Right middle cerebral artery aneurysm before (left) and after (right) Occlusion with GDC coils

GDC coils are placed within an aneurysm via an endovascular route, i.e. by passing a catheter (a tubular instrument) into certain blood vessels until the vessel containing the aneurysm is reached. The coils themselves are situated at the tip of the catheter. Once the coils have reached the aneurysm an electrical current is sent along a wire within the catheter causing the coils to detach from the rest of the instrument, thus packing them inside the aneurysm. The size and the shape of brain aneurysms vary; accordingly there are different coil shapes and sizes. In addition, the safety and efficacy of these devices is augmented by the fact that the coils easily deform to the shape of the aneurysm. This procedure can be complicated by the blockage a healthy blood vessel. To prevent this the anticoagulant heparin is given while the coils are installed.

The alternative to endovascular coil treatment is the surgical "clipping" of brain aneurysms. Such surgical resection of the aneurysm is very effective. However, surgery may be dangerous in certain patients. A patient may not be in a good enough condition to withstand the operation. Also, the size and location of the aneurysm may make it surgically inaccessible. Therefore, the occlusion of a brain aneurysm with endovascular GDC coils is a safe and efficient way of preventing a rebleeding of the aneurysm when surgical removal of the aneurysm is not advised.

Cerebral Angioplasty

Caption: Stenosis of intracranial segment of left internal carotid artery before (left) and after (right) balloon angioplasty

A stroke is commonly the result of a blockage of blood flow to the brain, a condition known as cerebral ischemia. If the blood flow is stopped temporarily a patient experiences a transient ischemic attack or TIA. Cerebral ischemia can be due to a narrowing (stenosis) of a blood vessel supplying the brain. Stenosis is commonly the result of atherosclerotic plaque building up on the walls of a vessel. If a vessel is narrowed by the presence of plaque a blot clot (or thrombus) can become lodged in that vessel, halting blood flow.

An operation known as percutaneous cerebral angioplasty can be performed to dilate the lumen of stenotic blood vessels. This operation is usually performed on the internal carotid artery, an artery in the neck which supplies blood to the brain. This procedure, performed by an interventional neuroradiologist, involves the placement of a small balloon in the area where the blood vessel is narrowed. The balloon is introduced on the tip of an angiographic catheter (a tubular instrument), which is passed through the circulatory tree until the stenotic region of the internal carotid artery is reached. Once there the balloon is inflated, thereby causing the vessel to dilate and improving blood flow to the brain.

In most cases, angioplasty is reserved for patients with multiple TIAs or small strokes related to stenosis of a cerebral blood vessel who have not responded completely to maximal medical therapy with blood thinners.

Ventricular Drainage

A common complication of many serious neurological conditions is an elevation of the pressure within the skull, the intracranial pressure or ICP. High intracranial pressure can accompany stroke, head injury, brain infections, and brain tumors. Intracranial pressure may be high for several reasons. ICP can be elevated if there is a rise in the pressure of the fluid circulating around the brain (the cerebrospinal fluid)-this condition is known as hydrocephalus. Alternatively, the blood vessels supplying the brain can leak fluid into the brain substance. This can cause the brain to swell with fluid, a situation referred to as cerebral edema. Whatever the underlying cause, however, an increase in intracranial pressure is extremely dangerous. High intracranial pressure can cause the compression of blood vessels supplying the brain resulting in a cessation of blood flow to the brain (cerebral ischemia). If blood flow to part of the brain is interrupted that part of the brain can die. In addition, increased intracranial pressure can cause the compression of the brain stem by the overlying brain hemispheres. Since the brain stem controls such basic body functions as respiration, heart rate, and arousal this compression can cause a loss of consciousness or even death.

A Neuro-ICU is highly specialized for the treatment of high ICP. The mainstay of such treatment is the installment of intraventricular catheters. A catheter (a tubular instrument) is placed inside fluid filled cavities within the brain called ventricles. Cerebrospinal fluid is synthesized within these cavities and then flows out of the ventricles to circulate over the surface of the brain. Intraventricular catheters allow cerebrospinal fluid to be drained from the ventricles, thus lowering the pressure within the skull. These instruments can be installed during brain surgery or in the Neuro-ICU under local anesthesia.

Intraventricular catheters are ideal treatment devices for increased intracranial pressure. Because they drain cerebrospinal fluid this fluid can be analyzed for the presence of blood or infectious agents. Also, these catheters can measure intracranial pressure, in addition to being able to reduce it. In fact, the intraventricular catheter is the device most commonly used to measure intracranial pressure. Therefore intraventricular catheters, unique to a Neuro-ICU environment, are safe and efficient instruments that can both monitor and reduce intracranial pressure.

Hypertensive Hypervolemic Hemodilution

Over the past twenty years, elevation of blood pressure with intravenous medications and administration of large volumes of intravenous fluids (a.k.a. hypertensive hypervolemic hemodilution or "triple-H therapy") has become the principle method for treating ischemic neurologic deficits from vasospasm after subarachnoid hemorrhage. This treatment improves cerebral blood flow in regions of ischemia by three mechanisms: (a) elevation of blood pressure, (b) elevation of cardiac output and total blood volume, and (c) reduction of blood viscosity. All three of these factors serve to "drive" blood flow through and around blocked arteries, which in turn can lead to immediate reversal of symptoms. Application of triple-H therapy has also been described for patients with ischemic stroke, and may be particularly useful in patients with high-grade stenosis or occlusion of the carotid artery and distal perfusion failure. Familiarity with application of this technique in a neuro-ICU setting is essential, as is invasive hemodynamic monitoring of blood pressure and cardiac output, which serves to guide treatment and minimize complications. Dopamine, phenylephrine or norepinephrine is most often used to raise blood pressure, and protein-rich fluid (colloid) is often used to increase the patients blood volume. Excessive strain on the heart (myocardial ischemia) or fluid overload (pulmonary edema), the most important potential complications, can be avoided with careful hemodynamic monitoring.

Thrombolysis

A stroke is commonly the result of a blockage of blood flow to the brain, a condition known as cerebral ischemia. Blood flow is interrupted in a vessel by the presence of a blood clot (or thrombus) in that vessel. Such clots can cause an ischemic stroke (if the clot occludes an artery in the brain) or a deep venous thrombosis (if a vessel draining blood from the brain is blocked). Thrombolysis is the use of drugs to restore proper flow in an artery by disrupting a clot (thrombo= clot; lysis= breaking).

There are two general categories of medications used in thrombolysis: those injected into the arterial circulation (intraarterial agents) and those injected into the venous circulation (intravenous agents). The intraarterial agents include the drugs urokinase (an enzyme produced by the kidney) and streptokinase (produced by bacteria). These agents work by activating the protein plasmin. Plasmin then serves to degrade the protein which comprises blood clots - fibrin. The intravenous thrombolytic agents include a recently developed drug known as tissue plasminogen activator (t-PA). Like streptokinase and urokinase, t-PA works by promoting the formation of plasmin, thereby disrupting fibrin clots. Once a clot is so degraded blood flow can be restored and the brain can once more be adequately perfused.

It is important that thrombolytic therapy begin within three hours of the onset of a stroke. Studies have shown that when administered in that "therapeutic window" t-PA can be extremely efficient at restoring blood flow. If delayed, however, such treatment can result in dangerous hemorrhaging. Therefore, the rapid administration of t-PA and related thrombolytics can vastly improve outcome following stroke by disrupting blood clots and thereby reperfusing the brain with blood, but only if given within a narrow timeframe. The one exception to this rule may be administration of intra-arterial thrombolytics for treatment of an evolving basilar artery occlusion.

Plasmapheresis

Neuromuscular diseases are characterized by muscle weakness and fatigability. If this weakness affects the muscles of respiration then a patient's breathing can be dangerously compromised. Myasthenia Gravis and Guillain-Barré syndrome are the two most common neuromuscular diseases. Both disorders are caused by the presence of antibodies in the bloodstream which are directed against part of the neuromuscular system. In the case of myasthenia gravis the antibodies are directed against the nerve-muscle junction, and in Guillain-Barré syndrome antibodies become directed against the lipid (myelin) sheath which insulates nerves.

To treat these illnesses a Neuro-ICU employs the technology of plasmapheresis. Plasmapheresis is the process of removing blood from the body, separating out the cellular elements of the blood, resuspending these cellular elements in a plasma substitute, and then reinfusing this mixture into the body. Most plasmapheresis machines are continuous flow devices. This means blood continuously flows into the machine and the cellular elements are separated from the plasma by centrifugation and resuspended in a plasma substitute. This mixture is reinfused into the patient at a rate that equals that at which blood is removed. The purpose of this technique is to "cleanse" the blood of the antibodies which are responsible for the muscle fatigue. Thus plasmapheresis is an effective technique of relieving the symptoms of muscle weakness and fatigue which accompany certain neuromuscular disorders.

Hypothermia

Lowering of brain temperature is an effective method for "protecting" brain cells from death due to trauma or lack of blood flow and oxygen. The application of therapeutic hypothermia has recently been rediscovered as a method for improving outcome after severe traumatic brain injury, and is currently under investigation as a treatment for severe ischemic stroke or brain hemorrhage.

Most studies have shown that lowering of brain temperature to a safe level (approximately 32 to 33 degrees centigrade) requires cooling of the entire body with cooling blankets and iced saline lavaged into the stomach. The patient must be paralyzed to prevent shivering, which counteracts the cooling process and leads to metabolic complications. Since paralysis leads to loss of the ability to perform neurologic examinations, most patients require placement of a fiberoptic intracranial pressure monitor that has been configured to simultaneously measure brain temperature.

Hypothermia was tested and abonded as a treatment for severe brain injury in the 1940's and 1950's because it was felt to be unsafe. Complications of hypothermia can include cardiac arrythmia, increased susceptibility to infections, thinning of the blood, and a variety of metabolic disturbances (e.g. low potassium, high glucose). However, with present technology and careful application and monitoring in a Neuro-ICU, moderate systemic hypothermia can be safely administered. In one recent study, hypothermia was reported to be the first direct treatment to improve outcome after severe traumatic brain injury. Further studies are required to establish the efficacy of this treatment for severe stroke.

Phrenic Nerve Pacing

In order to better understand the technology of phrenic nerve pacing one must have knowledge of how the diaphragm is innervated. Nerve cells originating in the brain stem travel down to the cervical portion of the spinal cord (that portion of the cord in the neck). The phrenic nerve originates in the cervical spinal cord and receives a rhythmic stimulation from descending brain stem neurons. The phrenic nerve can then stimulate the contraction of the diaphragm, a dome-shaped muscle beneath the lungs. When the diaphragm contracts it lowers, thus reducing the pressure in the chest cavity and causing air to rush into the lungs.

The nerve cells which stimulate the phrenic nerve may be damaged by injury to the high spinal cord or brainstem. With such damage the diaphragm is unable to contract and breathing is severely impaired or even halted. This injury is commonly the result of spinal cord trauma caused by traffic accidents, sporting accidents, or gunshot wounds. Alternatively, these important nerves can be injured by an organic lesion such as a stroke (i.e. a cessation of blood flow) or an infection (e.g. encephalitis).

In selected cases, patients who remain dependent on a respirator for breathing may benefit from phrenic nerve pacing. This technique provides a simple method of electrically stimulating the phrenic nerve (and thus secondarily the diaphragm) when normal brainstem inputs are absent. The method employs a pacemaker technology not unlike that used in heart pacemakers. The pacemaker rhythmically stimulates the phrenic nerve causing diaphragmatic contraction and breathing. This allows a patient with cord injury (e.g. a quadriplegic) to breathe comfortably without the assistance (or the restraint) of a mechanical ventilator.

Phrenic nerve pacing works via the placement of a small electrode around the phrenic nerve. The nerve originates in the neck and descends through the chest cavity to reach the dome-shaped diaphragm. The electrode is placed around that part of the nerve in the chest. Therefore, in order to reach the nerve a chest incision (called a thoracotomy) is performed and the surgeon sews the electrode to the nerve. A receiver is then placed just beneath the skin in the area of the lower rib cage. The receiver receives radio signals from an external transmitter. It is then able to generate electrical currents which are conducted to the electrode, thus initiating phrenic nerve stimulation.

Specialized Pharmacotherapies

A Neuro-ICU employs a variety of innovative drug therapies which have proven useful in treating serious neurological illness. Pentobarbital and Propofol are two medications which are specialized for the management of patients in a neurological critical care unit:

1. Pentobarbital

   . This drug is one member of a group of agents known as barbiturates. Like other barbiturates, pentobarbital acts to depress functioning of the central nervous system. It can thus act to alter mood, to sedate, or even to induce coma. Pentobarbital is used in two separate situations in a neuro-ICU setting. The first situation is to treat a severe seizure disorder known as status epilepticus. Status epilepticus is defined as a seizure disorder lasting over thirty minutes. Longer lasting seizures are treated with a variety of medications. If the seizure is prolonged for over thirty minutes barbiturate therapy is instituted. First the barbiturate phenobarbital is used. If this proves ineffectual the patient is considered to be in "refractory status epilepticus" and pentobarbital treatment is employed.
   

   Pentobarbital is also used to treat an increase in the pressure within the skull, the intracranial pressure. Increased intracranial pressure is a common and very dangerous complication of many neurological conditions. Most commonly pentobarbital is used to decrease high intracranial pressure following head trauma. Pentobarbital lowers intracranial pressure by decreasing brain metabolism, the brain's use of oxygen, and the amount of blood perfusing the brain. Pentobarbital has the side effect of markedly reducing blood pressure. As a result medications which increase blood pressure (known as pressors) are often required when pentobarbital is used.

2. Propofol

   . This drug is an intravenously administered anesthetic which is used in the operating room or intensive care unit setting. It is used to continuously sedate patients who are agitated following stroke or head trauma. To administer this drug the expertise of individuals skilled in the use of anesthetics is required. It is also required that a patient given this drug be on a mechanical ventilator to ensure proper breathing. Propofol has several advantages over conventionally used sedatives. It is rapidly acting, and smoothly induces hypnotic states with minimal excitation. Furthermore, patients wake up immediately after the use of propofol is discontinued. Therefore, propofol can quickly and efficiently sedate agitated critically ill patients in a Neuro-ICU, setting, making these patients more manageable and thus facilitating their treatment.