7.1 The Electroencephalogram
The electroencephalogram (EEG) is used to measure spontaneous electrical activity arising from the cerebral cortex via electrodes placed on the scalp. This electrical activity results from temporal summation of cortical postsynaptic potentials (not action potentials) in many neurons and is represented by waves (Fig. 7.1).
Fig. 7.1 Recording the electroencephalogram (EEG).
An EEG measures electrical activity in the brain using multiple electrodes placed on the scalp. Alpha (α) waves are typical of an awake, relaxed patient (with eyes closed) and are generally detected in multiple electrodes (synchronization). Beta (β) waves are typical of an awake, alert patient (with eyes open). The frequency and amplitude of β waves varies greatly from different electrodes (desynchronization). Theta (θ) waves are seen in drowsiness or very relaxed states, and delta (δ) waves occur during deep sleep.
EEG waves are described by their amplitude and frequency.
– EEG wave amplitude is determined by the following:
– The number of active synapses
– Synchronization of postsynaptic potentials
– The distance of these potentials from recording electrodes
–EEG wave frequency is determined by the state of central nervous system (CNS) arousal.
Table 7.1 lists the types of waves that are present normally in an EEG. Their appearance is shown in Fig. 7.2.
Fig. 7.2 EEG waves.
EEG waves have different frequencies and amplitudes. Localized or generalized paroxysmal spikes and waves are used to diagnose epilepsy.
Clinical Use of the EEG
The EEG is used to determine the foci of localized or generalized seizure (convulsive) activity. Derangement of the EEG is also seen with brain lesions, such as tumors, abscesses, and subdural or extradural hematomas, and with metabolic disorders, infections (e.g., encephalitis), and hypoxia.
Table 7.2 summarizes the EEG changes that occur in certain diseases or conditions.
Epilepsy is the tendency to have recurring seizures. These seizures take many forms, ranging from brief cessations of responsiveness without loss of conciousness to convulsions with accompanying loss of consciousness. It occurs in almost 17% of adults. In one-quarter of those the EEG and MRI finds a focal lesion on the brain. Anti-epileptic drugs (eg., phenytoin, valproate) are usually able to prevent further seizures. The 10–20% of patients in whom drugs are insufficient are candidates for surgical removal of the small area of the brain in which the seizures originate.
Sleep is a periodic and reversible state of decreased ability to interact with the external environment. It is accompanied by a significant reorganization of the neural, endocrine, and somatic systems. It is known that sleep follows a circadian rhythm, but the physiological causes of sleep onset, sleep maintenance, and waking are unknown, as is the need for sleep.
The daily sleep–wake cycle is thought to be controlled by a rhythm generator in the suprachiasmatic nucleus of the hypothalamus.
– As light levels are reduced in the evening, firing of cells in the nucleus increases, leading ultimately to the release of melatonin by the pineal gland. Melatonin is a sleep-inducing substance.
– The alert state is activated by nonspecific ascending activating impulses from the reticular formation of the brainstem via the thalamus to wide areas of the cerebral cortex. This activity involves both cholinergic and monoaminergic (norepinephrine, 5-hydroxytryptamine [5-HT], and dopamine) systems.
Stages of Sleep
There are five sleep stages: four synchronized slow-wave sleep stages and rapid eye movement (REM) sleep. These five sleep stages are identified by polygraphic recordings: EEG, EMG (electromyogram), and EOG (electro-oculogram), and by behavioral criteria.
Table 7.3 shows the EEG changes, eye movements, and other notable occurrences during wakefulness and each stage of sleep. In normal sleep, a person descends through stages 1 to 4 in order, ascends back to stage 2, and enters REM sleep. REM sleep is also exited through stage 2. Repeated cycles are made through the stages, and REM sleep is entered four to six times per night at an average inter-REM period of 90 minutes.
Sleep apnea is a sleep disorder characterized by episodic cessation of breathing during sleep. It may be central, in which breathing cessation occurs due to a lack of respiratory effort; obstructive, in which breathing cessation occurs due to airflow obstruction; or a mixture of the two (complex sleep apnea). Symptoms of sleep apnea include snoring, insomnia (difficulty staying asleep), hypersomnia (sleepiness in the daytime), morning headaches, awakening with a dry mouth or sore throat, memory problems, mood swings, and depression. Sleep apnea sufferers tend to be unaware of their difficulty breathing, except in cases of central sleep apnea, in which the patient can awaken abruptly with shortness of breath (dyspnea). Sleep apnea can place the cardiovascular system under great strain due to hypoxia, resulting in cor pulmonale (right heart failure due to pulmonary hyper-tension), sudden cardiac death, and stroke. Risk factors for this condition include excess weight, smoking, use of alcohol/sedatives/tranquilizers, a positive family history of the condition, and narrowed airway. It is more common in men and tends to occur after the age of 65. Treatment depends on the cause and severity and may include reducing risk factors, oral splints to help keep the airway open, CPAP (continuous positive airway pressure), or surgery (e.g., uvulopalatopharyngoplasty or tracheostomy).
Somnambulism (sleepwalking) is an arousal disorder that occurs in stage 4 sleep. The person may simply sit up in bed, or he or she may walk around and perform tasks such as getting dressed, cooking, or even driving. Enuresis (involuntary urination), when it occurs, is often correlated with the transition from stage 4 to 2 and REM sleep. This condition is usually not dangerous unless it causes the person to adopt dangerous behaviors (e.g., driving while asleep). Somnambulism is common in preteen children and is not indicative of any underlying pathology; however, in adults, it is often diagnostic of psychological disturbances. Usually, no treatment is required for this condition unless there is causative underlying pathology. Medication such as benzodiazepines may be useful in some cases.
– The dominant hemisphere as defined by speech and language capabilities is the left hemisphere in 90 to 95% of right-handed people (who represent 90% of people) and in 70% of left handed people (who represent 10% of people).
– Damage to the Broca area causes an expressive aphasia in which the patient is unable to produce language (written or spoken), but comprehension of language is intact.
– Damage to the Wernicke area causes a receptive aphasia in which the patient is unable to comprehend written and spoken language, but speech may be fluent and well articulated.
– The nondominant right hemisphere has executive control for spatial abilities and is more adept at tasks requiring spatial orientation.
– The corpus callosum provides communication between hemispheres, allowing information received on one side to be shared by both sides.
– Short-term memory involves synaptic changes. It can retain about seven units of information (e.g., groups of numbers) for a few seconds.
– Long-term memory involves neural changes. It has a very large capacity to store information for minutes to years.
Alzheimer disease is a progressive neurode-generative disorder producing marked atrophy of the cerebral cortex. It is the most common cause of dementia. It produces impairment of short-term memory, cognition, and language; increasing difficulty performing the activities of daily living; personality changes (e.g., anxiety, depression, aggression, and social withdrawal); and immobility leading to death. Treatment involves drugs such as tacrine, done-pezil, rivastigmine, and galantamine, which are centrally acting, reversible inhibitors of cholinesterase. They prevent the hydro-lysis of acetylcholine, thus increasing the concentration of acetylcholine available to neurons. This improves cognition in mild to moderate Alzheimer disease. Memantine, an N-methyl-d-aspartate (NMDA) receptor antagonist, may also be used in moderate to severe Alzheimer disease to protect neurons from damage caused by glutamate.
7.5 Barriers in the Brain and Cerebrospinal Fluid
Anatomy and Functions
– The blood–brain barrier is the barrier between cerebral capillary blood and cerebrospinal fluid (CSF). It is composed of the tight junctions between capillary endothelial cells and glial cells.
– The blood–brain barrier regulates the osmolarity of brain tissue and CSF and thereby the intracranial pressure and volume. It also maintains a constant environment for neurons in the CNS.
Disruption to the Blood–Brain Barrier
The blood–brain barrier may be disrupted by inflammation (e.g., meningitis), irradiation, and tumors.
Meningitis is inflammation of the meninges of the brain (pia mater and arachnoid), usually due to a viral infection, but it can also be caused by a bacterial or fungal infection. Symptoms include headache, stiff neck on passively moving the chin toward the chest, photophobia (sensitivity to light), irritability, drowsiness, vomiting, fever, seizures, and rashes (viral or meningococcal meningitis). Predisposing factors for meningitis include head injury (especially basal skull fracture), otitis media, sinusitis, mastoiditis, and a compromised immune system (e.g., carcinoma, acquired immunodeficiency syndrome [AIDS], diabetes, splenectomy, and immunosuppressant drugs). A lumbar puncture often provides a definitive diagnosis of meningitis. Blind treatment with a broad-spectrum antibiotic or prompt treatment with IV antibiotics that are sensitive to the causative organism is required for bacterial meningitis. For viral meningitis, treatment includes bed rest and fluids, but this normally resolves on its own in a week or two.
Formation and Composition
– CSF is produced in the choroid plexus and occupies the subarachnoid space and ventricles of the brain.
– CSF is an ultrafiltrate of serum and very similar in composition. It has less Ca2+, glucose, protein, and immunoglobulin G (IgG) compared with serum, but more Cl− and lactate.
– The primary function of CSF is to impart buoyancy to the brain. Decreased CSF production therefore increases pressure on the spine and renders the brain more susceptible to injury (less cushioning).
– CSF also transports nutrients and hormones into the brain and carries waste products out of it.
– Lipid-soluble substances (O2 and CO2) are able to freely diffuse across the blood–brain barrier and enter CSF.
– Proteins cannot pass through the blood–brain barrier due to their large molecular size.
– Lipophilic (nonionized) drugs will pass through the blood–brain barrier more readily than water-soluble (ionized) drugs.
Lumber puncture is a procedure for sampling CSF. It allows for the diagnosis of conditions such as meningitis, subarachnoid hemorrhage, and tumor metastases. To perform a lumbar puncture, the patient is asked to lie on his or her side with hips flexed. A needle is inserted precisely in the midline between the spinous process of L3 and L4 and advanced into the dural sac (lumbar cistern). A sample of CSF is then aspirated. CSF pressure may also be measured by connecting the needle to a manometer.