Kenneth R. Magee

Familial progressive bulbar-spinal muscular atrophy.

THIS PAPER presents a family with clinically and pathologically documented progressive muscular atrophy beginning in adult life, chronic in duration, with both spinal and bulbar manifestations. All affected members were examined by the author. In addition, the diagnosis was confirmed by electromyography, muscle biopsy and, in 1 case, necropsy. During the past century, there has been much discussion and confusion regarding the appropriate classification of degenerative motor neuron disease. Therefore, prior to a review of the genetic aspects of progressive muscular atrophy and presentation of the cases, it is important to d e h e my use of the term “progressive muscular atrophy.” A problem in classification can be anticipated in view of the lack of knowledge regarding the etiology (or etiologies) of this disorder. The literature contains many reports in which progressive spinal muscular atrophy, chronic poliomyelitis, and amyotrophic lateral sclerosis are regarded as the same disease. Other authors differentiate these disorders as well as their longitudinal variant, progressive bulbar palsy. Also adding to the confusion of definition is the occasional use of the term progressive muscular atrophy for CharcotMarie-Tooth disease, although more commonly the latter disorder is called progressive neural or peroneal muscular atrophy. Adams, Denny-Brown, and Pearson,’ Merritt,* Brain,3 and Nielsen” believe that progressive muscular atrophy is but a variant of amyotrophic lateral sclerosis, in which the lesions are limited to lower motor neuron. It is emphasized that many patients showing clinical lesions limited to the lower motor neuron often show evidence of corticospinal tract degeneration on postmortem examination. On the other hand, A lpe r~ ,~ Wechsler? and Miiller’ feel that, at present, it is better to consider progressive muscular atrophy, with lesions limited to the lower motor neuron, a separate clinical entity, particularly because of the better prognosis. This view is also expressed by Kinnier Wilson,* who states, “Difficult as it is to reach a firm conclusion, the lesions of the Charcot type are so characteristic, and, when advanced, so different from those of nuclear amyotrophy, that in my opinion the fact outweighs other considerations; they comprise much more than the mere addition of upper to lower motor neuronic disease.” Miiller7 considered prognosis in detail by reviewing 190 cases of progressive motor neuron idisease in adults in Sweden. In this group, he again confirmed that amyotrophic lateral sclerosis, especially when associated with bulbar palsy, was a relatively rapidly fatal disorder; 78% of patients in his series who did not have bulbar palsy and 92% of those who did, died within three years. On the other hand, 7 patients who clinically had lower motor neuron disease without upper motor neuron lesions or bulbar palsy were alive eight to thirty years after the onset of their disability. From his clinical data, he concluded that a pure progressive spinal muscular atrophy exists, constituting a different morbid state. He commented that even pathologic involvement of the corticospinal tract does not prove that the case is one of amyotrophic lateral sclerosis, for the same structures in the central nervous

Alzheimer's disease: Presentation of a case with pathologic and enzymatic-histochemical observations

THIS AHTICLE REPORTS the clinical features of a case of Alzheimer’s disease and a histochemical and morphologic analysis of a cerebral biopsy. In view of the provocative nature of the observations, it was very fortunate that ample material was available for histochemical studies within thirty minutes after it was removed from the patient, thus providing ideal material for histochemistry. The histochemical technics to be described are being used as a laboratory routine for extensive mappings of the normal human brain; their reliability has been well established.’ All of the findings which did not require fresh material were compared with numerous cases of Alzheimer’s disease from the collections of the Laboratory of Neuropathology of the University of Michigan.

Occurrence of neurologic abnormalities in infants of diabetic mothers.

A SURVEY of the literature on the offspring of diabetic mothers indicates a higher mortality rate and a greater incidence of congenital malformations as compared with non-diabetic controls. Pedowitz and Shlevinl estimated the mortality rate in offspring of diabetic mothers to be as high as 8.2 per cent. According to Kade and Dietel,2 the incidence of congenital malformations in diabetic pregnancies is 3.6 per cent (110 deliveries) as compared to 0.5 per cent in normal controls (1,000 deliveries). There are no statistical data on morbidity of the infants born to diabetic mothers. Similarly, very little information is available regarding the clinical manifestations and subsequent course of these patients. In the present communication an analysis is made of the neurologic abnormalities encountered in the offspring of diabetic mothers. Although many authors stress the increased incidence of congenital malformations and birth injury in the offspring of diabetic mothers, there are only a few reports in which the investigators described the type of abnormality or gave the size of their sample. LeCorche3 was probably the first to report abnormalities in children born from diabetic mothers; two of the infants described by him were born with pronounced hydrocephalus. In a series of 17 pregnancies in diabetic patients, Peckham4 found one infant stillborn with congenital syphilis and one child with a meningocele. Skippers investigated 37 pregnancies in diabetic women and found two malformed infants; one was born a “monster” workers6 stated that congenital defects occurred in three out of 35 patients; only one was considered to have a neurologic abnormality. Gasper7 analyzed histories of 49 pregnancies in diabetic women; one patient had three stillbirths and then delivered a “monster with many anomalies.” Palmer and Barnes8 mentioned the occurrence of a “deaf and dumb” child among those resulting from 68 pregnancies in diabetic mothers. Miller9 surveyed 19 consecutive autopsies of infants born to diabetic mothers and found single or multiple congenital malformations in six. One of them had anencephaly, another had malformation of the spine, harelip, and syndactyly, and the remaining four had malformations of various internal organs. Gonce’” stated that congenital abnormalities occur in one out of six children whose mothers were diabetic, whereas they occur in onlv one out of 55 normal births. The incidence of involvement of the central nervous system was not given. Hall and Tillmanll summarized the causes of fetal deaths occuring with diabetic mothers as follows: 1) spontaneous abortion, 2) hydramnios, 3) congenital abnormalities, 4) acidosis, 5) hypoglycemia, 6) toxemia, 7) prematurities, and 8) large babies. There were no congenital abnormalities in their series of 149 pregnancies in 112 diabetic patients. Kloos’2 reported that congenital abnormalities were found in three of four infants born to diabetic mothers. Two were siblings, however, and were born of a mother who herself was disproportional. Both had a congenital heart con-

Treatment of headache with ergotamine-caffeine suppositories.

ERGOTAMINE TARTRATE, first introduced for the symptomatic treatment of migraine by Maierl in ,1926, has been found to be the most specific drug for relief of this type of headache. Statistics on its efficacy vary with different observers, but it is generally conceded that if administered early enough in the attack, ergotamine tartrate either aborts or completely relieves migraine and certain related vascular headaches in from 70 to 90 per cent of cases.2 In fact, it is so specific that it may be used as a therapeutic test for migraine. Studies by W0H3 and others have demonstrated that the pain in migraine is produced by dilatation of certain cranial arteries, and the therapeutic effectiveness of the drug is due to the vasoconstriction which it produces. Ergotamine tartrate is much more effective if given parenterally (subcutaneously, intramuscularly, or occasionally intravenously) than if administered by mouth, but parenteral administration is definitely less practical for the majority of patients, especially because the drug must be given at the very onset of symptoms. Another drawback to parenteral administration is the frequency with which it causes gastrointestinal disturbances. Oral ergotamine tartrate is less effective because of its delayed absorption. Gastric motility is greatly reduced with the onset of headaches in most patients. Oral ergotamine tartrate is enteric coated, and this, together with reduced gastric motility, results in such slow absorption that the headache has advanced in severity before any effect of the drug is experienced, and by that time may be irreversible. Recently it has been found that a new compound, Cafergot, which is a combination of 1 mg. of ergotarnine tartrate, together with 100 mg. of caffeine, is more effective in many patients than ergotamine alone;4 there are fewer side effects, and the amount of ergotamine needed to control the headache may be reduced. Possibly the added caffeine works synergistically with the ergotamine. Friedman5 suggests that the caffeine acts by causing further cerebral vasoconstriction, bringing about psychic stimulation, and perhaps by increasing the rapidity of the absorption of the ergotamine. Cafergot thus far has been available only in a sugar-coated tablet for oral administration, and if large doses of ergotamine are needed, it is necessary to administer a rather

Phosphorylase deficiency associated with isometric exercise intolerance

In the patient reported here, most of the clinical and biochemical correlates of McArdles disease were present; however, symptoms developed after isometric rather than after isotonic exercise. Histochemical reactions and assay of muscle homogenates confirmed the absence of phosphorylase; however, venous serum lactate increased in the arm after isometric and isotonic ischemic exercise, although the increase was significantly less than in a normal control. Although the symptoms differ significantly from those in McArdles disease, this disorder could be a variant.

Isonicotinic acid hydrazide in multiple sclerosis.

Of 81 patients screened, 33 were accepted for the study. The remaining 48 were excluded for the following reasons: 1. Incorrect diagnosis-seventeen patients did not have multiple sclerosis, but had one of the following diseases: hereditary ataxia ( five ) , spinal cord meningioma ( one), pontine tumor (one) , cervical spinal arachnoiditis ( one ) , psychoneurosis (five), multiple cerebrovassions of the central nervous system.

Canine Neurology: Diagnosis and Treatment

This monograph, written as a doctorate thesis during the author’s term as resident on the neurosurgical service at Aarhus Municipal Hospital in Denmark, covers widely the subject of facial pain. I t gives an exceptionally good review of the literature on the anatomy and physiology of the nerves supplying the face. The author believes that the majority of painful conditions of the face are due to referred or projected pain. This explains his particular interest in referred facial pain from the temporomandibular joint. For this type of discomfort, he recommends the intra-articular injection of hydrocortisone which he found to give immediate relief in 64% of cases so treated. The clinical characteristics of trigeminal neuralgia and the various surgical methods of treating it are discussed. The author’s results in a series of 473 patients differ very little from those reported by American neurosurgeons. The tabular material is relatively simple, and detailed statistical analyses are not attempted. The monograph, although introducing no new concepts, is a well-written and concise account of the subject, well illustrated with case material from the clinic of Prof. Malmros. Consequently, this is an excellent reference book for the student who wishes to delve into the subject. The neurologist and neurosurgeon looking for a thorough review of the subject will find it in this book.

Gowers' local panatrophy; its relation to certain types of insulin lipodystrophy.

IN HIS TEXTBOOK of neurology (1886) and in a subsequent paper (1W3), Sir William Gowers reported a case of “local panatrophy” occurring in a 33 year old woman.lg2 Gowers’ patient was described in much greater detail in a subsequent paper by Barnes3 The patient showed wasting of all subcutaneous tissues “down to the bone” in various areas on the trunk, limb, and face. The wasted areas varied considerably in dimensions, from “the size of a nut to an orange.” The skin was thin and slightly discolored over the atrophic areas. The bones were not involved. The larger areas of wasting also involved the muscles. Barnes emphasized that the wasting of muscle tissue corresponded directly to areas of atrophic skin as though by a “punching out process,” so that only part of the muscle was affected. The muscles reported to be involved included on the left the deltoid, supraspinatus, infraspinatus, rhomboid, and erector spinae muscles, and on the right the second dorsal interosseus, lumbrical, and erector spinae muscles. The electrical irritability of the involved muscles remained normal. It was emphasized that the patches of atrophy were very distinct and the line of junction between healthy and diseased tissue was abrupt. Barnes stated that the subcutaneous tissue immediately surrounding an involved area seemed unusually lobular when rolled under the finger, but he thought this might be due to the finer details of the adjacent tissue being palpable in areas of wasting. This disorder has received very little attention. Oppenheim suggested that it was probably a form of scleroderma and that it might also in many respects be similar to facial hemiatr~phy.~ Wilson’s textbook of neurology briefly discusses and illustrates a patient with local panatrophy.6 In contrast to local panatrophy, lipodystrophy resulting from other causes has received more attention. In particular, the lipodystrophy resulting from injection of insulin in diabetic patients has been described by numerous authors. Localized lipodystrophy has also been reported following injection of substances other than insulin, including grass pollen and pituitrin.69‘ Localized atrophy of the subcutaneous fat has also been reported after a jelly-fish sting.*

Peripheral Entrapment Neuropathies

This book contains a review and elaboration of the authors’ studies on entrapment neuropathies peviously published in a series of articles in major medical journals. Entrapment neuropathies are defined by the authors as “regions of localized injury and inflammation in a peripheral nerve caused by mechanical irritation from some impinging anatomical neighbor.” In addition to the carpal tunnel syndrome, meralgia paresthetica, and other neuropathies familiar to clinical neurologists, the authors postulate similar compression or irritative mechanisms of dysfunction for approximately 20 peripheral nerves. These include entrapment neuropathies in regions along the course of the suprascapular and dorsal scapular nerves in areas not commonly considered subject to compression neuropathies. Chapters are organized with an initial explanation of the anatomy of the peripheral nerve including excellent diagrams and followed by the postulated mechanisms of entrapment, concluding with details of diagnosis and treatment. Since the book results from the clinical experience of the authors who are orthopedic surgeons, orthopedic mechanisms in production of these syndromes are emphasized. Neurologists may object to some of the authors’ theories but will find them interesting. The book will challenge the neurologist to study patients presenting symptoms compatible with the diagnosis described so that he may support or disagree with the authors’ opinions.