Hypotheses concerning the etiology of Alzheimer’s disease are numerous but perhaps two of the most probable involve either an unconventional infectious agent of the scrapie, Creutzfeldt-Jakob family or an error in gene expression. Strong circumstantial evidence supports both hypotheses; however, definitive evidence will require an extensive understanding of the molecular biology of this common cause of senile and presenile dementia.

Positron emission tomography provides a method for the quantitation of regional function within the living human brain. Studies of cerebral metabolism and blood flow in patients with Huntington’s disease, Parkinson’s disease and focal dystonia have revealed functional abnormalities within substructures of the basal ganglia. Recent developments permit assessment of both pre-synaptic and post-synaptic function in dopaminergic pathways. These techniques are now being applied to studies of movement disorders in human subjects.

Awake, unrestrained monkeys were trained to reach out with the forelimb and touch a button. Extracellular spike trains were recorded from pairs of neurons in contralateral precentral cortex with the same or separate microelectrodes. The neurons were located in the same or different functional columns as defined by intracortical microstimulation and passive sensory stimulation. Cross correlation analysis showed patterns consistent with synaptic excitation and/or inhibition between members of the cell pairs during the voluntary movement. The strength of correlation was inversely related to distance between columns, with the strongest correlations found between cells within the same column. Inhibitory correlations were virtually restricted to cell pairs within a single column. Temporal analysis showed that direct synaptic interaction and shared input patterns could be clearly distinguished in this physiologic setting. Spatial analysis indicated that shared input was concentrated among columns in the same and adjacent joint controlling zones as well as within a single column. No directional preference of shared input was present, a finding which was consistent with the observed nested organization of the forelimb area.

Simultaneous extracellular unit recordings were made from each cell of 237 pairs in two awake monkeys, during a voluntary reaching movement of the forelimb. The cells were located in contralateral precentral cortex and functionally coupled to single forelimb joints, as indicated by intracortical microstimulation and passive sensory stimulation. Cross correlation analysis showed that 72 of these pairs exhibited significant event-related correlation over periods of up to 780 ms, comparable to and coincident with the forelimb movement. Spatial analysis showed that such correlation extended across contiguous portions of all four forelimb joint zones of precentral cortex, over distances up to 3.5 mm. No preferred direction of correlation was observed. The data confirm the previously described nested organization of the forelimb area of precentral cortex. Findings are discussed in terms of mechanisms by which columns of neurons in motor cortex participate in the reaching movement.

High resolution ultrasound has been used intraoperatively on forty-five patients with various intracranial lesions. The technique is quickly and easily carried out under sterile conditions in the operating room. Successful localization of both primary and metastatic tumors of various sizes, depths and consistencies have been made prior to extirpation or biopsy. Several of the biopsies were done through small burr holes. Arteriovenous malformations, abscesses, bone fragments from trauma, gliotic epileptic foci and ventricles for shunt placement have been readily found. No significant complications have been encountered. A new technique for localizing superficial lesions is described. An overall reduction in operating time and unnecessary trauma to the patient has resulted from more accurate intraoperative localization of intracranial lesions with real time ultrasound.

The management of pineal region tumors has changed considerably since the introduction of microsurgery and CT scanning. Analysis of our own series of 36 patients, comparing those treated in the pre-CT scan and microsurgery era with those treated afterwards, shows the important role these two techniques play. Current controversies in treatment and our own approach to management of pineal region tumors are discussed.

Twenty patients with chronically progressive multiple sclerosis (MS) were randomised in a double-blind controlled study to assess the efficacy of plasma exchange therapy. All patients were immunosuppressed with prednisone and azathioprine and underwent either plasma exchange or sham apheresis. The 10 patients in each group were similar in age, sex, duration of disease and degree of disability. Clinical and laboratory responses were assessed immediately following the course of exchange or sham therapy, and 3 to 6 months later, by individuals blinded to the type of therapy administered. Although modest improvement was suggested on clinical examination in 7 of 10 patients exchanged and 3 of the 10 sham treated group, this was transient and was not accompanied by any change in disability status scores. No differences in abnormal laboratory investigations were demonstrable between the two patient groups following therapy. We conclude that plasma exchange therapy using this protocol is unlikely to be of clinical benefit as an adjunct in the management of chronically progressive M.S.

Cough syncope is a more common complication of childhood asthma than formerly recognized. We report twelve children with typical cough syncope who were identified in a pediatric clinic over a period spanning seven years. The condition may be confused with epilepsy because of frequently associated brief clonic convulsive movements during the height of the cerebral anoxia. Cough syncope is readily distinguished from epilepsy by a thorough history. The management and prevention of cough syncope is directed at the aggressive control of bronchospasm in children with asthma.

Among 38 children with pseudotumor cerebri only 3 cases were due to ear disease or its complications. The commonest cause was a refeeding syndrome either due to nutritional deprivation or as an early finding in the treatment of cystic fibrosis. It is uncommon to find the cause of pseudotumor in older children but in those under 6 years the cause was found in 85%. Because of the adverse effects of steroids we use this treatment in the more resistant cases.

Advances in fetal diagnostic techniques have opened many areas to prenatal anatomical scrutiny. Intrauterine hydrocephalus and ventriculomegaly are conditions which are readily diagnosed. Fetal intervention has been undertaken in humans in order to minimize the craniofacial disfigurement and to maximize the growth potential of the brain. To justify such an approach, the significance of all anomalies should be recognized prior to treatment. The authors have reviewed 41 cases of hydrocephalus diagnosed in utero in order to define associated anomalies and patient outcome.

75% of our personal series and 72% of the reviewed literature cases had other anomalies of the central nervous system. Other system malformations, some of which proved fatal, were seen commonly. Prenatal diagnostic techniques did not always reveal these additional problems.

The outcome of these pregnancies is not good. Approximately one third of these fetuses have survived to be treated postnatally and to be followed up clinically. Only 7.5% of this series were felt to have attained normal developmental milestones. The remainder of the survivors have various focal and/or global cerebral deficits.

Mu- and delta-opioid subtype receptor antagonists were tested in the mouse for their effects on vertical climbing activity, an index of striatal dopaminergic activity. The selective delta-opioid antagonist ICI 154 129 (1/1) by itself enhanced vertical climbing activity in a dose-related manner, whereas the mu-opioid antagonist naloxone by itself was inactive on climbing behavior. Naloxone increased the climbing-stimulant effect of I/I. Unstimulated vertical climbing activity was reduced, and all opioid-antagonist enhancement of climbing behavior was antagonized, by the competitive dopamine antagonist haloperidol in dose-related fashion. The observed motor-enhancement effect of a selective delta-opioid receptor antagonist is the first demonstration of physiologically-significant tonic activity on a central opioid receptor. Our observations suggest that 1/1 may be useful clinically in striatal dopamine-deficient disease conditions such as parkinsonism.

Adenoid cystic carcinoma, or cylindroma, usually presents in the salivary glands or in the upper respiratory passages. We report an unusual case of adenoid cystic carcinoma in a 45-year-old woman who presented with a three-year history of progressive right trigeminal sensory palsy, most pronounced in the second division. There was, in addition, a right trigeminal motor palsy and a partial right 6th nerve palsy. CT scanning showed only a small soft tissue mass spanning an enlarged right foramen ovale. Solid adenoid cystic carcinoma was resected from Meckel’s cave via a middle cranial fossa approach. A subsequent biopsy of the right maxillary antral mucosa found tumor tissue. We concluded that the tumor originated in the maxillary antrum and spread posteriorly along the infraorbital nerve to enlarge in the foramen ovale. Radiation to a total of 5,000 cGy was given. At 22 months there was neither radiographic nor clinical evidence of recurrence. At 30 months, the development of unsteady gait signalled the presence of recurrent tumor extending backwards from Meckel’s cave into the right cerebello-pontine angle.

A 72-year-old woman presented with painful proptosis of the right eye and a large destructive tumour of the middle cranial fossa. A diagnosis of IgDK multiple myeloma was made, based on histopathologic and immunologic studies of the biopsy. Biochemistry and bone marrow examination further confirmed the myeloma as IgDK type. The clinical, radiological, and pathological findings are presented. The patient was treated with radiotherapy with satisfactory results.

We report a 47 year old woman who was initially diagnosed as having multiple sclerosis. She has subsequently been found to be heterozygous for adrenoleukodystrophy (ALD). The female carrier state for ALD may be associated with intermittent symptoms and it is therefore important to consider ALD in patients diagnosed as multiple sclerosis.

Kenneth Livingston was born in 1914 in Pendleton, Oregon. He attended Stanford University and obtained his BA in 1936. His medical student days were spent at Harvard where he graduated MD in 1939.

His neurosurgical education began in 1942 at Strong Memorial Hospital, Rochester, N.Y.; then, after two years at the U.S. Naval Hospital in Oakland, California, he was appointed to the Attending Staff at the Lahey Clinic in Boston from 1946-1948. He returned to Oregon as Assistant Clinical Professor of Neurosurgery at the University of Oregon Medical School in 1948.