Injuries, Diseases, and Disorders of the Central Nervous System

Traumatic Brain Injury

Traumatic brain injury (TBI) occurs when an external force injures the brain and can be caused by a direct impact or by acceleration alone.

Learning Objectives

Recognize the severity of traumatic brain injuries

Key Takeaways

Key Points

  • Traumatic brain injury (TBI) occurs when an external force injures the brain and can be caused by a direct impact or by acceleration alone.
  • Following the initial injury, brain trauma causes secondary events, like changes in cerebral blood flow and intracranial pressure, that contribute to the damage caused by the trauma.
  • Brain injuries can be classified into mild, moderate, and severe categories; the Glasgow Coma Scale (GCS) is the most commonly used system for classifying TBI severity.
  • Symptoms of TBI depend on the severity of the injury, whether the injury is diffuse or focal, and the part of the brain that is affected.
  • A famous case of personality change following TBI is that of Phineas Gage, who survived a construction accident where a large iron rod was driven through the front of his head.

Key Terms

  • Glasgow Coma Scale: (GCS) A neurological scale that aims to give a reliable, objective way of recording the conscious state of a person for initial as well as subsequent assessment.

Examples

Examples of the causes of TBI include violence, transportation accidents, construction accidents, and sports. Examples of the symptoms of TBI include headache, nausea, dizziness, confusion, and trouble with memory, which can vary depending on the severity of the injury. Common long-term symptoms of moderate to severe TBI are changes in social behavior and cognitive changes, including problems with attention and planning.

Traumatic brain injury (TBI), also known as intracranial injury, occurs when an external force traumatically injures the brain. TBI can be classified based on severity, mechanism (closed or penetrating head injury), or other features, such as whether it occurs in a specific location or over a widespread area. Head injury usually refers to TBI, but is a broader category because it can involve damage to structures other than the brain, such as the scalp and skull.

TBI is a major cause of death and disability worldwide, especially in children and young adults. Causes include falls, vehicle accidents, and violence. Prevention measures include use of technology to protect those who suffer from automobile accidents, such as seat belts and sports or motorcycle helmets. Efforts to reduce the number of automobile accidents are also implemented, such as safety education programs and enforcement of traffic laws.

Causes of Traumatic Brain Injury

Brain trauma can be caused by a direct impact or by acceleration alone. In addition to the damage caused at the moment of injury, brain trauma causes secondary injury, a variety of events that take place in the minutes and days following the injury. These processes, which include alterations in cerebral blood flow and the pressure within the skull, contribute substantially to the damage from the initial injury.

Types of Brain Injuries

Brain injuries can be classified into mild, moderate, and severe categories. The Glasgow Coma Scale (GCS), the most commonly used system for classifying TBI severity, grades a person’s level of consciousness on a scale of 3–15 based on verbal, motor, and eye-opening reactions to stimuli. It is generally agreed that a TBI with a GCS of 13 or above is mild, 9–12 is moderate, and 8 or below is severe.

Side Effects and Complications

In this image, a subdural hematoma is evident on the right side, which is putting pressure on the brain and shifting the midline from center to the left.

Subdural hematoma is a possible result of traumatic head injury: In this image, the single arrow marks spread of the subdural haematoma and the double arrow marks the midline shift.

TBI can cause a host of physical, cognitive, social, emotional, and behavioral effects, and the outcome can range from complete recovery to permanent disability or death. The 20th century saw critical developments in diagnosis and treatment that decreased death rates and improved outcome. Some of the current imaging techniques used for diagnosis and treatment include CT scans (computed tomography) and MRIs (magnetic resonance imaging). Depending on the injury, treatment required may be minimal or may include interventions such as medications, emergency surgery or surgery years later. Physical therapy, speech therapy, recreation therapy, and occupational therapy may be employed for rehabilitation.

Complications are distinct medical problems that may arise as a result of the TBI. TBI can cause prolonged or permanent effects on consciousness, such as coma, brain death, persistent vegetative state (in which patients are unable to achieve a state of alertness to interact with their surroundings), and minimally conscious state. Lying still for long periods can cause complications including pressure sores, pneumonia or other infections, progressive multiple organ failure, and deep venous thrombosis, which can cause pulmonary embolism. Complications involving the blood vessels include vasospasm, in which vessels constrict and restrict blood flow, the formation of aneurysms, in which the side of a vessel weakens and balloons out, and stroke. Movement disorders that may develop after TBI include tremor, ataxia (uncoordinated muscle movements), myoclonus (shock-like contractions of muscles), and loss of movement range and control (in particular with a loss of movement repertoire). The risk of post-traumatic seizures increases with severity of trauma and is particularly elevated with certain types of brain trauma such as cerebral contusions or hematomas.

Cerebrovascular Accident

A cerebrovascular accident results from loss of oxygenated blood to a region of the brain and is typically accompanied by neuronal loss.

Learning Objectives

Describe what is a cerebrovascular accident or stroke

Key Takeaways

Key Points

  • A stroke, or cerebrovascular accident (CVA), is the rapid loss of brain function due to disturbance in the blood supply to the brain.
  • Different types of strokes have different underlying causes.
  • Stroke is currently the second leading cause of death in the western world.
  • The most important modifiable risk factors for stroke are high blood pressure and atrial fibrillation, although other risk factors can also be modified to decrease risk.

Key Terms

  • embolus: An obstruction causing an embolism: a blood clot, air bubble, or other matter carried by the blood stream and causing a blockage or occlusion of a blood vessel.
  • thrombosis: The formation of thrombi in the blood vessels of a living organism, causing obstruction of the circulation.
  • embolism: An obstruction or occlusion of an artery by an embolus, that is by a blood clot, air bubble, or other matter that has been transported by the blood stream.

Examples

  • Examples of risk factors for stroke include high blood pressure, high cholesterol, diabetes, cigarette smoking, lack of physical activity, and obesity.
  • The physical disabilities that can result from stroke are varied and depend on the severity of the stroke and the affected areas of the nervous system. Examples of possible disabilities caused by stroke include loss of motor control, muscle weakness, numbness, appetite loss, speech loss, vision loss, and pain.

A stroke, or cerebrovascular accident (CVA), is the rapid loss of brain function(s) due to disturbance in the blood supply to the brain. This can be due to ischemia (lack of blood flow ) caused by blockage ( thrombosis, arterial embolism ) or a hemorrhage (leakage of blood). As a result, the affected area of the brain cannot function, which might result in an inability to move one or more limbs on one side of the body, inability to understand or formulate speech, or an inability to see one side of the visual field.

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An Example of a Stroke: A intra-parenchymal bleed with surrounding edema.

A stroke is a medical emergency and can cause permanent neurological damage, complications, and death. It is the leading cause of adult disability in the United States and Europe and the second leading cause of death worldwide.

Risk Factors

Risk factors for stroke include old age, hypertension (high blood pressure), previous stroke or transient ischemic attack (TIA), diabetes, high cholesterol, cigarette smoking, and atrial fibrillation.

High blood pressure is the most important modifiable risk factor of stroke. An ischemic stroke is occasionally treated in a hospital with thrombolysis (also known as a “clot buster”), and some hemorrhagic strokes benefit from neurosurgery. Treatment to recover any lost function is termed “stroke rehabilitation,” ideally in a stroke unit and involving health professions such as speech and language therapy, physical therapy, and occupational therapy. Prevention of recurrence may involve the administration of antiplatelet drugs such as aspirin and dipyridamole, control and reduction of hypertension, and the use of statins. Selected patients may benefit from carotid endarterectomy and the use of anticoagulants.

Causes

Different types of strokes are caused by different mechanisms.

In thrombotic stroke a thrombus (blood clot) usually forms around atherosclerotic plaques. Since blockage of the artery is gradual, onset of symptomatic thrombotic strokes is slower. A thrombus itself (even if non-occluding) can lead to an embolic stroke if the thrombus breaks off, at which point it is called an ” embolus.” Two types of thrombosis can cause stroke: large vessel disease involves the common and internal carotids, vertebral, and the Circle of Willis.

An embolic stroke refers to the blockage of an artery by an arterial embolus, a travelling particle or debris in the arterial bloodstream originating from elsewhere. An embolus is most frequently a thrombus, but it can also be a number of other substances including fat (e.g., from bone marrow in a broken bone), air, cancer cells, or clumps of bacteria (usually from infectious endocarditis).

Systemic hypoperfusion is the reduction of blood flow to all parts of the body. It is most commonly due to cardiac pump failure from cardiac arrest or arrhythmias, or from reduced cardiac output as a result of myocardial infarction, pulmonary embolism, pericardial effusion, or bleeding. Hypoxemia (low blood oxygen content) may precipitate the hypoperfusion.

Cerebral venous sinus thrombosis leads to stroke due to locally increased venous pressure, which exceeds the pressure generated by the arteries. Infarcts are more likely to undergo hemorrhagic transformation (leaking of blood into the damaged area) than other types of ischemic stroke.

A silent stroke is a stroke that does not have any outward symptoms, and the patients are typically unaware they have suffered a stroke. Despite not causing identifiable symptoms, a silent stroke still causes damage to the brain and places the patient at increased risk for both transient ischemic attack and major stroke in the future. Conversely, those who have suffered a major stroke are at risk of having silent strokes.

Prevention and Treatment

Given the disease burden of strokes, prevention is an important public health concern. Primary prevention is less effective than secondary prevention (as judged by the number needed to treat to prevent one stroke per year). Because a stroke may indicate underlying atherosclerosis, it is important to determine the patient’s risk for other cardiovascular diseases such as coronary heart disease. Conversely, aspirin confers some protection against first stroke in patients who have suffered a myocardial infarction or patients with a high cardiovascular risk.

The most important modifiable risk factors for stroke are high blood pressure and atrial fibrillation (although magnitude of this effect is small). The evidence from the Medical Research Council trials is that 833 patients have to be treated for one year to prevent one stroke. Other modifiable risk factors include high blood cholesterol levels, diabetes, cigarette smoking, heavy alcohol consumption, and unhealthy diet.

Transient Ischemic Attacks

A transient ischemic attack is similar to a stroke; though without permanent damage, it can serve as an important risk factor for stroke.

Learning Objectives

Describe the effects of transient ischemic attacks

Key Takeaways

Key Points

  • A transient ischemic attack (TIA) is often referred to as mini-stroke and is a transient episode of brain dysfunction caused by ischemia, or loss of blood flow to the brain.
  • TIAs and strokes cause similar symptoms such as paralysis, weakness, numbness, slurred speech, and mental confusion.
  • Unlike a stroke, the symptoms of a TIA can resolve within 24 hours.
  • Treatment is limited. A TIA may be prevented by changes in lifestyle.
  • Having a TIA is a risk factor for future stroke.

Key Terms

  • ischemia: Local disturbance in blood circulation due to mechanical obstruction of the blood supply, such as by a narrowed artery or clot.

Examples

Example drugs used to prevent future TIAs include anti-coagulant medications, like heparin and warfarin, and anti-platelet medications such as aspirin.

A transient ischemic attack (abbreviated as TIA, often referred to as mini stroke) is a transient episode of neurologic dysfunction caused by ischemia—either focal brain, spinal cord, or retinal—without acute infarction (tissue death).

TIAs share the same underlying etiology (cause) as strokes: a disruption of cerebral blood flow (CBF). TIAs and strokes cause the same symptoms. Unlike a stroke, the symptoms of a TIA can resolve within a few minutes or 24 hours. Brain injury may still occur in a TIA lasting only a few minutes. Having a TIA is a risk factor for eventually having a stroke or a silent stroke.

Symptoms

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Heart-Great Vessels: Cardiac Myxoma: This image is the left atrial mass of a 71 year old man who had TIAs.

Symptoms vary widely from person to person, depending on the area of the brain involved. The most frequent symptoms include:

  • temporary loss of vision (typically amaurosis fugax)
  • difficulty speaking (aphasia)
  • weakness on one side of the body (hemiparesis)
  • numbness or tingling (paresthesia), usually on one side of the body.

There have also been cases of temporary and partial paralysis affecting the face and tongue of the afflicted. The symptoms of a TIA are short-lived and usually last a few seconds to a few minutes, and most symptoms disappear within 60 minutes. Some individuals may have a lingering feeling that something odd happened to the body. Dizziness, lack of coordination, or poor balance are also symptoms related to TIA. Symptoms vary in severity.

Causes

The most common cause of a TIA is an embolus that occludes an artery in the brain. This usually arises from a dislodged atherosclerotic plaque in one of the carotid arteries or from a thrombus (i.e., a blood clot) in the heart because of atrial fibrillation. In a TIA, the blockage period is very short-lived and hence there is no permanent damage.

Other reasons include excessive narrowing of large vessels resulting from an atherosclerotic plaque and increased blood viscosity caused by some blood diseases. TIA is related to other medical conditions such as hypertension, heart disease (especially atrial fibrillation), migraine, cigarette smoking, hypercholesterolemia, and diabetes mellitus.

Risk Factors

Risk factors include:

  • Family history of stroke or TIA
  • People 55 years or older
  • Males have a slightly higher risk of TIA than females, but females are more likely to die from a stroke.
  • African Americans generally tend to have a high risk of dying from a stroke, chiefly due to high blood pressure and uncontrolled diabetes.

Prevention and Treatment

A TIA may be prevented by changes in lifestyle. Although most of these recommendations have no solid empirical data, most medical professionals believe them to be so. These include:

  • Avoiding smoking
  • Cutting down on fats and cholesterol to help reduce plaque build up
  • Eating a healthy diet including plenty of fruits and vegetables
  • Limiting sodium in the diet, thereby reducing blood pressure
  • Exercising regularly
  • Moderating alcohol intake
  • Maintaining a normal weight
  • Controlling blood pressure and keeping blood sugars under control

The mainstay of treatment following acute recovery from a TIA should be to diagnose and treat the underlying cause. It is not always immediately possible to tell the difference between a CVA (stroke) and a TIA. Most patients who are diagnosed at a hospital’s emergency department as having suffered from a TIA will be discharged home and advised to contact their primary physician to organize further investigations. A TIA can be considered as the last warning. The reason for the condition should be immediately examined by imaging of the brain.

The initial treatment is aspirin, second line is clopidogrel (PLAVIX), third line is ticlopidine. If TIA is recurrent after aspirin treatment, the combination of aspirin and dipyridamole is needed (Aggrenox).

Alzheimer’s Disease

Alzheimer’s disease is an age-linked neurodegenerative disorder characterized by marked dementia.

Learning Objectives

Describe Alzheimer’s disease and its effect on the brain

Key Takeaways

Key Points

  • Alzheimer’s disease (AD) is the most common form of dementia and was first described by German psychiatrist Alois Alzheimer in 1906.
  • There is no cure for AD, which worsens as it progresses and eventually leads to death. Current treatments only help with the symptoms of the disease.
  • A small number of cases of AD are inherited and usually have an onset before age 65. This form of the disease is known as early-onset familial AD.
  • AD is associated with deposits of amyloid-beta peptide, called plaques, and aggregates of the microtubule-associated protein tau, called tangles, in the brain, which contribute to neuron death.

Key Terms

  • amyloid-beta peptide: A peptide of 36–43 amino acids that is processed from the Amyloid precursor protein, best known as a component of amyloid plaques in association with Alzheimer’s disease.

Examples

Examples of common symptoms of AD include difficulty remembering recent events and, as the disease advances, confusion, irritability, aggression, mood swings, trouble with language, and long-term memory loss.

Alzheimer’s disease (AD), also known in medical literature as Alzheimer disease, is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death. It was first described by German psychiatrist and neuropathologist Alois Alzheimer in 1906 and was named after him.

Most often, AD is diagnosed in people over 65 years of age, although the less-prevalent early-onset Alzheimer’s can occur much earlier. In 2006, there were 26.6 million sufferers worldwide. Alzheimer’s is predicted to affect 1 in 85 people globally by 2050.

Symptoms and Prognosis

Although Alzheimer’s disease develops differently for every individual, there are many common symptoms. Early symptoms are often mistakenly thought to be “age-related” concerns or manifestations of stress. In the early stages, the most common symptom is difficulty in remembering recent events. When AD is suspected, the diagnosis is usually confirmed with tests that evaluate behavior and thinking abilities, often followed by a brain scan if available.

As the disease advances, symptoms can include confusion, irritability, aggression, mood swings, trouble with language, and long-term memory loss. As the sufferer declines they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Since the disease is different for each individual, predicting how it will affect the person is difficult. AD develops for an unknown and variable amount of time before becoming fully apparent, and it can progress undiagnosed for years. On average, the life expectancy following diagnosis is approximately seven years. Fewer than three percent of individuals live more than fourteen years after diagnosis.

Causes

The cause for most Alzheimer’s cases is still essentially unknown (except for 1% to 5% of cases where genetic differences have been identified). Several competing hypotheses exist trying to explain the cause of the disease. The oldest, on which most currently available drug therapies are based, is the cholinergic hypothesis, which proposes that AD is caused by reduced synthesis of the neurotransmitter acetylcholine. The cholinergic hypothesis has not maintained widespread support, largely because medications intended to treat acetylcholine deficiency have not been very effective. Other cholinergic effects have also been proposed, for example, initiation of large-scale aggregation of amyloid, leading to generalized neuroinflammation.

In 1991, the amyloid hypothesis postulated that amyloid beta (Aβ) deposits are the fundamental cause of the disease. Support for this postulate comes from the location of the gene for the amyloid beta precursor protein (APP) on chromosome 21, together with the fact that people with trisomy 21 (Down syndrome) who have an extra gene copy almost universally exhibit AD by 40 years of age. Also APOE4, the major genetic risk factor for AD, leads to excess amyloid buildup in the brain. Further evidence comes from the finding that transgenic mice that express a mutant form of the human APP gene develop fibrillar amyloid plaques and Alzheimer’s-like brain pathology with spatial learning deficits.

This image shows enzymes cutting fragments of proteins.

Amyloid Plaque Formation: Enzymes act on the APP (Amyloid precursor protein) and cut it into fragments of protein, one of which is called beta-amyloid and its crucial in the formation of senile plaques in AD

In 2009, this theory was updated, suggesting that a close relative of the beta-amyloid protein, and not necessarily the beta-amyloid itself, may be a major culprit in the disease. The theory holds that an amyloid-related mechanism that prunes neuronal connections in the brain in the fast-growth phase of early life may be triggered by ageing-related processes in later life to cause the neuronal withering of Alzheimer’s disease. N-APP, a fragment of APP from the peptide’s N-terminus, is adjacent to beta-amyloid and is cleaved from APP by one of the same enzymes. N-APP triggers the self-destruct pathway by binding to a neuronal receptor called death receptor 6 (DR6, also known as TNFRSF21). DR6 is highly expressed in the human brain regions most affected by Alzheimer’s, so it is possible that the N-APP/DR6 pathway might be hijacked in the ageing brain to cause damage. In this model, beta-amyloid plays a complementary role, by depressing synaptic function.

This image shows an image of a healthy brain and an image of a brain with Alzheimer's. In the brain with Alzheimer's, the hippocampus and cerebral cortex have shrunk, and the ventricles are severely enlarged.

Brain Scans: This is a combination of two brain diagrams in one for comparison. In the left normal brain, in the right brain of a person with Alzheimer’s disease.

Brain Tumors

A brain tumor is a pathological abnormal growth of cells in the brain.

Learning Objectives

Describe the affects of brain tumors

Key Takeaways

Key Points

  • A brain tumor is a neoplasm, or abnormal growth of cells, within the brain or the spinal canal.
  • Detection of brain tumors usually occurs in advanced stages when the presence of the tumor has caused unexplained neurological symptoms.
  • Neurological symptoms of a brain tumor depend on size and location, but may include impaired judgment, memory loss, lack of recognition, spatial orientation disorders, personality or emotional changes, visual impairment, and more.
  • Treatment for a brain tumor depends on the tumor type and location and may include surgery, radiotherapy, and chemotherapy.
  • Detection of brain tumors usually occurs in advanced stages when the presence of the tumor has caused unexplained neurological symptoms.
  • Neurological symptoms of a brain tumor depend on size and location, but may include impaired judgment, memory loss, lack of recognition, spatial orientation disorders, personality or emotional changes, visual impairment, and more.
  • The most common primary brain tumors are gliomas, meningiomas, pituitary adenomas, and nerve sheath tumors.

Key Terms

  • chemotherapy: Chemical treatment to kill or halt the replication and/or spread of cancerous cells in a patient.
  • glioma: A tumor that arises from glial cells in the brain or spinal cord.

Examples

An example of a highly treatable brain tumor subtype is medulloblastoma. An example of a brain tumor subtype with a poor prognosis is glioblastoma multiforme. Other examples of brain tumor subtypes include oligodendrogliomas and astrocytomas.

A brain tumor is an intracranial solid neoplasm—a tumor (defined as an abnormal growth of cells)—within the brain or the central spinal canal.

Brain tumors include all tumors inside the cranium or in the central spinal canal. They are created by an abnormal and uncontrolled cell division, usually in the brain itself, but also in lymphatic tissue, blood vessels, the cranial nerves, the brain envelopes (meninges), skull, pituitary gland, or pineal gland. Within the brain itself, the involved cells may be neurons or glial cells (which include astrocytes, oligodendrocytes, and ependymal cells). Brain tumors may also spread from cancers primarily located in other organs (metastatic tumors).

Signs and Symptoms

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Metastasis in the Right Hemisphere: Brain metastasis in the right cerebral hemisphere from lung cancer shown on T1-weighted magnetic resonance imaging with intravenous contrast.

Visibility of signs and symptoms of brain tumors mainly depends on two factors: tumor size (volume) and tumor location. The moment that symptoms become apparent, either to the person or people around him (symptom onset), is an important milestone in the course of the diagnosis and treatment of the tumor. The symptom onset—in the timeline of the development of the neoplasm—depends in many cases on the nature of the tumor but in many cases is also related to the change of the neoplasm from “benign” (i.e., slow-growing/late symptom onset) to more malignant (fast growing/early symptom onset).

Symptoms of solid neoplasms of the brain (primary brain tumors and secondary tumors alike) can be divided into three main categories:

  • Consequences of intracranial hypertension: Large tumors or tumors with extensive perifocal swelling (edema) inevitably lead to elevated intracranial pressure (intracranial hypertension), which translates clinically into headaches, vomiting (sometimes without nausea), altered state of consciousness (somnolence, coma), dilation of the pupil on the side of the lesion (anisocoria), papilledema (prominent optic disc at the funduscopic eye examination).
  • Dysfunction: Depending on the tumor location and the damage it may have caused to surrounding brain structures, either through compression or infiltration, any type of focal neurologic symptoms may occur, such as cognitive and behavioral impairment, personality changes, ataxia, visual field impairment, impaired sense of smell, impaired hearing, double vision, dizziness; more severe symptoms might occur, such as including partial paralysis or impairment to swallow.
  • Irritation: abnormal fatigue, weariness, absences, tremors, and epileptic seizures.

Treatment

Neurosurgeons take the time to observe the evolution of the neoplasm before proposing a management plan to the patient and his/her relatives. Various types of treatment are available depending on neoplasm type and location, and they may be combined to give the best chances of survival:

  • Surgery: complete or partial resection of the tumor to remove as many tumor cells as possible
  • Radiotherapy: the most commonly used treatment for brain tumors, the tumor is targeted with alpha and beta rays to shrink the tumor
  • Chemotherapy: a treatment option for cancer, however it is seldom used to treat brain tumors as the blood and brain barrier prevents the drugs from reaching the cancerous cells

A variety of experimental therapies are available through clinical trials. Survival rates in primary brain tumors depend on the type of tumor, age, functional status of the patient, the extent of surgical tumor removal, and other factors specific to each case.

Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is caused by degeneration of upper and lower motor neurons, resulting in muscle weakness and atrophy.

Learning Objectives

Describe amytrophic lateral sclerosis and its effect on the body

Key Takeaways

Key Points

  • ALS is sometimes referred to as Lou Gehrig’s disease after the New York Yankees baseball player who was diagnosed with the disease in 1939.
  • ALS is characterized by rapidly progressive weakness, muscle atrophy, muscle spasticity, difficulty speaking, difficulty swallowing, and decline in breathing ability. Most patients with ALS die of respiratory failure or pneumonia.
  • For the majority of patients without a family history of the disease, there is no known cause for ALS. Familial ALS is a heritable condition that can be traced to the dysfunction of specific genes.
  • Most people with ALS die of respiratory failure or pneumonia. The median survival time from onset to death is around 39 months, and only 4% survive longer than 10 years.
  • In “respiratory onset” ALS, the intercostal muscles that support breathing are affected first.
  • For the majority of patients without a family history of the disease, there is no known cause for ALS. Familial ALS is a heritable condition that can be traced to the dysfunction of specific genes.

Key Terms

  • lateral: Pertaining to the left or right of the body; further from the midline.
  • amyotrophic lateral sclerosis: A chronic, progressive disease characterized by degeneration of the central nervous system and the loss of voluntary muscle control.

Examples

An example of a gene mutated in some cases of familial ALS is superoxide dismutase, or SOD1, which is an enzyme that acts as a powerful antioxidant.

Amyotrophic lateral sclerosis (ALS), also referred to as motor neuron disease in British English, is the most common form of the motor neuron diseases. The condition is sometimes called Lou Gehrig’s disease in the U.S., after the New York Yankees baseball player who was diagnosed with the disease in 1939. The disorder is characterized by rapidly progressive weakness, muscle atrophy and fasciculations, muscle spasticity, difficulty speaking (dysarthria), difficulty swallowing (dysphagia), and decline in breathing ability.

Symptoms of ALS

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Coronal MRI of an ALS patient: MRI (parasagittal FLAIR) demonstrates increased T2 signal within the posterior part of the internal capsule and can be tracked to the subcortical white matter of the motor cortex, outlining the corticospinal tract), consistent with the clinical diagnosis of ALS.

The disorder causes muscle weakness and atrophy throughout the body as a result of degeneration of the upper and lower motor neurons. Unable to function, the muscles weaken and atrophy. Affected individuals may ultimately lose the ability to initiate and control all voluntary movement, although bladder and bowel sphincters and the muscles responsible for eye movement are usually, but not always, spared. Cognitive function is generally spared for most patients although some (~5%) also have frontotemporal dementia. A higher proportion of patients (~30%–50%) also have more subtle cognitive changes that may go unnoticed but are revealed by detailed neuropsychological testing. Sensory nerves and the autonomic nervous system are generally unaffected meaning the majority of people with ALS will maintain sight, hearing, touch, smell, and taste. Bladder and bowel functions are also rarely affected by ALS.

The earliest symptoms of ALS are typically obvious weakness and/or muscle atrophy. Other presenting symptoms include muscle fasciculation (twitching), cramping, or stiffness of affected muscles; muscle weakness affecting an arm or a leg; and/or slurred and nasal speech. The parts of the body affected by early symptoms of ALS depend on which motor neurons in the body are damaged first. About 75% of people contracting the disease experience “limb onset” ALS (i.e., first symptoms in the arms or legs). Patients with the leg onset form may experience awkwardness when walking or running or notice that they are tripping or stumbling, often with a “dropped foot” which drags gently along the ground. Arm-onset patients may experience difficulty with tasks requiring manual dexterity such as buttoning a shirt, writing, or turning a key in a lock. Occasionally, the symptoms remain confined to one limb for a long period of time or for the whole length of the illness; this is known as monomelic amyotrophy.

Over time, patients experience increasing difficulty moving, swallowing (dysphagia), and speaking or forming words (dysarthria). Symptoms of upper motor neuron involvement include tight and stiff muscles (spasticity) and exaggerated reflexes (hyperreflexia) including an overactive gag reflex. Symptoms of lower motor neuron degeneration include muscle weakness and atrophy, muscle cramps, and fleeting twitches of muscles that can be seen under the skin (fasciculations). To be diagnosed with ALS, patients must have signs and symptoms of both upper and lower motor neuron damage that cannot be attributed to other causes.

Difficulty swallowing and chewing making eating normally very difficult and increase the risk of choking or aspirating food into the lungs. In later stages of the disease, aspiration pneumonia and maintaining a healthy weight can become a significant problem and may require insertion of a feeding tube. As the diaphragm and intercostal muscles (rib cage) that support breathing weaken, measures of lung function such as forced vital capacity and inspiratory pressure diminish. In respiratory onset ALS, this may occur before significant limb weakness is apparent. Most people with ALS die of respiratory failure or pneumonia. The median survival time from onset to death is around 39 months, and only 4% survive longer than 10 years. The best-known person with ALS, Stephen Hawking, has lived with the disease for more than 40 years, though his is an unusual case.

Causes and Treatments of ALS

For patients without a family history of the disease, which includes ~95% of cases, there is no known cause for ALS. Potential causes for which there is inconclusive evidence includes head trauma, military service, and participation in elite sports. Many other potential causes including chemical exposure, electromagnetic field exposure, occupation, physical trauma, and electric shock have been investigated but without consistent findings.

Riluzole (Rilutek) as of 2011 is the only treatment that has been found to improve survival, but only to a modest extent. It lengthens survival by several months, and may have a greater survival benefit for those with a bulbar onset. It also extends the time before a person needs ventilation support. Other treatments for ALS are designed to relieve symptoms and improve the quality of life for patients. This supportive care is best provided by multidisciplinary teams of health care professionals working with patients and caregivers to keep patients as mobile and comfortable as possible.