Robert J. Joynt

Brain swelling of unknown cause.

PATIENTS exhibiting evidence of increased intracranial pressure and suspected of harboring brain tumors continue to present a challenge to the neurologist and neurosurgeon. In 1939 Sahs and Hyndman,l reporting upon experiences with five cases in which this syndrome presented, postulated that they were dealing not with serous meningitis, hydrocephalus, or encephalitis but with brain edema of unknown cause. Since then 17 additional cases have been encountered. These have been studied more thoroughly than was feasible in the earlier cases. In the present communication microscopic observations and long-term follow-up studies are emphasized. These cases have been variously designated pseudotumor, serous meningitis, serous arachnoiditis, chronic arachnoiditis, otitic hydrocephalus, toxic hydrocephalus, and so on. Before the advent of ventriculography a great deal of confusion attended attempts to identify the condition, and present day understanding of the pathogenesis of the disorder has been delimited by the fact that for the most part we are dealing with a nonfatal process. Quincke2 appears to have been one of the first to recognize the condition. He reported ten cases of “serous meningitis” and emphasized that the signs of increased intracranial pressure were associated with clear spinal fluid. A review of his series indicates that the application of modern diagnostic technics probably would have excluded several of his cases. Warrington3 reviewed the literature up to 1914 and expressed the opinion that the most common associated condition is otitis media. He called attention to the possibility that toxins circulating in the blood stream are responsible for the intracranial disorder. A critical review of his cases suggests that he was dealing with a rather heterogeneous group of conditions. Passot* suggested that the disorder might be considered a hypertensive state and mentioned that the condition is more common among children and adolescents than adults. He described the clinical picture as characterized by progressive headache, drowsiness, papilledema, and clear spinal fluid under increased pressure and having normal constituents. Passot believed that the condition was produced by an excess of fluid in the

Low spinal fluid pressure syndromes.

THE MECHANISMS of production and the factors participating in the control of cerebrospinal fluid dynamics have been the source of many intriguing studies. That cerebrospinal fluid issues from the choroid plexus was suggested by Cushing,l who observed the appearance of drops of fluid on the surface of the choroid plexus during surgery. Dandy2 provided further evidence when he occluded the outlet of one lateral ventricle and produced a unilateral ventricular dilation. Such observations, however, were not universally accepted, and other sources of cerebrospinal fluid were described.3.4 The accumulated evidence from numerous experimental and clinical studies on the problem has now given most support to the theory that the choroid plexus certainly represents the most important site of fluid formation. After formation, many and vaned factors are responsible for maintaining an equilibrium, so that the relationships of the intracranial contents in their rigid skeletal container remain relatively constant. With certain disturbances of these regulating mechanisms, clinical syndromes of cerebrospinal fluid hypertension or hypotension appear. Those entities associated with intracranial hypotension are the subject of this report. It has long been known that clinical symptoms could result from alterations in intracranial pressure. H o ~ e m a n , ~ in 1909, provided one of the original reports on headache from cerebrospinal fluid hypotension after spinal anesthesia. Thereafter, many reports conceming the various forms of intracranial hypotension and its management appeared in the foreign literature. A classification of low spinal fluid pressure syndromes might be listed as follows: [ 11 spontaneous or primary, [2] postoperative (cranial), [3] after head trauma, either with or without manifest external loss of cerebrospinal fluid, [4] after lumbar puncture or nerve sleeve

THE MEMOIR OF MARC DAX ON APHASIA.

THE ASSOCIATION of aphasia with right hemiplegia is now regarded as one of the verities of clinical medicine, There are well-known but infrequent exceptions, almost all of them occurring in left-handed patients. It is remarkable that the almost constant relationship of aphasia and right hemiplegia was not recognized generally until the last half of the 19th century. Perhaps, as has been suggested by Benton and Joynt,l this correlation was not made because it made little “sense.” Even today, its basic psychoneurological significance eludes us, although there has been much theoretical speculation. The discovery of this association is usually ascribed to B r ~ c a , ~ ? ~ but this distinction is often dimmed by an accompanying mention of Marc Dax’s earlier contribution in 1836, a quarter of a century before Broca’s first observation. Dax’s memoir is not only interesting in that it is the first mention of the role of the left hemisphere in the function of speech but also because it raises once again the problem of “priority” in scientific observation. Marc Dax was born in 1770 and died in 1837. He studied medicine in Montpellier, his graduate thesis being an interesting survey of the incidence and nature of the diseases occurring over a five-year period in the small town of Aigues-Mortes. As Gibson4 has recently pointed out, in this thesis Dax called attention to the occasional occurrence of postseizure focal paralysis in some children he observed. This observation preceded by many years those of Bravais and Todd who are usually credited with the first descriptions of the phenomenon. Dax had a keen interest in the study of language, and this may account for the special attention which he paid to language disturbances. In 1836, one year before his death, he wrote a paper5 on the association between aphasic disorders and lesions of the left hemisphere for presentation at a regional medical congress at Montpellier. The paper was not published and, as will be seen, there is no evidence that Marc Dax actually presented it at the congress. When it was belatedly submitted for publication in 1865 by his physician-son, Gustav Dax, four years after Broca’s initial observation,Z it initiated a controversy about priority which has persisted up to the present day. At the same time, together with his father’s memoir, Gustav DaxG published a summary of his own observations and views on aphasia. Since an English version of the memoir by Marc Dax is not available, a full translation of it is presented below:

Behavioral and pathological correlates of motor impersistence

MOTOR INPERSISTENCE is the term which has been suggested by Fisher’ to denote the inability of some brain-damaged individuals to sustain certain volrintary motor acts that have been initiated on verbal command. Hughlings Jackson’s2 well-known observation that some aphasic patients cannot protrude their tongue or direct their eyes on verbal command perhaps may be considered to represent an extreme form of this phenomenon. Oppenheim,3 Roth? Lewandowsky,5 Pineas: Schilder,’ and Zutt8 have previously reported instances of inability either to close the eyes or to maintain them closed when requested to do so. More recently, BerlinU has noted that many brain-damaged patients were unable to keep the eyes closed, the mouth open, or the tongue protruded for more than thirty seconds. The most extensive investigation of the phenomenon of motor impersistence has been reported b!. Fisher.’ He considered the main features of the syndrome to be the inability to: (1) keep the eyes closed; (2) maintain the tongue protruded; (3) fiu gaze centrally; (4) deviate the eyes persistently to the left; (5) hold the breath; and (6) keep the mouth open. The patients could initiate these motor acts without difficulty but could not sustain them. Fisher also noted inability to inhibit eye movements during the confrontation test, a tendency to look toward the part of the body undergoing sensory testing, and an occasional inability to maintain a steady hand grip when tested for strength. He did not consider these latter phenomena as central features of the syndrome, but rather as further expressions of the inability to maintain a fixed motor set. Fisher found that ten patients with motor impersistence had a lesion of the nondominant hemisphere, as indicated by a left hemiplegia. He emphasized that not all patients with left hemiplegia manifest motor impersistence and

Neuropeptides in aging and dementia

Although senile dementia of the Alzheimers type (SDAT) is a common disease associated with advancing age, recent studies have suggested that SDAT should not be considered synonymous with old age but a disease process separate from normal aging. This study examined the morphology of two neurochemically-defined neuronal populations (i.e., neurophysin, somatostatin) in the cortex and hypothalamus to determine if structural changes in these neuropeptide systems associated with advancing age are similar to those seen with SDAT. Our findings suggest that morphological changes consistent with neuronal degeneration occur in somatostatin but not neurophysin-containing neurons in cases diagnosed to have SDAT, and these structural changes are different from those seen in aged brain without central nervous system disease. These data support the concept that senile dementia of the Alzheimers type is not a single neurochemical related disease, but may be associated with anatomical lesions and biochemical imbalances among a number of neuropeptide and neurotransmitter systems.

Mechanism of production of papilledema in the Guillain-Barre syndrome.

THE PRESENCE of increased intracranial pressure and papilledema in cases of the GuillainBarri? syndrome (infectious polyneuritis, infectious neuronitis, encephalomyeloradiculitis) has been reported a number of times.l-13 Judging from the paucity of such case reports, it appears that increased cerebrospinal fluid pressure and papilledema rarely occur with the Guillain-Barr6 syndrome or are frequently overlooked. However, the mechanism of its production when present raises points of theoretical and ractical importance. Drew and

Functional significance of osmosensitive units in the anterior hypothalamus

PROPER REGULATION of the intake and output of water is one of the most essential functions performed by the body in adjusting to its environment. The role of the central nervous system, particularly in regard to the antidiuretic hormone, in this function is well established. Thus, the site of production, the chemical nature, the pathways for transport, and the physiological action of the antidiuretic hormone are well known.1 How the central nervous system responds to various internal and external environmental influences to effect the appropriate release of the antidiuretic hormone for homeostasis is not as well elucidated. The concept of “osmoreceptors” has been introduced by Verney2 to explain part of this mechanism. He concluded, along with Jewell,3 that these receptor elements were in the region of the anterior hypothalamus and were responsible for monitoring the osmolarity of the blood and then determining the rate of antidiuretic hormone release by the posterior lobe of the pituitary. Verney2 showed that the osmoreceptors reacted differently to different solutions. Hypertonic saline, for instance, had a greater effect than hypertonic glucose in releasing the antidiuretic hormone and inhibiting urine flow. This difference, Verney postulated, was due to the different permeability of the receptor elements to various solutions. Jewell,4 acting on the original observation of Verney,2 suggested that the neurons in the hypothalamus, especially in the supraoptic nucleus, might be these receptor elements. Presumably, their increased activity would then correlate with an increase in the release of the antidiuretic hormone. Recently, unit activity, presumably of a

Changes, People, Comments

New Chair named at Creighton University Sanjay Singh, MD, was named Chairman of the Department of Neurology, Creighton University School of Medicine, Omaha, NE. Dr. Singh plans to expand the neurology services at Creighton to provide stateof-the-art care to patients with neurologic disorders. He will also be starting the Creighton Epilepsy Center to provide comprehensive care to epilepsy patients in the region. Singh will become medical director of neurologic services at Creighton University Medical Center, and serve as a neurologist with Creighton Medical Associates and as a professor of neurology with the School of Medicine. “Dr. Singh is a renowned neurologist, and I am excited to have him join Creighton University’s School of Medicine and Creighton Medical Associates. His vision and abilities will be a driving force for the growth and development of Creighton’s Department of Neurology,” said Rowen Zetterman, MD, Creighton Medical School Dean. Singh has served as program director of the joint Creighton-UNMC neurology residency program since 2008. He has been named teacher of the year more often than any other faculty member in the history of the residency program. Singh joined the faculty of University of Nebraska Medical Center (UNMC) in 2002. He is founder of the Nebraska Epilepsy Center and was Vice Chairman of education for UNMC’s Department of Neurological Sciences. In 2009, Singh was honored with the prestigious A.B. Baker Teacher Recognition Award by the American Academy of Neurology. In 2007, he earned the Chancellor’s Gold U Award/Kudos Award from the University of Nebraska Board of Regents for his commitment to improving the lives of epilepsy patients and his contributions to the field of epilepsy. Dr. Singh’s research focuses on the medical and surgical treatment of epilepsy patients.

Meningiomas in a mother and daughter. Cases without evidence of neurofibromatosis.

THE FAMILIAL OCCURENCE of meningiomas without evidence of neurofibromatosis was first reported by Gaist and Piazza,’ who found this type of tumor in a brother and sister. They could discover no previous similar instance, nor could w e in a subsequent survey. We have encountered typical and similar meningiomas in ;I mother and daughter. While it is possible that, in both circumstances, the familial occurrence of meningiomas represents a simple coincidence, this report is made to add to the body of information relative to familial and hereditary aspects of neoplasia.

Neurogenetics and Primary Care

The application of molecular genetic techniques to the study of disease is generating astounding advances in our knowledge of basic mechanisms, diagnosis, and treatment. This is true in all fields of medicine but is particularly heartening in the study of neurologic disorders. These disorders often have long-term and devastating effects, and diagnosis and treatment have been limited. Many of the disorders are rare, but some, as Alzheimer disease (AD), are increasing in occurrence as the population ages. The lay press has, appropriately, seized on this area as one of the new and exciting frontiers in medicine. The reports have, at times, proposed a quicker and brighter outcome than can be achieved. The result is a patient population eager for information from their doctors. It is difficult for specialists in the field to keep up with all the new information. For example, in the last few months, gene sites have been identified and the genes characterized for most of the early onset familial cases of AD. [1-3] Most scientific journals have one or more articles dealing with genetics, and newer journals are created that deal only with genetics. The new studies often use new and complicated techniques and are explained in very specialized terms. A simple demonstration of the rapid output of scientific information in this area is to access the Grateful Med system of the National Library of Medicine and note the number of offerings on the genetic aspects …