It takes years of medical education to become a doctor and even more years of specialized training to become a neurologist, neurosurgeon, or psychiatrist. However, it does not take very long to understand the basic mindset of doctors when they are thinking about your brain and planning a treatment strategy, because there are really only a few basic options available for treating disorders of the nervous system.
Strategy 1: Damage Control/Neuroprotection
Because the central nervous system has a low capacity for self-repair, the highest priority for your doctor will almost always be protecting your brain or spinal cord from damage. The irreversibility of many kinds of brain or spinal cord damage means that doctors tend to be both highly impatient about initiating treatments and extremely conservative in the treatments they use. They are intensely focused on trying to prevent any further brain damage that may be caused by the condition, but they’re also concerned about the possibility that the treatment itself could cause harm. For example, since neurons can die very quickly after their blood supply is interrupted, doctors have a very strong sense of urgency about restoring blood flow after a stroke. However, they may delay starting treatment if they are unsure which type of stroke they are dealing with, because the blood thinners used to treat the most common type of stroke (caused by a clot) can make the other type of stroke (caused by a brain bleed) even worse.
Neurosurgeons are generally the least knife-happy surgeons you will find. If a condition can be treated either with medication or with surgery, a neurosurgeon will want to make sure that all medication options have been exhausted first before considering surgery. On the other hand, if surgery is clearly necessary, neurosurgeons can be quite impatient to get started. Every minute spent explaining to the family how they want to treat a patient with a ruptured cerebral aneurism or serious head injury means that more of the patient’s neurons are dying. Therefore, doctors often push consent forms in front of the family member in the ER, giving them very little explanation of a treatment plan and almost no time to think about their decision. In these situations, the family member almost always just signs the consent form and hopes they’re doing the right thing. After all, what are you going to do? Just let your loved one die?
Many medications and other treatments prescribed by neurologists are aimed at neuroprotection. When doctors chemically induce a coma after a severe head trauma, their goal is to minimize brain activity—and hence oxygen demand and neurotransmitter release—thereby reducing swelling and giving the brain more time to repair blood vessels before the neurons start needing a lot of oxygen and glucose. Likewise, the anti-inflammatory drugs prescribed for meningitis, encephalitis, transverse myelitis, or recent spinal cord trauma are intended to minimize the damage caused by inflammation. Immunomodulatory drugs prescribed for multiple sclerosis (MS) and plasmapheresis used to treat Guillen-Barré syndrome both aim at preventing the patient’s own immune system from attacking myelin-forming cells. Even the surgical destruction of a part of a patient’s brain that is initiating epileptic seizures is done as much to prevent the repeated releases of large amounts of neurotransmitters from literally over-stimulating other neurons to death as it is to relieve the seizures themselves.
The conservative tendencies of neurologists and psychiatrists also apply to their prescribing practices. Doctors treating brain conditions tend to try to use the lowest dosage of medication possible. They prefer older drugs that have been well-studied for decades over newer drugs that may work better in the short term but whose long-term side effects are not known. This attitude is more-or-less the opposite of what pharmaceutical companies would like. They therefore spend a lot of money on TV advertisements and slick web sites trying to persuade patients to ask their doctors for the newest and most profitable drugs. This cautious attitude of doctors can also sometimes be at odds with the patient’s desire for rapid and complete symptom relief. Doctors generally want to bring medication levels up slowly and stop when the patient reaches an acceptable level of relief, rather than start with dosages closer to the expected therapeutic level or continuing to raise them until maximum symptom relief is achieved. The “start low and go slow” approach is preferred by doctors because overshooting the mark with drug doses can often create serious problems. If the immune system of someone with MS is suppressed enough to eliminate all disease progression, they may be unable to fight off common infections. If the dosage of antiepileptic medication is high enough to prevent all seizures, other brain functions may become impaired. Furthermore, since the nervous system tends to adapt to high-drug levels by down-regulating responses, medication that are overused can quickly become ineffective.
The combination of urgency and caution applies to psychiatric disorders as well as neurological conditions. A psychiatrist’s first priority is making sure that a person in crisis does not harm himself or herself or do something that will land them in jail and subject them to more emotional duress. Psychiatrists are inclined to use fast-acting antipsychotics and/or tranquilizing medications rather liberally if they believe there is a significant risk that the person might harm themselves or others. Even though their patients usually prefer not to be in a hospital, doctors are inclined to prefer treating patients initially on an inpatient basis where their responses to medications can be carefully monitored and the risk of adverse drug reactions can be minimized. This is just one of many areas where doctors and patients may need to negotiate a mutually acceptable risk profile.
Strategy 2: Altering Synaptic Transmission/Targeting Neurotransmitters and Their Receptors
Nerve cells (neurons) communicate with one another using of a small number of chemicals called neurotransmitters. Neurotransmitters are released from specialized sites (synapses) on the first cell and travel across a short distance to bind to receptors on the second cell (synaptic transmission). The binding of neurotransmitters to these receptors results in a small electrical change in the second cell. All of the electrical changes occurring on the thousands of sites on each neuron combine to produce a decision about whether or not to fire off messages to the next cell in the series. If there aren’t enough cells producing one type of chemical signal, or if cells haven’t made enough connections or aren’t producing enough neurotransmitters, or, alternatively, they are producing and releasing too much neurotransmitter, the network of cells as a whole will not work properly. At this point, whatever function the network is supposed to perform will not be carried out. Depending on the network or networks affected, the person will not be able to see, or control their muscles, or control their thoughts or emotions.
Many drugs prescribed by neurologists and/or psychiatrists target one of the neurotransmitter-receptor systems, either by mimicking the neurotransmitter, or by binding to one of the receptors and keeping it from responding to the signal, or by causing the first neuron to make more of the neurotransmitter or to keep it around longer in the space between the two cells.
The list of medications that affect one or more neurotransmitter systems is a long one, and their mechanisms of action are diverse. Opioids block pain and produce a “high” by mimicking opioid-like chemicals in parts of the brain involved in perception of pain/pleasure and reward. Drugs that mimic the neurotransmitter GABA can act as sedatives by stimulating receptors that send signals which tell neurons to remain silent and not fire. L-Dopa causes surviving dopamine-producing cells in the cerebellums of patients with Parkinson’s disease to produce more dopamine, compensating for the neuronal losses which cause the symptoms of the condition. Serotonin selective reuptake inhibitors (SSRIs) cause the neurotransmitter serotonin to hang around longer after it has been released, amplifying serotonin-based signals in the emotional centers of the brain. Drugs that block the type of acetylcholine receptor that is most common in the brain can be used to prevent motion sickness or dizziness, while drugs that block the type of acetylcholine receptor on muscle cells can act muscle relaxants by blocking the nerves signals which trigger muscle contractions. Lithium binds to some of the enzymes that produce neurotransmitters, as well as some neurotransmitters receptors, both increasing serotonin synthesis and decreasing noradrenalin release. This changes the balance of positive and negative signals in networks of neurons regulating emotional states and dampens both emotional extremes for individuals with bipolar disorder.
Strategy 3: Blocking Ion Channels/Playing with Electricity
Electrical signals are generated by neurons and transmitted along their length by the rapid opening and closing of sodium ion channels. Neurons are restored to their normal electrical state by opening and closing of potassium ion channels. When the electrical signal reaches the end of the line and is ready to be converted to a chemical signal in order to be passed on to the next cell, calcium ion channels are locally opened in order to trigger the release of the chemical signals (neurotransmitters), and then the calcium channels are closed. The opening of calcium channels in muscle cells, including the smooth muscle cells surrounding blood vessels, also triggers muscle contraction, and therefore reduces blood flow in the area.
Partially blocking any of these ion channels, either in an open or closed state, can affect the ability of neurons to generate or transmit electrical signals or convert them into chemical signals at the end of the line. Many anti-epileptic medications act by temporarily blocking sodium channels in a shut state immediately after they have opened and closed. This blockage prevents the sodium channels from generating another signal right away and thus prevents the neurons from firing rapidly enough to cause a seizure or to produce the intense burning sensation of neuropathic pain. Potassium channel blockers can prevent electrical signals from draining away before they get to the ends of processes (axons) that have lost their electrical insulation due to immune system attacks in multiple sclerosis. Calcium channel blockers can reduce the amounts of neurotransmitters released by neurons and relax the muscles surrounding blood vessels to increase local blood flow and reduce blood pressure. (Both the reduced blood pressure and lower neurotransmitter release may contribute to the ability of calcium channel blockers to prevent or reverse some types of severe headaches.)
Strategy 4: Targeted Activity-Dependent Synaptic Remodeling/Practice, Practice, Practice
Although the central nervous system is not very good at producing new neurons or re-growing long connections that have been severed, it is designed as a learning machine and is very good at adapting to new information by changing the strength and number of synaptic connections between cells. Essentially, the more active a line of communication is—and the more messages that get passed on—the stronger the connections will become over time.
Increasing the activity of a synapse can be thought of as synaptic pushups, bulking up connections and making them stronger. Physical therapy after a stroke or brain injury, cognitive behavioral therapy after a psychiatric crisis, and transcranial magnetic stimulation, which is beginning to be used to treat a range of neurological conditions, all have the effect of increasing the electrical activity of specific groups of neurons and increasing the numbers and strengths of their connections.
Some medications that become more effective over time, such as antidepressants, also encourage the brain to produce more and larger synapses. Improving functioning through use-dependent increases in synaptic strengths not only has fewer risks than medication, it also has the distinct advantage of producing a permanent fix, or at least a long-lasting improvement in muscle control or emotional balance. The gains made through physical therapy, speech therapy, or cognitive therapy can be kept even if treatment is interrupted or ends. For example, if someone has the flu and cannot keep their psychiatric medication down, the hallucinations, anxiety, and/or depression that were being controlled by medication will often quickly return—but the person can continue to use the cognitive skills that they developed to cope with their symptoms during this period.
The main disadvantage of synaptic remodeling strategies is that they take time and effort. Many repetitions are required before the person’s brain makes the necessary physical changes. Hundreds of attempts to speak or walk after a stroke will fail before the first word is formed or the first step taken. Furthermore, it is difficult for an individual to make these adaptive changes on his or her own. Just as an Olympic hopeful turns to an experienced trainer to help them reach their peak physical performance, a person who has had a stroke or head trauma or who suffers from post-traumatic stress disorder (PTSD) or some other neuropsychiatric condition turns to an expert to help with their brain training program.
New Treatment Options on the Horizon
Great advances have been made in understanding how the brain works, and new strategies for treating brain disorders have begun to be tested. Stem cell therapies, gene therapies, exosome-based therapies, deep brain stimulation, and neural prosthetics all show great promise for treating neurological conditions or at least relieving their symptoms. At present, however, these treatments are more science fiction than science fact. Clinical trials of novel, cutting edge treatments are underway at a few research centers for small numbers of individuals who fit very specific disease profiles, but they are not widely available for a typical patient and are usually not covered by insurance. Furthermore, experience has taught us that most of these treatments will not pan out. Some treatments that look promising now will have unanticipated side effects and, therefore, will do more harm than good. At present, these approaches can hardly be considered realistic treatment options. Choosing to participate in a clinical trial for one of these therapies should be considered more as an altruistic act of generosity to help future patients than as an act of hope for oneself. Over the longer term, however, the rapid expansion in knowledge about how the brain works gives reason to for optimism that cures, or at least much more effective treatments, will be found during the lifetimes of people currently diagnosed with some of these conditions.
Theory and Practice
One might think that with only such a small number of basic treatment approaches available, choosing the best treatment option would be relatively easy and straightforward. In reality, however, the process of finding the right treatment for a particular patient can be quite complex. Theory is simple but the practical application is much trickier. That’s what all the years of medical school and specialty training are for. Quite a bit of trial and error is often involved in finding the best medication or combination of medications, dosing schedules, and other treatments for each individual patient. Treatments may also have to be adjusted as the person ages and/or their condition progresses.
There are no magic bullets that target only the cells that are not functioning correctly. The same immune system that can damage the brain with too much inflammation or attack its myelin insulation is necessary to fight infections, remove dead cells after an injury, and stimulate the start of the repair process. The same neurotransmitters are used in many different parts of the nervous system to serve different functions. The same ion channels are present on all neurons, and the same or similar channels are present on all cells in the body. (There are slightly different variants of different ion channels on different cells, but current medications are not specific enough to target only the ones that you want.) Trying to make one part of the nervous system work better can cause other parts to malfunction. If a doctor tries to raise dopamine levels too much in order to control Parkinson’s Disease movement symptoms, the person may start to hallucinate. If a doctor tries to lower dopamine levels too much to control the cognitive symptoms of schizophrenia, the patient can develop a movement disorder. The same is true of nearly every medication in the neurologist’s treatment arsenal. Anti-epileptic medications can cause double vision or dizziness. Calcium channel blockers can cause kidney failure. The range of medication dosages that provide symptom relief without unacceptable side effects can be rather narrow. Furthermore, each person can have slightly different genetic variants of neurotransmitter receptors, ion channels, and enzymes that metabolize drugs. The effective dosage range can therefore be different for each individual, and two medications that target the same pathway and whose chemical makeup differs only slightly can have very different effects on different people. The responses of individual human patients to medications is not as predictable as the responses of inbred strains of laboratory mice.
For most people, trying to have in-depth conversations with their doctor about their condition is not likely to be very productive. An average person, without any medical training, is unlikely to be able to understand the results of the tests that their doctor has ordered or the differential diagnostic criterion for evaluating them. Likewise, members of the general public cannot be expected to understand all of the pathways of drug actions or the contraindications for when they should not use any particular drug. Furthermore, doctors are understandably reluctant to offer a preliminary diagnosis or lay out a tentative long-term treatment plan when they do not have all of the information they need. Few doctors are willing to offer simple predictions about the future course of a condition or say what the “best” treatment is. They just do not have these answers.
There are, however, a couple of questions that can be useful for patients to ask their doctors. When a doctor is in the process of determining a diagnosis, the patient might ask, “What possibilities have you been able to rule out?” The answer to this question can reduce the number of bad outcomes the patient has to worry about, as well as giving the person an idea about how far along the diagnosis process is. For example, it is nearly always a relief to know that brain cancer has been ruled out. Furthermore, if your doctor has been able to rule out whole categories of conditions quickly, it suggests that he/she is closing in on a diagnosis and the possibilities are centered on a small group of conditions. If test results are inconclusive or ambiguous, however, more specialist consultations may be called for. Once a diagnosis has been made and one or more treatment options has been proposed, it can be useful to ask, “Are there other treatment options that I should reasonably consider?” This question does not challenge the doctor’s skill or advice, but it does encourage him/her to share some of their decision-making process. It may be that there is only one treatment for your condition. However, for many conditions there are several different drugs or surgical approaches that could be employed. Doctors usually have good reasons for the strategies they propose, but it can be reassuring to know that there’s a treatment plan B, C, D, E, and F if plan A is not fully successful. In addition, in some circumstances your doctor’s risk/benefit calculations may not match your own values and preferences. Some individuals are much more willing to tolerate some kinds symptoms or side effects than others, especially if some of the symptoms could interfere with keeping their jobs and/or taking care of their kids.
In order for a patient to participate in their treatment decisions in a meaningful way, the patient needs to be able to start a dialogue with their doctor about the costs and benefits of different treatment options and their personal priorities. It can be useful to begin that dialogue by encouraging the doctor to share his or her thinking about the problem. After all, the doctor is the one who knows what the actual tradeoffs are for different treatment options, while the patient is the expert in how they feel about those tradeoffs.