Blood Tests, Lumbar Puncture and Antibody Testing in Epilepsy
When doctors need to look beyond EEG and MRI
There is no single blood test that can diagnose epilepsy.
EEG, MRI, seizure history and eyewitness accounts are usually much more important when doctors are deciding whether someone has epilepsy.
But blood tests — and, in selected cases, a lumbar puncture — can answer a different question:
Could something else be causing the seizures?
Doctors may investigate for:
metabolic disturbances
infection
inflammation
autoimmune disease
medication problems
or other conditions affecting the brain.
NICE specifically states that metabolic disturbances, including hypoglycaemia, can cause seizures. It also recommends considering antibody testing when someone has new-onset epilepsy and autoimmune encephalitis is suspected.
Blood tests do not prove epilepsy
A normal blood test does not rule epilepsy out.
An abnormal blood test does not automatically mean epilepsy is present.
Instead, blood tests can reveal conditions that:
provoke an acute seizure
make seizures more likely
alter antiseizure medication levels
or suggest another diagnosis entirely.
This distinction matters.
A person can experience a genuine epileptic seizure because of a temporary metabolic disturbance without necessarily having an enduring epilepsy disorder.
Blood glucose
One of the most important things to consider after a first seizure is blood glucose.
Very low blood glucose — hypoglycaemia — can disrupt normal brain function and cause:
confusion
abnormal behaviour
loss of consciousness
seizures
and, in severe cases, coma.
NICE specifically identifies hypoglycaemia as an important metabolic cause that should be considered after a suspected seizure.
If hypoglycaemia caused the seizure, treatment needs to address the underlying glucose problem rather than simply assuming the person has epilepsy.
Electrolytes
The brain depends on carefully controlled concentrations of salts and minerals in the blood.
Significant abnormalities can provoke seizures.
Doctors may therefore check substances such as:
sodium
calcium
magnesium
potassium
and other electrolytes depending on the circumstances.
Low sodium — hyponatraemia — is particularly important.
Severe hyponatraemia can cause:
headache
confusion
reduced consciousness
and seizures.
The cause of an abnormal sodium level then needs investigation.
Why might sodium be especially relevant in autoimmune epilepsy?
Low sodium can occasionally provide an additional clue when doctors suspect LGI1-antibody encephalitis.
People with LGI1-antibody encephalitis may develop frequent seizures together with:
memory problems
confusion
behavioural change
sleep disturbance
and hyponatraemia.
However, low sodium has many much more common causes.
It should never be treated as proof of autoimmune encephalitis by itself.
Kidney and liver function
The kidneys and liver help process many medicines.
Blood tests may therefore include:
kidney function
liver function
and other biochemical measurements.
This can be important when:
choosing an antiseizure medicine
investigating side effects
adjusting doses
or assessing someone who is acutely unwell.
Severe kidney or liver dysfunction can itself contribute to neurological symptoms.
Full blood count
A full blood count measures different types of blood cells.
It may help identify:
infection
anaemia
abnormalities in white blood cells
or problems with platelets.
It does not diagnose epilepsy.
It may, however, contribute to understanding why someone is unwell or help monitor medicines that can affect blood cells.
Infection markers
If infection is suspected, doctors may investigate for:
raised inflammatory markers
abnormal white blood-cell counts
evidence of a specific infection
or sepsis.
NICE includes sepsis among factors that should be considered when assessing adults after a first seizure.
A seizure occurring during severe infection may require very different treatment from recurrent unprovoked epilepsy.
Medication levels
Blood levels can be measured for some antiseizure medicines.
This may be useful when doctors need to investigate:
possible toxicity
treatment failure
suspected missed doses
pregnancy-related changes
medicine interactions
or changes in kidney or liver function.
Not every antiseizure medicine requires routine blood-level monitoring.
The clinical situation and medicine involved determine whether testing is useful.
Toxicology testing
In selected emergency situations, doctors may investigate whether:
prescribed medicines
recreational drugs
poisoning
alcohol withdrawal
or another substance
could have contributed to a seizure.
This is based on the clinical circumstances.
Routine toxicology testing is not required for everyone who has epilepsy.
Does prolactin diagnose a seizure?
No.
Blood prolactin can sometimes rise after certain epileptic seizures, particularly some bilateral tonic-clonic and focal impaired-awareness seizures.
But prolactin levels are influenced by many other factors, and the timing of the blood sample is critical.
It cannot reliably separate every epileptic seizure from:
fainting
functional seizures
or other events.
It is therefore not a simple “epilepsy blood test”.
Modern epilepsy diagnosis still depends primarily on the clinical history, video where available, EEG and appropriate investigation.
When might a lumbar puncture be needed?
A lumbar puncture is not routinely required simply because someone has epilepsy.
It becomes relevant when doctors suspect something such as:
encephalitis
meningitis
autoimmune inflammation
another central nervous system infection
or another neurological disorder involving the cerebrospinal fluid.
The NHS states that lumbar puncture can be used to investigate brain and spinal conditions, and cerebrospinal fluid can be tested for infection and immune-system disorders.
What is cerebrospinal fluid?
Cerebrospinal fluid, commonly shortened to CSF, is clear fluid that surrounds the brain and spinal cord.
It helps:
cushion the nervous system
maintain its chemical environment
and transport substances around the central nervous system.
Because CSF is in close contact with the brain and spinal cord, it can contain evidence of:
infection
inflammation
antibodies
or other neurological disease processes
that may not be obvious from ordinary blood tests.
What happens during a lumbar puncture?
A lumbar puncture is usually performed in the lower back.
The person is normally asked to:
lie curled on their side
or sit leaning forwards.
Local anaesthetic is used to numb the skin.
A thin needle is then passed between bones in the lower spine into the space containing cerebrospinal fluid.
Small samples of CSF are collected into tubes for laboratory analysis.
The procedure commonly takes around 15 to 20 minutes, although it can take longer.
The needle does not go into the brain
A lumbar puncture is performed in the lower back.
In adults, the spinal cord normally ends higher in the spine than the usual lumbar-puncture site.
The needle enters the fluid-filled space below this level.
This is why the phrase “spinal tap” can sometimes create a more frightening picture than the actual anatomy.
Does a lumbar puncture hurt?
Local anaesthetic is normally used.
People may experience:
pressure
discomfort
or a brief tingling sensation.
The NHS states that lumbar puncture may feel uncomfortable but should not normally be painful.
Tell the clinician immediately if significant pain occurs.
What is tested in cerebrospinal fluid?
The exact tests depend on what doctors suspect.
CSF may be examined for things including:
white blood cells
red blood cells
protein
glucose
infection
viral genetic material
inflammatory markers
oligoclonal bands
antibodies
or other specialised tests.
Not every CSF sample is tested for everything.
The clinical picture determines which investigations are appropriate.
Why would infection cause seizures?
An infection affecting the brain can make brain tissue inflamed and electrically unstable.
One important example is encephalitis.
The NHS describes encephalitis as inflammation of the brain that can cause symptoms including:
confusion
personality or behavioural changes
speech problems
loss of consciousness
and seizures.
Encephalitis can be life-threatening and requires urgent hospital treatment.
Infectious encephalitis
Encephalitis may be caused by infection.
Viruses associated with encephalitis include:
herpes simplex virus
varicella-zoster virus
and several other viral infections.
The NHS identifies herpes simplex as an important cause of viral encephalitis.
When infectious encephalitis is suspected, CSF testing can help identify the organism responsible.
Why speed matters with suspected encephalitis
Encephalitis can progress quickly.
A person developing:
seizures
rapidly worsening confusion
major behavioural change
reduced consciousness
fever
new neurological weakness
or severe speech disturbance
needs urgent assessment.
The NHS advises emergency help for serious symptoms suggestive of encephalitis.
Doctors may begin treatment before every laboratory result is available when the clinical suspicion is high.
What is autoimmune encephalitis?
The immune system normally protects the body from infection.
In autoimmune encephalitis, the immune system mistakenly targets components of the brain.
This can disturb neuronal communication and produce symptoms including:
seizures
memory problems
confusion
psychiatric symptoms
abnormal behaviour
movement disorders
sleep disturbance
reduced consciousness
or autonomic instability.
Autoimmune encephalitis is uncommon but important because some forms are highly treatable when recognised promptly.
Autoimmune encephalitis and epilepsy are not the same thing
A seizure caused by active autoimmune encephalitis is often considered an acute symptomatic seizure caused by inflammation.
Some people continue to have recurrent seizures after the inflammatory illness has resolved and may later develop an enduring epilepsy.
Other autoimmune conditions can produce a more persistent autoimmune-associated epilepsy.
Modern research therefore distinguishes between:
seizures occurring during active autoimmune encephalitis
and longer-term autoimmune-associated epilepsy.
This distinction matters because treatment may differ.
When should doctors suspect an autoimmune cause?
There is no single sign.
Suspicion is usually raised by a combination of features.
Examples can include:
new-onset frequent seizures
rapidly worsening memory
confusion
psychiatric or behavioural change
unusual movement disorders
seizures that rapidly become difficult to control
abnormalities on MRI or CSF suggesting inflammation
specific unusual seizure types
or new-onset refractory status epilepticus.
NICE recommends discussing antibody testing with a neurologist when someone has new-onset epilepsy and autoimmune encephalitis is suspected.
What are faciobrachial dystonic seizures?
One particularly distinctive seizure type is strongly associated with LGI1-antibody encephalitis.
These are called faciobrachial dystonic seizures, often shortened to FBDS.
They usually involve:
extremely brief
frequent
involuntary movements
affecting the face and arm, often predominantly on one side.
They can occur many times per day.
Recognising this pattern can be important because it may appear before more obvious cognitive symptoms.
Encephalitis International identifies these brief face-and-arm events as a characteristic clue to LGI1-antibody disease.
What antibodies can be associated with autoimmune encephalitis?
Examples include antibodies against:
NMDA receptors
LGI1
CASPR2
GABA-B receptors
AMPA receptors
DPPX
and other neuronal targets.
Other antibodies such as GAD65 can be associated with neurological autoimmunity including some forms of epilepsy.
The list continues to develop as new disorders are recognised.
What is anti-NMDA receptor encephalitis?
Anti-NMDA receptor encephalitis is an autoimmune disease in which antibodies target NMDA receptors involved in neuronal signalling.
People may develop combinations of:
psychiatric or behavioural symptoms
confusion
memory disturbance
seizures
abnormal movements
autonomic instability
and reduced consciousness.
It can occur in children and adults.
It is one of the best-established forms of antibody-mediated autoimmune encephalitis.
What is LGI1-antibody encephalitis?
LGI1-antibody encephalitis often affects memory and temporal-lobe networks.
Features may include:
focal seizures
faciobrachial dystonic seizures
memory loss
confusion
sleep disturbance
behavioural changes
and low blood sodium.
MRI may show abnormalities involving the medial temporal lobes, although scans can also be normal.
CSF can sometimes be surprisingly normal despite the illness.
What is CASPR2-antibody disease?
CASPR2 antibodies can be associated with several neurological syndromes.
These may involve combinations of:
seizures
memory or cognitive problems
peripheral-nerve hyperexcitability
pain
sleep disturbance
autonomic symptoms
and encephalitis.
The exact clinical presentation varies.
This is why antibody results must always be interpreted alongside the person's symptoms.
What about GAD65 antibodies?
GAD65 antibodies are more complicated.
They can be associated with neurological conditions including:
epilepsy
limbic encephalitis
stiff-person-spectrum disorders
and cerebellar ataxia.
But GAD65 antibodies can also occur in other autoimmune conditions, particularly type 1 diabetes.
Recent research continues to caution against interpreting a serum GAD65 result without considering:
antibody concentration
CSF findings
clinical syndrome
and other evidence of inflammation.
A positive number by itself does not automatically prove autoimmune epilepsy.
Why might both blood and CSF be tested?
The usefulness of serum and CSF varies depending on the antibody.
For many suspected autoimmune neurological disorders, specialists prefer testing paired serum and CSF.
Some antibodies are particularly informative in CSF.
Others may be easier to detect in serum.
A 2024 review of autoimmune neurological testing recommends using both serum and CSF in most situations, while recognising that the preferred specimen differs between particular antibodies.
Current NHS autoimmune-encephalitis laboratory guidance also recommends testing both CSF and serum to reduce the risk of misinterpretation.
Why shouldn't everyone with epilepsy have an antibody panel?
Because autoimmune neurological diseases are relatively uncommon.
Testing people who have a very low clinical likelihood of autoimmune disease increases the chance that a technically positive result will be:
incidental
weak
misleading
or clinically irrelevant.
Large-scale research has shown that even tests with high laboratory specificity can have limited positive predictive value when used indiscriminately for very rare diseases.
That is why NICE recommends antibody testing when autoimmune encephalitis is suspected, rather than routine antibody screening for everyone with epilepsy.
A positive antibody does not replace clinical judgement
The result has to fit the person.
Doctors consider:
how symptoms began
speed of progression
seizure type
MRI
EEG
CSF
cognition
behaviour
movement abnormalities
other autoimmune conditions
and sometimes evidence of cancer.
Modern reviews warn that autoimmune encephalitis can be overdiagnosed when antibody results or criteria are interpreted without the correct clinical context.
What about the old “VGKC antibody” test?
Older reports may refer broadly to VGKC-complex antibodies.
Research has since shown that the clinically useful targets are particularly:
LGI1
and CASPR2.
So-called “double-negative VGKC antibodies” that target neither LGI1 nor CASPR2 have poor clinical specificity.
Specialist authors have therefore recommended testing directly for LGI1 and CASPR2 rather than relying on the older broad VGKC-complex assay.
What are oligoclonal bands?
Oligoclonal bands, or OCBs, are particular immunoglobulin patterns that can be detected in cerebrospinal fluid.
When certain bands are present in CSF but not matching blood, they can suggest immune activity occurring within the central nervous system.
They are not specific to epilepsy.
They can occur in various inflammatory or infectious neurological conditions.
Therefore, oligoclonal bands are another clue rather than an epilepsy diagnosis.
Does normal cerebrospinal fluid rule out autoimmune encephalitis?
No.
Some forms of autoimmune encephalitis can have relatively normal routine CSF findings.
For example, LGI1- and CASPR2-antibody encephalitis may occur even when routine lumbar-puncture results show little obvious inflammation.
Doctors therefore consider:
clinical features
MRI
EEG
antibody testing
and CSF
together.
Does a normal MRI rule it out?
No.
MRI may show inflammation, particularly in temporal-lobe structures, but it may also initially appear normal.
Likewise, EEG abnormalities can support the diagnosis but are not necessarily specific.
Autoimmune encephalitis remains a clinical diagnosis supported by several investigations, not something excluded by one normal test.
Why might a tumour search be needed?
Some autoimmune neurological syndromes can be paraneoplastic.
This means an immune response associated with a tumour also mistakenly targets components of the nervous system.
The strength of the cancer association differs considerably between antibodies.
If a particular antibody or clinical syndrome suggests a paraneoplastic disorder, doctors may investigate for an underlying tumour.
This does not mean that everyone with autoimmune epilepsy has cancer.
Many autoimmune encephalitis syndromes occur without cancer.
What is autoimmune-associated epilepsy?
Some people develop persistent epilepsy associated with immune mechanisms rather than only having seizures during an acute encephalitis.
A 2026 clinical review describes autoimmune-associated epilepsy as a spectrum including:
antibody-associated epilepsies
post-encephalitic epilepsy
Rasmussen encephalitis
and some cases of otherwise unexplained drug-resistant temporal-lobe epilepsy.
Assessment may include:
MRI
prolonged EEG
CSF analysis
and appropriately selected serum and CSF antibody testing.
This is a specialist diagnosis.
What is new-onset refractory status epilepticus?
New-onset refractory status epilepticus, or NORSE, is a clinical presentation in someone without a relevant previous epilepsy disorder who suddenly develops refractory status epilepticus without an immediately obvious structural, toxic or metabolic cause.
NORSE has many possible causes.
These include:
autoimmune disease
infection
metabolic disease
genetic disorders
and causes that remain unknown despite extensive investigation.
Assessment can require extensive testing of blood and CSF, MRI, EEG, autoimmune and infectious studies and other investigations.
NORSE is a medical emergency and is not the same as ordinary new-onset epilepsy.
What if antibodies are negative?
Negative antibody tests do not completely exclude autoimmune encephalitis.
Some genuine immune-mediated disorders have no currently recognised antibody.
However, diagnosing antibody-negative autoimmune encephalitis requires particular care.
Specialists need evidence supporting brain inflammation and need to exclude alternative diagnoses.
A major 2023 review warned that autoimmune encephalitis is sometimes misdiagnosed when antibody-negative criteria are applied too loosely.
Why alternative diagnoses still matter
Features such as:
seizures
confusion
hallucinations
memory loss
abnormal movements
or behavioural change
can arise from many disorders.
Possible alternatives include:
infectious encephalitis
metabolic disturbances
toxic conditions
primary epilepsy
psychiatric illness
neurodegenerative disease
tumours
stroke
and other neurological conditions.
An autoimmune explanation should be investigated carefully rather than assumed.
Can autoimmune seizures respond differently to ordinary epilepsy medicines?
Sometimes.
Antiseizure medicines may still be needed to control seizures.
But if active brain inflammation is actually driving those seizures, treating the immune disease can be crucial.
Some neuronal-surface antibody encephalitides can respond strongly to immunotherapy, while long-standing autoimmune-associated epilepsy involving other mechanisms may be much less responsive.
This is one reason recognising active encephalitis early can matter.
What treatments are used for autoimmune encephalitis?
Treatment depends on:
antibody
underlying cause
severity
presence of a tumour
and response to initial treatment.
Specialists may use immune therapies such as:
corticosteroids
intravenous immunoglobulin
plasma exchange
rituximab
or other immunosuppressive treatments.
Seizures are also treated appropriately.
This treatment requires specialist medical supervision and should not be started purely because an antibody result appears positive.
Can seizures continue after autoimmune encephalitis has been treated?
Yes.
Some people recover from the active inflammation but remain susceptible to seizures because the illness has left lasting changes in the brain.
At that stage, recurrent seizures may behave more like structural epilepsy.
Other people become seizure-free after successful treatment of the autoimmune illness.
The long-term outcome depends greatly on the particular disease.
Lumbar puncture aftercare
Headache is one of the better-known side effects after lumbar puncture.
Other temporary effects can include:
back discomfort
soreness
or minor bleeding around the puncture site.
The NHS states that lumbar punctures are generally very safe and serious complications are rare.
Follow the instructions provided by the hospital after the procedure.
When should someone get help after a lumbar puncture?
The NHS advises seeking medical help after lumbar puncture for problems including a persistent significant headache, high temperature, severe pain or concerning leakage or bleeding.
Emergency help is needed for severe neurological symptoms such as new weakness, numbness, serious bladder or bowel problems or confusion.
What if all the blood and CSF tests are normal?
That does not mean nothing happened.
Many people with epilepsy have:
normal routine blood tests
no evidence of infection
no autoimmune antibodies
and normal cerebrospinal fluid.
That simply means these investigations have not identified one of the conditions they were designed to detect.
Doctors then interpret those findings together with:
seizure history
EEG
MRI
genetics where appropriate
video telemetry
and other specialist tests.
Not finding an autoimmune cause is still useful information
Sometimes testing is valuable precisely because it makes a proposed diagnosis less likely.
For example, doctors may initially need to exclude:
infection
metabolic disturbance
or active brain inflammation
before deciding that recurrent seizures are more consistent with a primary epilepsy disorder.
A negative investigation can therefore still influence treatment.
Questions to ask if blood tests are being ordered
Useful questions include:
What are you looking for?
Are you checking whether something caused this seizure rather than testing for epilepsy itself?
Was my glucose normal?
Were my sodium and other electrolytes normal?
Are my liver and kidneys functioning normally?
Could my medicine levels be contributing?
Do any results suggest infection or inflammation?
Questions to ask if a lumbar puncture is recommended
Useful questions include:
Why do you think I need a lumbar puncture?
Are you looking for infection, inflammation or autoimmune disease?
What will the cerebrospinal fluid be tested for?
Are you testing both my blood and CSF for antibodies?
Could my MRI or EEG findings be caused by encephalitis?
What happens if the CSF is normal?
How long will the results take?
Questions to ask about an antibody result
Useful questions include:
Which antibody was found?
Was it found in blood, CSF or both?
Does the antibody actually fit my symptoms?
How strong is the evidence that it is clinically significant?
Could this be an incidental result?
Does my CSF show inflammation?
Does my MRI support autoimmune encephalitis?
Do I need investigation for an underlying tumour?
Does this change my seizure treatment?
Do I need immunotherapy?
The most important message
Blood tests, lumbar punctures and antibody tests do not replace EEG, MRI or a careful seizure history.
They answer different questions.
Blood tests can reveal metabolic problems such as hypoglycaemia or electrolyte disturbance that can cause seizures.
A lumbar puncture allows doctors to examine cerebrospinal fluid for evidence of infection, inflammation and immune activity.
Antibody testing can identify particular autoimmune neurological conditions in selected people.
But autoimmune epilepsy should not be assumed simply because:
seizures are difficult to control
a blood test produces a weak positive result
or ordinary MRI is normal.
The strongest diagnosis comes when the complete picture agrees:
clinical symptoms + seizure pattern + EEG + MRI + blood + CSF + appropriately interpreted antibody testing.
For most people with established epilepsy, lumbar puncture and autoimmune testing will never be necessary.
But when seizures appear as part of a rapidly developing neurological illness, recognising an infectious or autoimmune cause can be extremely important because it may completely change the treatment.
Sources and further reading
NICE — Epilepsies in children, young people and adults (NG217).
NICE states that metabolic disturbances including hypoglycaemia can cause seizures and recommends considering antibody testing, in discussion with a neurologist, when new-onset epilepsy occurs and autoimmune encephalitis is suspected. Last updated January 2025.
NHS — Encephalitis: diagnosis and causes.
NHS guidance explains the role of lumbar puncture, brain imaging, EEG and blood testing in suspected encephalitis and notes that CSF can be examined for infectious and immune causes.
NHS — Lumbar puncture.
Current information explaining why lumbar puncture is performed, what happens during the procedure, recovery and possible complications.
Dalmau J, Graus F — Diagnostic criteria for autoimmune encephalitis: utility and pitfalls for antibody-negative disease. Lancet Neurology, 2023.
Highlights the importance of appropriate clinical criteria, assessment of MRI and CSF inflammation, exclusion of alternative diagnoses and careful interpretation of antibody-negative cases.
Autoimmune CNS disorders: antibody testing and clinical utility, 2024.
Reviews appropriate use of neural-antibody testing and the importance of serum and CSF testing according to the suspected clinical phenotype.
Autoimmune-associated epilepsy: definitions and diagnosis, 2026.
Current review of immune-mediated epilepsy, neuronal antibodies, clinical screening and combined MRI, EEG, CSF and antibody investigation.
North West London Pathology — Autoimmune encephalitis antibody testing.
Current NHS laboratory information covering antibodies including NMDAR, LGI1, CASPR2, AMPA, GABA-B and DPPX and recommending paired serum and CSF assessment. Updated March 2026.
Information reviewed: September 2026.
This page provides general educational information. New-onset seizures accompanied by rapidly worsening confusion, behavioural change, fever, reduced consciousness or other acute neurological symptoms require urgent medical assessment.
