Cigarette smoking. A risk factor for hemorrhagic and nonhemorrhagic stroke.

Cigarette smoking habit was studied in 621 patients with stroke and in 573 control subjects using case control methods. There was an excess of smokers among the stroke group when compared with control subjects. Relative risks of cigarette smokers compared with nonsmokers, after adjustment for the possible confounding variables for subarachnoid hemorrhage, intracerebral hemorrhage, and cerebral infarction, were 4.5, 1.8, and 3.2 for men and 2.5, 1.3, and 2.3 for women, respectively. For all subtypes of stroke combined, the increased relative risk was related to the daily intake of cigarettes, the heaviest smokers having a higher relative risk than that for light smokers. The estimated increase in relative risk among smokers was 1.5 for each 10 cigarettes smoked daily in both men and women. We conclude that cigarette smoke may be an important preventable factor for both hemorrhagic and nonhemorrhagic stroke.

Implantation of human fetal ventral mesencephalon to the right caudate nucleus in advanced Parkinson's disease.

Disaggregated ventral mesencephalic tissue from single aborted human fetuses of 11 to 18 weeks' gestation was implanted stereotaxically into a consistent striatal site in 12 patients with advanced Parkinson's disease. All were receiving optimum levodopa therapy and were examined preoperatively and at 3,6,9, and 12 months postoperatively. Immunosuppression was not used. There were significant sustained improvements at 12 months in three patients; motor fluctuations were absent in two. There were modest group improvements up to 6 months, with increased quality of "on" and "off" phases, quantity of on times, and specific improvements in contralateral upper limb bradykinesia. Preoperative levodopa requirements were reduced to a mean of 64% at 6 months and 61% at 12 months. Deterioration below baseline ratings occurred in three of nine patients who had consistent follow-up to 12 months. Grafting of midgestational human fetal tissue can lead to improvement in Parkinson's disease. Individual disease severity may be critical, and further trials are needed to identify host factors influencing outcome.

Oligoclonal immunoglobulin G in acute subarachnoid hemorrhage and stroke.

Oligoclonal Ig bands were found in serum and CSF of 13 of 83 patients (16%) with verified subarachnoid hemorrhage (SAH). Serum Ig bands were more common in patients with SAH than in those with cerebral ischemia. The reverse was true with oligoclonal Ig bands in CSF. These patterns suggest that there are two different mechanisms and sites of IgG synthesis: an inflammatory process after acute stage of vascular damage and a latent immunologic process--ie, polyclonal B-cell activation by injury to the brain.

Alcohol consumption--a risk factor for hemorrhagic and non-hemorrhagic stroke.

PURPOSE: The risks of alcohol consumption and its association with stroke were studied in 621 patients with stroke and 573 control subjects using case-control methods. PATIENTS AND METHODS: Patients with stroke were subdivided into 193 with subarachnoid hemorrhage, 91 with intracerebral hemorrhage, and 337 with cerebral infarction. Data on recent alcohol consumption were obtained by questionnaire in patients with stroke and compared with data from an occupational screening survey in control subjects. RESULTS: Relative risks, adjusted for confounding variables, exhibited J-shaped associations with increasing levels of alcohol consumption classified into four categories--abstainer, 1 to 90 g, 100 to 390 g, and greater than or equal to 400 g weekly). The individual risks were 1, 0.7, 0.5, and 1.3 for subarachnoid hemorrhage; 1.0, 0.6, 0.5., and 2.5 for intracerebral hemorrhage, and 1.0, 0.6, 0.7, and 2.4 for cerebral infarction for men and women combined. CONCLUSIONS: The results suggest that low levels of alcohol consumption may have some protective effect upon the cerebral vasculature, whereas heavy consumption predisposes to both hemorrhagic and non-hemorrhagic stroke.

Direct interaction with target-derived glia enhances survival but not differentiation of human fetal mesencephalic dopaminergic neurons.

Regulation of the developing nervous system involves attraction, guidance and modification of innervating neurons by target cells through diffusible and membrane-related factors. The trophic effects from specific cell types remain to be investigated and characterized. In a series of experiments in which human fetal mesencephalic dopaminergic cells were co-cultured with target or non-target neurons or glial cells in direct or contiguous contact, we demonstrate that striatal glial cells (target-derived glia) can enhance dopaminergic neuron survival by up to 400% compared to either non-target cell co-cultures or mesencephalic controls. When in direct contact with striatal neurons, a greater proportion of dopaminergic neurons had a more differentiated morphology. The enhancement of dopaminergic neuron survival by target-derived glia appears to be mediated both by direct contact, possibly through target membrane-specific phenomena, and by diffusible substances, whereas non-target glia appear to exert the trophic effects predominantly through the latter mechanism. The finding that target neurons influence mainly dopaminergic neuron differentiation and target glia their survival indicates multiple, target cell type-specific regulation of innervating neuron development. These findings also have relevance to the establishment of neuronal cultures for neural transplantation.

Recovery of cellular activity in cryopreserved human foetal brain tissue.

Since long-term cryopreservation can cause losses in neural tissue viability and function a prerequisite would be the ability to monitor and promote functional recovery in donor tissue intended for neural transplantation. Rapid assessment of cryopreserved tissue's functional status prior to grafting is presently difficult in a clinical setting. A convenient indicator of functional status may be the level of DNA synthesis activity taking place in the tissue. Using immunocytochemical detection of incorporated bromodeox-yuridine we have quantified and compared DNA synthesis activity (expressed as proliferative capacity (PC)) in human foetal mesencephalic, striatal, cortical and cerebellar tissue before and after a 275-376 day storage in liquid nitrogen. There was a post-storage reduction in viability of 48-73% and in PC of 26-59%; the higher the PC before storage the greater the reduction after. Incubation of cryopreserved tissue with fetal calf serum resulted in 2-4-fold higher PC levels than serum-untreated controls and reached 80% of fresh tissue levels in mesencephalic cells after 3-4 h incubation. Assuming that quantification of proliferative activity is a practical indicator of the tissue's functional status, these findings suggest that treatment of the tissue with serum can largely restore the lost function caused by cryopreservation.

Susceptibility of human foetal brain tissue to cool- and freeze-storage.

Human second trimester foetal brain tissue was stored for a period of 1-6 weeks under various conditions in an attempt to evaluate factors influencing its susceptibility (cell loss) and survivability. Post-storage viability of mesencephalon, striatum, cerebellum and occipital cortex was assessed by a protocol combining vital staining with cell density counts so that tissue viability and cell loss could be evaluated simultaneously; tissue survivability was evaluated by cell culture. A significant amount of cell loss occurred after 24 h storage at room temperature, after one week at 4 degrees C and by two weeks at -20 degrees C in all structures; storage at -196 degrees C resulted in 17-21% cell loss at the end of a 6 week period. At -20 degrees C the cryoprotective effect of 20% FCS was equivalent to that of 15% FCS + 7% DMSO combined, suggesting potential use of serum in replacement of chemical additives. The procedure for removal of DMSO was critical to cell viability and survivability: single step dilution led to 27-39% greater cell loss than slow, multi-step dilutions. In comparison to fresh, non-stored tissue, immunocytochemical characterization of in vitro propagated stored tissue revealed no changes in the populations of major constituent cell types including neurones, dopaminergic neurones, glial and fibroblast cells. These results provide information on possible conditions under which transplant tissue can be satisfactorily stored depending on the prevailing requirements.

Brain implants in man do not break down the blood-brain barrier to dopamine and domperidone.

We have evaluated the blood-brain barrier (BBB) in 8 Parkinsonian patients before and after stereotactic implantation of foetal mesencephalon (STIM) and one patient with an adrenal medullary implant. Parenteral administration of dopamine did not reverse Parkinsonism pre-operatively or at 5 days, 1, 2, 3, 4 months and 1 year post-operatively. Apomorphine and domperidone reversed Parkinsonism and produced dyskinesia in all patients pre- and post-operatively. We conclude that the BBB remains intact to dopamine following implantation.

Enhanced in vitro survival and growth of foetal human mesencephalic dopaminergic neurones on laminin and collagen: implications for cell banking.

Culture of second trimester mesencephalic cells on laminin and collagen substrata has been investigated in an attempt to ascertain the effects of these extracellular matrix components on survival and growth of central dopaminergic (DA) neurones. There were 156.8-186.4% more cells attached to laminin and collagen than poly-D-lysine 6 h post-plating. By 24 h there was statistically no significant difference in the total number of cells attached to the three substrate but in terms of cell type-specific survival the proportion of mesencephalic DA neurones surviving on laminin and collagen substrata after 7 days in culture increased significantly compared with poly-D-lysine (1.4-1.6% versus 0.4% of the total cellular population), an effect augmented by bFGF treatment, which led to levels of 2% or more, with a concomitant decrease in the proportion of attritic DA neurones. These results indicate a critical requirement for ECM proteins in the survival and growth of in vitro-propagated central DA neurones at the time of plating and throughout the culture period. They also imply survival-enhancing interactions of ECM proteins and neurotrophic factors in developmental neuronal regulation and provide paradigms for obtaining high yields of these cells for neural transplantation cell banks.

Visual evoked cortical responses and electroretinograms following implantation of human fetal mesencephalon to the right caudate nucleus in Parkinson's disease.

Pattern electroretinograms and visual evoked cortical responses following flash and checkerboard pattern reversal stimulation were performed in 7 patients with advanced Parkinson's disease before and after implantation of human fetal ventral mesencephalon to the head of the right caudate nucleus. Six to nine months following surgery there was bilateral enhancement of flash-evoked response amplitudes. Electroretinogram measurements were unchanged. Individual increases in amplitude and decreases in latency were seen following pattern stimulation which were not statistically significant. A relationship between change in dyskinesia, and change in checkerboard pattern stimulation amplitude at 2.4 cycles per degree suggests that amplitude effects at this stimulus frequency are mediated via altered dopaminergic receptor status in the grafted hemisphere. This may be relevant to the mechanisms leading to generalised clinical improvements following this grafting technique.

Comparative studies of the diagnostic value of cerebrospinal fluid spectrophotometry and computed tomographic scanning in subarachnoid hemorrhage.

Serial spectrophotometric scans of cerebrospinal fluid (CSF) and computed tomographic (CT) scans of 99 patients with a subarachnoid hemorrhage (SAH) were examined. The xanthochromic index (i.e., the sum of the absorption values at 416 nm (oxyhemoglobin) and 460 nm (bilirubin)) yielded an accurate diagnosis in 82%, as did the CT scan. When both spectrophotometric and CT scans were used, the accuracy of SAH diagnosis increased to 96%. The xanthochromic index was valuable in estimating the date of hemorrhage and also correlated well with the clinical outcome of these patients. Only 42% of the recurrent hemorrhages were diagnosed by CSF spectrophotometry; in this capacity, its role seems less clear. However, a positive diagnosis of recurrent hemorrhage by CT scan was made in 83%.

Diurnal variation of and activity during the onset of stroke.

The diurnal variation in the onset of stroke was examined in 557 consecutive patients aged over 70 years. These included 194 patients with subarachnoid hemorrhage, 118 with intracerebral hemorrhage, and 245 with thromboembolic cerebral infarction. All three types of strokes exhibited a peak incidence between 1000 and 1200 hours. Intracerebral hemorrhages occurred less frequently between 0400 and 0600 hours, but there were no differences between the groups for the other time periods. There was no difference in the time of onset of stroke between normotensive and treated or untreated hypertensive patients. There were more untreated hypertensive patients in the intracerebral hemorrhage group than in the other stroke type groups. Subarachnoid hemorrhage occurred more frequently in the lavatory and during sexual and sporting activity. Intracerebral hemorrhage occurred more commonly during driving or the consumption of alcohol. Cerebral infarction occurred more frequently during sleep or was noticed on waking. No differences were found for the other activities examined. The relationship between diurnal variation in stroke and the known variation in blood pressure is discussed.

Mononuclear cell infiltration in central portions of human astrocytomas.

The mononuclear cell infiltration in the central portion of human low- and high-grade astrocytomas has been examined using monoclonal antibodies to cell surface differentiation antigens. There was no significant difference between the number of T cells, B cells, or macrophages. The OKT8+ (suppressor/cytotoxic) T cell population was the major lymphocyte subset in the infiltrates. There was, however, indirect evidence for a proportion of the total OKT8+ cells being natural killer cells. Overall, there was a significant difference in the number of macrophages compared to the total lymphoid cell population. Several cell types seem to play an equal role in the cellular and humoral immune response within the center of the tumors, as distinct from that occurring at the periphery.

Reduced platelet function in subarachnoid hemorrhage.

The hypothesis that abnormalities of platelet function may relate to the occurrence or recurrence of subarachnoid hemorrhage (SAH) has been examined. Seventy patients with SAH and 65 control individuals were studied. The adenosine diphosphate (ADP) threshold for secondary platelet aggregation was significantly higher in the SAH group than in the controls. In tests using 4.0 micrograms/ml ADP, the percent platelet aggregation (at 2 minutes) and the maximum rate of platelet aggregation (over 20 seconds) were significantly lower in the SAH patients. There was no difference in total platelet count between the two groups. Platelet adhesiveness was lower in the SAH patients when compared to controls. Circulating microaggregates did not differ between the two groups. The results indicate that reduced platelet function does relate to SAH and may either contribute to aneurysmal rupture in cases of SAH or be a consequence of it.

Lateral sinus reconstructive surgery: treatment of intracranial hypertension by venous anastomosis.

Ten cases of venous by-pass for revascularization of the lateral sinus have been performed to treat intracranial hypertension following hindrance of cerebral venous drainage. Principles and indications of this technique are discussed. In correctly selected cases this technique proved to be efficient in normalizing hypertension of venous origin.

A comparison of results from center-median and basal thalamotomies for pain.

In a personal series of 43 patients with chronic pain treated by thalamotomy, 23 patients had basal thalamotomy and 19 had center-median thalamotomy. Forty-nine procedures were performed. The best results occurred in patients with pain in the upper part of the body and in patients who had bilateral center-median thalamotomy. Bilateral center-median thalamotomy was superior to basal thalamotomy and had fewer side effects. Despite adverse reports, thalamotomy remains a useful analgesic procedure.

Emission and transmission tomography of the brain in cerebrovascular disease.

Transmission and emission computed tomography (T-CT and E-CT, respectively) scans of the brain in 149 patients with cerebrovascular disease were compared to establish the diagnostic accuracy of the two methods. The T-CT scan yielded an overall rate of true-positive results of 80.75% in major infarcts, 80% in intracerebral hematomas, and 75.9% in subarachnoid hemorrhage. In contrast, the percentages of true-positive results yielded by the E-CT scan were 92.3, 55, and 34.5%, respectively, in each type of cerebrovascular disease. The false-negative results obtained with the T-CT scan were higher in infarcts but lower in hematomas and subarachnoid hemorrhage; the reverse was true for the diagnoses obtained with the E-CT scan. The false-positive diagnoses produced by the T-CT scan were high for hemorrhagic strokes compared to those of the E-CT scan. The diagnostic sensitivity of each scan was not affected by the location of the lesion. Thus, the E-CT scan is more sensitive for thromboembolic disease and less so for hemorrhagic types of stroke. The reverse is true for the T-CT scan.