Brain tumor causes seizures

The Link Between Seizures and Brain Tumors

Medication can help to reduce or stop seizures, although patients who are already receiving brain tumor treatment might be battling lethargy and other negative side effects, and seizure medication need to be well chosen. Epilepsy surgery can be an option in some patients who cannot be controlled by medication.

“You can’t take a simplistic approach because of the complexity,” Dr. Templer continues. “We’re always visiting the quality of life at each visit, so they can continue to do what they want.”

How to Spot a Seizure

Each person experiences seizures differently, and seizures may last anywhere from seconds to minutes. During a seizure, you may notice the following:

  • Aura, a sudden, brief, unusual sensation
  • Uncontrolled jerking
  • Brief time gaps or confusion
  • Falls
  • Bystanders may notice staring, unresponsiveness or stiffening and jerking followed by confusion

It is often the first bigger seizure which makes patients to have brain imaging including magnetic resonance imaging (MRI) or a computed tomography (CT). Many patients already had smaller events or auras which went unrecognized.

Most seizures stop by themselves within two to three minutes, although there can be a prolonged period of confusion afterwards. For seizures longer than five minutes, a call for an ambulance should be placed.

How to Manage Seizures

A number of lifestyle changes can reduce the chance of triggering a seizure. “The best thing you can do is make yourself a priority,” says Dr. Templer. She suggests getting the recommended amount of sleep, exercising frequently and avoiding alcohol.

Find out what to do — and what not to do — if someone near you has a seizure.

ON THIS PAGE: You will find out more about body changes and other things that can signal a problem that may need medical care. Use the menu to see other pages.

People with a brain tumor may experience the following symptoms or signs. Sometimes, people with a brain tumor do not have any of these changes. Or, the cause of a symptom may be a different medical condition that is not a brain tumor.

Symptoms of a brain tumor can be general or specific. A general symptom is caused by the pressure of the tumor on the brain or spinal cord. Specific symptoms are caused when a specific part of the brain is not working well because of the tumor. For many people with a brain tumor, they were diagnosed when they went to the doctor after experiencing a problem, such as a headache or other changes.

General symptoms include:

  • Headaches, which may be severe and worsen with activity or in the early morning

  • Seizures. People may experience different types of seizures. Certain drugs can help prevent or control them. Motor seizures, also called convulsions, are sudden involuntary movements of a person’s muscles. The different types of seizures and what they look like are listed below:

    • Myclonic

      • Single or multiple muscle twitches, jerks, spasms

    • Tonic-Clonic (Grand Mal)

      • Loss of consciousness and body tone, followed by twitching and relaxing muscles that are called contractions

      • Loss of control of body functions, such as loss of bladder control

      • May be a short 30-second period of no breathing and a person’s skin may turn a shade of blue, purple, gray, white, or green

      • After this type of seizure, a person may be sleepy and experience a headache, confusion, weakness, numbness, and sore muscles.

    • Sensory

      • Change in sensation, vision, smell, and/or hearing without losing consciousness

    • Complex partial

      • May cause a loss of awareness or a partial or total loss of consciousness

      • May be associated with repetitive, unintentional movements, such as twitching

  • Personality or memory changes

  • Nausea or vomiting

  • Fatigue

  • Drowsiness

  • Sleep problems

  • Memory problems

  • Changes in ability to walk or perform daily activities

Symptoms that may be specific to the location of the tumor include:

  • Pressure or headache near the tumor

  • Loss of balance and difficulty with fine motor skills is linked with a tumor in the cerebellum.

  • Changes in judgment, including loss of initiative, sluggishness, and muscle weakness or paralysis is associated with a tumor in the frontal lobe of the cerebrum.

  • Partial or complete loss of vision is caused by a tumor in the occipital lobe or temporal lobe of the cerebrum.

  • Changes in speech, hearing, memory, or emotional state, such as aggressiveness and problems understanding or retrieving words can develop from a tumor in the frontal and temporal lobe of the cerebrum.

  • Altered perception of touch or pressure, arm or leg weakness on 1 side of the body, or confusion with left and right sides of the body are linked to a tumor in the frontal or parietal lobe of the cerebrum.

  • Inability to look upward can be caused by a pineal gland tumor.

  • Lactation, which is the secretion of breast milk, and altered menstrual periods in women, and growth in hands and feet in adults are linked with a pituitary tumor.

  • Difficulty swallowing, facial weakness or numbness, or double vision is a symptom of a tumor in the brain stem.

  • Vision changes, including loss of part of the vision or double vision can be from a tumor in the temporal lobe, occipital lobe, or brain stem.

If you are concerned about any changes you experience, please talk with your doctor. Your doctor will ask how long and how often you’ve been experiencing the symptom(s), in addition to other questions. This is to help figure out the cause of the problem, called a diagnosis.

If a brain tumor is diagnosed, relieving symptoms remains an important part of your care and treatment. This may be called palliative care or supportive care. It is often started soon after diagnosis and continued throughout treatment. Be sure to talk with your health care team about the symptoms you experience, including any new symptoms or a change in symptoms. Learn more about managing symptoms of a brain tumor in the Types of Treatment section.

The next section in this guide is Diagnosis. It explains what tests may be needed to learn more about the cause of the symptoms. Use the menu to choose a different section to read in this guide.

Understanding Brain Tumor-Related Epilepsy

Epilepsy is rather common in people with brain tumors – seizures can be the presenting symptom (i.e., seizures may be the reason an individual with a brain tumor seeks medical help) or may occur later in the course of progression of the brain tumor. The incidence of seizures depends on the type and location of the brain tumor. For example, in certain kinds of slow-growing tumors, seizures may be seen in as many as 80% of the patient population.

Brain tumors can be primary (tumors that begin in the brain or spinal cord) or secondary (tumors that reach the central nervous system from another part of the body). Brain tumors can also be classified as benign (slow-growing masses that have a defined edge and do not usually spread to other parts of the body) or malignant (tumors that grow quickly, have hard-to-define edges and do usually invade the surrounding tissues).

The reasons why brain tumors can be associated with seizures are not completely known, but some hypotheses are that the tumor may apply physical pressure on surrounding brain tissue and may release substances like glutamate that cause seizures.

Treating Brain-Tumor Related Seizures

The first line of treatment for brain tumor-related epilepsy is anti-epileptic medication. Although these drugs do limit seizures in some people with brain tumors, they may be associated with substantial side-effects and resistance. In the context of brain tumor-related epilepsy, resistance is defined when two anti-epileptic drugs fail to effectively stop seizures.

When this happens, the decision to resect the tumor is made. Oftentimes, resection of the tumor may lead to seizure reduction, but there are also occasions when tumor resection does not stop seizures. In summary, epilepsy related to brain tumors can be thought of as a separate entity that requires a unique treatment and management plan.

An interesting molecule that has been shown in the lab to have anticonvulsant effects is adenosine. The enzyme adenosine kinase (ADK) is responsible for metabolism (breakdown) of adenosine – hence, increased ADK activity will decrease levels of adenosine. A study that was published a few years ago looked at ADK in resected brain tumor tissue. The scientists found that tumor cells and the peritumoral tissue (area surrounding the tumor) had higher levels of ADK than normal control tissue. There was also higher ADK expression in resected tissue of patients with brain tumors that had epilepsy, as compared to people with brain tumors that didn’t have epilepsy. Hence, adenosine and ADK may provide clues into the presence of seizures in brain tumors.

A brain tumour or its treatment can sometimes cause seizures, which are disruptions to the normal patterns of electrical impulses in the brain. They may also be called fits or convulsions.

Seizures can often be prevented with anticonvulsant medicines (also called anti-epileptic or anti-seizure medicines). You can also reduce your seizure risk by making sure you don’t get too tired or fatigued.

Generalised seizures

These types of seizures typically affect the whole body. The most common type is called a tonic-clonic seizure (previously known as a grand mal seizure). A seizure often starts with a sudden cry, followed by the person falling down and losing consciousness. The person’s muscles may twitch violently and their breathing may be shallow for up to two minutes. They may lose bladder and bowel control, and bite their tongue.

Partial seizures

These affect one part of the body, such as an arm or leg. Symptoms include twitching; jerking; tingling or numbness; and altered sensations (hallucinations), such as changed vision or hearing, strange tastes or smells, or a feeling of deja vu. Partial seizures may cause a brief loss of consciousness, changes in memory loss just before, during and after the seizure.

Learn more about:

  • Ways to help someone having a seizure
  • Anticonvulsant medicines

Ways to help someone having a seizure

  • Remain calm and stay with the person while they are having a seizure, but do notrestrain them or put anything in their mouth.
  • Protect the person from injury (e.g. move hazards, lower them to the floor if possible, loosen clothing, place a soft pillow under their head and shoulders).
  • Lie the person on their side to clear their airway after jerking stops. This is particularly important if the person has vomited, is unconscious or has food or fluid in their mouth.
  • Call 000 for an ambulance if it is the first seizure the person has had; if the person is injured; if there was food or water in the person’s mouth; if the seizure lasts longer than five minutes; or if you are in any doubt.
  • Observe the person until they have recovered or the ambulance arrives. Time how long the seizure lasts so you can tell the paramedics.
  • Talk to the person and explain what has occurred. In many cases, people are confused after a seizure.
  • If the seizure occurs while a person is in a wheelchair or car, support their head and leave them safely strapped in their seat until the seizure is over. Afterwards, remove the person from their seat, if possible. Roll them onto their side if there is food, water or vomit in their mouth.
  • Allow the person to rest afterwards as most seizures are exhausting.
  • For detailed information and an online tool for creating a Seizure Management Plan, visit Epilepsy Action Australia or call 1300 37 45 37.

Anticonvulsant medicines

There are many types of anticonvulsant drugs, which are used to prevent seizures. You may require blood tests while you are taking anticonvulsants. This is to check whether the dose is effective and how your liver is coping with the medicine.

Side effects of anticonvulsant drugs vary, but they may include tiredness, gum problems, shakes (tremors), nausea, vomiting, weight changes, depression, irritability and aggression. If you are allergic to the medicine, you may get a rash. Tell your medical team if you have any skin changes or other side effects. Your doctor can adjust the dose or try another anticonvulsant. Do not stop taking the medicine or change the dose without your doctor’s advice.

If you are taking anticonvulsants, you may need to avoid eating grapefruit and Seville oranges, and check with your doctor before taking any herbal medicines, as these can change the way some anticonvulsants work. You should also limit your alcohol intake.

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Dr. Benjamin Deneen and Dr. Chad Creighton.

Detecting brain tumors at the earliest possible stage and eliminating them before seizures begin might be possible one day, according to research by scientists at Baylor College of Medicine and Texas Children’s Hospital.

In the study, which is published in the journal Nature Neuroscience, the scientists report that the emergence of specific brain cells during brain tumor progression in a mouse model marked the onset of seizures and brain tumor invasion. An improved understanding of how brain tumors cause seizures can potentially lead to strategies to prevent them or treat them.

“We began this project by studying normal brain cells,” said co-senior author Dr. Benjamin Deneen, associate professor in the Center for Stem Cell and Regenerative Medicine at Baylor and the Neurological Research Institute at Texas Children’s Hospital. “The brain has billions of cells of which only 30 percent are neurons. Astrocytes are the predominant cell type of the remaining 70 percent. Surprisingly, astrocytes have not been studied in as much detail as neurons have.”

“Although astrocytes are often broadly categorized as one cell type, a lot of diversity exists in the functions carried out by these cells,” said co-senior author Dr. Chad Creighton, associate professor of medicine and member of the Dan L Duncan Comprehensive Cancer Center Division of Biostatistics at Baylor.

Astrocytes play diverse roles in the brain, from supporting the functions of neurons, participating in synapse formation and function and in the release of neurotransmitters, to making the blood-brain barrier and other functions. What is not known is whether all these functions are carried out by different subpopulations of astrocytes. This study explores the cellular and functional diversity of the most enigmatic, yet most abundant cell type in the brain. Answering this fundamental question served as the starting point for this investigation.

Better understanding the underappreciated astrocyte

The researchers took populations of mouse astrocytes, which until now have been considered to be a cell type with little diversity, and used molecular markers expressed on the cells’ surface to divide the cells into subpopulations according to the cell surface markers expressed. They identified five subpopulations – the scientists called them subpopulations A, B, C, D and E – each containing a unique combination of cell surface markers. These subpopulations were consistently present across several different regions of the brain.

Further studies showed that each subpopulation of astrocytes expressed distinct sets of genes. These molecular signatures suggested that each subpopulation might play different roles in the brain. In particular, the scientists were interested in subpopulation C, which expressed a significant number of genes associated with synapses, the junctions that transmit nerve impulses that connect networks of neurons in the brain.

The researchers compared the ability of the different subpopulations of astrocytes to support the formation and function of synapses between neurons.

“In the laboratory, we combined individual subpopulation of astrocytes with neurons and measured synapse formation and function,” said Deneen. “We found that neurons incubated with subpopulation C made more synapses than neurons incubated with the other subpopulations.”

Taken together, these results revealed that astrocytes in the normal mouse brain comprise at least five distinct subpopulations that differentially support synapse formation and function.

Linking astrocytes to human glioma

“Astrocytes are associated with numerous neurological conditions, including injury, multiple sclerosis, autism, schizophrenia, Alzheimer’s and Parkinson’s disease and brain tumors. Given that we found diverse astrocyte subpopulations, we wondered whether these subpopulations could also explain astrocyte contributions to a host of different neurological diseases,” Deneen said.

One of the interests of the Deneen lab is identifying mechanisms that regulate astrocyte development and how these cells contribute to neurological diseases, in particular human glioblastoma multiforme, the most aggressive and deadly type of brain tumor. In these type of cancer, about 80 percent of the tumor comprises transformed astrocyte-like cells, and, just as in the case of normal brain tissue, the diversity of these tumor cell subpopulations and functions in brain tumors had not been studied in detail.

In this case, the scientists used a different approach to determine whether astrocyte-like cells in human glioblastoma include different astrocyte subpopulations.

“We used publicly available genomic datasets to help us understand what distinguishes the different types of astrocytes from each other,” Creighton said. “The genomic datasets compile entire genomes – all the genes – of different types of cells. Using this resource, we discovered that each type of human astrocyte showed very distinctive patterns of gene activation. It was by comparing these patterns with patterns associated with brain cancer or with epilepsy, using public data, that we discovered how specific types of astrocytes appear to have roles in these diseases.”

To support that astrocytes seemed to play a role in human glioblastoma, the researchers genetically engineered two mouse models of the disease and observed that the astrocyte subpopulations are also present in mouse tumors. The subpopulations are also present in primary human specimens of human glioblastoma multiforme.

Astrocytes and seizures

One striking characteristic of glioblastoma, which usually leads to the discovery of the tumor, is epileptic seizures.

On one occasion Deneen was talking with Dr. Jeffrey L. Noebels, about this research. Noebels, who is professor of neurology, neuroscience, and molecular and human genetics, director of the Blue Bird Circle Developmental Neurogenetics Laboratory at Baylor and is a leader in the field of epilepsy, asked Deneen, “do your mice with brain tumors have seizures?” “They do,” Deneen said.

This conversation led to planning a series of experiments in the mouse models of glioma to determine the time scale of the seizures and whether different sub populations of astrocyte-like cells within the tumor were associated with seizures.

The results of these experiments showed that as the tumor grows, the excitability of the adjacent neurons progressively increases. Seventy days after birth, the mice had visible seizures that correlated with the emergence of astrocyte subpopulation C. Further linking these astrocyte-like subpopulations to seizures, the scientists showed that subpopulation C expresses a significant number of genes linked to epilepsy.

While subpopulation C seems to be involved with seizures in the mouse model of glioblastoma, subpopulations B and D showed they were able to migrate more in laboratory assays than population C.

“Taken all together, the evidence from the mouse model of glioblastoma indicates that as the tumor evolves, different subpopulations of astrocyte-like cells develop within the tumor and execute distinct functions that are related to two important tumor characteristics, synaptic imbalance that can lead to seizures, and tumor migration that can lead to tumor invasion of other tissues,” Deneen said.

“Less than half of the patients with epilepsy caused by a brain tumor can be helped with existing antiepileptic drugs,” said Noebels, co-author of the work. “We do not understand exactly how malignant cells cause seizures, or why seizures persist after tumor surgery. Until now, we could only study this brain tissue at later misleading stages. I am excited that this next-generation experimental model in mice will allows us to study, for the first time, the earliest effects of human tumors on brain circuits before seizures actually begin and understand the mechanisms. These studies would be a major advance in patient care, allowing clinicians to bypass precious months spent searching for effective therapy to stop seizures. Because seizures themselves damage brain tissue, timely effective therapy is of the essence.”

Other contributors to this work include Chia-Ching Lin, Kwanha Yu, Asante Hatcher, Teng-Wei Huang, Hyun Kyoung Lee, Jeffrey Carlson, Matthew C Weston, Fengju Chen, Yiqun Zhang, Wenyi Zhu, Carrie A Mohila, Nabil Ahmed, Akash J Patel and Benjamin R Arenkiel.

This work was supported by grants from the Sontag Foundation, the National Multiple Sclerosis Society (RG-1501-02756), the Cancer Prevention Research Institute of Texas (RP510334 and RP160192), by the American Cancer Society (PF-15-220) and the US National Institutes of Health (NIH) (NS071153, NS089366, NS29709 and T32HL902332). This project was also supported in part by the Genomic and RNA Profiling Core at Baylor College of Medicine with funding from the NIH–NCI grant (P30CA125123), funding from the NIH (P30 AI036211, P30 CA125123 and S10 RR024574), and by IDDRC grant number 1U54 HD083092 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Chia-Ching John Lin, et al, Identification of diverse astrocyte populations and their malignant analogs, Nature Neuroscience, Feb. 2017, doi:10.1038/nn.4493.

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