The relationship between the morphology of astrocytomas and their prognosis is complex, with the localization of the tumour, the predominant cell type and the degree of anaplasia all playing an important part in determining the patient's future. Since many astrocytomas have a diversity of patterns, small needle biopsies taken from just one or a few areas may fail to elucidate the principal features of a given tumour. In addition to the astrocytoma subtypes listed in the WHO's International Histological Classification of brain tumours, new entities have been observed in the last few years. These include lipidized forms, such as the relatively benign pleomorphic xanthoastrocytoma and the highly malignant lipidized glioblastoma. Neoplastic astrocytes are capable of forming basal laminae and of phagocytosis, and often contain alpha-1-antitrypsin, features that may lead to confusing them with histiocytes. They may be arranged in a whorled pattern imitating meningiomas, their myxoid intercellular stroma may assume the morphology of cartilage and closely packed tumour cells in “epitheloid” astrocytomas come close to imitate metastatic carcinoma. Some astrocytomas contain cells indistinguishable from those of granular cell tumours of other tissues. The presence of reactive lymphocytes in astrocytomas and reactive astrocytes in malignant lymphomas can be the source of confusion between those two kinds of neoplasms.

Neuronal migration constitutes one of the major processes by which the central nervous system takes shape. Detailed knowledge about this important process now exists for different brain regions in rodent and monkey models as well as in the human. In the human, distinct genetic, chromosomal and environmental causes are known that affect neuronal migration, often in a morphologically distinct pattern, but the underlying pathological mechanisms are largely unknown. This review is intended to integrate our basic knowledge of the field with the accumulated intelligence on a large number of disorders and syndromes that represent the human part of the story.

The role of surgery in the management of acute spinal cord or cauda equina injuries remains controversial. The present study analyzed ten admission features and three outcome variables in 208 patients treated in an Acute Spinal Cord Injury Unit, 116 (56%) of whom underwent at least one spinal operation. The surgical and non-surgical groups showed no significant differences in the following seven clinical features: age, sex, distance travelled to the Unit, time interval between trauma and admission, type of accident, severity of injuries to the spinal cord, and severity of associated injuries. However, the two groups showed significant differences in level and type of vertebral column injury, and in the frequency of pre-existing spinal abnormalities. These differences were due to management policies which selected certain injuries for surgical or non-surgical treatment. One-third of the operative procedures were performed primarily for neural decompression, one-third primarily for reduction of bony structures and one-third for fusion. However, 95% of the operative patients had a fusion at the initial operation. Operative treatment was associated with a lower overall mortality rate (6.1%) than non-operative (15.2%), despite a higher frequency of thrombo-embolic complications in the surgical group. Overall, there was no difference between operated and non-operated patients in length of stay or neurological recovery. Surgical management of patients with acute spinal cord injury appears safe in terms of mortality rate and neurological recovery, but it has not been proven to improve the latter.

Studies which have attempted to define the outcome of multiple sclerosis (MS) have methodologic difficulties arising from patient referral biases and the length of follow-up required, which make prospective studies of an inception cohort unrealistic. Means to improve the validity of retrospective natural history studies are suggested. Results of existing series are summarized and compared. Survival is only rarely shortened by MS, but disability to the point of requiring aids for ambulation occurs in 30-70% of patients by 15 years from onset of symptoms. Disagreement as to the percentage of patients who are ultimately bedridden by MS likely arises in large part due to differences in patient ascertainment and follow-up. The need to develop early clinical markers for the patient at high risk for rapid development of major disability is stressed.

There is much current interest in excitatory amino acids and their receptors because of their postulated involvement in several disorders of the nervous system. They function as neurotransmitters, but can act as neurotoxins in some situations. They have been implicated in the pathogenesis of cerebral hypoxic/ischemic and hypoglycemic damage, in epilepsy, in some degenerative diseases, and in some forms of neurotoxin-induced cerebral dysfunction. These diseases may reflect abnormality in a system which has evolved to provide synaptic plasticity essential for learning and memory. The purpose of this paper is to explore the ramifications of such a hypothesis.

Sleep apnea (Ondine's Curse) is an uncommon but potentially fatal complication of percutaneous cervical cordotomy. The authors have had the opportunity to review the case histories of 6 patients who have died of sleep apnea following this procedure. In a series of 112 patients, 144 cervical percutaneous cordotomies were performed from 1977 to 1985 — 80 unilateral cordotomies and 32 staged bilateral cordotomies. Six (5%) patients died as the result of sleep apnea. Five patients (16%) died following bilateral cordotomy and one (1%) patient with pulmonary disease died following unilateral cordotomy. The clinical data of these 6 patients are presented and unique spinal cord pathology is described in this report. The pathophysiology of the sleep apnea syndrome is also discussed.

Controversy exists as to the neural network whereby peripheral arterial baroreceptor information is transmitted to vasopressin (VP)-secreting neurons of the hypothalamic supraoptic nucleus (s.o.n.). In vivo electrophysiological studies in the rat were undertaken to characterize the selective depression of VP cell activity consequent to activation of peripheral baroreceptors. Electrical stimulation of the diagonal band of Broca (DB) in the rat evoked a similar selective inhibition of vasopressinergic neurons of the s.o.n. Local application of bicuculline, a GABA antagonist, abolished both the DB-evoked and baroreceptor-induced inhibition of VP-secreting neurons. In addition, recordings from DB neurons antidromically activated from the s.o.n. displayed an increase in firing consequent to baroreceptor activation, coinciding with the suppression of firing in s.o.n. VP neurons. These observations collectively indicate that an intrinsic GABA projection arising in the DB cell group selectively inhibits vasopressinergic neurons of the s.o.n. and that this pathway mediates peripheral arterial baroreceptor activity that influences the release of VP in the neurohypophysis. These data may be of critical importance in our understanding the etiology of those forms of experimental hypertension where abnormalities in central baroreceptor pathways have been implicated but not proven.

Parkinsonism (P) with progressive dementia (D) of the Alzheimer type is recognized as a clinical variant of a form of amyotrophic lateral sclerosis (ALS) that has occurred in high incidence among the Chamorro people of the islands of Guam and Rota in the Marianas chain of Micronesia. The declining annual incidence, upward shifting of the age of onset, narrowing of the sex ratio, and occurrence of the disease among non-Chamorros, point to a disappearing environmental causation peculiar to the traditional culture of these islands. Evidence is presented in support of the proposal that heavy use of certain toxic plants, notably cycads, a traditional source of food and medicine for the Chamorro people, plays an important etiological role. Clinical and epidemiological approaches are offered to test for a relationship between ALS/P-D and long-latency plant toxicity.

In the three year period of 1982 to 1985, 152 patients with intracranial vascular malformations were referred to the Bicetre Hospital in Paris, France and the Toronto Western Hospital in Canada. Sixty-six patients with cerebral vascular malformations and 48 patients with dural vascular malformations underwent endovascular treatment. In 8 patients surgery was performed in combination with the embolization procedure. Detailed analysis of the angio-architecture of the vascular malformation reveals certain characteristics which may be of value in predicting the clinical outcome. Comprehensive data analysis and long term follow-up is necessary to assess the role of embolization in the treatment of intracranial vascular malformations.

A 17th century B.C. Surgical Papyrus known as “The Edwin Smith Papyrus” was published in facsimile and hieroglyphic transliteration with translation and commentary by James Henry Breasted in 1930. The Papyrus was acquired by Edwin Smith in Luxor, 1862. This document was conceived in the Pyramid Age (3000-2500 B.C.) and remains in material form from the 17th century B.C. It is of importance to the history of Neurology as it contains the earliest mention in oriental literature of (a) the brain and meninges (b) calvarial and cervical vertebral injuries in details of pathology, symptomatology, treatment and prognosis and (c) functional localization in the brain and spine. Most importantly, Papyrus Smith is a statement of the medical ethic of its time.

For more than 150 years, Chamorro natives of the Mariana Islands in the Western Pacific Ocean, have developed fatal paralysis in middle and later life, which we term amyotrophic lateral sclerosis/parkinsonism-dementia (ALS/PD). The cause of the disease might be exposure to seeds of the indigenous cycad. Motor system disease is induced in cynomolgus monkeys by feeding them beta-N-methylamino-L-alanine (BMAA), an amino acid present in cycad seeds. We believe that the cycad seeds which usually cause no immediate adverse symptoms when prepared and eaten as flour, or applied topically as medicine, can give rise to widespread and severe nerve cell degeneration after a latency of many decades. Furthermore, it may be that only a single exposure to this potent but silent toxin(s) can result in fatal neurological disease years later.

Thirty cases of Alzheimer's disease and 30 age-matched controls were studied to determine the incidence of cerebral amyloid angiopathy and its relationship to age, neuritic plaque formation, and amyloid plaque content. Cerebral amyloid angiopathy (CAA) was present in 86% of AD cases and 40% of age-matched controls. Its frequent occurrence in AD is not merely a reflection of the advancing age of this group: it was seen only in the presence of neuritic plaques, regardless of age, and represents an integral component of AD. Neuritic plaques however, did occur in the absence of CAA in 17% of all cases. The amount of vascular and plaque amyloid tended to be of comparable severity in many cases, but significant discrepancies were observed, with preferential deposition of amyloid in either plaque or vessel. Our results suggest that neuritic plaque formation and amyloid deposition are linked genetically or etiologically, but independently expressed, without a cause-and-effect relationship.

We analyzed the charts and CT scans of 49 cases of civilian .22 caliber gunshot wounds of the brain admitted to the University of Alberta and Royal Alexandra Hospitals between 1975 and 1985. The average age of the patients was 30 years, 88% were males, 88% were suicide attempts. There were no deaths among patients with an initial coma score above 12 whereas the mortality rate was 85% for those admitted with a score of 7 or less. All those with fixed pupils on admission died. The overall mortality rate of 61% is comparable to that of other series of civilian gunshot wounds including those in which more aggressive surgical management was undertaken. We recommend that no treatment be given those cases with an admission coma score of 3 and/or fixed pupils and that simple scalp wound debridement be employed with those having a coma score of 7 or less. Tract exploration and retrieval of bullet fragments is not indicated, as retained fragments carry a very low incidence of complications (e.g. abscess formation). In patients in good condition (GCS ≥ 12) the management of intracranial hematomas should be independent of their etiology and approached aggressively.

Management of patients with symptomatic spinal metastasis is designed to (1) relieve pain, and (2) restore or preserve neurologic function. The surgical strategy must include provisions for decompression of the dural sac and nerve roots, and stabilization of the spinal column. The optimal surgical approach, whether from in front or from behind is determined by a number of factors including (1) tumour location, (2) spinal level, (3) fixation factors, (4) patient debility.

Six patients with an aortoiliac vascular disease and a peripheral neurological deficit are presented. Clinical and electromyographic findings revealed lumbosacral plexus, sciatic and femoral nerve lesions. A correlation is made between the level of the vascular lesion (aortic, aortoiliac or distally) and the type of peripheral nerve deficit observed. In a patient complaining of pain, weakness, or numbness in a leg, the differential diagnosis should include aortoiliac vascular disease. The peripheral neurological symptoms may be the initial manifestation of the vascular disease or may appear in the early post-operative period.

Using immunohistochemical techniques, we localized several glycoproteins of the extracellular matrix in paraffin-embedded sections of 4 normal brain and 38 primary intracranial tumour specimens. All specimens were positively immunostained to various degrees by monoclonal antibodies to type IV collagen and procollagen III and by antisera to laminin and fibronectin. Staining was consistently most intense at sites of contact between neuroepithelial and mesenchymal or leptomeningeal elements; there was no demonstrable staining within or between neuroepithelial elements in the neuropil. Tumour cells from meningiomas and from the sarcomatous portion of a gliosarcoma were positively immunostained for fibronectin and laminin. The integrity of the glial limitans externa was demonstrated by the positive linear reaction product produced by immunostains for type IV collagen and laminin, even in the most malignant gliomas. The deposition of extracellular matrix glycoproteins at the glial-mesenchymal interface observed in this study of primary human brain tumours is a manifestation of one of the interactions between tumour and stromal cells in the central nervous system. A loss of coordination and an alteration in the interactions between epithelial cells and stromal cells across extracellular matrices such as basement membranes are thought to be fundamental steps in the development and progression of cancer. Further characterization studies focusing on other markers of the extracellular matrix are needed to elucidate completely the function of this structure in the central nervous system.

A 40-year-old female with a recurrent mixed astrocytoma/oligodendroglioma was treated with intraarterial BCNU at six week intervals. Phosphorus magnetic resonance spectroscopy was performed before, and on two occasions after her third treatment.

Before treatment, phosphodiesters were 25% less than normal and intracellular pH was 7.14 (normal 6.97 ± 0.02). Eight hours following treatment phosphocreatine and phosphodiesters were reduced by ∼40% and pHi increased to 7.24. Thirty-two hours after treatment, phosphocreatine and phosphodiesters had reversed their decline, but pHi had increased further to 7.35. MRI and x-ray CT scans did not show any change during this period.

This study demonstrates that chemical changes can be observed in a glioma by magnetic resonance spectroscopy shortly after chemotherapy in a clinical setting and before changes are observable by imaging modalities. This approach evidently offers a possible means of monitoring the acute metabolic response of tumours to chemotherapy or other forms of treatment by a non-invasive repeatable quantitative method.

Acridine orange fluorochrome of nucleic acids was applied to sections of cerebral tissue from 20 patients showing acute or chronic reactive gliosis. The results were compared with the findings in 39 well differentiated and malignant astrocytomas. The orange cytoplasmic fluorescence of ribonucleic acid is lacking in reactive astrocytes of all ages including gemistocytes, but is uniformly present in astrocytoma cells. Acridine orange is a useful supplementary stain for distinguishing between astrocytosis and astrocytoma, paticularly for small cerebral biopsies showing scattered or diffusely infiltrating pleomorphic glial cells.