What is Headache With Neurological Deficits and CSF Lymphocytosis (HaNDL syndrome)?
Headache with neurological deficits and cerebrospinal fluid (CSF) lymphocytosis, also known as HaNDL syndrome, is a rare, often misdiagnosed health condition that is harmless in nature. This syndrome is recognized by severe headaches similar to migraines, accompanied by temporary neurological issues such as weakness on one side of the body (hemiparesis), abnormal or diminished sensations (hemiparesthesia), and difficulty swallowing (dysphagia). Interestingly, it shows an increased number of lymphocytes, a type of white blood cell, in the fluid that surrounds the brain and spinal cord (cerebrospinal fluid).
Recent studies reported patients with severe migraines paired with temporary neurological issues, including increased lymphocytes in the CSF. Some of these patients showed signs of a previous viral infection, increased pressure inside their skulls, raised CSF protein levels, or irregularities in their brain activity readings (electroencephalogram abnormalities).
Given the varied symptoms of this syndrome among different patients, doctors managing their treatment need to be mindful of similar neurological disorders and the common lack of signs pointing towards infections of the central nervous system (brain and spinal cord).
What Causes Headache With Neurological Deficits and CSF Lymphocytosis (HaNDL syndrome)?
The exact cause of HaNDL syndrome isn’t completely known yet, but there are several theories. Initially, many thought it was linked to inflammation or infection due to common flu-like symptoms, a one-time occurrence, and increased white blood cells in the fluid surrounding the brain and spinal cord. However, thorough testing for various viral infections didn’t show any particular link to a specific infection, except for a couple of cases associated with echovirus 30, human herpesvirus 6 and 7, and borrelia infection.
Advanced imaging studies, like single-photon emission computed tomography, head computed tomography perfusion imaging, magnetic resonance imaging perfusion techniques, and transcranial Doppler, suggested that the triggers and progression of HaNDL syndrome might be similar to migraines. This theory includes decreased blood flow associated with changes in nerve cell activity in the brain.
With these findings, researchers turned their attentions to the possibility of a non-infectious form of meningitis caused by inflammation or viral infection. For instance, they looked at whether an inflammatory or viral disease might trigger the production of autoantibodies – antibodies that mistakenly attack the body’s own tissues. These autoantibodies might target nerve or blood vessel structures, causing inflammation in the membranes surrounding the brain and spinal cord.
In recent studies, some patients with HaNDL syndrome were found to have autoantibodies against a type of calcium channel known as CACNA1H. However, other patients didn’t have pathogenic variations in a related calcium channel gene. A few patients with HaNDL syndrome also had antibodies against a protein molecule involved in cell growth and another protein molecule that is part of the DNA copying process.
Several studies have suggested that autoimmunity, a condition in which your immune system mistakenly attacks your body, plays a role in HaNDL syndrome. For example, researchers have found antibodies against three DNA repair proteins in some patients. The presence of these antibodies could indicate that DNA damage and inflammation are contributing factors to HaNDL syndrome.
Risk Factors and Frequency for Headache With Neurological Deficits and CSF Lymphocytosis (HaNDL syndrome)
The HaNDL syndrome is a condition that is more common in males between the ages of 15 and 40, and it’s characterized by headaches accompanied by neurological problems such as motor issues, sensory issues, speaking problems, and sometimes visual problems. Not every individual who suffers this syndrome has a previous history of migraines. The usual experience is a moderate to intense headache occurring from 1 to 12 times along with neurological problems. In most cases, these episodes come back within a 3-month time period.
Despite its distressing symptoms, the good news is that HaNDL syndrome is benign, and it goes away by itself. However, while it is rare in both adults and children, it can reoccur within the first three months.
In younger patients, symptoms may include recurring headaches for half a year, with each episode lasting a week. Linked with these episodes are ‘pins and needles’ feelings and an abnormal number of white cells in their spinal fluid. However, tests for infections and vein inflammation are negative. The good news is that symptoms improve with migraine preventing medication.
In some cases, there might be a severe headache in the forehead starting suddenly on the 10th day of an infection, along with signs of a speech disorder, weakness on the right side and a general lack of muscle tone. Less often, younger people may experience higher pressure inside their skull causing swollen optic nerves and migraines. Even though the way the disease behaves suggests it has a connection with migraines, this is still not confirmed.
Signs and Symptoms of Headache With Neurological Deficits and CSF Lymphocytosis (HaNDL syndrome)
HaNDL syndrome, a neurological disorder, may be influenced by imbalances in how blood circulates in our brain, specifically in the middle cerebral artery. These imbalances can cause inconsistent blood flow pulses, as detectable by a particular type of ultrasound called transcranial Doppler ultrasound. Some research also shows that during a HaNDL episode, blood flow to the brain may decrease on the side opposite to the neurological symptoms.
Research has pointed out the possible roles of vasomotor changes in HaNDL syndrome:
- A pattern of reduced blood flow supporting a decrease in blood circulation caused by a wave of reactions in the brain’s tissues (cortical spreading depression or CSD). This study suggested that these changes in blood vessel behavior due to CSD spread across abnormal blood vessels.
- When HaNDL symptoms coincide, they suggest changes in blood vessel behaviour, reactions in brain tissues, and excessive activity of a chemical called glutamate that can cause swelling in the protective layers around nerve fibres. Notably, a patient with a fortnight history of on-and-off headaches and acute one-sided sensory deficit got better after 4 weeks, with both increased white blood cells in their spinal fluid and an MRI lesion in a specific part of their brain, the corpus callosum, clearing up.
Meanwhile, some researchers suggest that the body’s immune response after viral or autoimmune diseases may trigger inflammation without infection, affecting certain brain vessels, causing increased white blood cells in spinal fluids and neurological symptoms. For instance, a recent study found high levels of antibodies against a type of protein in T-type calcium channels in 2 out of 4 patients with HaNDL, providing some evidence for the role of an immune response in the disease’s development.
A recent study concluded some patients might have a viral cause for HaNDL. Regardless of its cause, the mechanism of the disease might be due to a virus or another agent causing brain vessels to constrict, explaining the symptoms and headaches. Possible treatments include drugs called calcium channel blockers.
Additional cases due to viruses are also documented, particularly a type of viral meningitis caused by the Rotavirus. For example, one healthy patient with temporary loss of speech, fever, and headaches after a week of stomach flu showed signs of lymphocytic meningitis in their spinal fluid. Initial treatment with a drug called aciclovir was started. Tests on their spinal fluid and from a stool sample were positive for viral meningitis, but brain imaging showed no signs of brain inflammation. The speech loss resolved in less than a day, with no return of neurological symptoms after the aciclovir treatment was stopped. This case presents the idea that the headaches and neurological symptoms following HaNDL syndrome could be due to previously unidentified direct viral infections in the brain and nervous system. Another case talked about a patient with clinical and spinal fluid findings like HaNDL syndrome, in which tests showed the presence of Borrelia lusitaniae in the spinal fluid.
Testing for Headache With Neurological Deficits and CSF Lymphocytosis (HaNDL syndrome)
Some people might experience a rare neurological disorder called HaNDL (Headache with Neurological Deficits and Cerebrospinal fluid lymphocytosis). To determine whether someone has HaNDL, doctors look for certain key symptoms. These symptoms can include intense migraines that can last a few hours, an increase in a type of white blood cell called lymphocytes in the spinal fluid, sudden neurological issues that arise with or right after a headache, and repeated episodes of headaches and these neurological issues within three months.
Doctors often use brain scans to further investigate these symptoms. However, these brain scans usually do not show any abnormalities for HaNDL. One exception, however, can involve changes in certain areas of the brain relating to blood flow and communication between brain hemispheres. There have also been instances of visible brain lesions appearing on scans, but this is not common.
To differentiate HaNDL from other similar neurological disorders, doctors might check for particular proteins in the spinal fluid, like neurofilament light chain (NFL). In some studies, NFL levels in HaNDL patients were significantly lower than in patients with a different neurological disorder called multiple sclerosis.
Additional tests can also provide valuable information. For example, a specialized brain test called a Single-Photon Emission Computerized Tomography can reveal decreased blood flow to certain parts of the brain during a neurological episode. An electroencephalogram, a test that monitors brain waves, might show slowed down brain activity. In some patients, the slowed activity was prevalent in the front part of the brain or on one side of the brain.
Another relevant test might be a transcranial Doppler ultrasound. This is a non-invasive test that checks blood flow in the arteries of the brain. The test can be particularly useful to detect any alterations in blood flow that could potentially relate to the disorder. Hence, such a test could be a helpful early diagnostic tool for HaNDL.
Treatment Options for Headache With Neurological Deficits and CSF Lymphocytosis (HaNDL syndrome)
Treating HaNDL syndrome (short for Headache with Neurologic Deficits and Lymphocytosis) varies based on how severe it is. This condition, which involves severe headaches along with other neurological issues, often resolves itself and has a high rate of recovery even without specific treatment. However, given that it tends to come back, it’s essential for patients to be educated about the illness and reassured that they will likely recover from it. During a severe episode, managing the headaches is the primary goal.
Standard medical tests like brain imaging and spinal tap (a procedure to test the fluid surrounding the brain) might be done in the first two instances of these episodes. Yet if the diagnosis of HaNDL is confirmed, there may be no need for such exhaustive tests every time.
Medicines often used for epilepsy or preventing migraines may help avoid acute HaNDL attacks as the headaches involved often resemble migraines. But it can be tough to determine if these medicines are indeed effective since the condition generally resolves on its own.
If the headaches return or if new symptoms like visual disturbances develop after recovery from HaNDL, it’s recommended that the patient is reevaluated promptly for raised pressure within the skull. In such cases, measures to drain the spinal fluid (also known as Cerebrospinal Fluid or CSF) and using a medication called acetazolamide might be necessary to avoid vision loss.
Consider an example of a patient who had HaNDL syndrome and experienced severe headaches, motor aphasia (difficulty generating spoken language), and agraphia (loss of ability to write). This patient made a full recovery between episodes and had a normal neurological examination. Testing of the patient’s brain and spinal fluids didn’t reveal any infections or diseases. The brain imaging test and activity tracing were normal too. However, there was an area of reduced activity detected in the frontotemporal area of the brain. This patient was treated with ibuprofen, a common pain reliever, and showed excellent response, remaining symptom-free with no relapses for six months.
Additionally, some patients with HaNDL syndrome showed recurring transient headaches, involuntary movements in the left hand and arm, and paralysis. They exhibited signs of high intracranial pressure and abnormalities in the spinal fluid. The symptoms and high pressure within their skulls were relieved after steroid administration, suggesting that steroids might be a viable treatment strategy for HaNDL syndrome. These findings also lend support to the theory that HaNDL might be an immune response triggered by an infection.
What else can Headache With Neurological Deficits and CSF Lymphocytosis (HaNDL syndrome) be?
Headaches coupled with neurological symptoms and an unusually high number of white blood cells (lymphocytes) in the cerebrospinal fluid—or CSF—but no indicators of a brain infection usually occur as headache episodes. Here, the MRIs of the brain appear normal. While the exact cause remains unknown, a viral infection could be a contributing factor. Patients usually respond well to treatment, with symptoms generally clearing within a week to three weeks. However, these symptoms do resemble those of other neurological disorders, so other severe diseases need to be eliminated from the possible diagnoses. These include:
- Migraine with aura and HaNDL syndrome: These conditions have similar changes in brain blood vessels but differ in the aura symptoms and the presence of white blood cells in CSF.
- Forms of hemiplegic migraine, either inherited or sporadic, do not exhibit high levels of white blood cells in CSF.
- An acute stroke features neurological deficiencies, such as difficulty with speech, weakness or numbness in one side of the body, and long-lasting headaches. Unlike the case under discussion, MRIs reveal positive findings while CSF cell count remains normal.
- Infections like meningoencephalitis, meningitis, and encephalitis cause headaches which present with additional symptoms like high fever, neck stiffness, and skin rashes. Analysing the CSF can help identify the cause.
- In conditions like viral encephalitis and repeated cerebral ischemic events, CSF characteristics and symptoms similar to migraines, weakness on one side, and confusion are seen.
- Epilepsy may be a possible diagnosis in patients who recently suffered a seizure and present with neurological deficiencies. However, a high white blood cell count in CSF is rare.
- Bacteria that can cause Neurobrucellosis are often contracted from close animal contact, leading to headaches, fever, fatigue, and muscle pain.
- Neurosyphilis usually occurs in patients with a history of multiple sexual partners or sexually transmitted infections.
- Neuroborreliosis can cause similar symptoms in people who have traveled to areas with a high prevalence of Lyme disease and exhibit a characteristic bull’s-eye skin rash.
- Reversible posterior leukoencephalopathy syndrome differs from HaNDL by causing seizures and altered mental status. These patients demonstrate specific brain imaging abnormalities.
Comprehensive tests, examinations and careful analysis of the patient’s history will assist in distinguishing these conditions to determine the correct diagnosis.
What to expect with Headache With Neurological Deficits and CSF Lymphocytosis (HaNDL syndrome)
Headache with neurological deficits and an excessive amount of lymphocytes in the cerebrospinal fluid (the fluid that surrounds the brain and spinal cord) is generally not a severe condition. It usually gets better over time without any treatment. That being said, in the past, drugs like corticosteroids (which reduce inflammation), calcium channel blockers (which relax and widen blood vessels), and acetazolamide (which reduces fluid production) have been used for treatment.
Possible Complications When Diagnosed with Headache With Neurological Deficits and CSF Lymphocytosis (HaNDL syndrome)
In the long run, HaNDLE syndrome may cause restlessness and severe mental confusion, often needing hospital stays. Rarely, this condition can also bring about vision loss due to brain damage, swelling in the optic nerve (the nerve connecting the eyes to the brain), and paralysis of a specific cranial nerve that controls eye movement.
- Long-term restlessness and severe mental confusion
- Potential hospital stays
- Rarely, vision loss due to brain damage
- Rarely, swelling in the optic nerve
- Rarely, paralysis of a specific cranial nerve controlling eye movement
Preventing Headache With Neurological Deficits and CSF Lymphocytosis (HaNDL syndrome)
If you or a loved one is diagnosed with HANDL syndrome, it’s helpful to understand what the condition is and how it behaves. Although it sounds scary, this condition is actually harmless and tends to resolve itself over time, which means it doesn’t often cause long-term health problems. It’s true this condition can start suddenly and intensely, but it doesn’t mean it’s going to last forever or put your health at serious risk.
It’s also important to know that HANDL syndrome is quite rare, so there are some risks and potential complications associated with it. But don’t worry, these are also quite rare, and your doctor will explain everything to you and your family to ensure you fully understand.
