The treatment of unruptured, intracranial aneurysms has been the topic of debate. Although recent studies have advocated surgical intervention for unruptured aneurysms, the risk of such treatment in comparison to outcome from ruptured aneurysms has not been established.

This retrospective study examines the outcome of 134 patients with 179 ruptured and unruptured intracranial, saccular aneurysms treated by a single surgeon.

Of the 98 ruptured aneurysms where early surgical intervention was undertaken (less than 48 hours post hemorrhage), 70 had an excellent outcome, 13 were good, four were moderate, two poor and nine patients died postoperatively. Outcome assessment in these cases was correlated to preoperative neurological status. Patients who presented with unruptured aneurysms fell into two categories: symptomatic and asymptomatic. Seven incidental, asymptomatic aneurysms were clipped concurrently to the surgical isolation of the culprit lesion following subarachnoid hemorrhage without influencing outcome, whilst, for varying reasons, eight unruptured aneurysms were not operated upon. Of the remaining 66 surgically treated, unruptured aneurysms, 64 had an excellent postoperative result, one was good (persisting right incomplete third nerve palsy) and one was moderate (left hemiparesis). Thirteen of these aneurysms were symptomatic, whilst 21 were asymptomatic, multiple aneurysms requiring secondary elective repair and 32 were true incidental aneurysms.

Unruptured aneurysms less than 25 mm in size may be safely, surgically treated relative to the expected natural history and, certainly, with less risk than operative intervention upon ruptured cerebral aneurysms.

Despite the potential importance of endoneurial microvessel abnormalities in diabetic neuropathy, the pathogenesis of these abnormalities is incompletely understood. We wished to evaluate the effect of experimental diabetes on endoneurial microvessels and determine if an aldose reductase inhibitor alters any of the changes induced by diabetes.

We compared streptozocin diabetic rats with and without aldose reductase inhibitor treatment to non-diabetic rats after 10 months of diabetes. Transverse microvessels from the mid-sciatic level were studied by electron microscopic morphometric evaluation.

Microvessel endothelial, pericyte, basement membrane and total mural area were greater in untreated diabetic animals than non-diabetic animals. Aldose reductase inhibitor treated diabetic animals had greater endothelial area and possibly pericyte area but not basement membrane or total mural area.

This study demonstrates that endoneurial microvessel abnormalities can be detected in experimental diabetic neuropathy. Microvessel basement membrane thickening will be prevented by an aldose reductase inhibitor. One mechanism by which abnormal polyol pathway activity may contribute to diabetic neuropathy could be through damage to microvessels.

To study the frequency, clinical features and clinical genetics of familial Parkinson’s disease (PD).

Family history for PD and tremors was studied in 100 consecutive PD cases. Spouses served as controls. Clinical features were compared between personally verified familial and sporadic PD cases, from the same consecutive clinical series. Clinical genetic analysis was performed in a larger group of non-consecutive multicase PD families.

Family history for PD was positive in 24% of consecutive PD cases and in 6% of spouse controls (p < 0.001). When family history for isolated tremor is also considered, the number of positive cases rises to 43% compared with 9% in controls (p < 0.001). Nine of the consecutive cases had at least one living affected relative, for a total of 20 familial PD cases. These familial cases showed an earlier onset age when compared with sporadic ones from the same consecutive series. Within 22 non-consecutive PD families with at least two living and personally examined PD cases (total 52 PD cases), the crude segregation ratios were similar for parents and siblings and the lifetime cumulative risks approached 0.4 in siblings and tended to be comparable, but at later ages, in parents. Ancestral relatives were all unilaterally distributed. In some families, anticipation of onset age in new generations was observed.

The frequency of positive family history for PD and for PD and tremor is higher among PD cases than controls. Familial and sporadic PD only differ in onset age. The clinical genetic analyses support autosomal dominant inheritance with strongly age-related penetrance as most likely in familial PD.

Oligodendrogliomas respond to nitrosourea-based chemotherapy and are induced in rats following transplacental exposure to ethylnitrosourea, observations suggesting that neoplastic and normal cells of the oligodendrocyte lineage are “sensitive” to nitrosoureas. Nitrosoureas alkylate DNA at O6-guanine with repair mediated by O6-methyIguanine-DNA methyltransferase (MGMT). The cytotoxic and carcinogenic properties of the nitrosoureas appear related to MGMT activity.

To explore why oligodendrogliomas respond to chemotherapy, we measured MGMT activity in five chemosensitive human oligodendrogliomas and in rat oligodendrocyte lineage cells. We also measured MGMT activity in rat astrocytes and compared the cytotoxic effects of carmustine (BCNU) on oligodendrocyte lineage cells and astrocytes.

Low levels of MGMT activity were found in five of five human oligodendrogliomas. Cultures of neonatal rat glia enriched for oligodendrocyte lineage cells also had low levels of MGMT activity, approximately one-third that found in astrocytes (p < 0.02), and oligodendrocyte lineage cells were more sensitive to BCNU than astrocytes.

Low MGMT activity may contribute to the chemosensitivity of some human oligodendrogliomas and rat oligodendrocyte lineage cells also have low levels. If drug resistance mechanisms in tumors reflect the biochemical properties of their cells of origin, then normal glia may serve as a laboratory substitute for human glioma.

We have quantified the effects of levodopa treatment in Parkinsonian subjects during maintained stance.

Electromyographic muscle activity during quiet stance was assessed in subjects with Parkinson’s disease, who exhibited a fluctuating response to levodopa, and in age-matched control subjects. Stance stability was also assessed from mean displacement and velocity of the center of pressure excursions during stance.

Lower extremity and trunk muscles showed high amplitude activity in all Parkinson’s subjects when “off”, and a 4–5 Hz tremor in three of these subjects. When “on”, the amplitude of muscle activity was reduced in the distal muscles more than the proximal, while tremor was suppressed in all muscles. Corresponding to the excessive muscle activity, the Parkinson’s subjects had increased velocity and variability of velocity in the anterior-posterior center of foot pressure excursions, but the mean displacement of the center of pressure excursion was not different from the controls. The velocity of center of pressure excursions in the Parkinson’s subjects “on”, approached those of the control subjects suggesting that the excessive distal muscle amplitude and tremor contributed to the high velocity of the center of pressure.

These findings suggest that dopaminergic systems are involved in the regulation of muscle tone during stance. Depletion of dopaminergic transmission results in increased muscle tone and tremor in the lower extremities which may contribute to changes in posture and stability.

In two previous studies we have demonstrated prevention of electrophysiological abnormalities of nerve in experimental STZ (streptozotocin)-induced diabetes (ED) of rats using nonsteroidal anti-inflammatory agents: indomethacin and sulindac. Sulindac might benefit ED because it inhibits both cyclo-oxygenase and aldose reductase.

In this work, we examined whether 1 month of sulindac treatment reversed or improved established biochemical and electrophysiological abnormalities in experimental diabetes of 3 months duration. Sulindac-treated diabetic rats (6.0 mg/kg 5/7 days weekly by gavage) were compared to untreated diabetics, nondiabetic controls and sulindac treated control rats.

Diabetic rats developed slowing of conduction velocity in caudal sensory, sural sensory, caudal motor and sciatic tibial motor fibers. Sulindac improved caudal motor and, to a lesser extent sural sensory conduction but not caudal sensory or sciatic tibial motor conduction. Sulindac did not alter sciatic sugars or polyols.

Sulindac provided modest improvement in some indices of experimental neuropathy in this reversal study, but there was less efficacy than in the preventative study. Reversal paradigms should be examined in all experimental therapies for diabetic neuropathy.