Arden F. Reynolds

4′‐Demethyl‐epipodophyllotoxin‐β‐D‐thenylidene‐glucoside (PTG) in the treatment of malignant intracranial neoplasms

Twenty evaluable patients, 19 with primary intracranial neoplasms, were treated with intravenous PTG at weekly doses of 100 mg/m2 to 130 mg/m2 in a Phase II study. A total of 63 courses (6–8 doses/course) was administered. Antineoplastic activity was demonstrated by objective neurologic improvement in 5 of 13 patients with progressive neurologic findings at the outset of therapy. Of the remaining 7 asymptomatic patients, there has been a median progression‐free interval of 15+ months, with 5 patients remaining on study. Anemia and mild leukopenia, the most frequent toxicities, were clinically insignificant in 12 previously untreated patients. Among 8 patients with extensive prior chemotherapy, pancytopenia required discontinuation of therapy in 1 and decreased frequency of administration in 2 others. PTG is presented as an effective drug, with minimal toxicity, for the treatment of intracranial neoplasms. It would appear to offer potential as an agent for Phase III trials as well as a mode of therapy for those patients no longer able to tolerate nitrosoureas, or with disease progression on nitrosoureas.

Bleeding patterns from ruptured intracranial aneurysms: An autopsy series of 205 patients

The autopsy records from 205 patients who died from ruptured intracranial aneurysms were reviewed. Special emphasis was placed on the cause of death and the time after rupture that death occurred. One hundred and sixty-eight patients (82%) died within one week of their last aneurysmal rupture. Eighty-eight died within one week of their initial rupture. Massive subarachnoid hemorrhage was the cause of death in 53% and localized hematomas in 14%. Eighty patients died within one week following a subsequent rupture. Intracranial hematoma was the cause of death in 87%, with 31% harboring a localized mass potentially amenable to surgical therapy.

Left thalamic hemorrhage with dysphasia: A report of five cases

Abstract A specific type of “thalamic speech” is being recognized with increasing frequency. Paucity of spontaneous speech, fading vocal volume, anomia, perseveration, and neologisms, with intact comprehension and word repetition, characterize the speech disorder associated with thalamic lesions. Nine cases of left thalamic hemorrhage and speech disturbance have been reported previously. This report details the speech, neurological, and neuroradiological findings in five additional cases of thalamic hemorrhage with dysphasia.

Trapped fourth ventricle in coccidioidal meningitis.

A 4-year-old girl with known coccidioidal meningitis developed posterior fossa signs. CT scanning revealed a large fourth ventricle. Injection of contrast medium into the lateral ventricles revealed free flow into the fourth ventricle, and injection into the fourth ventricle revealed no flow into the aqueduct or third ventricle. The posterior fossa signs cleared after shunting of the fourth ventricle. A one-way aqueductal valve resulting from the ventricular inflammation is hypothesized.

A complication of nasogastric intubation: intracranial penetration.

A patient with severe maxillofacial trauma had a nasogastric tube inserted into the intracranial cavity. Two such case reports were found in the literature and in both instances the patients expired. The present patient is believed to be the first who survived intracranial passage of a nasogastric tube.

Intracellular recording during focal hypothermia of penicillin and alumina experimental epileptic foci

Abstract Intracellular records were obtained from penicillin and alumina experimental epileptic foci. The membrane of glia and neurons in the penicillin focus depolarized significantly more than those in normal cortex (20). The firing pattern of neurons in penicillin foci changed markedly with small temperature decrements. The depolarization shiffs and surface EEG spikes ceased at 33-32 C, returning as the cells were rewarmed. In the alumina focus, glial depolarization was the same as that of normal cortex. Neuronal membrane, in the alumina focus, followed the same pattern as that of normal cortex with initial hyperpolarization, plateau depolarization, postcool hyper-polarization, and return to precool levels. Action potential duration increased significantly greater than that in normal cortex with the rising phase more prolonged in the penicillin focus and the falling phase more prolonged in the alumina focus. Models are proposed to explain the observed behavior as impaired passive Na flux and impaired active NaK pumping in the penicillin focus. Impaired K flux and a greater magnitude of electrogenic NaK pumping are the neuronal membrane abnormalities in the alumina focus. These experimental foci, thus, contain “epileptic” cells with intrinsic membrane abnormalities, but the nature of the membrane abnormality is different in the two models.

Intracellular recording during focal hypothermia in cat pericruciate cortex.

Abstract Intracellular records were obtained from both glia and neurons in cat pericruciate cortex during focal hypothermia induced by a Peltier device. Glial membrane potential varied inversely and linearly with temperature. For 28 glia, the mean depolarization was 16.8 ± 7.0 mv for a temperature decrement of 5–6 C. Glial input resistance varied inversely and reversibly with temperature with a Q10 of 2.5. Neuronal membrane initially hyperpolarized 4.5 ± 3.3 mv until 3 min after the temperature decreased below 30 C. At that temperature and time a plateau depolarization occurred with a magnitude of 14.7 ± 5.5 mv. During rewarming, the membrane again hyperpolarized 5.9 ± 4.0 mv with return to precool values on complete rewarming. Action potential firing patterns also changed with hypothermia. The regular firing pattern was supplanted by a doublet, triplet, and quadruplet mode during the period of initial hyperpolarization. Tonic firing occurred on the upramp of the plateau depolarization and the multiple spike mode returned during the postcool hyperpolarization. Models are proposed to explain the glial depolarization with hypothermia as a result of decreased glial NaK pumping with a resultant increase in extracellular K. Neuronal hyperpolarization was a result of accelerated electrogenic NaK pumping in response to the increasing extracellular K. The tendency to the multiple spike mode is explained as a result of quantitative differences in somatic-dendritic interactions.

Single pyramidal-tract fiber analysis of neocortical propagated seizures with reference to inactivation responses

Abstract Intracellular records from pericruciate pyramidal-tract cells and extracellular records from ipsilateral medullary pyramid pyramidal-tract axons were obtained during major propagated neocortical seizures initiated by repetitive electrical stimulation of the homotopic contralateral pericruciate cortex. Comparisons of the soma-dendritic with the axonal responses during the ictal event was possible because of the close temporal correspondence between these and cortical surface EEG. During seizures, the majority of pyramidal-tract cells responded with “inactivation responses” when the soma-dendritic membrane depolarized by 25–30 mv above the pre-ictal steady state value. However, the axonal output of the pyramidal-tract cells consisted of high-frequency bursts of spikes during all phases of the ictal event. It is suggested that axonal recordings more accurately reflect the neuronal output during major neocortical seizures and that inactivation responses of neocortical neurons are due, in large part, to the trauma of microelectrode penetration.

Postpartum acute subdural hematoma; a probable complication of saddle block analgesia.

The author present a patient who developed an acute intracranial subdural hematoma approximately 35 hours after an uncomplicated delivery under saddle block analgesia. The proposed mechanism is that of cerebrospinal fluid efflux through the lumbar puncture site during uterine contractions and straining; shift of the intracranial structures, especially veins; venous hypertension; venous rupture; and subdural hematoma formation.

Jejunoileal bypass: a reversible cause of dementia.

Neurological complications consisting of recent memory loss, visuospatial disorientation, and poor concentration disabled three patients years after a jejunoileal bypass for morbid obesity. The metabolic evaluation and computed tomography gave normal results. The neurological dysfunction cleared completely after reconstitution of normal intestinal anatomy. Neurological recovery was documented by formal neuropsychological testing.