder problems, tingling sensations, numbness and weakness in their limbs. Not surprisingly, these patients are occasionally wrongly diagnosed as having multiple sclerosis (MS).
The cause for these types of symptoms is not clearly understood, but it could be a type of myelitis: a disease involving inflammation of the spinal cord, which disrupts central nervous system functions linking the brain and the limbs.
Transverse myelitis is a condition where one particular level of the spinal cord is involved and can sometimes be a manifestation of an autoimmune disease. If antiphospholipid antibodies are associated with transverse myelitis, it is possible that blood clots occur in the small vessels that supply the spinal cord.
It can be almost impossible to differentiate between MS and APS clinically and, to complicate matters further, the results of MRI scans in both conditions can be similar.
Diagnosis will often depend on the patient experiencing clear symptoms of APS, such as severe migraine, previous thrombosis, recurrent miscarriage, livedo reticularis and positive blood test results for antiphospholipid antibodies.
However, in some cases, one way to establish whether a person has APS as opposed to MS is to treat them with low-dose aspirin and see if their condition improves. Warfarin is not recommended, given the risks of bleeding associated with warfarin, especially in older patients.