What is Headache With Neurological Deficits and CSF Lymphocytosis (HaNDL syndrome)?
Headache with neurological deficits and a specific type of white blood cell increase in the cerebrospinal fluid (also known as HaNDL syndrome) is a harmless but very rare condition. It’s often not identified correctly because it’s not common. The condition is recognized by headaches similar to migraines along with short-term neurological problems like weakness on one side of the body, abnormal skin sensations like numbness, and trouble swallowing. It’s also linked to an increased number of a specific type of white blood cells in the fluid that surrounds the brain and spinal cord.
Recent studies have mentioned patients with intense headaches similar to migraines combined with short-term neurological issues and an increased number of particular white blood cells in the cerebrospinal fluid. Some patients had a prior viral syndrome, increased pressure within the brain, elevated levels of protein in the cerebrospinal fluid, or abnormalities noted in tests measuring the brain’s electrical activity.
As patients may have different symptoms, doctors treating them should be mindful of related neurological disorders and the usual lack of signs that suggest infections in the central nervous system (brain and spinal cord).
What Causes Headache With Neurological Deficits and CSF Lymphocytosis (HaNDL syndrome)?
The cause of HaNDL syndrome, a neurological disorder with symptoms like headaches and temporary numbness or weakness, is still unclear. It was initially believed to be caused by inflammation or infection, due to common symptoms such as a viral illness before the syndrome develops and changes in the brain’s fluid composition. Despite this, large-scale virus testing has not given any strong links to a particular infectious agent.
With the use of advanced scanning technologies, researchers have suggested that HaNDL syndrome could be similar to migraines, featuring decreased blood flow associated with a sort of ‘brainwave’ that travels across the brain, resulting in symptoms.
After realizing the similarities to migraines, researchers have suggested that the symptoms could be due to a type of non-bacterial meningitis, caused by viruses or inflammation. Immune responses activated by inflammation or viral diseases, which act against brain or blood vessel structures, causing sterile inflammation in the thin layers of tissue covering the brain and spinal cord, are being studied for this explanation.
Some recent studies have discovered that some HaNDL patients have autoimmune responses to a type of calcium channel, a sort of ‘gateway’ for cellular communications. However, a mutation in a specific gene associated with a different type of calcium channel was not found in some patients tested. That said, a small number of HaNDL patients have been found to have antibodies against proteins involved in cellular growth and DNA regulation.
Research has indicated that autoimmune reactions could be involved in the cause of HaNDL. Certain antibodies, or proteins produced by the immune system, have been linked to the muscles needed for DNA repair. Damage to DNA and inflammation might contribute to the cause of HaNDL syndrome according to the presence of these antibodies.
Risk Factors and Frequency for Headache With Neurological Deficits and CSF Lymphocytosis (HaNDL syndrome)
The syndrome that causes headaches with neurological deficits and an increase in lymphocytes in cerebrospinal fluid is seen more commonly in men aged between 15 and 40 years (68%). But it’s also found in younger patients and women, although this isn’t consistently reported. The condition is slightly more likely to occur in people who already have a history of migraines, with only 26% of patients reporting this. People with this syndrome usually experience moderate to severe headaches, which could occur from 1 to 12 times along with neurological deficits. These episodes tend to happen again within a short span of 3 months. While the symptoms may vary, all patients generally experience a recurrence of migraine-like headaches, variable neurologic deficit and an increase in lymphocytes in their cerebrospinal fluid. This whole condition is often referred to as HaNDL syndrome.
HaNDL syndrome is actually a harmless condition that gets better on its own over time. The name of the syndrome describes its symptoms, which include temporary neurological deficits such as issues with movement, sensory perception, speech, and sometimes vision. These are often seen along with moderately to severely painful headaches and an increase in lymphocytes in cerebrospinal fluid. The syndrome is relatively rare in adults and even less common in children. Even though the symptoms can come back within the first 3 months, people diagnosed with this syndrome usually have a very good prognosis.
There have been reported cases of younger patients with HaNDL syndrome which have highlighted some specific symptoms:
- Occurrences of a headache that could last for a week and come back over a period of 6 months, which was observed in a case of a patient who had been symptomatic for 3 days. The patient also had associated symptoms of numbness or tingling and had an increase in lymphocytes in their cerebrospinal fluid but normal protein and glucose levels. The patient, who had a family history of migraines, showed no abnormalities on a brain MRI scan with contrast along with MR angiography and venography. No signs of infection or inflammation in blood vessels were found. Symptoms went away after being given preventative medication for migraines, and the patient had no episodes for the next 8 months.
- An incident of a severe headache which started suddenly on the tenth day of an infection along with clinical symptoms of speech disorder and weakness on the right side of the body which was followed by inability to speak and generalized low muscle tone.
Altered consciousness, a condition that’s rarely seen in adults, can also occur in younger patients along with increased pressure inside the skull, swelling of the optic disc due to increased intracranial pressure, and migraines. Given the benign nature of the syndrome and these symptoms, it argues in favour of HaNDL syndrome being related to migraines, which is still debatable.
Signs and Symptoms of Headache With Neurological Deficits and CSF Lymphocytosis (HaNDL syndrome)
HaNDL syndrome, which affects the brain, may be partly caused by migrainous pathophysiology, evident from changes in arteries and blood flow. This could impact blood flow to the brain and cause unbalanced pulses seen via ultrasound during and after an episode. In fact, research has noticed a decrease in the amount of blood reaching the brain on the side opposite of neurological deficits.
Here are some other factors that can contribute to the development of HaNDL syndrome:
- A pattern of poor blood flow in one half of the brain, thought to be caused by spreading depression in the brain’s cortex. This could be due to changes in blood vessels in the brain caused by this depression.
- The simultaneous presence of HaNDL symptoms indicating possible changes in blood vessels, depression of the cortex, and excess glutamate potentially leading to swelling within myelin (a type of nerve fiber). This has been observed in a patient who experienced intermittent headaches and sudden one-sided sensory loss. These symptoms improved after four weeks.
It is also believed that antibodies created by our bodies during viral or autoimmune diseases might cause sterile inflammation that affects the vessels in our meninges (membrane surrounding the brain and spinal cord). This could result in an increase in white blood cells in spinal fluid (CSF pleocytosis) and neurological deficits. Interestingly, in patients with HaNDL, scientists have found high levels of antibodies against protein CACNA1H, a part of a type of calcium channel, suggesting an autoimmune reaction as a contributing factor.
A widely accepted theory supports that viruses could play a key role in causing HaNDL. It is suggested that the disease-causing process could be associated with such viruses (or other agents) causing constriction in brain blood vessels, explaining both localized symptoms and headache. Treatment for these patients could include medications that help regulate calcium channels.
There are documented cases relating HaNDL with viral causes, particularly rotavirus. For instance, a previously healthy patient who had been suffering from a weeklong bout of gastroenteritis presented symptoms such as temporary language impairment, fever, and headache. Tests showed inflammation in their spinal fluid and they started treatment with aciclovir. Tests turned up positive for rotavirus in both the spinal fluid and a stool analysis. There were no signs of brain inflammation detected via an MRI. The language impairment subsided within half a day and even with the discontinuation of the medication, no neurological symptoms recurred It is proposed that the cause for these post viral headaches and neurological deficits, symptomatic of HaNDL syndrome, could be an undetected direct virus-based infection in our central nervous system. In another similar case with HaNDL syndrome, scientists found Borrelia lusitaniae, a type of bacterium, in the spinal fluid.
Testing for Headache With Neurological Deficits and CSF Lymphocytosis (HaNDL syndrome)
If your doctor suspects that you may have HaNDL (a rare condition affecting the brain’s blood vessels), they will evaluate you based on a set of specific characteristics.
These symptoms might include severe migraine-like headaches lasting for a few hours, temporary neurological issues (such as difficulty in speaking or moving, or visual disturbances), and the recurrence of these symptoms within three months. An important clue is increased white blood cells in CSF or Cerebrospinal Fluid (the fluid around your brain and spinal cord) but no cause for this increase can be found. Sometimes this condition could lead to increased pressure in the brain. These signs can last longer than your other symptoms.
When doctors use imaging techniques like CT or MRI for a person with HaNDL, these scans typically do not show any unusual findings. However, in certain cases, some irregularities could be noticed in the corpus callosum (a part of the brain) and the amount of blood reaching your brain. One such study showed decreased levels of a protein called ‘neurofilament light’ (a marker for nerve damage) in the CSF of people with HaNDL. However, some patients did exhibit increased levels of this protein, indicating possible nerve damage, which normalised again after several months.
Other diagnostic tests might include an EEG (Electroencephalogram – a test of electrical activity in your brain), which may reveal unusual brain wave patterns during a HaNDL episode. Some reports have shown slower brain waves or less pronounced signals in the blood vessels of the brain’s veins in people with HaNDL.
Lastly, a patient’s blood flow in the brain using a test called transcranial Doppler (TCD) ultrasound could provide a useful tool to help diagnose HaNDL. TCD can detect blood flow alterations that often accompany HaNDL and thus might be useful in making an early diagnosis.
Treatment Options for Headache With Neurological Deficits and CSF Lymphocytosis (HaNDL syndrome)
HaNDL syndrome treatment depends on how severe it is. Though it tends to get better on its own without any treatment, it often returns, so it’s important for patients to be aware of this and be reassured that it’s part of the syndrome’s pattern. Managing headache symptoms can also help during an acute, or sudden, attack. During their first two appointments, patients usually go through thorough testing like brain imaging and spinal tap, but once HaNDL is diagnosed, these exhaustive tests are not typically needed again.
Medications that prevent seizures and migraines may help reduce the risk of acute attacks, which often include migraine-like headaches. But because the syndrome can improve on its own, it can be hard to say whether these drugs are making a difference or if it’s just the natural course of the disease. If headaches come back or if vision problems develop after recovering from HaNDL, it’s recommended patients urgently seek medical help. In the short to medium-term, doctors may need to manage the syndrome with CSF (cerebrospinal fluid) drainage and a medication called acetazolamide to prevent vision loss.
There was a case of a patient with HaNDL, who had a history of severe headaches, difficulty speaking and writing, but showed full recovery in-between episodes with normal neurological checkups. A lumbar puncture, which is a test where a needle is inserted into the lower back to withdraw spinal fluid, showed an increased number of lymphocytes indicating inflammation or infection. Further analysis ruled out any infection or autoimmune causes. Brain scans and EEG (a test that measures electrical activity in your brain) were normal too. However, an area of decreased blood flow was detected in the brain using single-photon emission tomography, a type of imaging test. The patient was successfully treated with ibuprofen and had no symptoms or relapse for six months.
In another study, patients with HaNDL who suffered from repeated sudden headaches, involuntary movements and even paralysis, showed elevated intracranial pressure (pressure inside the skull) and inflammation in cerebrospinal fluid. Their symptoms and the elevated pressure were relieved after the administration of steroids. This suggests steroids could be a helpful treatment for HaNDL and supports the idea that the syndrome could be triggered by an infection or an autoimmune process happening after an infection.
What else can Headache With Neurological Deficits and CSF Lymphocytosis (HaNDL syndrome) be?
Headaches accompanied by neurological symptoms and an increased count of lymphocytes in the cerebrospinal fluid (CSF) are usually not related to any central nervous system infection. Brain scans like MRIs usually come out normal in such cases. Although the cause isn’t fully understood, a viral infection is one possible explanation. The good news is that people with these symptoms generally get better within 1 to 3 weeks. Because these symptoms can be similar to other neurological disorders, it’s critical to rule out more serious conditions:
- Migraine with aura and HaNDL syndrome: These conditions have similar changes in brain blood flow, but differ in the presence of visual disturbances (aura) and the amount of white blood cells in the CSF.
- Hemiplegic migraine: This type of migraine, whether it runs in families or not, does not show an increased lymphocyte count in the CSF.
- Acute stroke: It involves neurological symptoms such as trouble speaking, weakness or numbness on one side of the body, and sustained headaches. Brain MRI may show abnormalities but without an elevated CSF white blood cell count. There have been cases where a patient was initially treated for stroke but later diagnosed with HaNDL syndrome.
- Meningoencephalitis, meningitis, and encephalitis: These are infectious causes of headaches, often coming with high fever, neck stiffness, and skin rashes. Studying the CSF may help identify the cause of the condition.
- Anti-NMDA receptor encephalitis: It presents as a severe multi-stage neuropsychiatric syndrome with episodes similar to HaNDL, including visual loss on one side, trouble speaking, right-sided weakness, throbbing headaches, confusion, and agitation.
- Viral encephalitis and recurrent cerebral ischemic events have similar symptoms as migraine, such as unusual sensations or weakness on one side of the body, and confusion.
- Epilepsy: In some patients, after a seizure, they may present with neurological deficits. It is rare to have elevated white blood cells in CSF.
- CNS vasculitis, granulomatous, and neoplastic arachnoiditis: These conditions can be differentiated through brain imaging.
- Neurobrucellosis: It usually results from close contact with animals and causes headaches with fever, feeling unwell, and muscle pain, but not neurological deficits.
- Neurosyphilis: It can be suspected in people with a history of multiple sexual partners or sexually transmitted infections.
- Neuroborreliosis: Associated with traveling to areas endemic for Lyme disease and presence of a bull’s-eye skin rash.
- Reversible posterior leukoencephalopathy syndrome: In these cases, seizures and altered mental status occur. The brain imaging presents noticeable abnormalities.
So, it’s important to remember that when dealing with these kind of symptoms, many diseases can look similar, and careful testing is required to determine the real cause.
What to expect with Headache With Neurological Deficits and CSF Lymphocytosis (HaNDL syndrome)
A headache that comes with neurological deficits and an increase in a type of white blood cell, called lymphocytes, in the spinal fluid, typically has a good outlook. This condition usually resolves on its own and does not need treatment. However, medication like corticosteroids (which reduce inflammation), calcium channel blockers (which helps relax and widen blood vessels), and acetazolamide (used to treat glaucoma) have been used in the past to treat this condition.
Possible Complications When Diagnosed with Headache With Neurological Deficits and CSF Lymphocytosis (HaNDL syndrome)
Over time, HaNDLE syndrome might lead to certain conditions. These include agitation and psychosis, which can sometimes be so severe that hospital admission is necessary. In rare instances, this syndrome might also cause cortical blindness (loss of vision due to damage to the brain’s visual processing areas), papilledema (swelling in the optic nerve leading to the eye), and sixth cranial nerve palsy (a condition that affects eye movement).
- Long-term agitation
- Psychosis that may require hospitalization
- Cortical blindness
- Papilledema
- Sixth cranial nerve palsy
Preventing Headache With Neurological Deficits and CSF Lymphocytosis (HaNDL syndrome)
Patients who have been diagnosed with HANDL syndrome should be taught about the characteristics and behavior of this disease. It’s important for them and their families to understand that HANDL syndrome is generally harmless and tends to resolve itself over time. Despite its sudden and intense beginning, HANDL usually doesn’t create long-lasting, life-altering issues. The uncommon risks and complications tied to this condition should also be clearly communicated to the patient and their loved ones.