Chapter 12 Clinical Connections

Neurotoxins

Found in certain shellfish and other organisms. Are substances that produce thier poisonous effects by acting on the nervous system. One particularly lethal neurotoxin is tetrodotoxin (TTX), present in the viscera of Japanese pufferfish. TTX effectively blocks action potentials by inserting itself into voltage-gated Na+ channels so they cannot open.

Dysthymia

A person with dysthymia experienced episodes of depression that alternate with periods of feeling normal.

Major Depression

A person with major depression experiences symptoms depression that last for more than 2 weeks.

Seasonal Affective Disorder (SAD)

A person with seasonal affective disorder experiences depression during the winter months, when day length is short.

Guillain-Barre syndrome (GBS)

An acute demyelinating disorder in which macrophages strip myelin from axons in the PNS. It is the most common cause of acute paralysis in North America and Europe and may result from the immune system's response to a bacterial infection. Most patients recover completely or partially, but about 15% remain paralyzed.

Neuropathy

Any discordeat affects the nervous system but particularly a disorder of a cranial or spinal nerve. An example is facial neuropathy (Bell's palsy), a disorder of the facial VII nerve.

Partial Seizures

Begin in a small area on one side of the brain and produce milder symptoms

Multiple Sclerosis (MS)

A disease thaauses a progressive destruction of myelin sheaths surrounding neurons in the CNS. It afflicts about 350,000 people in the U.S and 2 million people worldwide. It usually appears between the ages of 20 and 40, affecting females twice as often as males. MS is most common in whites, less common in blacks; and rare in Asians. MS is an autoimmune disease - the bodies own immune system spearheads the attack. The condition's name describes the anatomical pathology. In multiple regions the myelin sheaths deteriorate to scleroses, which are hardened scars or plaques. Magnetic resonance imaging (MRI) studies reveal numerous plaques in the white matter of the brain and spinal cord. The destruction of myelin sheaths slows and then short-circuts propagation of nerve impulses. Although the cause of MS is unclear, both genetic susceptibility and exposure to some environmental factor (perhaps a herpes virus) appear to contribute.

Rabies

A fatal disease caused by a virus that reaches the CNS via fast axonal transport. It is usually transmitted by the bite of an infected dog or other meat-eating animal. The syptoms are excitement, aggresiveness, and madness, followed by paralysis and death.

Neuroblastoma

A malignant tumor that consists of immature nerve cells (neuroblasts); occurs most commonly in the abdomen and most frequently in the adrenal glands. Although rare, it is the most common tumor in infants.

Bipolar Disorder

A person with bipolar disorder or manic-depressive illness, expereinces recurrent episodes of depression and extreme elation (mania).

Excitotoxicity

Caused by a high level of glutamate in the interstitial fluid of the CNS. Is the destruction of neurons through prolonged activation of excitaory synaptic transmission. The most common cause is oxygen deprivation of the brain tissue due to ischemia (inadequate blood flow), as happens during a stroke. Lack of oxygen causes the gluatamate transporters to fail, and gluatamate accumulates in the interstitial spaces between neurons and glia, literally stimulating the neurons to death. Clinical trials are underway to see whether antigluatamate drugs administered after a stroke can offer some protection from excitotoxicity.

Epilepsy

Characterized by short, recurrent attacks of motor, sensory, or psychological maction, although it almost never affects intellegence. The attacks called epileptic seizures, afflict about 1% of the world's population. They are initiated by abnormal, synchronous electrical discharges from millions of neurons in the brain, perhaps resulting from abnormal reverbating circuits. The discharges stimulate many of the neurons to send nerve impulses over thier conduction pathways. As a result, lights, noise, or smells may be sensed when the eyes, ears, and nose have not been stimulated. Moreover, the skeletal muscles of a person having a seizure may contract involuntarily. Epilepsy has many causes, including brain damage at birth (the most common cause); metabolic disturbances (hypoglycemia, hypocalcemia, uremia, hypoxia); infections (encephalitis or meningitis); toxins (alcohol, tranquilizers, hallucinogens); head injuries; and tumors and abscesses of the brain. Seizures associated with fever are most common in children under the age of two. However, most seizures have no demonstrable cause. Seizures can often be alleviated by antiepileptic drugs such as phenytoin, carbamazepine, and valproate sodium. An implantable device that stimulates the vagus (X) nerve has produced dramatic results in reducing seizures in some patients whose epilepsy was not well controlled by drugs. In very severe cases, surgical intervention may be an option.

Local anesthetics

Drugs that block pain and other somatic sensations. Examples include procaine (Novocaine) and lidocane, which may be used to produce anesthesia in the skin during suturing of a gash, in the mouth during dental work, or in the lower body during childbirth. Like TTX, these drugs act by blocking the opening of voltage-gated Na+ channels. Action potentials cannot propagate past the obstructed region, so pain signals do not reach the CNS. Localized cooling of a nerve can also produce an anesthetic effect because axons propagate action potentials at lower speeds when cooled. The application of ice to injured tissue can reduce pain because propagation of the pain sensations along axons is partially blocked.

Selective Serotonin Reuptake Inhibitors (SSRIs)

Drugs that provide relief from some forms of depression. By inhibiting reuptake of serotonin by serotonin transporters, SSRIs prolong the activity of this neurotransmitter at synapses in the brain. SSRIs include fluoxetine (Prozac),paroxetine (Paxil), and sertraline (Zoloft).

Generalized Seizures

Involve larger areas on both sides of the brain and loss of conciousness.

Depression

Is a disorder that affects over 18 million people each year in the United States. People who are depressed feel sad and helpless, have a lack of interest in activities they once enjoyed, and experience suicidal thoughts. There are several types of depression. Although the exact cause of depression is unknown, research suggests that depression is linked to an imbalance of the neurotransmitters seratonin, norepinepherine, and dopamine in the brain. Factors that may contribute to depression include heredity, stress, chronic illness, certain personality traits (such as low self-esteem), and hormonal changes. Medication is the most common treatment.

Modifying the Effects of Neurotransmitters

Substances naturally present in the body as well as drugs and toxins can modify the effects of neurotransmitters in several ways: 1. Neurotransmitter synthesis can be stimulated or inhibited. For instance, many patients with Parkinson disease recieve benefit from the drug L-dopa because is is a precursor of dopamine. For a limited period of time, taking L-dopa boosts dopamine production in affected brain areas. 2. Neurotransmitter release can be enhanced or blocked. Amphetamines promote release of dopamine and norepinephrine. Botulinum toxin causes paralysis by blocking release of acetylcholine from somatic motor neurons. 3. The neurotransmitter receptors can be activated or blocked. An agent that binds to receptors and enhances or mimics the effect of a natural neurotransmitter is an agonist. Isoproterenol (Isuprel) is a powerful agonist of epinepherine and norepinepherine. It can be used to dilate the airways during an asthma attack. An agent that binds to and blocks neurotransmitter receptors is an antagonist. Zyprexa, a drug prescribed for schizophrenia, is an antagonist of serotonin and dopamine. 4. Neurotransmitter removal can be stimulated or inhibited. For example, cocaine produces euphoria - intensely pleasurable feelings - by blocking transporters for dopamine reuptake. This action allows dopamine to linger longer in synaptic clefts, producing excessivstimulation of certain brain regions.

Strychnine Poisoning

The importance of inhibitory neurons can be appreciated by observing what happens when thier activity is blocked. Normally, inhibitory neurons in the spinal cord called Renshaw cells release the neurotransmitter glycine at inhibitory synapses with somatic motor neurons. This inhibitory input to thier motor neurons prevents excessive contraction of skeletal muscles. Strychnine is a lethal poison that is mainly used as pesticide to control rats, moles, gophers, and coyote. When ingested, it binds to and blocks glycine receptors. The normal, delicate balance between excitation and inhibition in the CNS is disturbed, and motor neurons generate nerve impulses without restraint. All skeletal muscles, including the diaphragm, contract fully and remain contracted. Because the diaphragm cannot relax, the victim cannot inhale and suffocation results.

Relapsing-Remitting MS

The most common form of the condition is relapsing-remitting MS, which usually appears in early adulthood. The first symptoms may include a feeling of heaviness or weakness in the muscles, abnormal sensations, or double vision. An attack is followed by a period of remission in which the symptoms temporarily disappear. One attack follows another over the years, usually every year or two. The result is a prossive loss of function interspersed with remission periods, during which symptoms abate.Since 1993, many patients with relapsing-remitting MS have been treated with injections of beta interferon. This treatment lengthens time between relapses, decreases the severity of relapses, and slows formation of new lesions, in some cases. Unfortunately, not all MS patients can tolerate beta interferon, and therapy becomes less effective as the disease progresses.