NARCOLEPSY
IN CHILDREN
Robert E. Yoss, M.D., and David D. Daly, M.D.
Section of Neurology, Mayo Clinic and Mayo Foundation, Rochester Minnesota
(Accepted November 30, 1959; submitted October 23.)
The Mayo Foundation, Rochester, Minnesota, is a part of the Graduate School of the University of
flIlCSOtd.
ADDRESS FOR REPRINTS: Section of Publications, Mayo Clinic, Rochester, Minnesota.
1025
PimlAmIcs, June 1960
N
ARCOLEPSY is a syndrome of which the outstanding characteristic is persistent and excessive sleepiness. Most patients with narcolepsy say that their symptoms began early in life and yet, surprisingly, the con-rect diagnosis usually was not made until the patient had reached adult age. The fre-quency with which adult persons withnarcolepsy are seen by neurologists sug-gests that tile disease may occur in children far ii#{252}recommonly than has been suspected. Since in most instances treatment will allevi-ate symptoms, early diagnosis is important. These reasons have led us to review the records of patients with narcolepsy seen at the ‘slayo Clinic for whom the diagnosis had been established by the age of 15 years. We have attempted to compare the characteristics of the disease in adult per-sons with those of the disease as it is seen in children. It is hoped this study will result
ill an increased interest in the occurrence of the syndrome in children.
In the years 1950 through 1957 400
pa-tients with tile diagnosis of narcolepsy were seen at the Mayo Clinic. Of these, 16 (4%) were 15 years of age or younger. Before these cases are discussed in detail, a brief review of the syndrome of narcolepsy as it
OCCUS III adult persons may be in order.l
THE NARCOLEPTIC TETRAD
Tile narcoleptic tetrad consists of these symptoms: 1) narcolepsy proper, 2) cata-plexy, 3) sleep paralysis, and 4) hypnagogic hallucinations.
Narcolepsy
Patients may have either narcolepsy alone or various combinations of the symptoms. Tile universal symptom of the tetrad is
cx-cessive and abnormal sleepiness. The insidi-ous appearance of this symptom often be-clouds any attempt to date the onset of disease; however, careful questioning of a
large group of adult patients has disclosed
that symptoms of the disease had made
their appearance by the age of 15 years in
59% of patients (Fig. 1). The degree of
ab-normal sleepiness varies widely among
dif-ferent patients, ranging from rather
per-sistent drowsiness with only infrequent
episodes of sleep to moderate sleepiness
which may cause a patient to fall asleep
while driving, reading, watching television or viewing motion pictures. When severe
forms of the disease are present the patient
may fall asleep during a conversation, while eating or in unusual situations, such as when
taking a shower bath or while walking.
Brief naps may alleviate the abnormal
sleepiness, but shortly after awakening the
patient with narcolepsy often drifts once
more into a state of drowsiness from which
he may fall asleep repeatedly. We would
emphasize, therefore, that the person
afflicted with narcolepsy spends much of
his time suspended in “intenphase”-neither
asleep nor fully alert. In contrast to the im-pression held in earlier years, there is no precipitous transition from complete alert-ness to sleep; thus, narcoleptic sleep is in
110 way related to the abrupt transitions of
consciousness seen in epilepsy.
Cataplexy
Cataplexy, the second most frequent
symptom of the tetrad, occurs in two-thirds
of adult patients. It consists of muscular
weakness induced by emotion. Cataplectic
attacks are most commonly precipitated by
25
20
15
10
5
VIe. 1. Age at onset of narcolepsy as reported by 85 consccutivc adult patients.
8) \O
0 ,‘ \Ib’ V)> ‘i,’_ .,
Age of onset (years)
1026 NARCOLEPSY
5”
121.
0
E
muscular weakness ranges from a
subjec-tive sense of weakness to complete paralysis
ill \Vllicll tile Patiellt collapses to the ground.
Consciousness remains unimpaired, even in the face of total paralysis. Tile attack is short, rarely lasting more than a minute. Cataplectic attacks may first appear many years after the onset of sleepiness.
Sleep Paralysis
Sleep paralysis, which is perhaps analogous to cataplexy, occurs in a minority of patients. When patients are dozing or awakening they may suffer transient in-ability to move. This paralysis is brief and in most instances can be relieved by touching or speaking to the patient.
Hypnagogic Hallucinations
The last element of tile tetrad is
hypna-gogic hallucinations or illusions which often accompany sleep paralysis. Hypnagogic hallucinations consist of vivid visual or auditory experiences occurring in the drift-ing phase between sleep and wakefulness.
The content of these hallucinations usually
is benign and often tile patient relates them to whatever is happening at that moment
in his environment. These episodes are analogous to the dreams that may occur in
normal persons just prior to sleep.
PATIENT MATERIAL
\Vitli these considerations in I1ind, an
anal-sis of tile records disclosed 16 children with
narcolepsy. Tell ‘ere girls and six were boys,
ill contrast to the large
group
of adtilt Patielits in which men olltnufllbered womell.’ In viewof the small number of cllildren in this series we do Ilot regard this disparity between tile
two groups as significant. By definitioll, all
patielltS had excessive sleepiness or narcolepsy proper. Cataplectic attacks had occurred in 1:3 cilildren, sleep paralysis in 3 and hvpnagogic hallucinations in 5. The various conihinations of svmptonls are given in Table I. Tile fre-quencv with whicli the symptoms of the tetrad occurred parallels that of the same srnptoms
iii the adult group. The ages of the children at the onset of symptoms \arie(l from 3 to 14
‘ears, save for one child whose parents felt he had suffered from the colldition “all his life.”
To illustrate some of the problems in
diagnosis, four typical patients will be pre-sented. We shall emphasize the problems
of misinterpretation of symptoms and
‘ .1ge
(ase \o.
(yr) Sex Syrnptorns
1 9 M Narcolepsy 3 6
1 M Narcolepsy
Cataplexy
9 3
3 11 F Narcolepsy
Cataplexy
Ilypnagogic hallucinations
10 I
4 9 1I Narcolepsy
Cataplexy
8
.5 15 F Narcolepsy
Cataplexy
Sleep paralysis
Hypnagogic hallucinations
Present “all
life”
15-6 15 F Narcolepsy
Cataplexy
10 5
7 12 F Narcolepsy
Cataplexy
1
S W F Narcolepsy
Hypnagogic hallucinations
6 6
9 7 II Narcolepsy 3 4
10
Ii
15 F Narcolepsy
Cataplexy
14 1
15 F Narcolepsy
Cataplexy
Sleep paralysis
liypnagogic hallucinations
14 1
1
i3
13 M Narcolepsy
Cataplexy
Sleep paralysis
Hypnagogic hallucinations
3 10
I
13 F Narcolepsy
Cataplexy
1
14 13 F Narcolepsy 9 4
15 14 F Narcolepsy
Cataplexy
13 1
15 12 3
TABLE I
CIINIcAL I)ATA ON 16 PATIENTS WITH NARCOLEPSY
M Narcolepsy
Cataplexy
Age at Onset
(yr)
1028 NARCOLEPSY
CASE REPORTS AND
COMMENT
Case 1
A 9-year-old boy was first seen at the Mayo
Clinic in May, 1957, because of “spells,” thought to be epileptic, which had begun when tile patient was 3 years old. The parents said that several times each day the boy would lie down and sleep for 10 to 20 minutes. They had observed him falling asleep while standing, raking leaves and even while playing “cow-boys and Indians” with his friends. In school he had fallen asleep repeatedly in the classroom. As a rule the boy would sleep only a few mm-utes and then would awaken refreshed. He said he was not drowsy between the episodes of sleep; however, he was noted to yawn re-peatedly at times when he said he was alert. We were unable to elicit a history of cataplexy, sleep paralisis or hypnagogic hallucinations.
Results of neurologic examination were
nega-tive. Roentgenograms of the skull were inter-preted as disclosing nothing abnormal. The pattern of an electroencephalogram was within ilormal limits for a child of his age.
An analeptic, methylphenidate (Ritalin
hy-drochlonide), was prescribed; this relieved the patient’s diurnal sleep. When he was examined again in October, 1958, his mother said that while he was taking the analeptic agent he had had 110 more episodes of abnormal sleepiness.
He had fallen asleep in school on only one
oc-casion, when he had forgotten to take the mcdi-cine. Because of financial difficulties the parents were unable to purchase methylphenidate for 3 weeks; during this time the abnormal
sleepi-IlSS promptly recurred with the same severity
as originally. Resumption of medication once more alleviated the patient’s symptoms.
This patient had the symptoms of
narco-lepsy proper without the other elements of
the tetrad. However, cataplexy, sleep
pa-ralysis or hypnagogic hallucinations may yet develop. In our experience cataplexy
develops in approximately one-third of
adult patients 1 year to 10 years after the
onset of abnormal sleepiness. The point
should be emphasized that abnormal
sleepi-ness alone may be sufficient to justify the
diagnosis of narcolepsy; in our larger series
of patients 25% suffered only from abnormal
sleepiness.’
The episodes of sleep were interpreted as
loss of consciousness on an epileptic basis.
Such an error would not have arisen had
the precise details of his “spells” been
ob-tamed from the parents.
Case 2
In August, 1956, a 12-year-old bo’ was
registered at the Clinic because it was thought that he might have epilepsy or an emotional disorder. For 3 years prior to that time the boy had complained of excessive diurnal sleepi-ness in spite of sleeping 1 1 hours each ilight.
He would fall asleep in tile classrooms, in
Sun-day school or when viewing television pro-grams. He invariably fell asleep when riding in an automobile.
In the preceding 18 months the patient had experienced about 10 episodes of sudden
weak-ness during “hearty” laughter. If he was stand-ing, his knees would buckle and he would fall.
If an attack occurred while he was sitting, his
head would fall forward. He had never lost consciousness and would regain his strength within a matter of seconds. The boy said he
did not have sleep paralsis or hvpnagogic
hal-lucinations.
Results of neurologic examination andl of roentgenograms of the skull were normal. The pattern of an electroencephalogram was
inter-preted as being within normal limits for a child of his age.
Treatment with Il analeptic agent provided
almost complete relief of drowsiness and
cliur-nal episodes of sleep.
Falling asleep wilen riding in an
auto-mobile is a difficulty encountered in adults
with narcolepsy, many of whom are unable
to drive an automobile for this reason. In
this patient the attacks of cataplexy and not
the episodes of sleep were regarded as
epileptic. Since a cataplectic attack is
abrupt in onset, brief in duration and often
accompanied by muscular weakness and
failing, it is not surprising that it is confused
with a seizure. However, the precipitation
of the attack by emotion, the preservation
of consciousness and the associated disorder
of wakefulness serve to distinguish it from
epilepsy. Because such attacks are strange
and unfamiliar to the physician, they are
often regarded as psychogenic. Such a
diagnosis by default. Recent studies2 have given I1() evidence that narcolepsy is a psy-chogenic disorder.
Case 3
An 1 1-year-old girl was referred to the Clinic
in January, 1953, after conflicting diagnoses of narcolepsy, Huntington’s chorea or
encephali-tis had been made elsewhere. Extensive stud-ies, including examination of the cerebrospinal fluid , electroencephalography and
pneumoen-ce)halography had yielded normal results. The preceding autumn the child had corn-l)iained of diplopia while reading. Shortly
thereafter she told of episodes of muscular
weakness ill which her head fell forward; laughter often caused these episodes. About a iiioiith later her parents had noticed that she seemed excessively drowsy and would nap sev-eral times each day. In November, 1952, while hospitalized for examinations, the child had
clainled to see and to hear animals in her room during the night. Durillg the next month the episodes of muscular weakness increased in se-verity and caine to involve all extremities. Laughter and anger were the most common precipitants, although occasionally the attacks had seemed to occur without cause.
The parents reported that she could fall asleep anytime’ and that often her head nodded and her eyelids drooped.
Examination revealed the child to be
somno-lent all(l inattentive. She performed voluntary
movements in a halting, unsteady manner.
Dur-ing tile examination her lids seemed heavy, she nodded repeatedly and she finally fell asleep. When thoroughly aroused she gave no
evidence of ataxia or weakness.
Roentgcnograms of the skull disclosed noth-ing abnormal. The pattern of an electroen-cephalogranl was interpreted as being within normal limits for a child of her age; however, electroencephalographic evidence of drowsi-ness appeared within 2 minutes after the re-cording was begun and this state persisted throughout the remainder of the recording.
Administration of an analeptic agent alle-viated both narcoleps and cataplexy. When the patient was re-examined in September,
1953, she was much improved.
In this patient the initial symptom of
diplopia, if considered apart from the other syniptoms, might suggest a serious
intra-crallial disease. The clue to the significance
of the diplopia lies in its occurrence during
reading. Most patients with narcolepsy
corn-plain of difficulty in reading, since this
repetitious act regularly induces drowsiness
and sleep. Many patients also say that
read-ing at these times is associated with
di-plopia. Our studies’ have shown that
dipio-pia occurs in patients who have a high
degree of exophonia. In the alert state such
patients can compensate for the exophoria,
but when drowsiness supervenes they lose
the ability to maintain fusion and
experi-ence diplopia. In these patients close
ques-tioning as to the circumstances in which
dipiopia occurs will clarify its nature.
Encephalitis often is considered as a
diag-nosis in children who actually have
nanco-lepsy. Again, encephalitis in such instances
is considered primarily because of
concen-tration on an isolated symptom. The vague
term, “sleeping sickness,” is unfortunately
too often used as a synonym for viral
en-cephalitis, despite the fact that disturbance
of consciousness is but one facet of the
dis-ease. Viral encephalitis begins acutely with
signs of systemic illness such as fever and
tachycardia. The child may be persistently
drowsy or somnolence may progress into
coma. Signs of focal disturbances of the
brain may be manifested by abnormal
muscle-stretch reflexes, abnormal plantar
re-sponses, focal or generalized convulsions,
cranial nerve palsies or tremors and
twitch-ings of the limbs. Stiffness of the neck
sug-gests meningeal irritation and examination
of the cerebnospinal fluid will reveal
pleo-cytosis. This picture of an acute and
catas-trophic illness is quite distinct from that
which has been painted of the narcoleptic
syndrome.
Case 4
A 9-year-old boy was referred to the Clinic
I 030 NARCOLEPSY
which led to the suspicion that he had
hypo-thyroidism. This impression was strengthened when the basal metabolic rate was found to be “very low”; however, administration of desic-cated thyroid extract in amounts up to 3 grains daily did not ameliorate the symptoms.
The parents reported that during the year
prior to the time of his referral he had seemed excessively drowsy and had fallen asleep re-peatedly during the day in spite of obtaining adequate sleep at night. As a consequence of sleeping in school, his work deteriorated. His
parents said that rather than play with his friends he would come home after school and sleep. They also said that he would fall asleep while listening to the radio or watching motion pictures.
His parents commented that on numerous occasions laughter had caused the boy’s knees to buckle. At other times, if he was sitting down, laughter had made the muscles of the neck so weak that the patient’s head dropped forward on his chest.
While being examined the boy fell asleep several times. Results of both physical and neurologic examinations were normal. Roent-genograms of the skull showed no abnormality.
The pattern of an electroencephalogram was
interpreted as being within normal limits for a person of his age, although the recording showed signs of drowsiness within 1 minute after the recording began and these persisted throughout the examination. The basal meta-bolic rate was reported as - 17%; however, cx-amination of the boy before and after with-drawal of the use of thyroid extract led the consultant in endocrinology to conclude that
the patient was euthyroid.
Narcolepsy was diagnosed and an analeptic
agent was prescribed. The patient’s diurnal drowsiness abated, the frequency of episodes
of sleeping decreased, and he again did well
in his schoolwork.
This patient also had been considered to
have encephalitis because he was
exces-sively sleepy; however, once again, lack of familiarity with the symptoms of
narco-lepsy and encephalitis had generated the
misapprehension. Subsequently, because of
the sleepiness and gain in weight, he was
suspected of having hypothyroidism. This
suspicion seemingly was confirmed by the
“low” basal metabolic rate. In actual fact the
metabolic rate, although decreased, was not
basal, since the patient was not in a normal
state of alertness. In persons with
narco-lepsy decreased values for the metabolic
rate usually result from permitting the
pa-tient to drowse on fall asleep during the
test. The low rate, then, reflects only tile
reduced consumption of oxygen in this
somnolent state. In such patients more
di-rect and objective tests of thyroid function
disclose no abnormalities.
DIAGNOSTIC CONSIDERATIONS
The complete narcoleptic tetrad is such a
unique combination of symptoms that it
should not be difficult to recognize. Since
the full tetrad occurs only in a minority
of patients, clinicians must be familiar witil
the pictures produced when one or more
elements of the tetrad are missing. This is
particularly true in the case of children,
since catapiexy may develop months or
years after the abnormal sleepiness.
Further-more, patients may not speak overtly of
repeated episodes of diurnal drowsiness and
sleep, but their complaints may be so
worded as to obscure the presence of
ab-normal sleepiness. For example, patients
often complain of fatigability, of “being
tired all the time” on of “lack of energy.”
Many patients tend to equate sleepiness
with fatigue and to use the terms
inter-changeably. The practice of requiring
pa-tients to define their complaints in detail
and of questioning them carefully as to the
exact manifestations of their illness vill
clarify the nature of the symptoms. If the
physician persists in his inquiries,
indica-tions of the occurrence of persistent
drowsi-ness will emerge.
Misinterpretation of the complaint of
“fa-tigue” or lethargy often suggests the
diag-nosis of hypothyroidism. Determination of
the basal metabolic rate may give values
lower than normal and seemingly
substanti-ate this diagnosis. As has been suggested,
such findings are in the nature of an artifact,
proper basal state of relaxed alertness
dur-ing tile procedure. The decreased
consump-tion of oxygen during drowsiness results
riot from a true decrease in the basal
meta-bolic rate but rather from the reduced oxygen requirement associated with the somnolent state.
Accurate determination of basal metabolic
rates in these patients often is difficult. We
have obtained data on 104 determinations
of tile basal metabolic rate in 77 adult
pa-tients. The median value for the initial
de-termination, when only the usual precau-tions to maintain alertness were taken, was
- 13%. In many instances, however,
repe-tition of the test with concerted efforts to
maintain alertness yielded normal values.
Objective measures of thyroid function,
such as determinations of protein-bound
iodine or the uptake of radioactive iodine
by
tile tilyroid gland, have convinced ourcolleagues in endocrinology that no clinical
or laboratory evidence for hypothyroidism occurs in these patients. Confirmation of
tilese conclusions comes from our
observa-tions that administration of thyroid extract does not alleviate abnormal sleepiness.
Many authors have emphasized obesity
as an accompaniment of narcolepsy, using
obesity as additional evidence of endocrine disorder. We have not found that patients
with narcolepsy are any more obese than
are persons in the general population, or
that a gain in weight or an increase in
appe-tite is associated with the onset of the
disease.
In some children the consequences of persistent drowsiness are misinterpreted as
the major complaint. For example, the
teacher may report a decline in the quality
of the child’s schoolwork and attribute this decline to inattentiveness or “lack of
con-centration.” Such apparent apathy and
in-difference may lead to increasing parental
pressure for the child to maintain his
previ-ous performance. The child’s constant
strug-gle to remain awake in the face of
con-tinuing pressure from parents and teachers
may cause him to behave in an impatient
and irritable manner, suggesting some
emo-tional disorder. Paradoxically, some parents
recognize the child’s excessive sleepiness
but dismiss it as the result of “growing too
fast” or as another of the presumed
eccen-tnicities of adolescence.
Some persons with narcolepsy come to
the physician complaining that their eyes
“tire out” or are “weak.” They confuse cause
and effect by presuming that use of their
eyes makes them sleepy rather than that
the reverse is true: that drowsiness impairs
their capacity to maintain fusion. Patients
who have marked exophonia usually
expeni-ence frank diplopia during episodes of
drowsiness. Undue concentration on this
isolated symptom may suggest serious
intra-cranial disease, such as multiple sclerosis.
In other patients the association of ptosis
and diplopia has led to a diagnosis of
myasthenia gravis. The transient nature of
these visual symptoms and the invariable
concomitant drowsiness should clarify the
problem.
Errors in diagnosis can result from
mac-curate terms used to describe symptoms.
For example, the ambiguous phrase,
“sleep-ing sickness,” although in a sense
descnip-tive of narcolepsy, often is used
synony-mously with viral encephalitis. As has been
indicated, encephalitis is an acute febnile
disease characterized by altered states of
consciousness ranging from hyperkinetic
de-lirium through lethargy to profound coma.
The insidious onset and chronic course of
narcolepsy are quite different.
Similar confusion often results when
pa-tients refer to their episodes of sleep as
“black-outs.” The unwary physician may
view such episodes as epileptic seizures. An
epileptic attack begins abruptly, in contrast
to the drowsiness gradually giving way to
sleep, which typifies narcolepsy. The
rela-tively long duration of the sleep and the
ease with which the patient can be aroused
further distinguish narcolepsy. In other
pa-tients nodding of the head during
drowsi-ness or episodes of cataplexy have been
1032 NARCOLEPSY
invariable precipitation of cataplexy by
emotion and the preservation of
conscious-ness throughout the attack distinguish it
from the akinetic seizure.
In a minority of patients abnormal
sleepi-ness is the only symptom of the tetrad of
narcolepsy. If this type of sleepiness is
severe, the physician can be satisfied that
it is unquestionably abnormal. However,
if the sleepiness is not striking, doubt may
arise. In such instances the occurrence of
abnormal sleepiness or other elements of
the tetrad in siblings or parents may
illumi-nate the problem. In our experience it is
rather common to encounter families in
which more than one member is known to
have narcolepsy. Recently we have reported
a family in whom narcolepsy occurred in
12 members of 4 generations.4
We emphasize again that the diagnosis of
narcolepsy rests upon the taking of a
thor-ough and accurate history. Scrupulous
at-tention to details and precise delineation
of complaints are the most valuable
diag-nostic tools. Electroencephalography,
al-though contributing significantly to an
understanding of the pathophysiology of
this disorder, is of little diagnostic value.5
The electroencephalograms of these patients
in both the waking and sleeping states
dis-play patterns that are normal. However,
these patients will show electrical evidence
of drowsiness recurring throughout the
pe-nod of recording. Repeated attempts to
alert them are fruitless, and they may doze
even while hyperventilating. Such
observa-tions should arouse the suspicion of the
technician obtaining the
electroencephalo-gram, even though they are not
pathog-nomonic of narcolepsy.
TREATMENT
The treatment of narcolepsy consists in
the administration of analeptic agents to
alleviate the excessive sleepiness. Such
drugs produce only symptomatic relief;
withdrawal of the drug results in a return
of the excessive sleepiness, as occurred in
Case 1. Several analeptic drugs are
availa-ble, but in our experience the most
effec-tive one has been methylphenidate (Ritalin
hydrochloride).6 Methylphenidate is
ad-ministered in divided doses at least 30
mm-utes before meals. In children the daily dose
usually is 40 to 60 mg. In all patients both
the amount of the drug and the frequency
of administration must be adjusted by trial
and error. Inadequate stimulation will result
if the drug is taken immediately before on
after meals. In children the last dose should
be given in the late afternoon to avoid
cx-cessive stimulation and insomnia. No
sig-nificant toxic effects have resulted after the
continuous administration of
methylpheni-date for more than 3 years. Minor side
effects, consisting of nervousness and
anorexia, can occur in a minority of
pa-tients, but rarely are they of such severity
as to require discontinuance of use of the drug.
An occasional patient who does not
re-spond to methyiphenidate may be
bene-fited by amphetamines, either
dextro-amphetamine sulfate (Dexednine#{174} sulfate)
or methamphetamine hydrochloride
(Des-oxyn#{174}). In general, tile incidence of
un-desirable side effects from amphetamines
has been fan greater than that from
methyl-phenidate. For this reason we regard
methylphenidate as the drug of choice.
Although the response to this agent is
less consistent, about 50% of patients report
a reduction in the frequency and severity
of attacks of cataplexy while they are taking
methylphenidate. Analeptic agents have no
effect upon sleep paralysis or hypnagogic
hallucinations, except when these occur in
conjunction with diurnal drowsiness. These
latter symptoms rarely constitute a major
complaint of the patient; but if they do,
administration of a rapidly acting sedative
at bedtime may resolve the problem.
In our experience analeptic agents are
the only effective drugs against the
condi-tion in question. Anticonvulsant drugs have
their advocates, but there are no theoretic
reasons why such drugs could be expected
to benefit the patient. We have seen no
instance in which anticonvulsants have had
BARTON Cmus, M.D.
SUMMARY
In adult persons the narcoleptic syndrome
consists of narcolepsy proper, cataplexy, sleep paralysis and hypnagogic hallucina-tions. The characteristics of these phe-nomena are discussed.
The disease is not often recognized in
children, although anamnestic evidence sug-gests that in the majority of patients the
onset of the disorder is in childhood or adolescence. Data are presented concerning
16 children in whom narcolepsy was
cvi-dent. Problems in diagnosis are reviewed and common pitfalls and misinterpretations are discussed. The use of analeptic drugs for treatment is outlined.
REFERENCES
1. Yoss, R. E., and Daly, D. D. : Criteria for
the diagnosis of the narcoleptic syndrome.
Proc. Staff Meet. Mayo Clin., 32:320,
1957.
2. Smith, C. M. : Psychosomatic aspects of narcolepsy.
J.
Ment. Sc., 104:593, 1958.3. Keefe, W. P., Yoss, R. E., Martens, T. G.,
and Daly, D. D. : Ocular manifestations
of narcolepsy. Unpublished data.
4. Daly, D. D., and Yoss, R. E. : A family
with narcolepsy. Proc. Staff Meet. Mayo
Clin., 34:313, 1959.
5. Idem: Electroencephalogram in narcolepsy.
Electroencephalog. & Clin. Neurophysiol.,
9:109, 1957.
6. Yoss, R. E., and Daly, D. D. : Treatment of
narcolepsy with Ritalin. Neurology, 9:
171, 1959.
HUMAN BIocHExfIcL GENETICS, H. Harris,
M.D. Cambridge, Cambridge University
Press, 1959, 310 pp., $7.00.
In 1953 Dr. Harris published a previous book entitled An Introduction to Human
Bio-chemical Genetics. This book was a part of The Galton Laboratory Memoir Series, was paperbound and numbered 96 pages. The present volume represents a thoroughly revised and updated version of the first. It has hard covers, 310 pages, and a striking, handsome dust jacket. In 1953 human genetics, still a little off-beat, was just beginning to attract the attention of physicians. Today we are aware that genetics is the connective tissue of the fabric of human biology, just as it is in the biology of other species. The genes determine the rate and scope of all chemical reactions and developmental changes through their control over the design and function of proteins. The genetic material, therefore, presents a list of potentialities whose realization depends upon the environments in which the genes act. Genetics consists of the study of the heritable components of variation and one of the most rewarding ways to do this is to study the
chem-ical attributes of gene action. Dr. Harris’ book
illuminates rather than summarizes all the available information in this field. His book
is not a compendium, but rather an interpreta-tive review in which principles are stated and
illustrated by means of examination of
charac-teristics.
In the first two chapters are presented clearly
and simply the fundamentals of Mendelian
genetics. In subsequent chapters variations in the metabolism of amino acids and
carbohy-drates; of hemoglobin; of the blood group
sub-stances; the plasma proteins; and of other metabolic systems are treated in some detail.
In a final chapter there is a useful and lucid
discussion of gene action. It is interesting that
the author has placed this chapter at the end
of the book. There is historical precedent for
this since the chemical properties of gene ac-lion have been intensively studied only ne-cently, and long after advances in other aspects
of genetics. But one wonders also if this is not
a pedagogical technique, and if so it has merit.
Dr. Harris seems to be saying that if one would
understand genetics, one might well begin by
coming to grips with the genetic analytical
method.
My own opinion is that this is an excellent
book, and that students of human biology and
medicine will find it most useful and reward-ing. It is clearly written and the diagrams are very helpful. It should be added that Dr.
Han-ris is well equipped by experience and
capabil-ity to write such an authoritative work. It is
