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Vot IX. MAY. 1897. No. 8 
CONTENTS. 
raxes, sax .a. txa» nr advaitcii 
SEPTEMBER, 1897 
HEREDITARY LATERAL SCLEROSIS. 
BY AUGUSTUS A. ESHNER, M.D., 
Professor of Clinical Medicine in the Philadelphia Polyclinic ; Visiting Physician to the Philadelphia Hospital. HEREDITARY LATERAL SCLEROSIS.1 
By Augustus A. Eshner, M.D., 
Professor of Clinical Medicine in the Philadelphia Polyclinic ; Visiting Physician to the 
Philadelphia Hospital. 
M. G., a widow, 59 years old, applied at the Philadelphia Ortho- 
pedic Hospital and Infirmary for Nervous Diseases, in the clinical 
service of Dr. S. Weir Mitchell, on January 15, 1897, complaining of 
twitching of the legs, both subjective and objective, that had been 
noticed for a period of ten years. Similar muscular manifestations 
had gradually extended to all parts of the body, including the head. 
The twitching was said to be worse during rest, and especially at night, 
and it was believed to persist during sleep, which was disturbed 
thereby, so that the patient was compelled to arise and walk about. 
On account of this annoyance she had not gone to bed at all for six 
weeks, simply reclining upon a sofa at night. There had never been a 
convulsion or loss of consciousness or any paralysis. The appetite 
was good, the tongue coated, the bowels constipated. From time to 
time hemorrhage took place from the bowels, probably in consequence 
of a hemorrhoidal condition. There was neither nausea nor vomit- 
ing, and no loss of flesh, no chill, fever, or sweating. There was 
headache every morning, lasting from twelve to twenty-four hours, 
and susceptible of relief by bromides. There was subjective vertigo. 
The prominent symptoms in the case were uninfluenced by heat, cold, 
dryness, or moisture. Gait and station were steady and exhibited no 
abnormality. The knee-jerks were exaggerated. When the patellar 
tendon was struck, in addition to the active extension of the leg, the 
thigh became flexed and the patient jumped visibly. Ankle-clonus 
was present on the right, but could not be elicited on the left. Co- 
ordination was good in the upper extremities and the reflexes were 
normal. There was no tremor of the extended hands and fingers. 
Sensibility was preserved. The pupils were equal and regular and 
reacted sluggishly to light. There was no nystagmus. 
Examination of the ocular apparatus, by Dr. A. G. Thomson, 
yielded the following findings : V.r= R. T2T0¥ ; L. The pupils 
reacted normally both to light and in accommodation. 0. D. The 
media were clear, the disk a trifle gray. The fundus was normal. 
0. 5. Disk and fundus were normal. There was high myopia, and a 
macula was present on the cornea, resulting from measles in child- 
1 Read before the Section of Neurology of the American Medical Association, June 
1897. 2 
Augustus A. Eshner. 
hood and impairing vision. The fields of vision for both form and 
color were normal. The muscular balance was well maintained. 
The patient exhibited and was conscious of a general restlessness, 
to secure relief from which she sometimes tapped her foot, sometimes 
rocked from side to side, sometimes rotated her head. The action of 
the heart was rhythmic, its sounds clear. There was no difficulty in 
speech and none in swallowing. The complexion was muddy and the 
patient stated that she had been pale as long as she could remember. 
There was no spinal tenderness and no evidence of spinal deformity. 
There was no difficulty in micturition and the action of the sphincters 
was unimpaired. The blood was found to contain a full complement of 
red corpuscles, although the hemoglobin-valuation was only 50 per 
cent. There was no consanguinity between the patient and her hus- 
band. Her mother had suffered a good deal from headache, and a 
brother’s son had been melancholy. There had been no difficulty in 
birth and no traumatism; and there was no history indicative of spinal 
meningitis or of syphilis. 
A hesitant diagnosis of incipient lateral sclerosis was made in this 
case and the possible dependence of the lesion upon the state of the 
blood taken into consideration. When, however, the patient, a few 
weeks later, brought her son, and he too was found to be suffering 
from similar symptoms, the conclusion could hardly be avoided that 
we had here to deal with a mild degree of lateral sclerosis in parent and 
in child, and I am inclined to believe the disease to be hereditary, or 
at least familial. It is noteworthy that both patients exhibit manifest 
pallor, and this fact suggests the possibility of a common etiology, 
either the blood-state acting as a cause of the spinal degeneration or 
with this representing the common effect of some undetermined cause. 
Against this hypothesis is the fact that the spinal lesions of the pro- 
found anemias are situated by preference in the posterior columns, 
while in both of the cases here reported there is no evidence of pos- 
terior-column disease. 
M. G. (a son of the patient whose case has just been reported), 
18 years old, employed as a machinist, was born at term, without 
complication or instrumental aid. He had a convulsion at the age 
of three months, while nursing at the breast, during the period of den- 
tition. He learned to walk and to speak readily and early. At the age 
of eleven months he suffered from the presence of spool-worms in 
the intestine, associated with attacks of crying and throwing back 
of the head. He had measles at the age of two years, and fever and 
ague at the age of eleven. On September 24, 1896, the patient was 
operated on for appendicitis successfully. He had for two months 
previously suffered from pain in the left lumbar region, and this had Hereditary Lateral Sclerosis. 
3 
persisted. His habits were good. He was a total abstainer from 
alcohol and from tobacco; he used no tea and but very little coffee. 
Four years before coming under observation he had been struck with 
a fist in the temporal region, losing consciousness temporarily, 
although only ringing in the ears followed for a few days. There was 
no history of masturbation or of venereal disease. The patient had 
complained of a sense of lightness in the head from childhood. On 
sudden change of position a mist would come before the eyes and 
quickly pass away. For a period of six months he had noticed that 
frequently there would occur an involuntary twitching of the left leg. 
He had never fallen or lost consciousness. He complained of a feel- 
ing of nervousness and often had a sense of trembling; at times he 
actually shivered. The appetite was good; at times pain followed 
the act of eating, together with acid eructations. The bowels were 
naturally constipated, but they were kept free by cod-liver oil, which 
the patient was taking as a nutrient. He had lost a considerable 
amount of flesh in the six months preceding the time he came under 
observation. About once a week he suffered from headache, lasting 
for two or three hours at a time, and being relieved by the use of 
bromides. He slept well, although he talked in his sleep and was at 
times restless. He had been pallid for five or six months. Gait and 
station were steady. The knee-jerks were deliberate, large, and ex- 
aggerated. Front-tap contraction could be elicited in the left leg; 
ankle-clonus also was present on the left; it was less distinct upon the 
right, unless the tendo Achillis was struck when the foot was flexed 
upon the leg. By this means ankle-clonus could be very readily in- 
duced on both sides. The induction of these reflexes was followed by 
fine tremor, especially marked in the thighs. When the partially 
flexed foot was tapped on the plantar aspect the foot was extended. 
The reflexes in the upper extremities and also the chin-jerk were 
active. The pupils were equal, regular, and reactive to light. There 
was no nystagmus. General sensibility was preserved. The cremas- 
teric, abdominal, and epigastric reflexes were preserved. The action of 
the heart was rhythmic, its sounds clear. No physical abnormality 
could be detected in the situation of the abdominal uneasiness of which 
the patient complained. There was no spinal tenderness and none over 
the kidneys. It was further learned that for several years, until a 
bougie had been passed, there had been difficulty in the expulsion of 
urine, but there had never been any evidence of the presence of a 
urinary concretion. There was no difficulty in swallowing and no 
affection of speech. Dr. A. G. Thomson found no change in the 
fundus of either eye. 
From a consideration of the symptomatology, and especially of 4 
Augustus A. Eshntr. 
the physical phenomena, of the foregoing two cases the conviction can 
scarcely be escaped that the clinical manifestations depend upon 
sclerosis of the pyramidal fibres of the spinal cord. I prefer to speak 
of the probable pathologic process rather than employ the clinical 
designation spastic paraplegia or spinal spastic paralysis, inasmuch 
as the motor disability is as yet inconsiderable. Whether this process 
be primary or secondary I will not assume to state positively; but 
there is no tangible evidence of any antecedent condition upon which 
it could be held to be dependent, and in the absence of this I am dis- 
posed to view the pyramidal sclerosis as primary. A review of the 
literature upon the subject of spastic paraplegia does not entirely 
resolve the doubt as to the uncomplicated occurrence of primary lateral 
sclerosis, although the evidence, so far as it goes, tends to support 
such a possibility. In a fatal case of spastic paraplegia, reported by 
(Archiv fiir Psychiatrie, Band x, 1880, p. 711), occurring 
in a man whose older brother presented like symptoms, together with 
others of multiple sclerosis, post-mortem examination disclosed sym- 
metrically distributed primary sclerosis of the pyramidal tracts, most 
marked in the lumbar region, gradually diminishing in an upward direc- 
tion, and not extending beyond the decussation in the medulla; together 
with sclerosis of the cerebellar tracts and the postero-internal columns 
of Goll (Striimpell, Archiv fiir Psychiatrie, Band xvn, 1886, p. 217). 
In other cases of combined system-disease of the spinal cord Striimpell 
(Archiv fiir Psychiatrie, Band xi, 1881, p. 27) found also primary de- 
generation of the pyramidal tracts. Minkowski (Deutsches Archiv fiir 
klinische Medicin, Band xxxiv, 1884, p. 433) has reported the case of 
a syphilitic woman, dead of pulmonary tuberculosis, in which, after 
death, sclerosis of the lateral pyramidal tracts and of the cerebellar 
tracts only was found. Dejerine and Sottas (Archives de Physiologie 
normale ct pathologique, 1896, p. 630) have also reported a case of slowly 
developing spastic paraplegia, progressing for twelve years and then 
becoming stationary, in which, after death from pneumonia, there was 
found isolated and systematic sclerosis of the pyramidal fibres of the 
spinal cord and slight sclerosis of the columns of Goll, with integrity 
of the brain, the meninges, the spinal nerve-roots, and the spinal gray 
matter. Upon a priori grounds there is no obvious reason why 
primary sclerosis of the pyramidal tracts should not take place; and if, 
as seems probable, we may look upon locomotor ataxia as essentially 
dependent upon disease of the centripetal neuron we may equally look 
upon spastic paraplegia as dependent upon disease of the centrifugal 
neuron. 
The more interesting feature of our cases, however, is their occur- 
rence in parent and child. We have much to learn concerning the Hereditary Lateral Sclerosis. 
5 
hereditary and familial distribution of disease, and especially of dis- 
eases of the nervous system; but in the absence of definite knowledge 
upon the subject we may conceive of the existence of some develop- 
mental defect resulting either in gross structural abnormality, or in 
those undiscernible alterations in texture so delicate as to elude the 
most rigid physical scrutiny, yet capable of manifesting themselves in 
aberrant function, or finally in an undue vulnerability to morbific in- 
fluences. A very considerable number of cases of spastic paraplegia 
of familial distribution have now been reported, but in many of these 
there have been present also symptoms of disease of other parts than 
the pyramidal fibres. Among the earliest are four cases reported by 
Seeligmuller (Deutsche medicinische Wochcnschrift, 1876, Nos. 16, 17) 
and occurring in children the mothers of whose parents (cousins) were 
sisters. Three other children in the family were healthy. In two of 
the affected children there was, in addition to the spastic manifesta- 
tions, also muscular atrophy, and in two there was impaired mobility 
of lips, palate, and tongue, with defect of speech. Somewhat later 
Dreschfeld (Medical Times and Gazette, February 9, 1878, p. 140) re- 
ported two cases of disseminated sclerosis in brothers 8 years and 9 
months and 7 years and 4 months old respectively, presenting spastic 
phenomena. In one of these there had been convulsions in infancy. 
In reporting a group of cases illustrative of the pathology of the 
spinal cord Striimpell {Archiv fur Psychiatrie, Band x, 1880, p. 711) 
includes the two cases already referred to, occurring in brothers, which 
he considered clinically instances of spastic paralysis, although he 
appreciated that in the one, in which there was a history of convulsions 
in infancy, there were present also symptoms of multiple sclerosis. 
Bloch (Archiv fur Psychiatrie, Band xn, Heft 2, 1881, p. 470), in 
relating the history of a family presenting peculiarities in the knee- 
jerk, in connection with a neuropathic diathesis, refers to two brothers, 
19 years and 17 years and 6 months old respectively, who exhibited 
manifestations of lateral sclerosis. 
Pelizaeus (Archiv fur Psychiatrie, Band xvi, 1885, p. 698) has re- 
ported five cases in members of one family, although not of one gener- 
ation, presenting symptoms of spastic paralysis, in conjunction with 
cerebral symptoms, which he attributes to multiple sclerosis. 
Philip {Brain, vm, 1886, p. 520) has reported a family of nine 
children, in which the father presented symptoms of gradually ad- 
vancing spastic paralysis, the youngest son early symptoms of the 
same order, and three other sons symptoms of pseudo-hypertrophic 
muscular paralysis. 
Schultze {Deutsche medicinische Wochcnschrift, April 11, 1889, p. 
287) reports three cases, in two sisters and one brother, presenting 6 
Augustus A. Eshner. 
spastic manifestations in the lower extremities, in both girls associated 
with strabismus, and in one of them also with increased size of the 
head. The first child in the family, which was healthy, had been born 
without complication, while the subsequent labors were slow and 
difficult. 
Gee (St. Bartholomew’s Hospital Reports, 1889, Vol. xxv) has re- 
ported a father and a son and daughter who presented symptoms of 
spastic paraplegia, associated in father and son with wasting of muscles 
of the hands. 
Latimer (Transactions of the American Pediatric Society, Vol. 1, 
1890, p. 195) has reported two cases of spastic paraplegia in brother 
and sister, aged 20 and 18 years respectively, in the former of whom 
also speech was slow and thick, and there was occasionally involun- 
tary discharge of urine and feces. There had, however, been no diffi- 
culty in birth, no convulsions, and no antecedent disease. The father 
was a chronic alcoholic. 
Bernhardt (Archiv fiir pathologische Anatomic and Physiologie and 
fiir innere Medicin, Band cxxxvi, 1891, p. 59) has reported the case 
of a man, 46 years old, who presented symptoms of spastic paralysis, 
together with others indicative of involvement also of the pons and 
medulla, all being suggestive of multiple sclerosis, and three of whose 
brothers and also a sister presented similar symptoms. 
Tooth (St. Bartholomew’s Hospital Reports, Vol. xxvn, 1891, p. 7) 
reports four cases of what he believed to be sclerosis of the crossed 
pyramidal tracts, occurring in two brothers in different families, and 
presenting symptoms of spastic paraplegia, in two associated with 
stammering speech. 
Krafft-Ebing (Wiener klinische Wochenschrift, 1892, No. 47, p. 681) 
reports three cases of spastic paraplegia in a sister and two brothers, 
which he thinks may be due to congenital hydromyelus. 
Freud (Neurologisches Centralblatt, xn, Jahrg. 1893, p. 512) reports 
two brothers with spastic extremities, nystagmus, optic atrophy, con- 
vergent strabismus, and bradylalia, believed to be due to cerebral 
diplegia. 
Striimpell (Deutsche Zeitschrift fur Nervenheilkunde, Band iv, 
1893, P- 172) cites the case of a man, presenting symptoms of spastic 
spinal paralysis, whose grandfather had for a long time suffered from 
“paralysis of the legs,” and whose brother and father and two of the 
latter’s brothers had a peculiar gait like the patient’s. Of this disorder, 
which Striimpell designates the hereditary form of spastic paralysis, he 
considers the characteristics its occurrence only in males and its fa- 
milial or hereditary distribution. The first symptoms appear at the 
age of 25 or 30, and consist in an alteration of the gait due to muscular Hereditary Lateral Sclerosis. 
7 
rigidity, without weakness, and which increases until the gait is spastic. 
The disorder progresses slowly, and only the lower extremities are 
involved. 
Newmark (American Journal of the Medical Sciences, 1893, Vol. cv, 
p. 432) reports the case of sister and brother, 15 and 5 years old respec- 
tively, born without difficulty, who presented symptoms of spastic 
paraplegia, and whose mother and a sister exhibited increased reflexes. 
In a sister of the mother also the reflexes were exaggerated, and of 
her eight children the first was dead after delivery; the second was 
born after a difficult labor, had convulsions, and presented symptoms 
of bilateral spastic hemiplegia; the third labor was difficult; the fourth 
labor also was difficult, and the child exhibited increased reflexes; the 
fifth, sixth, and seventh labors were difficult, the last child dying after 
birth, and the other two presenting exaggerated reflexes. Newmark 
reports another family, of eleven children, of which four boys and a girl 
exhibited spastic symptoms, and two other girls and a boy increased 
reflexes. One of the boys and one of the girls presenting spastic mani- 
festations had been delivered with forceps; and in the birth of 
one of the girls with increased reflexes, who died from “water on the 
brain,” labor had lasted two days and nights, although delivery was 
non-instrumental. Newmark (Medical Nezvs, January 16, 1897) re- 
ports two additional cases of spastic paraplegia occurring in sisters, 
6 and 4 years old respectively, in the birth of the older of whom forceps 
had been used. In both articulation was indistinct. Forceps had also 
been employed in the delivery of an older sister still, who, however, 
exhibited no spastic phenomena. 
Souques {Revue neurologique, Tome in, 1895, p. 1) has reported 
two cases of spastic paraplegia in brother and sister, 10 and 7 years old 
respectively, born at term without complication, whose mother ex- 
hibited increased reflexes. He contends that clinical and anatomic 
considerations warrant the recognition of a disorder characterized 
clinically by spastic paraplegia and anatomically by primary system- 
sclerosis of the pyramidal fibres, either isolated or combined with de- 
generation of the columns of Goll. The ultimate cause still eludes 
detection. It may be toxic or infectious, perhaps syphilitic. 
Erb {Deutsche Zcitschrift fiir Nervenhcilkunde, Band vi, 1895, p. 
137) reports two cases of spastic spinal paralysis in sisters, 12 and 6 
years old respectively, in whose family history consanguinity was a 
prominent feature. 
Jendrassik {Deutsches Archiv fiir klinische Medicin, Band lviii, 
Hefte 2, 3, p. 137) has reported three families, in one of which a boy 
of 8 years presented symptoms of spastic paralysis, while the mother 
had an awkward gait from childhood, and a sister of 5 years had in- Augustus A. Eshner. 
8 
creased reflexes; in another family a girl of 8 and a boy of 12 years 
exhibited symptoms of spastic paralysis; in the third family two sisters, 
18 and 10 years old respectively, exhibited symptoms of spastic paral- 
ysis. In four of these cases there was advanced optic atrophy. 
Ganghofner (Zcitschrift fiir Heilkunde, Band xvn, 1896, p. 303) 
has reported, among a series of cases of cerebral spastic paralysis, a 
brother and a sister presenting difficulty in walking, with weakness 
and trembling in the legs, scanning speech, ataxia of the upper ex- 
tremities, increased knee-jerks and ankle-clonus, and in one also with 
strabismus. 
Raymond and Souques (Semetine Medicate, 1896, p. 315) have re- 
ported the occurrence of progressive spastic paraplegia in two sisters, 
19 and 15 years old respectively, both bom at term, without difficulty. 
One brother and the paternal grandfather were chronic alcoholics. 
Higier (Deutsche Zcitschrift fiir Nervenheilkunde, Band ix, 1896, 
Hefte 1, 2) reports four sisters, 24, 20, 18, and 17 years old respectively, 
who presented spastic manifestations, with tremor of the hands, dys- 
phagia, bradylalia, strabismus, nystagmus, optic atrophy, defective 
intelligence, and muscular atrophy. The parents were cousins and the 
births had been normal. In all a diagnosis of cerebral spastic diplegia, 
with degeneration of the ganglion-cells of the anterior horns of the 
spinal cord, was made. Higier cites further two cases, in brothers, 
reported by Pribram (Neurologisches Centralblatt, 1895), and presenting 
symptoms of neural atrophy of peroneal type, in conjunction with 
those of cerebral diplegia. He also refers to a report by Melotti and 
Cantalemessa (Revue neurologique, 1896) of the occurrence of familial 
spastic paraplegia in two brothers and one sister, of whom a grand- 
mother also was supposed to have suffered from the same disease. 
There had been no difficulty in birth. Finally, Higier cites the report 
by Koshewnikoff (Meditzinskoje 0bozrenije,i8g$) of progressive spas- 
tic-paretic symptoms in two children in the same family attributed to 
cerebral diplegia. 
Hochhaus (Deutsche Zeitschrift fiir Nervenheilkunde, Band ix, 
1897, P- 291) has reported three cases of spastic spinal paralysis in a 
sister and two brothers 21, 13, and 8 years old respectively, all born 
at term without difficulty. He attributes the symptoms to disease of 
the lower segment of the pyramidal tracts, resulting from a congenital 
defect in development. 
Of the cases here cited it must be evident that the lesions are not 
alike in all, as the clinical manifestations are not alike in all. In some 
there would appear to be cerebral lesions, either developmental or 
acquired, intrauterine, parturient, or postnatal. Even developmental 
defects must eventually be referred to some ultimate cause, as it is diffi- Hereditary Lateral Sclerosis. 
9 
cult to conceive of their spontaneous origin. Once established, how- 
ever, they may be perpetuated by hereditary transmission. In cases 
of congenital spastic paralysis of cerebral origin, in which a history 
of difficult or protracted or complicated labor cannot be elicited, it is 
possible that the fetus may have been subjected to traumatism or 
have suffered from disease in ntero. Ganghofner (Zeitschrift fur Heil- 
kunde, Band xvn, 1896, p. 303) attaches much importance to the in- 
fluence of hereditary syphilis as an etiologic factor. Whilst the 
fetus is ordinarily well protected from physical injury, it may be that 
occasionally, from causes that escape scrutiny, this protection may be 
inadequate. Further, while dystocia may not be sufficient to delay 
labor notably, it may yet be sufficient to result in injury to the yielding 
and resilient calvarium of the fetus and its semifluid contents. The 
conditions favoring lesions of the cerebro-spinal axis of the fetus, 
either during the continuance of pregnancy or at parturition, once 
established, it is not surprising that occasionally more than one child 
in the same family should suffer from this cause. 
In some of the cases it is probable that disseminated sclerosis or 
multiple lesions of other sort existed,—in some amyotrophic lateral 
sclerosis; while in a small number the symptoms of degeneration of the 
pyramidal tracts alone were present. 
While existing evidence points to the possibility of primary 
lateral sclerosis, it is not so conclusive with regard to the isolated oc- 
currence of this lesion, although the clinical testimony rather justifies 
its recognition. The explanation of the occasional familial distribution 
of the various disorders that have been under consideration in this 
communication must be sought in those indeterminate influences in- 
cluded in the term heredity, and it may be that these will be found to 
depend upon variations in cellular nutrition. 
As an illustration of the familial distribution of cerebral spastic 
paralysis I shall detail a brief account of a family that came under my 
observation several years ago. Of nine children (six males and three 
females) of healthy parents three (two males and one female) presented 
classic symptoms of cerebral spastic paralysis. One (a male) had had 
a convulsion at the age of 14 months, but was in good health at 
the time of observation. Two (females) had died in infancy during 
dentition. Three (females) were quite well. There was no history 
of any difficulty in birth. One of the affected children had had an 
acute illness during childhood, following which speech was lost for 
several days and spastic symptoms appearing shortly afterwards. All 
three had suffered from measles at one time. No other etiologic in- 
fluence could be determined.