Positron emission tomographic (PET) data on local cerebral metabolic rates for glucose (LCMR) are reported for 32 regions of interest (ROI)s in cross-sectional studies on 57 patients with clinically diagnosed Alzheimer's disease (AD) and 20 neurologically normal controls, and in serial studies on 13 of the AD cases, including a familial, young-onset case where the diagnosis has been confirmed at autopsy. Extensive psychological testing was done on all the AD cases. Almost all cortical regions showed a significant decline in LCMR with age in the control subjects. There were the expected cortical metabolic deficits in AD and the serial studies showed a general increase in such deficits over time in 12 of the 13 cases. The regions showing the greatest declines with time in serial studies are the same as those showing the most severe deficiencies in cross-sectional studies. The young-onset case did not show a greater rate of metabolic decline than many of the older cases studied. Results on individual psychological tests tended to correlate with metabolic rates in multiple, rather than single, cortical regions, suggesting intact neuronal networks are required for good performance. The correlations with cortical metabolic activity found were of a sign indicating that the higher the metabolic rates and the better the left:right asymmetry index, the better was the performance.

We report two cases of Alzheimer disease (AD) — one of them familial — in which the patient also had amyotrophic lateral sclerosis (ALS), and one patient with familial AD who had a son with ALS. Three further cases of probable ALS were found in pedigrees of AD reported from the literature. It is proposed that this association is not coincidental, but may suggest an etiological factor in common.

Evidence for the astrocytic lineage in medulloblastomas rests largely on the detection of the glial fibrillary acidic protein (GFAP) from which intermediate filaments (IF) specific for astrocytes are assembled. Astrocyte progenitor cells from the mouse neopallium however express another IF protein, vimentin, before they acquire GFAP in vivo and in vitro. The purpose of the current study was to determine if cells obtained from a focally GFAP-positive posterior fossa medulloblastoma previously shown to acquire GFAP in response to dibutyryl cyclic AMP (dBcAMP), also express vimentin before expressing GFAP. More than 80% of cells in the tumor section contained vimentin while fewer than 1% of cells contained GFAP; occasional clusters of malignant GFAP-positive cells and clusters of cells negative for both vimentin and GFAP were also identified in the tumor. One hundred per cent of cultured cells in the first 10 passages from the tumor contained vimentin and no cells expressed GFAP. When cells were cultured in the presence of dBcAMP, Western immunoblotting showed an increase in vimentin which reached maximal values within 24 h followed by an increase in GFAP which reached maximal values at 72 h. The increase in vimentin followed by that of GFAP in cultured medulloblastoma cells has not previously been reported and suggests that most astrocyte progenitors which are derived from medulloblastoma and cultured in vitro may be at a developmental stage which corresponds to the proastroblast stage in the developing mouse brain. Most medulloblastoma cells in tumor sections in which vimentin is present but GFAP is absent may be in maturation arrest in vivo at the proastroblast stage of normal astrocyte development while vimentin and GFAP-negative islands of cells may represent astrocyte progenitor cells at an earlier stage of differentiation (e.g. glioblasts).

The National Cancer Institute of Canada Clinical Trials Group conducted a phase II trial of trimetrexate given in a daily × 5 intravenous bolus schedule every 3 weeks in patients with measurable recurrent anaplastic glioma and limited prior treatment. There were no responses in 14 evaluable patients. We conclude that trimetrexate, given as described, is not an active agent in this disease.

Intracortical microstimulation (ICMS) was used to map the primary motor cortex of four adult female baboons, anesthetized with a mixture of halothane and nitrous oxide and supplemented with sodium pentobarbital. The sequence of observed muscle contractions in response to ICMS provided evidence of an orderly mototopic representation of the tongue, face, hand, forearm and upper body. A zone of cortex unresponsive to microstimulation was consistently observed at the border between the face and hand representation of the mototopic map. This zone was observed in all four animals and was consistent over time. Repeated confirmations of the unresponsive nature of these regions were obtained both early and late in the same experiment. No motor-unit responses or muscle contractions were detected by electromyographic (EMG) recording during stimulation of the unresponsive zones. The absence of both visually observed and EMG-recorded contractions and the fact that muscle contractions could be elicited from adjacent regions of cortex with ICMS as low as 1-5 μA provide compelling evidence that the finding reflects a true physiological condition rather than an experimental artifact.

Methaqualone (Mtq; quaaludes or 'ludes) is a controlled substance, having a molecular structure related to the imidiazobenzodiazepine series of drugs, that has gained some notoriety recently due to its history of widespread abuse on the street. Users report experiencing peripheral paresthesia and transient numbness on body parts receiving dense cutaneous innervation (lips, fingertips, etc.). Since the receptive-field (RF)-sizes of many primary somatosensory (SI) cortical neurones are controlled by local, gamma-aminobutyric acid (GABA)-mediated inhibitory processes, we tested Mtq to see whether its clinical symptoms might have a basis in an action through central GABA-mediated synaptic processes. This report supports this contention and describes a likely pharmacological mechanism involved as one being related to the Ro 15-1788-sensitive benzodiazepine (Bzd) recognition site(s) of the GABA receptor complex.

During the investigation of intractable epilepsy, neuronal migration anomalies [NMA] were discovered in three patients. The first patient had abnormally positioned gray matter within the walls of both lateral ventricles. The second patient had a post operative cystic area in the right parietal-occipital lobes and an area of NMA within the right temporal lobe. The third patient had abnormally thickened gray matter in the right operculum. Long term CCTV-EEG monitoring of these three patients revealed ictal discharges originating from the area of abnormal gray matter in patients 2 and 3. PET scanning showed the areas of NMA in all three patients to have similar metabolic activity to normal gray matter. These cases illustrate the value of various imaging modalities and suggest some interesting physiology of a spectrum of neuronal migration anomalies.

Twenty-three children with acute transverse myelopathy (ATM) are reviewed. Antecedent minor trauma or exercise was reported in 10 patients. Despite a positive history in 7 patients no preceding infection was documented. Two patients had a history of less severe ATM followed by recovery prior to a second more severe episode. The most common initial symptom was back pain and the most prominent clinical signs were weakness, sensory level and sphincter disturbances. Myelography and CT myelography at presentation was performed to exclude a compressive lesion. Spinal cord enlargement was demonstrated in 6 of 21 cases. Magnetic resonance imaging (MRI) of the spinal cord, performed in one patient, showed enlargement of the cord. Poor prognostic features were severity of weakness at the time of maximum deficit and a delayed onset of recovery. Maximum motor recovery occurred at a mean of 6½ months but did not occur in one patient until 1½ years. Normal or good outcome was obtained in 64%.

Dysarthria, dysphagia and repeated aspiration in a 54-year-old woman diagnosed and treated for myasthenia gravis 7 years earlier were initially thought to represent a late exacerbation of myasthenia. A cervical mass invading the jugular foramen and causing multiple lower cranial nerve palsies was biopsied and found to represent invasive ectopic thymoma.

Les mots de Neurochirurgie et de Créativité, semblent à priori antagonistes. D'une part, le monde de cumul, d'érudition, d'exactitude, de codification de la science neurochirurgicale, et d'autre part, celui de la fantaisie et de la liberté de I'improvisation et de l'aléatoire.

Pourtant, devant la stagnation de certaines «récupérations» cérébrales, nous avons senti la nécéssité d'une démarche supplémentaire affranchie des normes traditionnelles.

The epidemiology of multiple sclerosis (MS) and the planning and interpretation of clinical therapeutic trials were the subjects of a symposium on MS held on June 13, 1989. Several speakers addressed whether MS is a genetic or an environmental disease. An environmental trigger would resolve the relatively low penetrance of the disease in susceptible individuals, although the alternative hypothesis that MS is a multigenic disease would also account for this observation. Clinical trials have to date failed to confirm the efficacy of any immunosuppressive or other agent in the management of progressive MS. Magnetic resonance imaging (MRI) appears to be highly sensitive for monitoring the activity of MS. Preliminary evidence suggests that MRI activity correlates with longitudinal clinical assessments of disability. Immunologic tests, while valuable in determining pathophysiology of MS, have not been strongly correlated with clinical outcome.

During the past 25 years, 77 giant pituitary adenomas have been treated surgically, including suprasellar extensions of type C in 66 cases and of type D in 11 cases. Non-secreting adenomas were present in 53 and secreting adenomas in 24 cases. All patients except 3 presented with significant visual field defects; including bitemporal hemianopia, superior quadranopia or unilateral temporal hemianopia, contralateral blindness in 73% of the cases, and one case with sudden bilateral blindness due to acute pituitary apoplexy. A single transsphenoidal procedure was carried out in 74% of the patients while 11 patients (7%) required re-operations for recurrent or residual tumor. Only 3 patients required a subsequent transcranial procedure. Complications included 1 CSF-leak, 1 empty-sella syndrome and 4 fatal post-operative hematomas. We prefer the transsphenoidal route even in very large or giant pituitary adenomas, since it allows rapid and adequate decompression of the optic nerves and chiasm, avoids major pituitary insufficiency in 60% of the cases and is associated with low morbidity-mortality rates.

The long-term follow-up of the transsphenoidal microsurgical treatment in 119 consecutively operated women with a PRL-secreting adenoma is presented. An apparent total removal of the tumor was achieved in 98 cases with an enclosed tumor (58 grade I and 40 grade II). In the remaining cases the removal was considered partial. The achievement of persistent normal PRL basal levels was verified in 61 patients (44 grade I and 17 grade II) who had an apparent total removal of the adenoma. In the 37 remaining patients who were thought at surgery to have had total removal we have distinguished two groups: 30 patients showed a “relapse” or “persistence” of PRL levels below 200 ng/ml without clinical and radiological signs of tumor regrowth, and 7 patients with a PRL level higher than 200 ng/ml who had evidence of PRL-secreting tumor recurrence.

Nineteen patients, seven women and twelve men, with macroprolactinomas characterized by extrasellar extension and basal prolactin levels above 6 U/I were treated with 10-20 mg bromocriptine daily in four divided doses for a mean period of 3.4 years (range 1.5-5.5 years). Plasma prolactin levels fell dramatically in all patients and values in the low normal range were obtained in sixteen patients. Tumor size was reduced by more than 75% in seventeen patients and by 50-75% in two patients. Tumor reduction was associated with the development of a partial empty sella in fourteen cases. In seventeen cases the pituitary became visible. Diminished visual acuity (six patients), bitemporal hemianopia (nine patients), unilateral and bilateral central scotomas (three patients) and oculomotor palsy (two patients) improved or normalized in all cases. Hypogonadism (all patients), hypothyroidism (nine patients) and hypocorticism (four patients) improved or normalized in most cases. It is concluded that in the medical treatment of macroprolactinomas 10-20 mg bromocriptine in four divided doses effectively reduces both plasma prolactin level and tumor size. The good results in this study may be related to the continued use of a fixed dose regimen of bromocriptine regardless of the plasma prolactin lowering effect.

A series of 100 prolactin secreting pituitary adenomas was reviewed and demonstrated an early cure rate of 85.2% with a cure rate of 89% if prolactin was less than 200 ng/ml. For macroadenomas the cure rate was 50% giving an overall cure rate of 71% for the entire group. When long term (> 5 years) followup was obtained a 17% incidence of recurrence was noted for the microadenoma group with a 20% recurrence rate for the macroadenoma group. Secretory dynamic studies were done shortly after surgery and then after a delay. Many showed a return to normal prolactin secretory dynamics suggesting that the underlying hypothalamic regulation is normal in most patients. Abnormal secretory dynamics at 6 weeks post operative testing were not predictive of which patients would relapse as many patients who had abnormal dynamics early did not relapse even during prolonged followup. Conversely a normal response to provocative testing did not preclude late relapse. A similar series of 40 consecutive patients with Cushing's disease was reviewed. Tumor was found in all but three cases. 84% of patients were cured and thus far only one patient (2.5%) has shown late recurrence with this occurring at 62/3 years following surgery with normal stimulatory dynamics present for five years. The implication is that hypothalamic regulation is normal in Cushing's disease as well. The differences in recurrence rates may be reflective of the aggressiveness with which one disease is treated, with the acceptance of a higher incidence of hypopituitarism as a consequence of more radical surgery for Cushing's disease.

Growth hormone (GH) serum levels in response to the administration of aminergic drugs and thyroliberine (TRH) were determined in a group of 34 acromegalics. Administration of bromocriptine (10 mg single oral dose) was followed by a decrease in GH below 60% control values in 35% of the cases. Administration of diazepam (10 mg single oral dose) to those cases not responding to bromocriptine induced a decrease in GH in 58% of the cases and an increase in GH in 42%. Administration of cyproheptadine (24 mg/day for one month) to those cases not responding to bromocriptine or with increased GH after the administration of diazepam, decreased GH in 75%, while increased GH in 25% of the cases. TRH 200 (Xg single I.V. dose induced increase of 128% GH basal level in 65% of cases (TRH positive) which correlated with more benign clinical course, decreased GH levels in response to bromocriptine, increased PRL levels, PRL-GH mixed secreting adenomas in immunohistochemistry studies, presence of granulated cells in electron microscopy studies and normalization of GH in the majority of surgically treated cases. By contrast, TRH negative cells correlated with aggressive tumor growth, lack of response to bromocriptine, normal PRL levels, pure GH secreting adenomas by immunohistochemistry, poorly granulated cells and lack of response to surgical treatment. Results suggest that there is more than one type of acromegaly that might be distinguished by the aminergic control on GH secretion.

Pituitary adenomas are considered rare tumors in the pediatric age group. The natural history in this age group is not well known, although many authors have suggested that pituitary adenomas in children tend to be extrasellar and invasive and that a subfrontal approach is mandatory in the majority. Our patients were part of a surgical series of 356 adenomas of all ages. We have divided these cases into three groups: the first consists of patients operated on before the age of 21 years (52 cases, 15%); the second, patients treated after the age of 20 but in whom the clinical history started before 21 years (52 cases, 15%); the third, patients with surgery and symptoms after 20 years (252 cases, 70%). Transsphenoidal removal of the adenomas was the initial procedure in all but one of these cases; a few required a second intracranial operation. In our series, pituitary adenomas in children were not more invasive than in other age groups.

In a series of 11 patients with classic pituitary apoplexy, two patients had the acute onset of bilateral blindness. After transsphenoidal decompressive surgery both patients had useful recovery of vision. Although impairment of neurologic function appears irreversible when central nervous tissue has been compressed to the point of total loss of function it would appear that the optic chiasm may be an exception to this experience. Our review of the literature and our experience suggests that decompression can be worthwhile even late in the course of this disease and visual loss should not be treated expectantly.

In 58 female patients with the primary empty sella (PES) syndrome, a study of the CSF dynamics was done by evaluating both the absorptive reserve by a lumbar infusion test at constant rate, and/or the ICP increase occurring during REM phase of nocturnal physiological sleep. In 33, prolactin (PRL) dynamics were also investigated evaluating both the response to sequential stimulating test with thyrotropin-releasing hormone (TRH) and metoclopramide (MCP) and/or the circadian variation of PRL levels. Impairment of CSF dynamics was found in the 84% who had a hormonal pattern characterized by an increase of the PRL response to TRH and MCP and a decrease of the PRL circadian variation. Twenty-one patients with impaired CSF dynamics underwent CSF shunting procedures with disappearance of the signs of intracranial hypertension. They also had restoration of normal PRL dynamics but the endocrine alterations improved only moderately. Altered CSF dynamics play a role in the pathogenesis of the PES syndrome. A correlation between elevated ICP and the hypothalamo-hypophyseal control of PRL secretion may exist.