backgroundOther than glycemic control, there are no treatments for diabetic neuropathy. Thus, identifying potentially modifiable risk factors for neuropathy is crucial. We studied risk factors for the development of distal symmetric neuropathy in 1172 patients with type 1 diabetes mellitus from 31 centers participating in the European Diabetes (EURODIAB) Prospective Complications Study. methodsNeuropathy was assessed at baseline (1989 to 1991) and at follow-up (1997 to 1999), with a mean (±SD) follow-up of 7.3±0.6 years. A standardized protocol included clinical evaluation, quantitative sensory testing, and autonomic-function tests. Serum lipids and lipoproteins, glycosylated hemoglobin, and the urinary albumin excretion rate were measured in a central laboratory. resultsAt follow-up, neuropathy had developed in 276 of 1172 patients without neuropathy at baseline (23.5 percent). The cumulative incidence of neuropathy was related to the glycosylated hemoglobin value and the duration of diabetes. After adjustment for these factors, we found that higher levels of total and low-density lipoprotein cholesterol and triglycerides, a higher body-mass index, higher von Willebrand factor levels and urinary albumin excretion rate, hypertension, and smoking were all significantly associated with the cumulative incidence of neuropathy. After adjustment for other risk factors and diabetic complications, we found that duration of diabetes, current glycosylated hemoglobin value, change in glycosylated hemoglobin value during the follow-up period, body-mass index, and smoking remained independently associated with the incidence of neuropathy. Cardiovascular disease at baseline was associated with double the risk of neuropathy, independent of cardiovascular risk factors. conclusionsThis prospective study indicates that, apart from glycemic control, the incidence of neuropathy is associated with potentially modifiable cardiovascular risk factors, including a raised triglyceride level, body-mass index, smoking, and hypertension.

No diabetes physician would question the fact that problems relating to nerve damage in diabetes mellitus are extremely common and result in much patient morbidity and unhappiness [1]. However, as the cause and natural history of diabetic peripheral neuropathy remain unknown, attempts at defining minimal criteria for the presence of neuropathy have proved difficult [2]. This is probably the most important reason for the widely varied estimates of the prevalence of diabetic peripheral neuropathy. Other factors include differing patient selection criteria, the small size of cohorts and the employment of different diagnostic tests. Some studies have used the presence of neuropathic symptoms [3] alone for the diagnosis of neuropathy while others have used both symptoms and signs of neuropathy as minimal criteria for diagnosis [4,5]. The San Antonio Conference on Diabetic Neuropathy [6] recommended that for full classification of diabetic neuropathy, at least one measure from each of the following categories need Diabetologia (1996) Summary The EURODIAB IDDM Complications Study involved the examination of 3250 randomly selected insulin-dependent diabetic patients, from 31 centres in 16 European countries. Part of the examination included an assessment of neurological function including neuropathic symptoms and physical signs, vibration perception threshold, tests of autonomic function and the prevalence of impotence. The prevalence of diabetic neuropathy across Europe was 28 % with no significant geographical differences. Significant correlations were observed between the presence of diabetic peripheral neuropathy with age (p < 0.05), duration of diabetes (p < 0.001), quality of metabolic control (p < 0.001), height (p < 0.01), the presence of background or proliferative diabetic retinopathy (p < 0.01), cigarette smoking (p < 0.001), high-density lipoprotein cholesterol (p < 0.001) and the presence of cardiovascular disease (p < 0.05), thus confirming previous associations. New associations have been identified from this study -namely with elevated diastolic blood pressure (p < 0.05), the presence of severe ketoacidosis (p < 0.001), an increase in the levels of fasting triglyceride (p < 0.001), and the presence of microalbuminuria (p < 0.01). All the data were adjusted for age, duration of diabetes and HbA 1c . Although alcohol intake correlated with absence of leg reflexes and autonomic dysfunction, there was no overall association of alcohol consumption and neuropathy. The reported problems of impotence were extremely variable between centres, suggesting many cultural and attitudinal differences in the collection of such information in different European countries. In conclusion, this study has identified previously known and new potential risk factors for the development of diabetic peripheral neuropathy. [Diabetologia (1996[Diabetologia ( ) 39: 1377[Diabetologia ( -1384

There is still controversy over whether or not patients should be hyperventilated after traumatic brain injury, and a randomized trial has never been conducted. The theoretical advantages of hyperventilation are cerebral vasoconstriction for intracranial pressure (ICP) control and reversal of brain and cerebrospinal fluid (CSF) acidosis. Possible disadvantages include cerebral vasoconstriction to such an extent that cerebral ischemia ensues, and only a short-lived effect on CSF pH with a loss of HCO3-buffer from CSF. The latter disadvantage might be overcome by the addition of the buffer tromethamine (THAM), which has shown some promise in experimental and clinical use. Accordingly, a trial was performed with patients randomly assigned to receive normal ventilation (PaCO2 35 +/- 2 mm Hg (mean +/- standard deviation): control group), hyperventilation (PaCO2 25 +/- 2 mm Hg: HV group), or hyperventilation plus THAM (PaCO2 25 +/- 2 mm Hg: HV + THAM group). Stratification into subgroups of patients with motor scores of 1-3 and 4-5 took place. Outcome was assessed according to the Glasgow Outcome Scale at 3, 6, and 12 months. There were 41 patients in the control group, 36 in the HV group, and 36 in the HV + THAM group. The mean Glasgow Coma Scale score for each group was 5.7 +/- 1.7, 5.6 +/- 1.7, and 5.9 +/- 1.7, respectively; this score and other indicators of severity of injury were not significantly different. A 100% follow-up review was obtained. At 3 and 6 months after injury the number of patients with a favorable outcome (good or moderately disabled) was significantly (p less than 0.05) lower in the hyperventilated patients than in the control and HV + THAM groups. This occurred only in patients with a motor score of 4-5. At 12 months posttrauma this difference was not significant (p = 0.13). Biochemical data indicated that hyperventilation could not sustain alkalinization in the CSF, although THAM could. Accordingly, cerebral blood flow (CBF) was lower in the HV + THAM group than in the control and HV groups, but neither CBF nor arteriovenous difference of oxygen data indicated the occurrence of cerebral ischemia in any of the three groups. Although mean ICP could be kept well below 25 mm Hg in all three groups, the course of ICP was most stable in the HV + THAM group. It is concluded that prophylactic hyperventilation is deleterious in head-injured patients with motor scores of 4-5.(ABSTRACT TRUNCATED AT 400 WORDS)

✓ This study describes the relationship between raised intracranial pressure (ICP), hypotension, and outcome from severe head injury. The study is based on information derived from the Traumatic Coma Data Bank where ICP records from a relatively large number of patients were available to help delineate the major factors influencing outcome. From the total data base of 1030 patients, 428 met minimum monitoring duration criteria for inclusion in the present analysis. Outcome was classified according to the Glasgow Outcome Scale score determined at 6 months postinjury. Arrays of comparably defined summary measures describing the patient's course were considered for ICP, blood pressure (BP), central perfusion pressure, and therapy intensity level. For instance, the array of ICP summary descriptors included the proportion of ICP readings greater than x, for x = 0 to 80 mm Hg by increments of 5 mm Hg. A total of 187 candidate summary descriptors were considered. A stepwise ordinal logistic regression was used to select the subset of candidate summary descriptors that best explained the 6-month outcome. As established previously, age, admission motor score, and abnormal pupils were each highly significant in explaining outcome. Beyond these factors, the proportion of hourly ICP readings greater than 20 mm Hg was next selected and was also highly significant in explaining outcome (p < 0.0001). In addition to the ICP factor, the cutoff point of 20 mm Hg was selected by the procedure as most indicative of outcome. With these four factors modeled, the next selected factor was the proportion of hourly BP readings less than 80 mm Hg. Again, the BP factor was highly significant in explaining outcome (p < 0.0001). As with the ICP factor, the BP cutoff point of 80 mm Hg was objectively selected as most indicative of outcome. In summary, the incidence of mortality and morbidity resulting from severe head trauma is strongly related to raised ICP and hypotension measured during the course of ICP management. Moreover, these ICP and BP factors provide a better indication of outcome than the similarly defined factors of central perfusion pressure or therapy intensity level.

No abstract

In the belief that secondary cerebral compression, hypoxia, and ischemia materially influence the outcome from severe head injury, a standardized protocol was followed in 160 patients, with emphasis on early diagnosis and evacuation of intracranial mass lesions by craniotomy, artificial ventilation, control of increased intracranial pressure, and aggressive medical therapy. Of these patients, 36% made a good recovery, 24% were moderately disabled, 8% were severely disabled, 2% were vegetative, and 30% died. The mortality rate compares favorably with outcomes in similar patients reported from other centers and there has been no increase in the numbers of severely disabled or vegetative patients. It is proposed that vigorous surgical and medical therapy, by preventing or reversing secondary cerebral insults, enables some patients who would have died to make a good recovery without increasing the proportion of severely disabled patients.

The release of EAAs is closely linked to the release of structural amino acids and may thus reflect nonspecific development of membrane micropores, rather than presynaptic neuronal vesicular exocytosis. The magnitude of EAA release in patients with focal contusions and ischemic events may be sufficient to exacerbate neuronal damage, and these patients may be the best candidates for treatment with glutamate antagonists in the future.

Aims/hypothesis: The early pathological features of human diabetic neuropathy are not clearly defined. Therefore we quantified nerve fibre and microvascular pathology in sural nerve biopsies from diabetic patients with minimal neuropathy. Methods: Twelve diabetic patients underwent detailed assessment of neuropathy and fascicular sural nerve biopsy at baseline, with repeat assessment of neuropathy 8.7±0.6 years later. Results: At baseline, neuropathic symptoms, neurological deficits, quantitative sensory testing, cardiac autonomic function and peripheral nerve electrophysiology showed minimal abnormality, which deteriorated at follow-up. Myelinated fibre density, fibre and axonal area, and g-ratio were normal but teased fibre studies showed paranodal abnormalities (p<0.001), segmental demyelination (p<0.01) and remyelination (p<0.01) without axonal degeneration. Unassociated Schwann cell profile density (p<0.04) and unmyelinated axon density (p<0.001) were increased and axon diameter was decreased (p<0.007). Endoneurial capillaries demonstrated basement membrane thickening (p<0.006), endothelial cell hyperplasia (p<0.004) and a reduction in luminal area (p<0.007). Conclusions/interpretation: The early pathological features of human diabetic neuropathy include an abnormality of the myelinated fibre Schwann cell and unmyelinated fibre degeneration with regeneration. These changes are accompanied by a significant endoneurial microangiopathy.