Narcolepsy

Narcolepsy affects 0.03-0.1% of the general population, with the onset around adolescence and with boys and girls being equally affected. However, certain populations have higher prevalences of this condition: Japanese general population, 0.18%; French Caucasians, 0.05%; United Kingdom Caucasians, 0.04%; Finnish Caucasians, 0.026%; Czech Caucasians, 0.02%; and Israeli Jews and Arabs, 0.002%.

This debilitating condition is characterized by a tetrad of symptoms: (1) excessive daytime sleepiness, (2) cataplexy, (3) sleep paralysis and (4) hypnagogic hallucinations. Hypersomnolence is such a characteristic symptom of this condition that the term "narcolepsy" in fact is derived from Greek, "seized by somnolence." Cataplexy is sudden muscle atonia in response to emotional arousal, in particular laughter. Hypnagogic hallucinations are dream-like episodes when going to sleep.

Thus, patients with narcolepsy demonstrate two major abnormalities: inability to stay awake in the daytime and REM sleep interruptions leading to wakefulness or non-restorative sleep. An overnight polysomnogram followed by a multiple sleep latency test (MSLT) is essential in the workup. The MSLT is administered during the day to assess daytime sleepiness and to diagnose narcolepsy. It consists of four or five opportunities to take 15- to 20-minute naps, each separated by a two-hour interval.

In the late 1800s a familial tendency towards narcolepsy was first documented. First-degree relatives had a one to two percent risk of developing narcolepsy, which is 20-40 times higher than the general population. There is no known cause of primary narcolepsy. However, primary narcolepsy is thought to result from genetic predisposition, abnormal neurotransmitter functioning and sensitivity, and abnormal immune modulation. Secondary narcolepsy can be caused by head trauma, encephalopathy, brain tumors and cerebrovascular insufficiency.

In addition to the physically incapacitating effects of narcolepsy, this condition is also emotionally and socially awkward. Patients often feel embarrassed about their symptoms and can experience social isolation. They may not be able to drive, hold down a job or keep up with school work. In one study, 24% of narcoleptic patients had to quit working and 18% were terminated from their jobs because of their disease.

Case: Narcolepsy in a Twenty-five-year-old Man

A twenty-five-year-old man, who had been diagnosed years earlier with narcolepsy, lived in Arizona, where he was finding it impossible to continue to work or attend school. He would literally sleep all day and all night for days at a time. In fact, he made the comment that he would “have a two hour nap before going to sleep.” He had lost weight, motivation and was depressed. He rated his energy at a zero out of ten, with ten being best. He was unable to read more than a paragraph at any one time in a book. He simply could not focus his mind and he would begin to fall asleep. He was completely socially isolated.

By the time his mother found Dr. Neustadt to help her son, the family was literally exasperated and didn’t know what to do. The son did not want to move home with his parents, but if his health did not improve, he would have had no other option. This young man had been prescribed a series of different medications over the years to treat symptoms. The most recent of those was Ritalin. This amphetamine would make him feel “jittery” and “wired” but, paradoxically, he did not experience any increase in energy. On the contrary, he merely experienced an increase in anxiety and a decreased ability to focus.

His MetaCT 400 test results revealed:

Low aspartic and glutamic acids, both excitatory neurotransmitters

Elevated serum proline

Low fasting insulin

Low serum vitamins

Low omega-3 and omega-6 fatty acids

Low saturated fatty acids

Elevated whole blood aluminum

Interestingly, Dr. Neustadt was quite surprised to learn that this patient’s essential amino acids and markers for functional vitamin B deficiencies and mitochondrial dysfunction were all normal.

In researching the case to create the treatment plan, Dr. Neustadt discovered that low aspartic and glutamic acids have been associated with narcolepsy.Aspartic acid is a precursor to oxaloacetate, a Kreb’s Cycle intermediate, which is required for mitochondrial ATP production. Additionally, aspartic acid is a preferred substrate for the refilling pathway that restores Kreb’s Cycle levels of citrate and isocitrate, and can help to increase these energy producing intermediates. Aspartic acid is also involved in glucose synthesis, the urea cycle and a precursor of both DNA and RNA. Aspartic acid is a preferred substrate for the refilling pathway that restores CAC levels of citrate and isocitrate, and can help to increase energy producing intermediates. Low levels of aspartic acid may reflect lowered cellular energy-generating capacity, experienced as chronic fatigue. In a pharmacokinetic rat study published in 1982, the simultaneous administration of aspartic acid and arginine led to increases in neurostimulatory amino acids in the brain.

In 1935 none other than Hans Krebs himself, published a paper showing how proline can be converted to glutamic acid in the kidneys. The oxidation of proline to glutamic acid requires niacin as a cofactor. His proline was elevated, functional markers for niacin were normal (alpha-Ketoisovalerate, alpha-Ketoisocaproate and alpha-Keto-beta-Methylvalerate) and his glutamic acid was low. This could be interepreted that he has difficulty converting proline to glutamic acid.

The cause may be genetic and he may require long-term glutamic acid replacement therapy. However, one caveat is important to note here. Glutamic acid when too high is a neurotoxin. Therefore, this patient may require titration of glutamic acid to achieve maximal clinical results. Glutamic acid is involved in glucose synthesis, the urea cycle, glutathione synthesis and is a neurotransmitter. In fact, in the central nervous system (CNS), glutamic acid is the major excitatory neurotransmitter.

Dr. Pieczenik posits that, since destruction of dopaminergic neurons by glutamic acid is an etiological factor in Parkinson’s disease (PD), that narcolepsy may be viewed as the converse of PD. Therefore, Dr. Pieczenik believes that narcolepsy and PD may eventually be viewed on a spectrum of disease states associated with glutamate levels. He also speculates that schizophrenia, epilepsy and bipolar disorder are all affected the by glutaminergic system. Additional research obviously would be required to investigate these hypotheses.

After being on the plan (below) for one month, the patient had a follow-up with Dr. Neustadt. At that time the patient reported that his energy had increased to 6.5 out of ten, with ten being best. He was more alert, focused and had more mental and physical stamina. He was still sleeping more than was normal, from eight o’clock at night to about noon the next day, but when he was awake he functioned normally. He was awake for eight hours a day, compared to sleeping for days in a row before the program. He was even able read multiple chapters in books at a time without falling asleep.

This case is interesting for many reasons. While the clinical results showed improvement, Dr. Neustadt is not entirely sure why. Which agent or combination of agents prescribed created the improvement? Some may view this as a limitation of this approach in medicine; however, Drs. Neustadt and Pieczenik do not agree. The substances prescribed were nontoxic and resulted in benefit. While the case continues to progress at the time of writing this book, just like all treatment plans, the goal is to decrease the amount of dietary supplements at the end of the program and see if the clinical improvement continues. If symptoms regress, then individual agents are added back to the recommendations to maintain the benefits.