Raymond D. Adams

The inflammatory lesion in idiopathic polyneuritis. Its role in pathogenesis.

THE INFLAMMATORY LESION IN IDIOPATHIC POLYNEURITIS ARTHUR ASBURY;BARRY ARNASON;RAYMOND ADAMS; Medicine

The morbid anatomy of the demyelinative diseases

Abstract A demyelinative disease is one in which there is destruction of myelin sheaths with relative sparing of axis cylinders, nerve cells and supporting tissues, occurring usually in multiple foci within the central nervous system. The diseases which conform to these criteria are acute and chronic multiple sclerosis, acute disseminated encephalomyelitis, acute necrotizing hemorrhagic encephalomyelitis and Schilders diffuse periaxial encephalitis. Brain purpura and metachromatic leucoencephalopathy resemble the demyelinative diseases in some respects but because of significant pathologic differences probably should not be included in the group. The pathology of these diseases is described. Each of the demyelinative diseases exhibits distinctive pathologic changes from which the diagnosis can usually be made without difficulty. There are, however, rather impressive similarities that may be overlooked. The essential process in these diseases is a focal necrobiosis of nervous tissue which varies in degree from degeneration of myelin sheaths with sparing of the axis cylinders to an almost complete degeneration or necrosis of all elements of nervous tissue. Common to all of the demyelinative diseases is a tendency for this focal necrobiosis to occur in relation to small veins and to involve the white matter in particular. This latter feature suggests that some property of myelin determines the localization of the pathology. Exudates of inflammatory cells in the perivascular spaces is another important feature. Theories as to the etiology and pathogenesis of these diseases are evaluated in the light of the morbid anatomy.

Pregnancy and the Risk of Hemorrhage from Cerebral Arteriovenous Malformations

We conducted a retrospective analysis of 451 women with an arteriovenous malformation (AVM) of the brain to determine whether pregnancy is a risk factor for cerebral hemorrhages. A total of 540 pregnancies occurred among our patient population, resulting in 438 live births and 102 abortions. There were 17 pregnancies complicated by a cerebral hemorrhage. The hemorrhage rate during pregnancy for women with an unruptured AVM was 0.035 +/- 0.005 per person-year. The hemorrhage rate for nonpregnant women of childbearing age with an unruptured AVM was 0.031 +/- 0.002 per person-year. Pregnancy did not increase significantly the rate of first cerebral hemorrhage from an AVM (P = 0.35). We found that women with an AVM face a 3.5% risk of hemorrhage during pregnancy. Pregnancy is not a risk factor for hemorrhage in women without a previous hemorrhage. This conclusion assumes no selection bias exists in our study population; a bias would be introduced if the risk of fatal outcome after a hemorrhage were greater in pregnant women than in nonpregnant women.

Cerebro-hepato-renal syndrome of Zellweger: An inherited disorder of neuronal migration

SummaryA child afflicted with the hereditary cerebro-hepato-renal syndrome of Zellweger is reported. Important neurological features included: marked weakness and generalized hypotonia, recurrent seizures, and failure of development of visual, auditory or other sensory discriminations and “high-level” motor responses. Neuropathological study revealed a primary disturbance of development of the brain. The developmental disturbance consisted essentially of an incomplete migration of neuroblasts to form the cerebral cortical plate. The findings are discussed in relation to other types of cerebral dysgenesis. It is postulated that the precise disorder of neuronal migration in this disease delineates a specific step, probably mediated by a single protein, in the formation of the cerebral cortex. An additional finding, less certain of interpretation, is a widespread, diffuse degeneration of medullated nerve fibers in the cerebral white matter with phagocytosis of sudanophilic material by histiocytes and microglial cells.

Fabry disease Impaired autonomic function

Previous reports of extensive lipid accumulation within neurons of the autonomic nervous system in Fabry disease suggest an anatomicopathologic basis for the peculiar pain, diminished sweating, and gastrointestinal symptoms experienced in this disorder. To further assess autonomic function in Fabry disease, noninvasive clinical tests were performed on 10 patients. Diminished sweating was found in each; the loss was approximately uniform proximally and distally, suggesting sweat gland dysfunction rather than autonomic neuropathy. Impaired pupillary constriction with pilocarpine, and reduced saliva and tear formation were found in half the patients. Disordered intestinal mobility was demonstrated in the oldest patients. In all cases, the cutaneous flare response to scratch and intradermal histamine was diminished, and pruritus was not experienced. Signs of autonomic dysfunction are present in Fabry disease and correlate with the known lipid deposition in autonomic neurons.

Neurology and psychiatry: closing the great divide.

As we enter the next millennium, neurology and psychiatry are trying to define their future roles.1-5 In this context, we review the initially common, then divergent relationship between neurology and psychiatry. We trace the emergence of neuroscience over the last two decades that has informed both disciplines. We illustrate those recent advances that have fundamentally changed brain science, requiring the abandonment of several central dogmas while compelling improvement in reciprocal relationships. Based on these changes, we call for the introduction of new training curricula and accreditation criteria for both neurology and psychiatry and recommend more effective collaborations with neuropsychology, cognitive neuroscience, and neurosurgery. The scientific study of the brain and its relationship to complex behaviors began with Gall in the early 19th century.6 The anatomic studies of aphasia by Broca in 1861 and Wernicke in 1874 persuaded a number of scientists that the brain was the seat of intellectual competence as well as the potential site of mental problems.6 During the last half of the 19th century through World War II, figures from the ranks of European academia who engaged in the study of higher order mental dysfunction included Meynert, Liepmann, Pick, Oppenheim, Charcot, Korsakoff, von Monakow, Babinski, Janet, Freud, Jackson, Bleuler, Kraepelin, Bonhoeffer, and Alzheimer. All were considered to be neuropsychiatrists, interested in both neurology and psychiatry. Many held dual academic posts in neurology and psychiatry.6 Neuropathology arose from efforts, primarily based in Germany, to correlate changes in brain structure with mental illness.6 By the 1930s, many neurologic syndromes had been clinically defined and their neuropathologic bases identified.6 The elementary neurologic examination was refined with objective, consistent, and reproducible findings. Diagnostic tests such as CSF analysis and instruments such as the EEG were in place.2,6 These developments, as …

A STUDY OF THE NUTRITIONAL DEFECT IN WERNICKE'S SYNDROME: THE EFFECT OF A PURIFIED DIET, THIAMINE, AND OTHER VITAMINS ON THE CLINICAL MANIFESTATIONS

The salient clinical features of Wernickes syndrome (1) are partial to complete paralysis of extra-ocular muscles (most commonly the external recti), nystagmus, ataxia and mental disturbances. Postmortem examination reveals changes in the nervous structures adjacent to the third and fourth ventricles and the aqueduct. The lesions are characterized by varying degrees of necrosis of both nerve cells and nerve fibers with appropriate reactions of microglia and astrocytes, alteration of the small blood vessels, and in some cases, petechial hemorrhages (2-5). The syndrome is usually associated with chronic alcoholism and for that reason has sometimes been attributed to a neurotoxic effect of the alcohol; but the occurrence of the same clinical sequence in non-alcoholic patients with malnutrition (1, 2, 4-8) has directed attention to nutritional deficiency as the etiological basis. Moreover, similar pathological lesions have been produced in the rat (9, 10), fox (11, 12), and pigeon (3, 9, 13, 14), by maintaining these animals on thiamine-deficient diets.

The ultrastructural morphology of the muscle fiber in myotonic dystrophy

SummaryBiopsies from three patients with different clinical and pathological stages of myotonic dystrophy were studied by phase and electron microscopy. Large sarcoplasmic masses and spiral annulets were prominent in Cases 1 and 2 while in Case 3, featured clinically by atrophic weakness, they were infrequent. In the latter the residual fibers were either large and dystrophic or small and atrophic.Electron microscopically, nearly all components of the muscle cell, in places, were involved in the dystrophic or atrophic process, such as myofilaments, Z discs, triads, nucleic, mitochondria, and the sarcolemma. In addition, cytoplasmic cysts, multilammellated bodies, and lipofuscin granules were observed. The most characteristic feature of the disease were sarcoplasmic masses, filled with varying amounts of disoriented myofilaments and other sarcoplasmic components. Disoriented myofibrils often encircled the remaining core of normal myofibrils, thus forming the striated annulets (Ringbinden). Several other abnormalities, not previously reported in myotonic dystrophy or any other myopathy, were identified in slightly dystrophic as well as in severaly atrophic fibers. These were large, homogenous lacunes derived from the sarcoplasmic reticulum and peculiar geometric arrangements of terminal cisternae. The origin of some other structures remains obscure. The relation of the dystrophic process to segmental degeneration and atrophy, the principal histologic findings in Steinerts disease, is unsettled since segmental necrosis was not observed in our samples for phase and electron microscopy.ZusammenfassungDas Biopsiematerial von drei Patienten mit unterschiedlichen klinischen und pathologischen Stadien der myotonischen Dystrophie wurde phasenkontrast-und elektronenmikroskopisch untersucht. Beim 1. und 2. Fall waren “sarkoplasmatische Massen” und “Ringbinden” besonders zahlreich, während sie beim 3. Fall mit klinisch erheblich fortgeschrittener Muskelatrophie nur ausnahmsweise vorkamen.Elektronenmikroskopisch erschienen fast alle Elemente der Muskelfasern, zumindest an einigen Stellen, von dem atrophischen oder dystrophischen Prozeß betroffen: Myofilamente, Z-Streifen, Triaden, Kerne, Mitochondrien und Sarkolemm. Außerdem fanden sich cytoplasmatische Cysten, multilamellierte Körperchen, zahlreiche Lipofuscingranula und verschiedene andere abnorme Strukturen. Besonders kennzeichnend für die Erkrankung waren die “sarkoplasmatischen Massen”, die mit variablen Mengen von fehlorientierten Myofilamenten, aber auch von anderen Komponenten der Muskelzelle ausgefüllt waren. Die Ringbinden wurden von fehlorientierten Myofibrillen gebildet, indem sie meist kreisförmig die im Zentrum normal ausgerichteten Myofibrillen umschlossen. Einzelne Veränderungen, die bisher weder bei der myotonischen Dystrophie noch in irgendeiner anderen Muskelkrankheit nachgewiesen worden sind, konnten in leicht dystrophischen wie auch in hochgradig atrophischen Fasern nachgewiesen und identifiziert werden: Große homogene Lacunen, die sich vom sarkoplasmatischen Reticulum herleiten und eigenartige geometrische Anordnungen der terminalen Cisternen. Der Ursprung bestimmter anderer Strukturen blieb unklar.In unserem Material fanden sich keine segmentalen Nekrosen, so daß sich die Relation des dystrophischen Prozesses zur Zenkerschen Degeneration und zur Atrophie, den nach histologischen Untersuchungen wesentlichsten Befunden bei der Steinertschen Erkrankung, nicht eindeutig bestimmen ließ.

Brainstem auditory hallucinosis

We studied three patients with findings suggesting that auditory hallucinations may occur with lesions of the tegmentum of the pons and lower midbrain. The evidence was clinical (indicating location of the lesion), radiologic (CT), pathologic in one case, and physiologic (affirming integrity of the cochleas and auditory nerves). The condition is comparable with the Lhermitte peduncular-diencephalic visual hallucinosis.

Clinical presentations of vascular malformations of the brain stem: comparison of angiographically positive and negative types.

Clinical and radiographic features of 63 patients with a vascular malformation of the brain stem are described. On radiological grounds they were divided into two groups: one with angiographically visible lesions (AVAVMs), the other with lesions not seen angiographically, that is, occult (AOVMs). In the first group the initial clinical manifestation was due to haemorrhage in 20 of the 33 cases and consisted of a progressive neurological deficit in 12. In the second group 29 of the 30 initially presented with a brain stem haemorrhage. The latter was often characterised by development of symptoms over two days or more (16 cases), absence of headache (48 cases) and tendency to recurrence (20 cases). Clinical diagnosis was difficult in many cases especially in the AOVM group. Several of the patients were misdiagnosed as having multiple sclerosis. Clinical data in conjunction with magnetic resonance imaging were helpful in determining the nature of these lesions.