How TSC Affects the Brain: Seizures

Epilepsy is perhaps the most common medical condition of people with tuberous sclerosis complex (TSC). Although estimates vary, at least 60 percent and possibly more than 90 percent of people with the disorder experience epileptic seizures at some point in their life. Although there are many types of epileptic seizures, all are caused by a buildup of abnormal electrical activity in the nerve cells, or neurons, of the brain. If these abnormal signals spread to a large enough group of neurons, they can result in loss of consciousness, rhythmic muscle contractions, and other behaviors characteristic of seizures. Exactly how and to what severity a seizure manifests itself, however, depends on which region of the brain gives rise to the abnormal neuron activity, as well as how much of the brain is ultimately involved.

The abnormal cells that make up cortical tubers are thought to be involved in epileptic seizures in people with TSC. These masses of cells disrupt the highly organized neurological connections of the cerebral cortex, and their misfiring likely gives rise to the cascade of errant signals that create seizures. Indeed, studies have found a strong relationship between the location of tubers and the source of abnormal electrical patterns that result in epileptic seizures. However, neurologists aren't certain if cells that make up tubers cause seizures directly, since many show no electrical activity at all. Scientists think it may be possible that the abnormal tissue of the tuber irritates what appears to be normal brain tissue surrounding it, or that the brain tissue surrounding a tumor may also be dysfunctional in some way.

The role of tubers in seizures is made less clear by the fact that some individuals with TSC and intractable seizures have normal MRI scans with no visible tubers, or have seizures that originate in regions with no tubers. Consequently, this area remains an important subject for debate and continued research among neurologists who specialize in seizures.

The identification of seizures and the search for more effective methods of controlling them are critical to the health and well-being of many people with TSC. Not only do seizures cause a great deal of discomfort and anxiety, and pose a potential danger for those who experience them, they are also linked to learning disabilities and behavioral disorders associated with TSC. Although specialists are uncertain whether seizures cause these other neurological manifestations or simply share a common cause with them, understanding and effectively treating seizures will almost certainly lead to better behavioral and cognitive outcomes.

Diagnosis

Because seizures occur so frequently in the general population and are not highly specific to TSC, they are not classified as features in the diagnostic criteria for the disorder. Even so, they often provide one of the first symptoms that ultimately lead to diagnosis. It is not uncommon for parents to recognize behaviors that are out of the ordinary in their own child—behaviors that others might overlook. Often, it is insights and observations like these that lead parents to specialists who can diagnose TSC and provide the medical care necessary to treat the disorder.

Although seizures can begin at any age, in most people with TSC they begin during the first year and often as early as the first few months of life. It is critical that these early seizures receive prompt medical attention. People with TSC whose seizures have gone untreated or uncontrolled during infancy are more likely to experience learning disabilities and behavioral disorders later on.

People with TSC may display several different types of epileptic seizures at any given age, and these can change over time, or cease altogether, for unknown reasons. Brain development is probably the most important cause of variability in seizure type or frequency over time, but the onset of puberty and changes in various treatment regimens can also have an effect.

Epilepsy is perhaps the most common medical condition of people with tuberous sclerosis complex (TSC). Although estimates vary, at least 60 percent and possibly more than 90 percent of people with the disorder experience epileptic seizures at some point in their life. Although there are many types of epileptic seizures, all are caused by a buildup of abnormal electrical activity in the nerve cells, or neurons, of the brain. If these abnormal signals spread to a large enough group of neurons, they can result in loss of consciousness, rhythmic muscle contractions, and other behaviors characteristic of seizures. Exactly how and to what severity a seizure manifests itself, however, depends on which region of the brain gives rise to the abnormal neuron activity, as well as how much of the brain is ultimately involved.

The abnormal cells that make up cortical tubers are thought to be involved in epileptic seizures in people with TSC. These masses of cells disrupt the highly organized neurological connections of the cerebral cortex, and their misfiring likely gives rise to the cascade of errant signals that create seizures. Indeed, studies have found a strong relationship between the location of tubers and the source of abnormal electrical patterns that result in epileptic seizures. However, neurologists aren't certain if cells that make up tubers cause seizures directly, since many show no electrical activity at all. Scientists think it may be possible that the abnormal tissue of the tuber irritates what appears to be normal brain tissue surrounding it, or that the brain tissue surrounding a tumor may also be dysfunctional in some way.

The role of tubers in seizures is made less clear by the fact that some individuals with TSC and intractable seizures have normal MRI scans with no visible tubers, or have seizures that originate in regions with no tubers. Consequently, this area remains an important subject for debate and continued research among neurologists who specialize in seizures.

The identification of seizures and the search for more effective methods of controlling them are critical to the health and well-being of many people with TSC. Not only do seizures cause a great deal of discomfort and anxiety, and pose a potential danger for those who experience them, they are also linked to learning disabilities and behavioral disorders associated with TSC. Although specialists are uncertain whether seizures cause these other neurological manifestations or simply share a common cause with them, understanding and effectively treating seizures will almost certainly lead to better behavioral and cognitive outcomes.

Types of Seizures

• Infantile Spasms
  Infantile spasms are seen in about one-third of infants diagnosed with TSC. They occur most often at 5 to 9 months of age, and are rarely seen in infants younger than 3 months or in children older than 18 months. These repetitive muscle contractions, usually involving the head, trunk, and extremities, typically occur in clusters, in which one spasm follows another after a brief period of time in between. A cluster may last 15 to 20 minutes and consist of many spasms. Clusters of infantile spasms typically occur as the child is going to sleep, or soon after waking.
  
  The three main types of infantile spasms associated with TSC are flexor, extensor, and mixed spasms. During flexor spasms, infants contract muscles that cause their limbs to pull inward. During extensor spasms, infants contract muscles that cause them to extend their limbs. Mixed spasms are repetitive combinations of both flexor and extensor spasms. In addition to these three main types, infants may also experience subtle spasms that may involve eye shifts, head turns, grimacing, staring, or an appearance of general distractedness. Most infants that develop spasms also exhibit an overall change in behavior, often becoming irritable or appearing indifferent to various types of stimuli with the onset of spasm. Some of the infants can show developmental arrest or even lose some of their previously acquired milestones following the onset of infantile spasms.
  
  Although not all infantile spasms are immediately obvious, parents are still likely to pick up on the subtle cues that suggest something may be out of the ordinary with their child. Acting quickly on these suspicions, by seeking the advice of a pediatrician or TSC specialist, is often critical in these cases as well as those in which seizures are more obvious. Studies have found that reducing the frequency of or eliminating infantile spasms with medication may reduce the incidence and severity of learning disabilities and behavioral disorders, as well as the prevalence of other types of seizures.
  
  
• Partial Seizures
  Partial seizures originate from a localized, or specific, part of the brain. There are two types of partial seizures: simple partial seizures, which do not alter an individual's mood or consciousness, and complex partial seizures, which are associated with a change in the level of consciousness or responsiveness. The clinical features of a simple partial seizure depend on the region of the brain in which the seizure originates, and may be characterized by little more than a tingling sensation in the hands or feet or a visual distortion or hallucination. The clinical features of a complex partial seizure also depend on the region of the brain involved, and can have a similar onset as a simple partial seizure. However, the individual's responsiveness is impaired during the seizure episode. For example, if a seizure starts in the region of the brain controlling movement of the hand, a simple partial seizure could be characterized by jerking movements of the hand. If the person also begins staring and becomes unresponsive, the seizure would be considered a complex partial seizure.
  
  
• Generalized Seizures
  Generalized seizures can be divided into two types: primary generalized and secondary generalized. Primarily generalized seizures are thought to involve both hemispheres of the brain at seizure onset. Secondarily generalized seizures begin as partial seizures originating from a specific region of the brain, but very rapidly become generalized involving both sides of the brain.
  
  The best-known type of generalized seizure is tonic-clonic, formerly known as a grand mal seizure. It begins with the tonic phase, which often involves a fall to the floor, stiffening of the limbs, and clenching of teeth. This is followed by the clonic phase, which presents itself as the violent rhythmic jerking of the limbs and torso.
  
  All seizures associated with TSC, whether they become generalized or not, are thought to begin as partial seizures. These localized events typically originate at or near the location of a cortical tuber and may spread to other parts of the brain, becoming a generalized seizure.
  
  
• Other Seizure Types
  People with TSC may experience other types of seizures as well. Myoclonic seizures, for example, are single, intense muscular contractions that may result in a single powerful jerk of the limbs, trunk, or face. They may be partial, originating on one side of the brain, or generalized, involving both sides. Pure tonic seizures involve prolonged contraction of muscles and stiffening of limbs without the rhythmic motion characteristic of most seizures. Atonic seizures cause sudden, uncontrolled relaxation of most or all muscles in the body. All three of these seizure types—myoclonic, pure tonic, and atonic—may result in what experts generally refer to as drop attacks, in which an individual suddenly collapses or is thrown to the ground. Injuries caused by such events are common and may be severe.