Assessment of Progression-Free-Survival in Glioblastomas by Intratreatment Dynamic Contrast-Enhanced MRI.

PURPOSE: The efficacy of concomitant chemoradiation in patients with glioblastomas (GBMs) cannot be reliably assessed until several weeks after therapy completion. Our aim was to evaluate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as an early predictive assay for the progression-free-survival. METHODS AND MATERIALS: A total of 22 patients with primary GBMs underwent DCE-MRI before, during and after completion of adjuvant chemoradiation. K (trans) (transfer constant between the intravascular and extravascular, extracellular space), v(e) (extracellular, extravascular volume) and IAUGC (initial area under the gadolinium concentration time curve) and their changes into treatment were assessed as prognostic markers (12 months of progression-free-survival (PFS)). RESULTS: Both responders (7 subjects) and non-responders (15 subjects) experienced a reduction in the baseline IAUGC and v(e) values during the early phase of the treatment. This reduction was more prominent in the responders and was statistically significant for the v(e) (P = 0.04). Baseline K (trans) values among responders demonstrated statistically significant reduction during the early phase of treatment (P = 0.001). Multivariate Cox regression analysis demonstrated significant relationship between response and the early changes in K (trans) values during the treatment (P = 0.04). Trend to significant prognostic value demonstrated the baseline K (trans), v(e) and IAUGC as well as the changes of IAUGC and K (trans) upon therapy completion. CONCLUSIONS: Early perfusion changes during concomitant chemoradiation in GBMs can be detected by means of DCE-MRI and have significant prognostic value for the 12-month PFS.

Autonomic dysfunction in presymptomatic and early symptomatic Huntington's disease.

OBJECTIVES: Although autonomic dysfunction was found in advanced Huntington's disease (HD) patients it is not clear whether there is autonomic dysfunction in presymptomatic and early symptomatic HD. MATERIAL & METHODS: Different cardiovascular autonomic tests were performed in 14 presymptomatic HD mutation carriers (PHD), 11 early symptomatic HD patients (EHD) and in 25 sex and age matched controls. RESULTS: We found attenuated response to simple mental arithmetic test (relative heart rate in PHD and EHD was 10% lower than in controls; diastolic pressure was 10.6% lower in EHD than in controls; P < 0.05) and exaggerated response to the late phase of cold pressor test (relative heart rate was 10% higher in PHD and 7% higher in EHD than in controls; P < 0.05). The rest of the cardiovascular autonomic tests did not reveal significant differences between patients and controls. CONCLUSIONS: Our results suggest that subtle autonomic dysfunction occurs even in PHD and EHD.

Ingrowth of sensory axons into an end-to-side coapted nerve stump after donor nerve crush in the rat.

BACKGROUND: Target innervation through an end-to-side (ETS) nerve coaptation depends on axonal sprouting from the donor nerve. Terminal axonal sprouting in a partially denervated target tissue is more extensive from a crushed donor nerve than from an intact donor nerve. We hypothesized that axonal sprouting into an ETS coapted recipient nerve could be stimulated by crushing the donor nerve. METHOD: Twenty-seven rats were randomised into 3 groups. In all, the distal stump of the transected peroneal nerve was sutured to the side of the sural nerve in place of the epineural window. The control group received no additional treatment. In the experimental groups, the sural donor nerve was crushed either 8 mm proximal (proximal crush group) or 8 mm distal to the coaptation site (distal crush group). Sixteen weeks after the surgery, histomorphometric analysis of the recipient peroneal nerve stump 4 mm distal to the coaptation site was performed. FINDINGS: The number of myelinated axons in the recipient peroneal nerve stump was 758 +/- 247 in the control group, 503 +/- 246 in the distal crush group and 211 +/- 96 in the proximal crush group. The differences between the groups were statistically significant (p < 0.05). The majority of myelinated axons were thin myelinated axons and the frequency distribution of their cross-sectional areas was similar in all groups. CONCLUSION: Contrary to our expectations, a significantly lower number of myelinated axons were present in recipient nerves in the proximal and distal crush groups than in the control group. This suggests that sensory axon ingrowth into an ETS coapted nerve cannot be enhanced by crushing the donor nerve.

Which myelinated sensory axons sprout into an end-to-side coapted peripheral nerve in the rat?

BACKGROUND: The high-threshold sensory afferents, which express trkA, are predominantly involved in terminal collateral sprouting in the skin of adult mammals. We explored which sensory axons are capable of sprouting into the end-to-side coapted nerve in the rat. METHOD: The distal stump of the transected peroneal nerve was sutured to the side of the uninjured sural nerve. After 36 weeks, sprouting of sensory axons into the end-to-side coapted nerve was assessed by the electrophysiologic measurements of compound action potential and by counting the myelinated axons. The neurons in the dorsal root ganglia (DRG) L5 whose axons sprouted into the end-to-side coapted nerve were retrogradely labelled by the fluorescent dye Fluorogold. The expression of trkA in sprouting DRG neurons was investigated by immunohistochemistry. FINDINGS: Predominantly thin myelinated axons were found in the end-to-side coapted peroneal nerve. Their mean conduction velocity (CV) was between the average CVs of the Adelta and Abeta fibres in the normal sural nerves. About 90% of the sprouting DRG neurons were small and medium sized, and about 10% were large. About 85% of sprouting DRG neurons was immunoreactive to trkA, but the rest were not. CONCLUSIONS: Mostly the high-threshold sensory afferents sprouted into the end-to-side coapted nerve, which resembles the collateral sprouting of sensory axons in the skin. However, our results suggest that also some low-threshold mechanoreceptors can sprout after the end-to-side nerve repair.

Articaine is more effective than lidocaine or mepivacaine in rat sensory nerve conduction block in vitro.

The reasons for the relatively high failure rate after inferior alveolar nerve block in dentistry are not fully understood. Therefore, the effectiveness of different anesthetic solutions (2% and 4% lidocaine, 3% mepivacine, 2% and 4% articaine) in depressing the compound action potential amplitude of the sensory fibers in the rat sural nerve was examined under strictly controlled conditions in vitro. After application of an anesthetic solution and stimulation of the nerve with a supramaximal electrical stimulus, a complete disappearance of the compound action potential of the C fibers, but not of the A fibers, was observed in all the experimental groups. Both 2% and 4% articaine more effectively depressed the compound action potential of the A fibers than did other anesthetic solutions. These results are discussed in the light of recent clinical reports finding no differences in the effectiveness between 4% articaine and 2% lidocaine regarding the inferior alveolar nerve block.

Effect of generalized sympathetic activation by cold pressor test on cerebral hemodynamics in diabetics with autonomic dysfunction.

BACKGROUND: We examined the effects of the cold pressor test on the cerebral circulation in diabetics with autonomic dysfunction without orthostatic hypotension using transcranial Doppler. METHODS: Twenty diabetics with autonomic dysfunction and 19 age-matched healthy controls participated in the study. The mean arterial blood velocity was measured in the middle cerebral artery during the cold pressor test together with the mean arterial blood pressure. RESULTS: The mean arterial blood velocity significantly (p < 0.01) increased during the 1st, 2nd, and 3rd min of the cold pressor test by 10.6, 14.1, and 13.4%, respectively, in the control subjects and by 5.8, 7.2, and 6.8%, respectively, in the diabetics. Simultaneously, the mean arterial blood pressure significantly (p < 0.01) increased by 12, 26, and 23%, respectively, in the controls and by 9.4, 12.4 and 12.9%, respectively, in the diabetics. The increases in the mean arterial velocity as well as in the mean arterial blood pressure were significantly higher in the controls than in the diabetics (p < 0.01). The change in the mean arterial blood pressure related significantly to the change in the mean arterial blood velocity both in the controls (p < 0.01, r = 0.76) and in the diabetics (p < 0.01; r = 0.59). The slope of the regression line was significantly steeper in the controls (b = 0.42, SE = 0.05) as compared with the diabetics with autonomic dysfunction (b = 0.27, SE = 0.05; p = 0.02). Moreover, also the relative increase in the cerebrovascular resistance index was higher in the controls than in the diabetics (p < 0.05). CONCLUSION: These findings in the diabetics with autonomic neuropathy, but without orthostatic hypotension, suggest a failure in the cerebral autoregulation due to impaired cerebrovascular neurogenic control.

Coupling between visual evoked cerebral blood flow velocity responses and visual evoked potentials in migraneurs.

Neurovascular coupling may be altered in migraneurs. Therefore, visual evoked potentials (VEP) and visually evoked cerebral blood flow velocity responses (VEFR) were simultaneously recorded in 30 healthy controls and 30 migraneurs interictally using a checkerboard stimulus with visual contrasts of 1%, 10% and 100%. The VEFR were measured in the posterior cerebral artery using transcranial Doppler and VEP were recorded from occipital leads. We found an increase in VEFR and VEP in both the healthy and migraneur groups (P < 0.01). VEFR were significantly higher in migraneurs (P < 0.01), while VEP did not significantly differ between the groups (P > 0.05). Regression showed a significant association between VEP and VEFR in both healthy controls (r = 0.66, P < 0.01) and migraneurs (r = 0.63, P < 0.01). The regression coefficient of migraneurs (b = 0.88, SE = 0.08) was significantly higher than that of healthy controls (b = 0.55, SE = 0.07) (P = 0.04). We conclude that neurovascular coupling is increased in migraneurs interictally.

Nerve fibre composition of the palmar cutaneous branch of the median nerve and clinical implications.

Fifteen fresh human cadaver hands were dissected, using x2.8 loupe magnification, to study the subcutaneous innervation at the site of the incision (in the line with the radial border of the ring finger) for standard open carpal tunnel decompression. Subcutaneous nerve branches were detected and traced proximally to determine their origin. Morphometric analysis of nerve cross sections from the site of the incision and from the main nerve trunk proximal to cutaneous arborisation was performed using light and transmission electron microscopy and a computer-based image analysis system. At the site of the incision, the ulnar sub-branch (US) of the palmar cutaneous branch of the median nerve (PCBMN), which innervates the skin over the hypothenar eminence, was found in 10 of 15 cases. Branches from the ulnar side were not detected. The main trunk of PCBMN consisted on average of 1000 (SD 229) myelinated axons arranged in 1-4 fascicles. In the US of the PCBMN there were on average 620 (SD 220) myelinated axons, 80% of them smaller than 40 microm(2) i.e. thin myelinated axons, and on average 2037 (SD 1106) unmyelinated axons, arranged in 1-3 fascicles. The ratio of the number of myelinated axons in the US and the main trunk of the PCBMN was on average 63% (SD 19%). Frequency distribution of cross-sectional areas of myelinated axons shows no significant difference between the US and the main nerve trunk of the PCBMN. The importance of incision trauma to subcutaneous innervation of palmar triangle is emphasised and possible mechanisms of scar discomfort are discussed.

Sex-related difference in collateral sprouting of nociceptive axons after peripheral nerve injury in the rat.

Possible sex-related differences in the extent of collateral sprouting of noninjured nociceptive axons after peripheral nerve injury were examined. In the first experiment, peroneal, tibial, and saphenous nerves were transected and ligated in female and male rats. Eight weeks after nerve injury, skin pinch tests revealed that the nociceptive area of the noninjured sural nerve in the instep skin expanded faster in females; the final result was a 30% larger increase in females than in males. In the second experiment, the end-to-side nerve anastomosis was used as a model for axon sprouting. In addition to the previous procedure, the end of an excised peroneal nerve segment was sutured to the side of the intact sural nerve. Eight weeks later, collateral sprouting of nociceptive axons into the anastomosed peroneal nerve segment was assessed by the nerve pinch test and axon counting. There was no significant difference with respect to the percentages of male and female rats with a positive nerve pinch test. The number of myelinated axons in the anastomosed nerve segment was significantly larger in female (456 +/- 217) than in male (202 +/- 150) rats, but the numbers of unmyelinated axons were not significantly different. In normal sural nerves, the numbers of either all myelinated axons or thin myelinated axons did not significantly differ between the two sexes. Therefore, the more extensive collateral axon sprouting observed in female than in male rats is probably due to the higher sprouting capacity of thin myelinated sensory axons in females.