Showing papers in "Neurology in 1969"

Familial agenesis of the cerebellar vermis A syndrome of episodic hyperpnea, abnormal eye movements, ataxia, and retardation

Abstract: SOME TWO YEARS AGO we investigated a child with profound psychomotor retardation who had had an occipital meningoencephalocele removed at birth. Contrast studies were carried out which showed a large midline defect in the posterior fossa and absence of the vermis. At the time we disregarded the nurses’ comments about the child’s abnormal breathing. A year later, Dr. P. P. Demers referred this patient’s baby brother to us because he was concerned about his abnormal breathing and xetarded development. It was then found that a third and older child in this family was Tetarded, ataxic, and breathing abnormally. Finally we were able to trace yet another sibling who had died in fancy and who, at autopsy, proved to have agenesis of the vermis. This .diagnosis was then confirmed in the two affected living children by contrast studies. From this investigation there emerged a familial syndrome of episodic hyperpnea, abnormal eye movements, ataxia, and mental retardation associated with a common malformation in the four affected siblings, agenesis of the vermis. This syndrome has not previously been described in the literature. The affected children will be presented in the order in which the abnormality was identified, which happens to be in reverse to the birth order (Fig. 1).

The histographic analysis of human muscle biopsies with regard to fiber types. 4. Children's biopsies.

Abstract: Histograms were constructed of each biopsy, using the techniques previously described.’ The only modification was that the magnification used for taking the photographs from which histograms were made was altered in some cases. Magnifications of 2 0 0 ~ and 4 0 0 ~ were used when the standard 100 x -magnification was insufficient to produce a photograph containing about 200 fibers in an area of about 12 sq. in. Histograms were plotted independently for each of the two main fiber types. There was only one criterion for including a patient in the study and that was that the patient was 15 years of age or less. There were many different disease categories and many patients with diseases that did not fall into a clear-cut diagnostic category. Thus, to present the results by classifying the patients under disease categories would be a confusing and cumbersome approach. All of the 180 biopsies fell into one of five clear-cut histographic types. The patients are therefore presented according to the histographic appearance of their biopsies. These groups are de6ned more exactly below, but they may be summarized as [ l ] biopsies with fiber types I and I1 of equal size and apparently normal variability, 121 biopsies with type I1 fibers smaller than type I, [3] biopsies with type I fibers smaller than type 11, 141 biopsies with a twin-peaked histogram of one or both fiber types, and [5] biopsies with an abnormal variability in the size of individual fibers not fitting into one of the other groups.

Perceptual and associative disorders of visual recognition Relationship to the side of the cerebral lesion

Abstract: IN 1890, Lissauerl described the first welldocumented case of visual agnosia and proposed a subdivision of this disorder into an apperceptive and an associative form, according to which stage of the process of visual recognition was primarily af€ected. By apperception he meavt the higher level of processing of sense data (the lower level being designated as perception) which enables the subject to identify and discriminate complex patterns. In Lissauer's opinion, this impairment can be evaluated by requiring the patient to [I] describe the formal features of the pattern, [2] reproduce it by drawing, and [3] recognize it among similar alternatives. The associative stage, on the other hand, consists of the linkage of the processed visual data with memory images laid down in the brain through other sensory modalities and with names, which Lissauer considered as the most simple and basic representation ( Vorstellung ) aroused by objects. Only through these linkages does apperception acquire a meaning. Lissauer assumed that his patient was affected by associative agnosia since he did not recognize objects, although he performed fairly well on purely apperceptive tasks such as discriminating arabesques. In the subsequent history of visual agnosia, the dichotomy between associative and apperceptive disorders has been somewhat neglected and attention has been concentrated on the content of the patterns the patient fails to recognize, distinguishing object agnosia, color agnosia, face agnosia, and others. This classifi-

Chronic manganese poisoning. Individual susceptibility and absorption of iron.

Abstract: MANY MINEHS are exposed to manganese dusts, but few develop chronic manganism. Those who do (develop manganism) exhibit a selflimited psychiatric disorder, at the end of which neurological manifestations emerge.1-2 These manifestations persist after the excess metal acquired at work becomes cleared from the tissues.3 This low but unpredictable propensity suggests that the victims of manganism are being selected among exposed miners by some unusual factors which permit flooding of the brain with intolerable amounts of metal. These factors could conceivably bc genetic or industrial, but our patient population is too small for the application of genetic or epidemiologic techniques. A fitting inquiry was made into metabolic determinants which might render susceptible o d y some of the exposed workers. The lung has long been thought of as the cardinal portal of entry for the offending metal.‘ The evidence discussed below argues, however, that the bulk of the inhaled manganese becomes transferred into the gastrointestinal tract, from which it is either absorbed or eliminated;5 hence this canal must be a portal of entry, even for manganese which is first inhaled. Investigations of the intestinal absorption of manganese are complicated by the fact that absorption and reexcretion of this metal proceed almost concurrently.5 In the intact man, ingestion of a manganese tracer alone cannot permit the differentiation between fractions headed for elimination and those headed for absorption. The use of an additional marker

The histographic analysis of human muscle biopsies with regard to fiber types. 2. Diseases of the upper and lower motor neuron

Abstract: ’rm P ~ R P O S E of the present study is to evaluate the reIative sizes and ratios of histochemical type I and type I1 muscle fibers within normal muscle and within muscle from groups of patients who approximate closely to normal. As far as we are aware, this information is not available in the literature and yet it is of fundamental importance in view of the apparent difference in the behavior of each fiber type in certain pathological conditions.’-“ As R result of the present study, it is apparent that there are differences between male and feinale muscle biopsies which should be incorporated into any criteria used to evaluate normal muscle. The problems involved in the analysis of normal muscle are numerous, not the least being one of definition. Many of the previous studies*-‘ have no information on the histochemicaI patterns. Moreover, they often employ fixed material obtained at autopsy which cannot be accepted as normal in the strict sense, since the events leading to death from any conditioii may provoke changes within the muscle. It is also becoming evident that muscle may be invol~ed in diseases which are considered “iioiiiieuroi7i1iscular” and that muscle obtained at surgei-y for unrelated conditions cannot be included in a normal study without comment. In practice it is very difficult to obtain biopsies from entirely normal people. In evaluating no1 ma1 muscle there are two kinds of cltiesti:ii~s that c;in be answered. The first wnceriis thr presence or absence of certaiii isolated changes: Is a necrotic fiber ever seen in normal muscle? Are small angular fibers ever present? The second kind of change is a quantitative one and is exemplified by the size of fibers. The presence of a few angular fibers of small size is obvious when considered as an isolated change but would not materially affect the values of a histogram of several hundred fibers. Similarly, ;I muscle showing a small deviation in the size of all its fibers away from normal can still be used to assess the approximate value of the mean. Thus, in the investigation of histograms we have used not only normal patients but have also employed groups of patients who might be expected to show the least deviation from normal-the paranormal group. If the histogram values of the paranormal group have an insignificant deviation from the normal group, those values are accepted as normal. Normal in this case refers to the fiber size alone and not to other criteria.

Inherited predisposition to generalized amyloidosis. Clinical and pathological study of a family with neuropathy, nephropathy, and peptic ulcer.

Abstract: RECENT CONTRIBUTIONS have adequately reviewed the present status of our knowledge about amyloidosis.l-21 The challenge to unravel the pathogenesis of this disorder is now being met with increasing effort. The identification of a characteristic ultrastructure of amyloid has been a substantial step forward,l7 and biochemical and immunologic studies are currently of major interest.21 Study of a kindred with amyloidosis is another approach to investigation of this disorder. Several families with amyloidosis have been described and a pattern of dominant inheritance has emerged.zY-:+a Efforts to subclassify the family groups by symptoms have been of limited success. We are reporting a family in whom pathologic verification of amyloidosis has been possible in 8 members of 2 generations, including 3 father-son relationships. Clinical manifestations of the disease have arisen principally from involvement of the peripheral nervous system and the kidney and from peptic ulcer. Discovery of this afflicted family began with an effort to ideiitify the cause of peripheral neuropathy in patient 20 of the third generation (Fig. l ) . Investigation revealed that a brother, patient 23, also suffered from peripheral neuropathy, which had been explained by amyloid infiltration of neural tissue. Crmwlogy. The ancestors of our family immigrated from Scotland, England, and Ireland. Members 3 from England and 4 from Canada lived in Indiana for some years before moving

Nerve Excitation: A Macromolecular Approach

Abstract: This well-written monograph is designed for students and investigators. Full appreciation requires a high level of sophistication in physical chemistry, as well as biophysics and mathematics. However, the historical introduction, the textual development of ideas, and the summary (which may best be read first) should make the broad outline comprehensible to any reader who is reasonably familiar with a modern textbook understanding of the mechanism of membrane excitability in nerve and muscle. Tasaki’s new concepts are based largely upon recent experiments from his laboratory involving elaborate manipulations of both the internal and external fluid media bathing the excitable membrane of the squid axon. Using models of inanimate physical chemistry, especially ion exchanger membranes, Tasaki develops a hypothesis which not only accounts for the now classical Hodgkin-Huxley thesis but also for the complex newer data which are otherwise difficult to interpret. He suggests that the excitable membrane exists in two stable conformational statesthe resting and the excited. The macromolecular membrane complex is thought to have a relative excess of fixed negative charge at the external layer which provides cation exchanger properties. “In the resting stable state, the anionic sites in the membrane are occupied primarily by divalent cations (largely calcium) derived from the external medium; in the excited stable state these sites are occupied predominantly by univalent cations (largely potassium). The conformation of the membrane macromolecules and the properties of the cation exchanger are determined primarily by the univalent/divalent cation ratio within the membrane. . . . The excitation process is triggered by the transport of internal univalent cations (potassium) into the membrane. . . . When a limited area of the membrane is transformed into its excited conformation, a local circuit is effected.” The propagated impulse carries on as understood in the classical theory. The generally increased membrane conductance of’ excitation is associated with increased cation interdiffusion across the membrane and a consequent change in the local ionic environment of the excited membrane. Excitation is terminated (inactivation process) when divalent cations from the external medium diffuse back into the membrane in sufficient concentration again to form stable complexes with fixed anionic sites. This effort to bring together concepts of changing ionic conductance and the structure of the protein-phospholipid complex of the membrane is obviously significant. Although thermodynamic aspects are given important emphasis, metabolic features that distinguish the living from the inanimate membrane are not considered in these relatively short-term experimental studies. Although the material is complicated and controversial, the interrelations of electrophysiological function with membrane structure and electrolyte transport are clearly important to clinical neurology. This book provides a useful and necessary introduction to a field that requires our attention.

Tactile perception of direction and number in patients with unilateral cerebral disease

Abstract: A SUBSTANTIAL AMOUNT OF EVIDENCE has accumulated in recent years to suggest that the right hemisphere plays a distinctive role in the mediation of certain aspects of human behavi0r.l-3 For the most part, this evidence has been derived from comparisons of groups of patients with disease of the left and the right hemispheres, respectively, the essential findings being that patients with lesions apparently confined to the right hemisphere show more frequent and more severe deficit on a variety of task performances, most notably those involving constructiona1 praxis,4 facial recognition,5.6 certain types of auditory and visual perception and mem0ry,~-9 and motor persistence.10 One conclusion that has been drawn from these results is that the right hemisphere plays a special role in the mediation of the “spatial” aspects of behavior. One hindrance to a simple interpretation of these findings as indicating a predominant role of the right hemisphere in the mediation of these diverse performances is the consideration that the observed differences may be an artefact of case selection. It has been pointed out that extensive disease of the left hemisphere may render a patient severely aphasic and hence untestable; this limitation rarely applies to right hemisphere disease in the righthanded patient. Moreover, since left hemisphere disease at a relatively early stage may produce significant disability in the form of language disturbance and sensorimotor disability of the preferred hand, it seems likely that, on admission to a neurological service, patients with left hemisphere disease will have more recent and less extensive lesions than those with disease of the right hemisphere. Both circumstances may create a bias for testable patients with right hemisphere disease to have more extensive lesions than those with disease of the left hemisphere. As a consequence, study of unselected cases in the two hemispheric groups may, in fact, involve a comparison of a dominant hemisphere group having lesions of limited extent with a minor hemisphere group having lesions of unlimited extent.% No compelling evidence has been adduced to support this possibility and, indeed, the observations of Milnerll on patients with temporal lobe excisions of accurately defined extent indicate that it cannot be made to apply to at least certain performances on which patients with right hemisphere disease show specific deficit. In any case, an approach which may circumvent a bias in patient selection (if it exists) is to investigate patterns of performance as a function of hemispheric locus of lesion instead of merely comparing absolute levels of performance. This approach was utilized

Familial “myotubular” myopathy

Abstract: THE EXISTENCE of central nuclei, so-called myotubes, or type I fiber hypotrophy in muscle diseases has been described by several authors. These diseases were given different names. Spiro et al.,l Kinoshita et a1.,2 and Coleman et al.3 described their cases as “myotubular myopathy,” because the main pathology consisted of fibers resembling fetal myotubes. Sher et aL4 and Bethlem et al.5 called their cases “centronuclear myopathy,” because they regarded the presence of the many centrally placed nuclei as the most characteristic feature. Engel et al.6 reported a case as “type I fiber hypotrophy and central nuclei,” thus describing the two principal histopathological features. Bethlem et al.7 listed <‘type I fiber atrophy, central nuclei, and myotube-like structures” as the most conspicuous findings in their patient. The clinical picture of these cases was variable. Both males and females were affected. The onset was at birth or in early infancy. All patients showed widespread muscle involvement combined with areflexia. Involvement of extraocular or facia1 muscles or both was a frequent but not constant finding. In the family to be described, at least 6 siblings suffered from a muscle disease that showed many similarities to the above-mentioned cases.

Decreased postrotatory nystagmus in early infantile autism

Abstract: IN 1943 Kanner’ described the syndrome of early infantile autism and defined four features he considered pathognomonic of the disease: [l] inability to relate to people, [2] failure to use language for communication, [3] apparent desire to be alone and to preserve sameness in the environment, and [4] preoccupation with certain objects. During the ensuing twenty-five years other investigators have described similar children, using different theoretical perspectives and with differing notions of etiology. Thus, children with many symptoms in common are diagnosed today as having schizophrenic reaction of childhood,2 atypical ego development,s symbiotic psychosis,4 or “unusual sensitivities.”s We have recently reviewed637 our clinical experience with more than 150 such children, as well as the relevant psychiatric, neurologic, and neurophysiologic literature. From this perspective, it appears that most of the children referred to by the above diagnostic labels are suffering from a unitary disease process. Their symptoms can be grouped into five subclusters involving disturbances of [ 11 perception, [2] motility, [ 31 developmental rate, [4] relating, and [ 5 ] language. We have suggested that the disturbances of perception, motility, and developmental rate are primarily expressive of organic dysfunction and underlie the disturbances of relating and language. For example, such children fail to respond completely to sounds which at other times evoke screaming and panic-like reactions. At an early age, they may be referred for audiologic evaluation because of questioned deafness,8 yet careful examination will reveal that they respond to such sounds as a distant door slamming. A child who is reported to avoid eye contact, look through people, and ignore objects placed in front of him will spend hours staring at tops, record players, or cracks in a wall. These children are usually panicked by riding in elevators and being tossed in the air; yet they will spin themselves uninterruptedly for hours. These apparently paradoxical responses give the clinical impression that normal homeostatic regulation of perception cannot be maintained within the central nervous system of such children and that they experience perceptual inconstancy.6 Based on these clinical observations, experiments have been designed which indicate vestibular dysfunction during certain stages of sleep. It was found that the vestibularly mediated phasic inhibition of auditory-evoked responses seen in normal children during the eye movement bursts of rapid eye movement (REM) sleep was not present in a group of young autistic children.* Instead there was a relative enhancement of the amplitude of the late component of the auditory-evoked response during the eye movement bursts. Furthermore, there was a decreased duration of individual eye movement bursts during REM sleep in the youngest autistic children.10 As the eye movement bursts of REM sleep were mediated by the vestibular nuclei,’lJ‘ these

Auditory cortical areas of man

Abstract: CO\\f l ’CTEl l AVERAGING TECHNIQUES to extract small signals from the spontaneous background rhythms have been applied in recent years to the study of cortical sensory areas in mail during neurosurgical procedures. Somatosensoryevoked responses have been recorded directly from the cerebral cortex and thalamic nuclei,1-4 and detailed reports are therefore available on the configuration, latency, and physiological characteristics of these responses. By contrast, comparable studies oil the central auditory system are few. Celesia et x1.z recorded evoked potentials to clicks from the posterior part of the first temporal gyriis (nlso referred to as the superior tempoi~al gyrus) and the parietal and frontal opercnlnm, but ndmittedly they did not record from the trans\\reuse temporal gyri. Sem-Jacobsen et al.6 and Chatriaii et a1.7 obtained single evoked potentials to click stimulation from the human cortex with the use of chronically implanted electrodes. However, it is doubtful if their electrode placed on the superior surface of the tempoi-a1 lobe recorded primary auditory responses. A systematic exploration of the superior temporal plane was undertaken in the present work to determine the nature and location of the human primary auditory sensory area.

The pupillogram and narcolepsy. A method to measure decreased levels of wakefulness.

Abstract: WHEN A PERSON is awake and alert, his pupils are large; when he is asleep, they are sma1l.l The patient with narcolepsy spends much of his time in various levels of decreased wakefulness or drowsiness. The degree of daytime hypersomnia is difficult to assess accurately on a clinical basis. When the equipment became available for doing pupillography, the pupils of patients with narcolepsy were studied as to alterations in size and responsiveness. Results of such studies on 50 patients, untreated and treated, form the basis for this paper. The pupillogram is an accurate and objective method for measuring the severity of decreased wakefulness, as well as for assessing the efficacy of treatment.

Late motor neuron degeneration following poliomyelitis.

Abstract: A RELATIONSHIP between preceding acute anterior poliomyelitis and the later development of motor neuron disease has only occasionally been suggested since it was first postulated by Charcot in 1875. The clinical differentiation between “chronic spinal atrophy,” “chronic poliomyelitis,” and amyotrophic lateral sclerosis was not made clear in the earlier case reports and, except in a few instances, only one or two cases were reported and there is no record of the natural history of the disease. We therefore report five cases of disease of the motor neuron system developing many years after poliomyelitis in early life, and also emphasize the benign nature of this condition, in contrast to the very bad prognosis of classical motor neuron disease, where death usually occurs within four years of the onset.

The effect of phenobarbital on plasma diphenylhydantoin level and metabolism in man and in rat liver microsomes.

Abstract: DIPHEENYLHYDASTOIN and phenobarbital are frequently used in combination in the treatment of epilepsy.'-5 In recent years it has been reported that the plasma diphenylhydantoin level, which usually is quite stable in patients taking that drug alone, falls when phenobarbital is added. Also, patients taking a combination of diphenylhydantoin and phenobarbital were found to have lower average plasma diphenylhydantoin levels than patients taking diphenylhydantoin al0ne.6.~ There is also evidence that pretreatment of experimental animals with phenobarbital, chlordane, and other chemicals, or with starvation, modifies the response of these animals to subsequent doses of other drugsR-l2 including diphenylhydantoin.8 The administration of diphenylhydantoin to animals pretreated with phenobarbital results in a lower plasma diphenylhydantoin level and lower anticonvulsant activity than in control animals which received no phenobarbita1.S Our own in vivo experiments with rats are in agreement and confirm the rapid metabolism of diphenylhydantoin by the pretreated animals. The rapid metabolism of drugs by the pretreated animals is due to an increase in the activity and availability of drug-metabolizing microsomal enzymes. An increase of smoothsurfaced membranes of the endoplasmic reticulum has been demonstrated in the liver cells of pretreated animals, as well as an increase in the amount of microsomal proteins, cytochrome P-450, and nucleic acids.l3-l5 The lowering of the plasma diphenylhydantoin level by phenobarbital has aroused doubt about the rationale of giving diphenylhydantoin and phenobarbital simultaneously. In order to gain more information about this point, we studied patients who were taking the two drugs together in various combinations. Our main purpose was to study the extent and the limits of the influence of phenobarbital on plasma diphenylhydantoin levels in human beings. We also studied the effect of phenobarbital on diphenylhydantoin biotransformation in vitro in a rat liver microsomal preparation.

Problems in cerebellar hemorrhage and infarction.

Abstract: ONE PATIENT in ten with a spontaneous brain hemorrhage has the primary lesion limited to the cerebellum.]-2 Of the 286 hypertensive hemorrhages reported from Boston City Hospital, 231 (80%) were cerebral, 29 (10.1%) were cerebellar, and 26 (9.1%) were p ~ n t i n e . ~ In patients with “coma of unknown etiology,” cerebellar hemorrhage was ultimately found to be as frequent as cerebral infarction or brain tumor.‘ Since Brown-SCquard‘s description of the disease in 1801,5 single case reports have been published and later, more comprehensive series were documented.e.7 A very compIete survey of the literature was recently made by Fisher et a1.8 In spite of this, acute vascular lesions of the cerebellum often remain undiagnosed during life and are not recognized a5 potentially treatable neurological emergencies in patients presenting with “stroke” syndromes. Recent involvement in the diagnosis and management of several of these cases has prompted us to a closer scrutiny of the problems raised by this disease.

Hypokalemic periodic paralysis. Children with permanent myopathic weakness.

Abstract: THE CLINICAL SYNDROME of periodic paralysis is typically described as consisting of temporary weakness of skeletal muscle in individuals who are normal between attacks. Many conditions can produce periodic weakness. These include aldosteronism, hyperthyroidism, myophosphorylase deficiency, myasthenia gravis, hysteria, paramyotonia congenita, acute intermittent porphyria, idiopathic myoglobinuria, gastrointestinal and renal disease associated with excessive loss of potassium, and exposure to exogenous toxins. When these conditions have been excluded, there still remains a poorly understood group that is identified by changes in serum potassium during an attack. Many syndrome names are given to each group, but essentially they consist of periodic paralysis with low, high, or normal potassium in the serum during an attack. Despite the clinical requirements that the patient be normal between attacks, permanent interictal weakness has been reported in all three groups.l-21 At least 33 instances of permanent paresis have been reported in patients with assumed or proved hypokalemia during an attack (Table 1). Although nine of these cases were reported before Biemond and Daniels ( 1934)IO discovered that potassium dropped during an attack, Singer and Goodbody2* suggested treating t h i s condition with potassium salts in 1901. Usually the permanent weakness occurred late in the disease; in only one case reported did it definitely occur before the age of 14 years. The purpose of this paper is to present the clinical course and muscle biopsy and electromyographic findings in two children who had the syndrome of hypokalemic periodic paralysis and who developed permanent proximal weakness at the ages of 9 and 12 years. Although most biopsy reports describe vacuolization of muscle fibers, and electromyography has, on occasion, demonstrated neurogenic findings, these were not present in our cases.

Acute paralytic brachial neuritis: A clinical and electrodiagnostic study

Abstract: ACUTE PARALYTIC brachial neuritis is a welldefined clinical entity. The onset usually is marked by pain in one or both shoulders, followed within hours or days by severe weakness and atrophy in muscles innervated by the brachial plexus. Although the distribution is sumewhat variable, the proximal muscles of the arm and shoulder girdle are most frequently involved. Sensory loss is usually present, but less prominent, and is found in the nerve distribution corresponding to the maximal muscle weakness. While the disability often occurs during convalescence from an infectious disease, the patient is free of systemic symptoms when the neuritis becomes clinically overt. The prognosis for ultimate recovery is good but may require one or two years in some cases. Although acute paralytic brachial neuritis is generally thought to have been first described in the 1940s, we have found reports by Vulpian,l,2 almost a century ago, of typical cases developing during convalescence from variola and typhoid. Cases occurring after a number of other infectious diseases were later cited by Ross and Bury.3 Vulpian attributed the paralysis to a localized myelitis, but pathologic study of a case by Joffroy4 demonstrated sparing of the spinal cord and marked demyelination of the nerves of the brachial plexus, with some loss of axis cylinders. Kennedy6 reported the identical clinical picture associated with some cases of serum sickness. Since then cases have been known to occur following immunizations, even without obvious systemic allergic reactions.6 Large numbers of cases in military personnel were reported in the 1940s,7-14 and the essential clinical features of the entity were emphasized. Again it was noted that many of the cases developed during convalescence from infectious diseases or following surgery. However, these and later reportsl5-19 emphasized that in many instances no obvious precipitating factors could be identified. Nonetheless, the absence of any systemic symptoms, the norma1 CSF findings, the frequent occurrence during convalescence from an illness, and the observation that the identical picture can occur during serum sickness have led many authors to suspect an allergic etiology. We wish to report the findings on a group of 12 cases of this type, partly because of some differences from the typical clinical picture, but primarily because of the results of electrodiagnostic studies which were carried out in many instances.

Neuromuscular disease with type I fiber atrophy, central nuclei, and myotube-like structures.

Abstract: A MUSCULAH DISEASE, characterized by the presence of muscle fibers with central areas devoid of myofibrils and with central nuclei, was described in 1966 by Spiro, Shy, and Gnatas.’ These fibers resembled the myotubes ordinarily found in early fetal life. I t was postulated that the finding of myotubes indicates an arrest in development of the muscle at a cellular level, and the disease was consequently described as “myotubular myopathy.” Sher, Rimalovski, Athanassiades, and Aronson? found similar histopathological changes in two sisters. Since the pathogenesis of this unusual disease remained obscure, they preferred the descriptive term “familial centronuclear myopathy .” What appeared to be the same condition was described by Bethlem, Meijer, Schellens, and Vroom,s who found the above-mentioned abnormalities in both type I and type ‘TI fibers and also in fibers with medium enzyme activity. The clinical picture was strikingly similar in all these cases: onset in the first year of life, slow progression, involvement of the extraocular muscles and the muscles of the face, neck, and limbs, and absence of the deep tendon reflexes. There was no involvement of the extraocular muscles in the patient with myotubular myopathy described by Kinoshita and Cadman.4 In this case, too, both type I and type I1 fibers were affected. Another condition characterized by the presence of central nuclei was described by Engel, Gold, and Karpati.5 Their case showed a pattern of widespread hypotrophy and central nuclei affecting virtually all type I fibers and a minority of the type I1 fibers. This congenital muscular abnormality was described as “type I fiber hypotrophy and central nuclei.” We found type I fiber atrophy, myotube-like structures, and central nuclei in a patient who also showed indications of neurogenic muscle involvement. Reports will be presented on this patient, her diseased brother, and their clinically healthy parents and sister.

Enzyme-inhibiting factor in subacute necrotizing encephalomyelopathy.

Abstract: LEIGH’S subacute necrotizing encephalomyelopathy is a degenerative disease of childhood which often becomes symptomatic in the first year of life and usually progresses, stepwise, to a fatal termination within twelve months. Feeding problems, weakness, extraocular palsies, loss of vision, hearing and swallowing difficulties, ataxia, convulsions, disturbances of consciousness, and peripheral neuropathies all have been noted in different combinations. The absence of easily recognizable clinical features or helpful laboratory tests has made definite antemortem diagnosis difEcult in most cases in which no family history of the disorder was present. This has limited the number of metabolic studies which have been done. Postmortem findings have indicated lesions which have a striking similarity to those seen in Wernicke’s encephalopathy, although the mamillary bodies are often spared in subacute necrotizing encephalomyelopathy . This similarity in pathology has raised the possibility that a disorder of thiamine metabolism is present in this condition.14 Because involved children have not been malnourished until the later stages of their disease, and because of the inefficacy of the treatment with large daily thiamine supplements in several cases, the disease has been thought by some to represent a genetic disorder of thiamine rnetaboli~m.~J The high familial incidence of the disorder and the remarkable tendency to consanguinity in the parents of involved children have buttressed this view of the etiology. Recently we have had the opportunity of investigating a living child with this disorder. Although the usual tests of thiamine levels, such as red blood cell transketolase and blood lactate and pyruvate determinations were not abnormal, a factor in the child’s blood, urine, and spinal fluid has been found which inhibits thiamine pyrophosphate-adenosine triphosphate phosphotransferase. This enzyme is responsible for the reversible conversion of thiamine pyrophosphate (TPP) to thiamine triphosphate (TTP) as follows: TPP + ATPPTTP + ADP.

Effects of nervous system lesions on phantom experience in amputees

Abstract: AFTER AMPUTATION, many patients feel as though the missing limb is still present. This imaginary limb has been called a phantom limb, and it may seem quite normal or feel distorted or painful. Numerous theories have attempted to explain the phantom experience but so far none are wholly satisfactory. In the hope of furthering understanding of these phenomena, we have inquired into the effects of lesions of the nervous system on phantom experience in amputees.

Aspergillosis of the central nervous system: Report of a brain abscess due to A. fumigatus and review of the literature

Abstract: BRAIN ABSCESSES of low virulence pose particularly difficult diagnostic problems. When such abscesses are caused by fungal organisms, the difficulties are increased manyfold. Surgical intervention, in many instances, is necessary in order to identify the pathogenetic organism and thus permit initiation of appropriate medical therapy. Aspergillus fumigatus is a rare invader of the central nervous system; only 32 well-documented cases having been reported in the world literature, to our knowledge, since the first report of a case of aspergillus meningitis seventy-two years ago.1 Of these, only 8 instances of a solitary intracranial mass lesion have been recorded-3 granulomas and 5 abscesses. The present case report is presented in order to illustrate the difficulties of establishing the correct diagnosis and to serve as a means of reviewing the features of this disease as it appears in previously published cases of aspergillosis of the central nervous system.

Brain swelling in the newborn rhesus monkey following prolonged partial asphyxia

Abstract: SWELLING OF THE BRAIS is an occurrence of major concern to both the clinical neurologist and the neuropathologist. Brain swelling, when sufficiently severe, may itself contribute to patient death. When less severe, it may produce patterns of damage in the brain secondary to compression of major brain arteries; i.e., the posterior cerebral, the anterior choroidal, the superior cerebellar, and others.’,’ Despite the importance of brain swelling in clinical practice, knowledge of its pathophysiology and pathogenesis remains uncertain. In clinical circumstances, swelling of the brain may follow head trauma, asphyxia, and poisonings of various types, such as with carbon monoxide or cyanide or with lead or manganese. Brain swelling may aIso occur in relation to central nervous system infections and inflammations. In experimental studies, brain swelling may be induced by cold injury, trauma to the head, inflammation, intoxication with such agents as triethyl tin and mercury compounds, and by asphyxia. Brain swelling may also be produced by overhydration or by irradiation. This variety of circumstances associated with brain swelling suggests that no single pathogenic mechanism may account for all types of swelling, In most instances, experimental models utilized in the study of brain swelling have lacked relevance to the clinical circumstance. For instance, localized cold injury to the brain or intravascular injection of triethyl tin fails to relate to any of the many situations causing swelling in the human brain. By contrast, as-

Spinal fluid creatine kinase in neurologic disease.

Abstract: THE ESTIMATION of tissue enzymes released into body fluids as the result of pathological processes often serves to indicate the presence of disease, and, in some cases, the serial determination of enzyme activity may aid in assessing the patient’s clinical course. Measurements of serum creatine kinase activity have proved to be of value in the diagnosis of myocardial infarction, muscular dystrophy, and p~lymyositis.~ Transient elevations of serum creatine kinase have also been reported following cerebral infarction,2 head injury, and meningitis.3 In the spinal fluid, increased levels of lactate dehydrogenase,4 glutamicoxalacetic transaminase,6 and creatine kinasee97 have been observed in a number of neurological disorders. However, in many reports, the temporal relationship to clinical events, such as epileptic seizures, was not considered. Creatine kinase is an enzyme that catalizes the reversible reaction: creatine phosphate + ADP creatine + ATP. It is present in highest concentration in skeletal and cardiac muscle but considerable quantities are present in brain, where at least half of the total activity is present as a soluble cytoplasmic enzyme.8 Creatine kinase is believed to be primarily involved in supporting the level of adenosine triphosphate required to maintain the membrane potential of nervous tissue.0 It has been shown by Dawson et a1.10 that creatine kinase is a dimer, composed of a combination of two subunits termed B and M, respectively. The ontogeny of the different forms vanes with the tissue and species, but generally the “braintype” isoenzyme (BB) appears earlier than tbe “muscle” type ( M M ) . A hybrid form (MB) may also be present and is especially prominent in heart muscle. The enzyme activity in brain is thus characterized by a distinct isoenzyme which can be demonstrated by electrophoresis. The brain-type isoenzyme is also found in peripheral nerve and small amounts are also present in other tissues.11 The isoenzyme found in spinal fluid corresponds to that of brain, and the level of creatine kinase in spinal fluid, like many other enzymes, is independent of both serum enzyme activity and spinal fluid protein.12J3 The present study evaluates the potential clinical application of determinations of spinal fluid creatine kinase activity and demonstrates, by electrophoretic and immunological techniques, that the isoenzyme present in spinal fluid is the brain type.