Self-management of Fatal Familial Insomnia. Part 2: Case Report

Joyce Schenkein, PhD; Pasquale Montagna, MD

Abstract

Context: Fatal familial insomnia (FFI) is a genetically transmitted neurodegenerative prion disease that incurs great suffering and has neither a treatment nor cure. The clinical literature is devoid of management plans (other than palliative). Part 1 of this article reviews the sparse literature about FFI, including case descriptions. Part 2 describes the efforts of one patient (with the rapid-course Met-Met subtype) who contended with his devastating symptoms and improved the quality of his life.

Design: Interventions were based on the premise that some symptoms may be secondary to insomnia and not a direct result of the disease itself. Strategies (derived by trial and error) were devised to induce sleep and increase alertness. Interventions included vitamin supplementation, narcoleptics, anesthesia, stimulants, sensory deprivation, exercise, light entrainment, growth hormone, and electroconvulsive therapy (ECT).

Results: The patient exceeded the average survival time by nearly 1 year, and during this time (when most patients are totally incapacitated), he was able to write a book and to successfully drive hundreds of miles.

Conclusion: Methods to induce sleep may extend and enhance life during the disease course, although they do not prevent death. It is hoped that some of his methods will inspire further clinical studies.

Case Report

DF was a right-handed, 52-year-old, white, American man with a doctorate in naturopathy. DF's father, paternal uncle, and 2 male cousins were diagnosed with fatal familial insomnia (FFI). His father died at age 76; his uncle died at age 74; and each of DF's cousins died before the age of 50. Because disease onset beyond age 60 is rare, it is worth mentioning that DF's father was a prominent talk radio nutritionist who promoted the regular consumption of wheat germ and who richly supplemented his own diet with antioxidant vitamins. Because the trigger that begins FFI is unknown, the possibility that a specific diet might delay onset is worth considering.

Although DF had always been a short sleeper and nocturnally active, in March 2001, he experienced a marked reduction in the duration of his sleep and occasional nights of total insomnia. This symptom did not initially concern him. However, in subsequent months, the additional appearance of a hand tremor, fever spikes, profuse sweating, and problems with short-term memory led him to seek medical attention. The diagnosis of FFI (subtype Met-Met) was confirmed by DNA testing.

At this time, DF was 10 months into his illness (stage I). He resolved to make the most of his life before the onset of stage IV. DF purchased a motor home and embarked on a solo tour of the United States. He typically drove great distances, but only after a refreshing sleep; he would stay in rest stops for several days until again renewed by sleep. Before embarking, he required himself to recall many numbers, including his date of birth, social security number, etc, and drove only if he remembered all of these.

When he was stranded by prolonged insomnia, DF was frequently disoriented and confused. He reported sometimes finding himself in a parking lot without knowing how he got there, or discovering by the date on a newspaper that several days had elapsed. After 5 months of traveling in this fashion (18 months into his illness), he hired a professional driver and caretaker. During this period, DF was besieged by a number of medical illnesses that were either a consequence of his illness or his treatments, eg, fevers as high as 102°F, hypertension, cardiac arrhythmias, renal hypertension, diabetes, and a heart attack. Descriptions of DF's treatments were conveyed either by phone or emails from his caretakers. Unfortunately, corroborative physiologic measures were not always available.

Shortly after his diagnosis (at 10 months into the disease), DF received vitamin therapy at the Clymer Institute for Alternative Health in Quakertown, Pennsylvania. At 9:00 o'clock every evening, DF took a combination of niacin, antioxidant powder (comprising vitamins A, C, E, and D), blue-green algae, brewer's yeast, B complex, zinc (sublingually), magnesium, inositol, PABA, grape seed extract, CoQ-10, choline, Tiger's Milk nutrition bar, highly concentrated wheat germ oil, tryptophan, and 2 g of melatonin. He also injected a gelatinous form of B12 into his nasal cavity.

Within 30 minutes of this treatment, DF reported that he fell into a natural and restful sleep. On this regimen, he experienced 5 out of 6 consecutive nights of sleep, ranging from 5 to 6.5 hours per night. (Prior to these treatments, he had frequently endured 72-96 hours of total insomnia.)

Later in his illness, DF added what he referred to as massive, but unspecified, doses of octocosonal (a spinach derivative prepared with long-chain alcohols). Of all supplements, he found this to be most effective and quick-acting in masking symptoms of fatigue following long periods of sleeplessness.

By the 20th month, DF had added a commercially available combination of vitamin B12, B6, and folic acid formulated for sublingual absorption. Because this preparation was taken in conjunction with other medications, it cannot be evaluated independently.

By month 15 (early stage II), vitamins alone failed to induce sleep. Following 5 consecutive nights of insomnia, DF became intensely irritable and delusional. An evaluation at the Massachusetts General Hospital in Boston, Massachusetts, found that he had suffered a minor stroke; he was anesthetized until he fell asleep. While hospitalized, he slept for 3 consecutive days and was fully alert and refreshed afterward.

In later months, DF continued the strategy of anesthesia. Ketamine and nitrous oxide induced short (15-minute) periods of restful sleep, and were reapplied to offer more prolonged relief. Chloral hydrate in a light alcohol mix and/or chloroform also worked.

Approximately 15 months into his illness, DF began to take sleep medications on a rotating schedule. Ethclorvynol, zolpidem, and diazepam reliably relieved his insomnia for roughly 1 month. During subsequent months, only diazepam offered intermittent relief. DF took 90 mg daily before bedtime, plus 2 doses of 30 mg each during the day. In the 24th month of his illness, he retried the other narcoleptics and discovered that both zolpidem and ethclorvynol again helped him sleep. The ethclorvynol also functioned as a mood elevator.

At month 16, when the narcoleptics ceased to work, DF rarely slept. Indeed he lost awareness of whether he had slept or not and no longer felt refreshed. He likened his insomnia to the experience of approaching an open doorway, only to have it suddenly become inaccessible. He said that something of a "jolt" would overtake him and render him vitally awake. Subjectively, he found this experience to be exhilarating, similar to a drug-induced high. As his disease advanced and he was physically more debilitated, this phenomenon became less appealing. In addition, that doorway to sleep became progressively more remote, and was obliterated by any noise or distraction.

At 16 months, his symptoms included consistently elevated body temperature (as high as 102°F), profuse sweating, serious impairment of short-term memory (for which he compensated by keeping lists), difficulty maintaining attention (he often did not know that the phone was ringing), difficulty distinguishing reality from fantasy (he didn't remember whether he had called a friend or had only imagined doing so), persistent headaches, hallucinations while driving (believed he saw people on the road when it was, in fact, empty), panic attacks (which were treated with meprobate), and a complete loss of sense of time. His blood pressure was 160/90 mm Hg, from a premorbid 120/80 mm Hg.

Much of the time DF was confused, and sat entranced for hours. On occasion, he would get up for water, forget why he had gotten up, and return to the couch empty-handed. He might repeat this behavior for hours, never actually obtaining the water and not guided by the fact that he was thirsty. He could not decipher notes that he had written to himself on previous days. His speech was dysarthric.

By the 16th month of his illness, DF spent much of the day as an akinetic mute with terrible headaches, confusion, mood swings, and myoclonus of the left arm (treated with levodopa). Despite his outward "dementia," he inwardly pondered approaches to his condition, and, when again able to speak, he requested a regimen of stimulants.

He was prescribed phentermine HCl 37.5 mg (time-release), which he took twice daily and eventually 3 times daily (before meals and no later than 6:00 pm). The drug had immediate and dramatic effects, promoting not only alertness during the day, but apparently a sleep-inducing rebound when it wore off. He described the sleep experience as "natural"; he felt well upon arising, despite a slight headache that faded as the day wore on. For 4 consecutive nights, DF slept 5 hours each night, was able to drive, and returned to his daily routines, which included writing a novel. It was at this time when he began taking walks to physically tire himself. He no longer felt confused and reported that, aside from problems with his short-term memory and sense of time, he felt as well as before the onset of FFI. His blood pressure fell from 160/90 mm Hg to 140/80 mm Hg. His body temperature had returned to normal (98.2°F), and he did not experience any feverish surges in temperature while taking the medication.

Unfortunately, he was accidentally overmedicated by his caretakers and received 2 pills (75 mg) of phentermine in close succession. This overdose resulted in cardiac arrhythmias and another hospital stay. Medical examination revealed protein in his urine and tiny retinal hemorrhages, and stimulants were discontinued. He spent subsequent weeks sleeplessly and in the characteristic stupor of stage III. When the phentermine was resumed, DF regained his ability to function and drive, but after a week, believed that he had developed a tolerance to the drug. It was no longer alerting him, nor was he sleeping.

At that point, methylphenidate offered some relief. After a few days, however, DF had a grand mal seizure and was again hospitalized. Although his thinking was clear and oriented, his speech was labored, dysarthric, and perseverative, and his fever had returned.

During his last months, DF received a new stimulant protocol, and he took these on a daily rotating basis: diethylpropion + propoxyphene-acetaminophen (for headaches), methylphenidate, phentermine, modafinil, and a benzedrine inhaler (which is illegal in the United States, but which he was nevertheless able to obtain). Benzedrine enabled him to successfully drive 500 miles alone (on several occasions) during the 24th month of his illness. DF believed that the diethylpropion + propoxyphene-acetaminophen combination restored his function to that of a far earlier stage of the disease. However, phentermine was his preferred stimulant because he was always able to sleep well when it wore off. Of interest, DF said that if taken when he was exhausted, phentermine interfered with his sleep, whereas when rested, it improved both the quality of his day and his sleep. He believed that the benefit of phentermine was dose-related and that the exhausted person should take a much lower dosage to enable the sleep rebound.

While using these various stimulants, DF slept about 16-18 hours/week, or roughly half of his preillness baseline. Thus, many symptoms of FFI abated with the stimulants; however, the long-term effects of these medications in conjunction with his ongoing disease resulted in extensive kidney damage and may have contributed to the cardiac problems that appeared in the 25th month of his illness. In the 26th month, DF began taking time-released benzphetamine (90 mg) and a small amount of methylphenidate to reduce the stress on cardiovascular and renal systems.

Because the exhausted FFI patient tends to be inactive, DF implemented regular walks to increase natural fatigue and enhance the likelihood of sleep. An exhausted insomniac seems to be a poor candidate for physical rigor. Furthermore, if elevated temperature is toxic for patients with FFI (McGinty, personal communication, 2002), then heat loads and stress should be avoided. Ironically, regular exercise is considered critical for overall health, fitness, and quality sleep for most of these patients. In particular, because the homeostatic imbalance of the FFI patient is biased to sympathetic overdrive, some form of "fight-or-flight" activity may be appropriate. Because DF's response to rigorous exercise was rapid overheating with slow recovery to baseline temperature, he maintained moderate but persistent activity and believed that he derived benefit from the workout.

Noting that his grand mal seizure was followed by restful sleep, DF sought to duplicate the experience with electroconvulsive therapy (ECT). Beginning in the 19th month of his illness, he subjected himself to 30 sessions during several weeks. The ECT attendant placed the electrodes over the temporal lobes. The frontal area might have been a wiser choice because reduced function of the basal forebrain is common in FFI and previous research has shown that electrical stimulation to the basal forebrain can induce slow-wave sleep (SWS) in cats.[1]

Some form of sleep accompanied each of DF's experiences. Unfortunately, in his posttreated state, he experienced severe anomia, profound retrograde amnesia (extending back several years), and a disagreeable and paranoid overtone to his personality. Although these effects attenuated over the following weeks and long-term memory did return, DF was reluctant to repeat the experience. In retrospect, DF would have used a lower than conventional ECT voltage level and electrode placement over the frontal area.

Over time, the efficacy of DF's medications and strategies decreased. Despite occasional sleep lasting 5 hours in 1 night, periods of insomnia increased to as long as 3+ days. In tandem with insomnia, his cognitive functioning diminished.

At 22 months into his illness, DF purchased a sensory deprivation tank; a man-sized, egg-shaped chamber designed to eliminate all sensory input. DF became interested in this chamber because his sleep was constantly disturbed by any small sound, light, or motion.

In the sensory deprivation tank, the individual floats in concentrated Epson salt water at body temperature (experiencing no pain, gravity, temperature, touch, or kinesthetic information). Eyes and ears are shielded from light and sound, and the lid is shut. This device promotes total muscular relaxation. In the initial Hebb-Lilly experiments in the 1950s, subjects fell asleep shortly after entering one of these devices.[2] Upon awakening, most demanded immediate release. Those who remained experienced hallucinations, and had difficulty performing simple math calculations and tests of motor coordination (eg, walking and writing). The more time spent in the chamber, the more disoriented the later behavior.

Upon being immersed, DF was immediately anesthetized with nitrous oxide until he fell asleep. (Sleep was determined by a reduction in his heart and breathing rate). At his first attempt, he remained asleep for 4.5 hours. Subsequent use always resulted in the rapid onset of an unpredictable amount of sleep, ranging from 10 minutes to 8 hours. Similar to Hebb's subjects, upon awakening DF experienced disturbing hallucinations, - with the subjective uncertainty as to whether he was awake or dead. As always, long periods of sleep restored DF's mental clarity, suggesting, again, that at least some of the "confusion and dementia" of the FFI patient may be a consequence of insomnia.

For about 2 months, DF routinely used the deprivation chamber (unless hospitalized or traveling). Of note, while DF was away from his sleep tank, he was still able to sleep for 1-2 hours per night (see "Meditation"). Unfortunately, during one of his times away, winter temperatures froze the water in his outdoor tank and cracked its shell, rendering the device useless. DF chose not to replace it, noting that it limited his driving mobility and made him feel like the comic book freak Aquaman, who nightly slept in a fish tank.

To a person who lacks a circadian rhythm, "bedtime" is arbitrary. Early in the course of his illness, DF tried to maintain an artificial 24-hour diurnal rhythm. As his disease progressed, however, he took stimulants whenever he woke up, independent of chronologic hour, preferring to function at his best possible level, even if the hour corresponded to the normal local bedtime for others. Until roughly the 23rd month, DF's sleep patterns showed a definite cycle, which may have reflected his rotating schedule of the various medications. The first night, he slept well; the second night, less well; and the third, still less, followed by 1-2 sleepless nights. Then the cycle repeated.

Because of inconsistent results in the sleep tank, DF explored ways to externally bias his biorhythms to favor sleep at specific times. These involved daily exercise; exposure to sufficient sunlight; and timed use of melatonin, diazepam, and tryptophan. Early, but not later, in the course of his disease, this combination was effective. In the 24th month of his illness, DF began taking growth hormone (GH) prior to and after sleep. The immediate effect of GH was a dramatic reduction of his previously high blood sugar level. GH alsolowered his temperature from 102°F to normal. Because DF's experiments were interrupted by several, long, solo driving expeditions (away from his sleep tank), data collection was not complete.

Gamma-hydroxybutyrate (GHB) was administered during the last month of DF's life. To reduce the possibility of negative interaction with diazepam, he tapered his dosage for several days before trying GHB. According to his caretaker, GHB resulted in sleep within 30 minutes of administration, but did not last long enough for DF to feel rested. Similar to Reder's patient, described in Part 1, DF felt achy and irritable most of the time. He was unable to resume his stimulants because of potential heart and kidney failure.

During his last month, he was hospitalized for heart problems. Use of GHB was discontinued at this time and this was shortly followed by cardiac arrest. A causal association between stopping GHB and cardiac arrest cannot be made in view of the preexisting cardiac pathology and long-standing FFI. However, this reaction is also reminiscent of Reder's patient at the termination of the medication, and of the reports of others that abrupt cessation of GHB can lead to withdrawal symptoms, including tachycardia and hypertension.[3] At the minimum, it can be said that DF did not receive the expected benefit of GHB. Others have reported a nonresponse to GHB in patients with FFI.[4]

Whenever he traveled or was hospitalized and away from his sleep tank, DF practiced meditation. This technique enabled him to achieve what he described as "sleep," or a restful, restorative state.

Discussion

This article describes the various strategies that were attempted by an FFI patient to live with his symptoms. Because these approaches were arbitrarily selected, and often combined, altered unsystematically, and occasionally interrupted by medical emergencies, scientific rigor is obviously lacking. The study authors also are frustrated that DF's constant mobility made it difficult to monitor and document his vital signs.

FFI is a rare disorder and case management is not widely known, even among professionals. Each period of DF's hospitalization involved an abrupt and total disruption of treatment protocol, some of which might have compromised later responses to the same medications or even jeopardized his health. Furthermore, when unorthodox methods were tried, records were deliberately made unavailable. Therefore, interpretation of the results was speculative at best.

Finally, the progressive nature of the disorder complicates evaluation of the best approach. However, the fact that DF far outlived and functioned more efficiently than the typical Met-Met patient suggests that at least some of these strategies warrant further study.

The protective value of antioxidant supplements is already recognized in mainstream medicine. Their use may have slowed the progress of DF's disease, possibly by mopping up free radicals that are produced during apoptosis[5] and possibly by reducing tissue damage caused by frequent low-grade fever. VN-3 fatty acids, vitamin E, and coenzyme Q10 may be beneficial in reducing the risk for heart attack associated with emotional stress, physical exertion, and sleep deprivation (Singh, personal communication, 2001).

The use of vitamins does not reverse the disease. However, meganutrients (as provided by the Clymer institute) had the initial result of inducing sleep. Vitamins B6 and B12 and zinc participate in sleep biochemistry.[6] As additional support, DF's father, a lifelong nutritionist and vitamin advocate, did not develop FFI until he was in his mid-70s. No systematic trend has been determined to explain age of onset. In an Austrian family, different members were diagnosed at ages 20, 25, 37, 58, and 60 years.[7] Once the disease is established, the time course may be similar for all patients, that is, the age of onset does not predict the rate of progression.[8] In the absence of a better preventive treatment, a nutritional protocol might be tried for those identified as FFI carriers who have not yet shown signs of the disease.

Narcoleptics tend to be of limited value in FFI. However, ethchlorvynol became more helpful late in the course of the disease, suggesting that it is worthwhile to retry narcoleptic agents despite initial inefficacy. Only the GABA agonist diazepam had a reliable benefit. Physiologically, GABA contributes to the sleep-related reduction of activity in the basal forebrain,[9] to suprachiasmatic nucleus rhythms,[10] and to a drop in arterial pressure and heart rate, mediated through the mediodorsal nucleus of the thalamus.[11] Although DF believed that diazepam helped him sleep, supportive data were not available. Polysomnography performed on other FFI patients who had been medicated with benzodiazepines failed to demonstrate the same spindling activity that occurs in normals.[12-14]

Although the various stimulants improve vigilance during sleep deprivation, they differ in their pharmacologic actions and effects on sleep recovery. Comparative studies have shown modafinil to be relatively nondisruptive of subsequent sleep (in terms of reduced need for rebound sleep)[15,16] and subjective restfulness.[16,17] On the other hand, phentermine is associated with a decrease in REM sleep.[18] Amphetamines (eg, benzedrine) and amphetamine-like stimulants tend to reduce sleep efficiency in terms of increased sleep latency, intrasleep wakefulness, and reduction in total sleep time.[16,19] Methylphenidate is known to cause occasional problems with sleep induction, although these attenuate over time.[20] As mentioned, DF preferred the effects of phentermine compared with those of modafinil. This could be either idiosyncratic or reflect the FFI biochemistry.

The potential for an increase in blood pressure that is frequently associated with the use of sympathomimetics did not occur with DF's early use of stimulants. To the contrary, his blood pressure appeared to drop. However, during his illness he developed cardiac arrhythmias, and experienced a heart attack in the 25th month. As a medical precaution, his usual dose of stimulant was reduced. Use of stimulants represents a trade-off between physical and mental well-being.

Both internally (grand mal) and externally (ECT) induced seizures could offer some relief of symptoms through the action of forced sleep. The duration of SWS has been reported to increase significantly during the development of kindling in the hippocampus and amygdala, although later stages of kindling interrupt this process, presumably by interfering with SWS-inducing centers.[21]

The association between epilepsy and sleep deprivation is not normally regarded as therapeutic. In rats, 30 or more seizures results in permanent hippocampal damage.[22] Recent evidence suggested that seizures beget seizures and may be related to sudden premature death.[22] As reported by Cirelli and Tononi,[23] hundreds of genes change their expression in the dentate gyrus a few hours after seizures and electroconvulsive shock, in contrast to fewer than 100 genes of cortical cells, which respond during normal sleep states.[23] An electroencephalogram (EEG) taken of DF in his 24th month showed epileptiform activity, which, although characteristic of end-stage FFI, may reflect either sleep deprivation[24] or earlier ECT experience.

As opposed to ECT, which involves a random and massive impact on brain cells, another strategy may involve the implantation of an electrode into the anterior thalamus or basal forebrain with the hope of specifically activating hypometabolic neurons in the sleep circuit. (Of note, surgical instruments that are used in patients with FFI must receive special postoperative cleaning because prion contamination is not removed by routine sterilization).[25]

A device not tried by DF but which deserves mention is the so-called "sleep machine," which was used in the Soviet Union and Europe during the 1970s.[26] These devices delivered a weak rhythmic DC current to the brain. The subject wore a sleep mask with electrodes buried in it and experienced a pulsing square wave of 1 msecond duration over the eyes and occipital region. Treatments lasted about 30 minutes and were given once daily for several weeks. Subjective reports were of a pleasant and deeply relaxing experience. Insomniacs who were given this treatment experienced a shorter sleep latency than a placebo group (approximately 10 minutes vs 59 minutes).[27]

Exercise, such as long walks, helped DF to maintain overall fitness and permitted sunshine to externally entrain whatever was left of his circadian rhythms. Of interest, studies of prolonged sleep deprivation suggested that vigorous exercise is an effective tool against the excessive sleepiness accompanying sleep deprivation.[28]

At the most superficial level, immersion in the deprivation tank can be equated to a warm bath, which has been shown to induce a 25% to 33% increase in SWS.[28] An additional explanation is that sleep and arousal are governed by opposing systems originating in the pontine (PRF) and mesencephalic (MRF) regions, respectively. In normal sleep, the PRF mechanism predominates and shuts off the MRF waking mechanism. However, in FFI the PRF mechanism is flawed and cannot establish sleep. Therefore, the MRF mechanism always prevails. The only remaining strategy is to externally shut the MRF by dramatically reducing its input.

Classic studies showed that the destruction of the MRF region results in sleep, whereas cutting all of the sensory pathways in the brainstem does not.[29] The MRF region acts as a second type of sensory system in parallel with those of the specific sensory systems, receiving its afferents from various specific tracts passing alongside it.[30] The inputs are multisensory and respond to electrical stimulation of the auditory, visual, and somatosensory systems.[30] Maruzzi and Magoun[29] suggested that the MRF region acts on the nonspecific thalamic nuclei to interfere with their pacemaker activity. Recruiting waves from the thalamus, including the spindling of SWS, could be blocked by stimulation of the MRF region.[ 29,31] Because most of the input to the MRF region is sensory, then the total absence of sensory input should shift the balance in favor of the PRF region. This model does not explain why barbiturates, which are inhibitory of the MRF region,[30] are of limited usefulness in the treatment of FFI.[4,14]

Limited information is available on another FFI patient, a man in his 60s, who made 3 unsuccessful attempts to sleep in the deprivation chamber. Upsetting hallucinations prevented him from remaining in the tank long enough for sleep to result. However, information was not made available about the pretrial preparation — whether anesthesia or other premedication was used to "start the man off," as had been the case with DF. Those who try this method might consider the finding that, in rats, ketamine administration 4-5 hours before sleep onset is associated with an increase in SWS and delta EEG in subsequent sleep.[21]

Daily exposure to bright lights, which theoretically entrain the melatonin cycle, appears to have been important in establishing sleep for DF. Light exposure is typically not sought by a bedridden FFI patient, but may be of some help in clock setting. In normal subjects kept awake for 36 hours, melatonin release remained robust even during the nighttime of forced wakefulness.[32] GH secretion, however, was absent in this condition. The potential therapeutic value of melatonin and drugs that promote the production of GH in treating sleep disorders is under consideration for treatment of insomnia in the elderly.[33] Naturally cycling melatonin induces SWS and is associated with enhanced immunity, a nocturnal disinhibition of the pituitary-adrenal axis with an associated drop in corticoid levels.[6] Drugs that target ML-1 melatonin receptors (eg, TAK- 375) reduce sleep latency by approximately 15 minutes (and hence, increase the total time asleep by 15 minutes), but without increasing the subjective impression of restfulness compared with placebo.[34]

The effects of meditation are difficult to evaluate for DF, because he was relatively inexperienced with the technique. In addition, he did not begin meditating until his disease was already far advanced and substantial systemic damage had occurred. However, the approach is conceptually sound. Studies of meditating subjects showed a 20% reduction in metabolism (as measured by both O2 consumption and CO2 production), a decrease in skin conductance (or the galvanic skin response) (suggesting anxiety reduction), decreases in blood pressure, and a reduction in heart rate by 3 beats per minute.[35]

The concentration of lactic acid (an indicator of anaerobic metabolism) falls precipitously during transcendental meditation (TM), at a rate 4 times faster than in resting controls. Excesses of lactic acid are normally associated with anxiety, whereas lower levels of lactic acid are associated with a reduction in arterial pressure. EEG shows an increase in alpha waves in the frontal and central brain areas as well as theta in the frontal area. Wallace and Benson[35] postulated that TM results in a hypometabolic state (associated with a reduction in norepinephrine) that is directly opposite the fight-or-flight system of Cannon. To the extent that insomnia is a disorder of stress regulatory mechanisms,[33] TM may protect against the ravages of sympathetic overdrive.

Neuropsychological Insights

DF's resourcefulness in implementing treatment is in itself testimony to the essential preservation of intelligence in patients with FFI. Although formal neuropsychological testing was not performed, a gross assessment can be offered.

Stimulant medication greatly improved DF's attention. Without it, DF didn't know that the phone was ringing. With medication he could safely drive 60 mph for the entire day. Word finding was preserved; humor remained intact. The need to write "to do" lists reflects memory difficulties, whereas the foresight to write such lists and follow their instructions indicates executive efficiency. Subjectively, DF reported his greatest area of confusion to be temporal ordering; he could not keep track of time or days. He tended to speak on the phone for several hours without any notion of duration. However, enormous concentration was required for oral fluency. DF believed that his judgment was impaired. Late in his illness, he provided a needy family with a car by purchasing 2 vehicles and giving them a choice. This left him with a truck that he didn't need.

Unlike the typically mute FFI patient whose subjective serenity is unknowable, DF described his oneiric sleep as extremely gentle and pleasant — like entering a room filled with everyone who he would want to encounter, including deceased friends and relatives who would tell him that everything will be all right. In his words, "to the outside world, I am dead and gone, but to myself, I'm still here, in this wonderful place and it is they who have disappeared."

His "waking REM" was multisensory and included images, voices, and scents. It was experienced as a form of knowing everything about himself, with no more hidden secrets. As might be expected from a sustained "handshake" between the right and left hemispheres, DF's conscious mind experienced himself in a global way. He described his unconscious as filled with "wounded children" who bore "poor witness" to events that had injured them — unable to logically evaluate or rise above these damaging experiences. His FFI put him in the unique position to soothe these children with adult insight, which he often did in the form of written letters when he was "off-line." (Those interested in psychoanalytic theory and/or multiple personality disorder may learn a great deal from FFI patients).

The door that admitted DF into this other world became best defined after long periods of insomnia and was so inviting that he believed that others who have been in this place simply gave into it and allowed themselves to die. In fact, DF's fight against FFI specifically centered on this arena, with the wish to surrender to its serenity as opposed to his real life of handicap and degeneration.

Conclusion

The use of vitamins, narcoleptics, stimulants, sensory deprivation, exercise, light entrainment, and GH may offer some possibilities in patient management of FFI. Stimulant medication will provide a better quality of life, enabling the patient to overcome his or her stupor and fill the day with productive activity. A nocturnal rebound effect seems compatible with sleep inducement. However, stimulant medications tax the renal system and may lead to medical complications. The patient should be counseled about the possibility of such side effects when considering the potential benefit from the medication. ECT has some beneficial effects, such as immediate sleep relief, although numerous drawbacks, most notably profound memory loss in a disorder that already compromises memory.

Because this report describes the responses of a single patient, the same outcomes cannot be presumed for others. Certainly techniques that require expense, risk, or access to illegal medication are better studied in institutions under controlled conditions. It must be stressed that these approaches are exploratory and are hoped to stimulate further research.

The material presented here does not refute the prevailing belief that FFI patients ultimately die of neural degeneration. However, it may be proposed that death is hastened by the disruption of critical functions. Those functions are (1) normally subsumed by the areas, which, under positron emission tomographic (PET) scanning, demonstrate hypometabolism, and (2) are related to either insomnia or dysautonomia, specifically sympathetic overdrive (eg, a faster rate of depletion than replacement of cellular resources, greater energy expenditure, metabolic exhaustion, and a lack of restorative contribution of GH).

We suggest that strategies that attenuate sympathetic activation, promote sleep functions, and/or reduce stress may alter the time course of the disease as well as the quality of life.

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