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A Little History on Deep Brain Stimulation

DEEP BRAIN STIMULATION THERAPY

A deep brain stimulator (DBS) device is similar to a pacemaker for the heart, but instead of having electrodes (or electrical wires) implanted in the heart, the electrodes are placed into the brain. The electrodes carry electrical signals to specific brain locations. These electrical signals, like a heart pacemaker, cause the brain cells around the DBS electrode to change their activity. By changing the activity of brain cells, DBS can help the symptoms of many neurological disorders, depending on where the electrodes are placed.

Diseases treated with DBS include Parkinson’s disease, essential tremor (ET), dystonia, and a few other neurological and psychiatric disorders. Parkinson’s disease, essential tremor, and dystonia are examples of movement disorders. Movement disorders are neurological diseases that affect the ability to produce and control movements of the body. In individuals with these conditions, the firing patterns of nerve cells within certain parts of the brain become abnormal. These abnormal patterns spread through the electrical circuits of the brain to other areas such as the brain areas connected to the spinal cord that guide movement, the brain areas that steady the limbs and smooth movement, or the brain areas that help to start and stop movements. The abnormal activity in these brain circuits creates the symptoms of the disease condition, such as tremor in Parkinson’s disease and essential tremor or the abnormal muscle contractions in dystonia.

UNDERSTANDING THE MOTOR SYSTEM OF THE BRAIN

The way we move requires a lot of processes to occur in the brain in a coordinated way. Today, we know that there are two systems (or types of circuits) in the brain that control movement.

The “pyramidal system” is one of these motor circuits. It is composed of cells that directly control the motor neurons (or nerve cells) of the spinal cord. The principal area of the brain containing these cells is the primary motor cortex, which is located on the surface of the brain, just above the ear. Cells in this region extend portions of themselves (known as processes) down through a bundle of nerves called the internal capsule, through the brainstem (the connection between the brain and the spinal cord), and eventually to the spinal cord. The pyramidal system itself is named after the pyramid shape of these processes in the brainstem.

The “extrapyramidal system” is the second motor system of the brain. It is composed of the circuits of the brain whose fibers do not travel through the pyramids. The extrapyramidal circuits shape movement by influencing our reflexes, coordination, and posture. These circuits also break down our complex movements into sequences of simple ones.

The pyramidal system is largely located in the surface portion of the brain: the cerebral cortex. The extrapyramidal system is located deep within the brain, in structures such as the basal ganglia, brainstem, and cerebellum.

When we move as a result of a desire or goal, the movements are voluntary. When we move without such a desire, such as when we experience a tremor, the movements become involuntary. DBS systems are placed into extrapyramidal motor system circuits to control and reduce involuntary movements.

HISTORICAL UNDERSTANDING OF THE DISEASES TREATED WITH DBS

Parkinson’s Disease

Although the terms “Parkinson’s disease,” “essential tremor,” and “dystonia” were first used a century or more ago, these diseases have been known and treated for centuries. The disease now known as Parkinson’s disease was described and treated as early as 5000 BC by ancient civilizations in India that termed the disease “Kampavata.” Kampavata was treated with a tropical plant containing natural quantities of levodopa, one of the best medications for the treatment of Parkinson’s disease today. James Parkinson (1755–1824) was an English physician who first described the symptoms of the disease that now bears his name in a manuscript called “An Essay on the Shaking Palsy” in 1817. His description of the symptoms of Parkinson’s disease was remarkably accurate, especially because it was based on just six people, three of whom he did not even see in his practice, but observed on his daily walks. In the Western world, the first treatment of Parkinson’s disease was the use of belladonna drops by Jean-Martin Charcot (1825–1883) to treat the excessive salivation that occurred in some individuals. It was Charcot who recommended that the disease be named after James Parkinson.

Essential Tremor

Essential tremor has also been known since the ancient times. The Greek physician Galen (130–200 AD) wrote of an action tremor condition in his essay “De Tremore” between 169 and 180 AD. Other ancient accounts of essential tremor occur in the medical publications of Israel and India. Pietro Burresi was the first to use the term “tremore semplice essenziale,” or essential tremor, in 1874 to describe an 18-year-old man with a severe tremor of the arms when moving them. Dr. Charles Dana (1852–1935), a New York neurologist, was one of the first to extensively study essential tremor, publishing a study of several large families in 1887. Essential tremor has been treated with a class of medications known as beta-blockers since the 1960s [of which propranolol (Inderal) is the most commonly used] and with anticonvulsant medications such as mysoline (Primidone) since the late 1970s.

Dystonia

Dystonia has been also recognized for centuries. In fact, individuals with dystonia are often depicted in ancient works of art. In modern times, Hermann Oppenheim (1858–1919) applied the term “dystonia musculorum deformans” to four children with a progressive, generalized dystonia in 1911 and was the first to recognize dystonia as a movement disorder. Before Oppenheim, many physicians mistakenly believed dystonia to be a purely psychiatric disorder. Dystonia has been treated with anticholinergic medications such as trihexylphenidyl (Artane) since the 1950s and with muscle relaxants such as baclofen (Lioresal) since the 1960s.

EARLY BRAIN SURGERIES FOR MOVEMENT DISORDERS

The earliest surgeries for movement disorders were directed at the muscles producing the movements themselves rather than the brain. For example, surgery for dystonia was first performed in 1641 by the German surgeon Isaac Minnius and involved cutting the muscles in the neck that were involved in cervical (neck) dystonia (also known as torticollis).

During the 19th century, understanding of the regions of the brain involved in movement helped motivate surgeons to address movement disorders through operations on the brain. Gustav Fritsch (1838–1927) and Eduard Hitzig (1838–1907) reported experiments that helped to localize motor function in the cerebral cortex (the surface of the brain) in 1870. The earliest surgeries for movement disorders therefore involved removing these surface areas of the brain. These surgeries eliminated abnormal movements, but unfortunately, it caused weakness. Victor Horsley (1857–1916), a British surgeon, was the first to describe a procedure in which the primary motor cortex was removed to treat tremor. A. Earl Walker (1907–1995), an American, later described a less invasive procedure in which the nerve fibers of primary motor cortex cells, connecting the brain to the spinal cord, were partially cut to produce both weakness and relief of tremor. This procedure, called pedunculectomy, remained popular until the 1950s.

In the 1920s and 1930s, the role of the extrapyramidal system in movement disorders became more widely appreciated. Otfrid Foerster (1873–1941), Cecile Vogt (1875–1962), and Oskar Vogt (1870–1959) demonstrated that changes in the deeper structures in the brain were fundamentally involved in Parkinson’s disease and other movement disorders. Rolf Hassler (1914–1984) observed that Parkinson’s disease was associated with the loss of pigmented nerve cells in the substantia nigra. We now know that these pigmented nerve cells are dopamine-producing cells, and that the loss of these cells results in loss of dopamine in the brain, causing symptoms of Parkinson’s disease. Building on these findings, and those of others, Hugo Spatz (1888–1969) defined the extrapyramidal regions of the brain and proposed that movement disorders arose within this system.

Based on these findings, neurosurgeons developed surgeries directed toward the extrapyramidal motor system.

In 1942, Russell Meyers (1904–1999) first reported the effects of surgery on the basal ganglia (a major group of structures within the extrapyramidal system) for Parkinson’s disease. He removed the head and anterior segment of the caudate nucleus, one of the structures of the basal ganglia, and found that tremor and rigidity improved without the creation of weakness. Later surgeons improved on his technique, introducing the idea of using intense heat or cold to create a permanent lesion in the brain.

Some of the progress in brain surgery for movement disorders came by accident. Irving Cooper (1922–1985) was performing Walker’s pedunculectomy operation for tremor in 1952, and during the operation, noted bleeding forced him to stop. To his surprise, the tremor was eliminated, although the actual goal of the surgery was not achieved. Cooper knew which blood vessel had been injured in the surgery and reasoned that the area of the brain that was fed by the blood vessel must have been injured. He reasoned that intentionally injuring this area might improve tremor. This finding directed attention toward the pallidum, another structure in the basal ganglia, as a target for movement disorder surgery.

Once doctors treating movement disorders realized that lesions (or injuries) of specific structures deep within the brain could treat individuals safely and effectively, surgery for movement disorders began in earnest. To allow more precise targeting of structures deep within the brain, clinical neuroscientists and neurosurgeons developed methods of image-directed surgery. In 1947, Ernest Spiegel and Henry Wycis introduced the first frame-based human surgeries. The stereotactic frame is a metal device that is attached to the skull and allows precise targeting of structures within the skull by associating a coordinate system with structures within the skull. Lars Leksell (1907–1986), a Swedish neurosurgeon, introduced a more simply designed frame in 1949. Versions of these frames are used to this day.

Frame-based stereotactic surgery was performed extensively in the 1950s and 1960s. By utilizing a frame, internal brain structures could be reproducibly targeted. The two primary targets of surgery were the pallidum and the thalamus, and these structures were lesioned by burning or freezing the brain tissue in that area. Hirotaro Narabayashi (1922-2001) performed the first human stereotactic pallidotomy (destruction of cells in the pallidum) in 1951. Rolf Hassler described stereotactic lesioning of the ventral intermediate (VIM) nucleus of the thalamus for parkinsonian tremor in 1954.

In 1968, George Cotzias (1918–1977) discovered and developed a way to give levodopa to people living with Parkinson’s in large-enough doses to treat the symptoms with minimal side effects. Levodopa was (and still remains) an effective therapy for the symptoms of Parkinson’s disease. Because of this, the risks of surgery exceeded the risks of medical therapy, and the number of surgeries for Parkinson’s disease dropped dramatically.

ELECTRICAL THERAPIES IN THE BRAIN

Today, we take it for granted that the brain is an electrical organ and that the cells of the brain communicate with each other through chemical and electrical signals. However, the role of electricity in the body was not always known. Luigi Galvani (1737–1798) reported that electrical stimulation could produce contractions in frog muscles in 1791. His nephew, Giovani Aldini (1762–1834), was the first to demonstrate the therapeutic role of electricity in the human nervous system, in 1801, using electricity to treat a person with depression.

During the 19th century, understanding of the electrical characteristics of the brain increased significantly. Fritsch and Hitzig utilized electrical stimulation to study the motor function in the brain in 1870. These findings were extended in the work of David Ferrier (1842–1928) and Robert Bartholow (1831–1904).

Although electrical stimulation in the form of individual shocks was utilized to treat depression in the 18th century, the technology to produce reliable ongoing stimulation was not available until the 20th century. In 1948, J. Lawrence Pool (1906–2004) was the first neurosurgeon to utilize deep brain stimulation in a person living with Parkinson’s disease. This individual, who suffered from appetite loss and depression associated with Parkinson’s disease, was treated for eight weeks with stimulation of the caudate, yet another basal ganglia structure. At the time, brain stimulation was primarily used to predict the outcomes of stereotactic lesions in the brain, particularly for the treatment of pain. Less frequently, stimulation and lesions to the thalamus, pallidum, and cerebellum were performed for the treatment of tremor. This practice continued until the 1960s, when the demand for movement disorder surgery was reduced after the introduction of levodopa.

DEEP BRAIN STIMULATION IN THE MODERN ERA

Yoshio Hosobuchi first performed chronic deep brain stimulation using implanted electrodes for the treatment of pain in 1973. The technology was adapted from the heart pacemaker, which had been introduced in 1958. In the early years, DBS was applied to regions of the brain controlling pain as well the cerebellum to treat spasticity and tremor.

A French neurosurgeon, Alim Louis Benabid, noticed in 1987 that chronic stimulation in the thalamus resulted in the disappearance of tremor. Chronic stimulation was used to confirm the precise location in the brain that was going to be lesioned. Instead of making a lesion in this patient, he decided to implant a deep brain stimulator at that location instead. In 1993, he reported the impressive results of long-term deep brain stimulation on tremor. The long-term results of pallidal stimulation for Parkinson’s disease were reported in 2002. With these final steps forward, the field of DBS was born.