Abnormalities of sensorimotor integration in focal dystonia: a transcranial magnetic stimulation study.

It has been postulated that sensorimotor integration is abnormal in dystonia. We investigated changes in motor cortical excitability induced by peripheral stimulation in patients with focal hand dystonia (12 patients with hand cramps) and with cervical dystonia (nine with spasmodic torticollis) compared with 16 age-matched normal controls. Motor evoked potentials (MEP) to focal (figure-of-eight coil) transcranial magnetic stimulation of the hand area were recorded from the right abductor pollicis brevis (APB), first dorsal interosseus (FDI), flexor carpi radialis and extensor carpi radialis muscles. Changes of test MEP size following conditioning stimulation of the right median nerve (or of the index finger) at conditioning-test (C-T) intervals of 50, 200, 600 and 1000 ms were analysed. Peripheral stimulation significantly reduced test MEP size in the APB and FDI muscles of normal control and spasmodic torticollis patients. The inhibitory effect was larger upon median nerve stimulation and reached a maximum at the C-T interval of 200 ms. On the contrary, hand cramp patients showed a significant facilitation of test MEP size. This study suggests that MEP suppression following peripheral stimulation is defective in patients with focal hand dystonia. Central processing of sensory input is abnormal in dystonia and may contribute to increased motor cortical excitability.

The angiogenesis marker ED-B+ fibronectin isoform in intracranial meningiomas.

Fibronectins (FNs), adhesive glycoproteins mainly expressed in the extracellular matrix, are polymorphic molecules whose various isoforms are dependent on alternative splicing patterns. The isoform containing the ED-B sequence and occurring in foetal and neoplastic tissues (oncofoetal or B+FN) has been previously recognized as a marker for angiogenesis. The distribution of this isoform was analyzed in a consecutive series of 134 surgically obtained intracranial meningiomas, using specific monoclonal antibodies. Oncofoetal FN was found to be widely distributed in the vessels of anaplastic meningiomas, with its expression being restricted in the vasculature of the typical subtypes. and absent in the neighbouring cerebral tissue. The ubiquitous vascular expression of B+FN in meningiomatous malignancies might provide a potential target for the in vivo delivery of angiosuppressive agents.

Use of Emdogain in the treatment of deep intrabony defects: 12-month clinical results. Histologic and radiographic evaluation.

The objective of this study was to evaluate the application of an enamel matrix derivative (Emdogain) in deep periodontal pocket therapy. Twenty-one patients presenting intrabony and interproximal defects that could be treated with guided tissue regeneration were selected. The intrabony defects were divided into deep (< 9 mm) and very deep (> or = 9 mm) defects. Bleeding on probing, Plaque Index, probing pocket depth, mobility index, gingival recession, probing attachment level, and surgical bone level were measured at baseline. At 12 months, cases were reexamined and indices recorded again. The mean probing depth decreased from 8.1 +/- 2.1 mm to 3.2 +/- 1.5 mm; attachment level decreased from 10.4 +/- 2.4 mm to 7.0 +/- 1.8 mm; recession increased from 2.3 +/- 1.4 mm to 3.8 +/- 1.8 mm; and surgical bone level decreased from 9.6 +/- 1.9 mm to 7.1 +/- 1.5 mm. No significant difference wa noted between bone defects with one or 2 walls, between local and generalized periodontitis, or between smokers and nonsmokers. Significant statistical difference was found, however, between deep intrabony defects and very deep defects when attachment gain was considered. No adverse reaction to the substance was noted. The good clinical results obtained were not confirmed by radiologic results; standardized and computerized radiographs at 12 months did not reveal significant improvement. The histologic examination carried out on 2 samples did not show evidence of new attachment. Further studies are necessary to clarify the action mechanism and to evaluate the long-term results of this method.

Value of early variables as predictors of short-term outcome in patients with acute focal cerebral ischemia.

Reliable, simple and safe criteria are needed for the early prediction of short-term outcome in patients with acute ischemic stroke. The aim of our study was to evaluate, in terms of their individual and combined power, the prognostic value of a few widely available clinical and instrumental variables obtained during the acute phase. The study involved 351 consecutive patients who were examined within 48 hours of their first ischemic stroke. Eight variables were chosen: age, initial level of consciousness, limb paresis, arterial blood pressure, glycemia, the results of electrocardiography and electroencephalography, and the infarct size revealed by computed tomography. Mortality and disability were evaluated on Day 30, when the variables that significantly correlated with disability were the severity of limb paresis, electroencephalographic abnormalities, infarct size and (less significantly) the level of consciousness and hyperglycemia. There was no statistical correlation with blood pressure. Logistic analysis confirmed only infarct size, the severity of limb paresis and electroencephalographic abnormalities as independent variables. The variables that significantly correlated with early death were the severity of limb paresis, infarct size, electrocardiographic abnormalities, the level of consciousness, electroencephalographic abnormalities and hyperglycemia. More intriguingly, logistic analysis confirmed only the electroencephalographic and electrocardiographic abnormalities as independent variables. The predictive prognostic value of limb paresis, infarct size, the level of consciousness and hyperglycemia is well known, but we would like to stress the fact that only a few independent variables are predictive of early death (electroencephalographic and electrocardiographic abnormalities) and poor recovery (infarct size, the severity of limb paresis, electroencephalographic abnormalities). The prognostic value of electroencephalography may express the potential involvement of dynamic non-structural phenomena, such as penumbra ischemica and diaschisis.

Assessment of the CO2 response by means of non diffusible contrast media and angio-CT in patients with cluster headache.

We analyzed the possibility of assessing functional vasomotor changes by means of Arm-Brain Circulation Time (rABCT) and Vascular volume images (Vv) obtained with Angio-CT, in basal condition and following CO2 inhalation, in a sample of 48 patients with cluster headache. CO2 inhalation resulted in the appearance of local changes, which were detected in 28 regions. Analysis by indicator images of Vv-dependent rABCT distribution showed two main patterns: abnormal rABCT mostly evident at the smallest Vv pixels and abnormal rABCT dependent on abnormal Vv distribution. The former pattern was linked to abnormality at the circle of Willis; the latter to abnormal local vasomotor responses. Patients with cluster headache showed both patterns, which prompted us to conclude for the presence of low-degree stenosis in carotid arteries and vasomotor instability in peripheral brain vessels.

Assessment of regional cerebral blood flow images with non-diffusible contrast media and angio-CT. Comparison with Xe-CT.

We derived rCBF (ND-rCBF) images using non-diffusible contrast agent time-density curves obtained by monitoring the first pass with an angio-CT sequence. An appropriate elaboration of the sequence of the images led to the generation of vascular volume (Vv) and regional Arm-Brain circulation time images (rABCT). ND-rCBF was obtained by dividing the Vv image by the rABCT image after having rendered them suitable for such an operation. Regional cerebral vascular volume (rCBF) was assessed by standardizing Vv values with blood contrast concentration and intracranial circulation time (rICT) by subtracting from the rABCT image the inflow mean time, assessed as the lowest rABCT value of the slice. The ND-rCBF images were qualitatively fairly well comparable with synchronous rCBF (D-rCBF) images obtained with the Xe-CT technique. However quantitation of the values by ROI use gave different results, the ND-rCBF image showing considerably higher values. Using indicator images to analyse the rCBF values at different levels of rCBV and rICT, it was shown that there was a significant relation between the two ND-rCBF and D-rCBF values in the 70-80% pixels with higher rABCT and lower rCBF values.

Functional circulation images by angio-CT in the assessment of small deep cerebral infarctions.

We analyzed circulation time (rABCT) and vascular volume density images obtained by angio-computerized tomography (angio-CT) in 63 patients with small deep cerebral infarctions. Abnormalities in the rABCT image were found in 88% of the patients and in the vascular volume image in 48%. Two groups with different clinical pictures were picked out by rABCT changes: one with major-vessel involvement, the other with small-vessel involvement. The perfusional changes found were mainly due to altered vascular canalization rather than to altered vasomotility. The hemodynamic theory could explain the spatial relations between perfusion changes and CT hypodense areas without needing assumptions linking blood flow and metabolism.

Functional perfusion and blood-brain barrier permeability images in the diagnosis of cerebral tumors by Angio CT.

We performed rapid sequential CT scanning following iv injection of a bolus of contrast medium and generated three functional images relating to intravascular circulation time (rABCT), vascular volume (Vv) density and blood-brain barrier (BBB) unidirectional constant uptake rate (Ki), respectively. This was accomplished by calculating the first mathematical moment of the monitored time-density curves about the injection time and from the multiple time graph analysis described by Patlack and co-workers. A satisfactory resolution was achieved, allowing separate appreciation of changes in rABCT both in large vessels and in tissue small vessels. Combined evaluation of rABCT and Vv images allowed us to differentiate between tumors.

Functional circulation and blood-brain permeability images by Angio CT in the assessment of cerebral ischemia.

We performed rapid sequential computerized tomography (CT) scanning following i.v. injection of a bolus of contrast medium, and generated three functional images related, respectively, to intravascular circulation time (rABCT), vascular volume density (Vv) and blood-brain barrier (BBB) unidirectional constant uptake rate (Ki). This was accomplished by calculating the first mathematical moment of the monitored time-density curves about the injection time, and by the multiple time graph analysis described by Patlack and coworkers. A satisfactory resolution was achieved, allowing separate appreciation of changes in rABCT both at large vessels and at tissue small vessels. Combined evaluation of rABCT and Vv images allowed us to draw qualitative conclusions about blood flow and perfusion reserve.

Impairment of central motor conduction in diabetic patients.

In 70 patients with diabetes mellitus (DM) we recorded the motor evoked potentials (MEPs) following magnetic stimulation of the motor cortex and spinal roots. Central motor conduction time (CMCT) was determined as the difference between MEP latencies after cortical and spinal stimulation. The mean CMCTs for the biceps, thenar and tibialis anterior muscles were prolonged in the DM group, as compared to normal controls, and 21 patients exceeded the CMCT upper confidence limit for at least one muscle. CMCT changes and peripheral conduction velocity abnormalities occurred independently and were related to different clinical parameters. We conclude that a subclinical impairment of central motor conduction is present in 30% of DM patients, independently from the occurrence of a diabetic peripheral neuropathy and possibly reflecting different pathophysiological mechanisms.

Effect of protein kinase C activators on the uptake of GABA by rat brain synaptosomes.

Synaptosomes were prepared from rat brain by a discontinuous Ficoll gradient method and used for studying the uptake of labelled GABA. Two GABA uptake components were evidenced, a high (Km = 3.13 microM) and a low (Km = 92.4 microM) affinity one. Preincubation of synaptosomes with two different activators of protein kinase C, phorbol 12, 13-diacetate (PDAc) and oleyl-acetyl glycerol (OAG), resulted in a change of GABA uptake. In particular, the low affinity component increased its Vmax by 58-74%, with no change in the Km. No statistically significant modification was detected for the high affinity component.

Functional vascular volume and blood-brain barrier permeability images by angio-CT in the diagnosis of cerebral lesions.

We performed angio-CT following i.v. administration of an iodinated contrast medium and analyzed the pixel contrast time-density curves from 4 to 10 min postinjection to derive vascular and volume BBB permeability images. This was performed by applying multiple regression analysis of pixel contrast curves versus blood contrast and integrated blood contrast curves. The two regression coefficients, mapped pixel by pixel, correspond respectively to vascular volume and BBB unidirectional transport rate. Initial application in a small number of normal subjects and patients allowed us to characterize areas of steady-state contrast enhancement according to changes of vascular volume and BBB permeability.

Hemodynamic assessment of vascular malformations by angio CT with generation of functional transit time images.

We performed a CT dynamic study during the first pass of an intravenously injected bolus of a iodinated contrast medium, followed by generation of the regional arm-brain circulation time (rABCT) image, in 11 patients with vascular malformations. All lesions could be detected as changes of rABCT, and the comparison with values of normal arteries and veins allowed the deduction of the hemodynamic conditions of the lesions. Seven cases showed evidence of altered distribution of rABCT in the corresponding brain hemisphere, suggesting a perfusion reserve impairment.

Functional circulation time images in the diagnosis of cerebral lesions by angio CT.

An application of angio CT as an adjunct to contrast enhancement evaluation of cerebral lesions is presented. We performed rapid sequential scanning following intravenous bolus injection of an iodinated contrast medium, analyzed the time contrast curves and generated a functional circulation time image. This was accomplished by calculating on a pixel-by-pixel basis the first mathematical moment of the monitored time-density curves about injection time which corresponds to regional arm brain circulation time (rABCT). This method increased the rate of detection of cerebral lesions by contrast enhancement from 30 to 90%.

Assessment of 99mTc-HM-PAO parameters with SPECT for improved evaluation of blood flow in cerebral lesions.

A method for investigating the linearity between blood flow and distribution of 99mTc-HM-PAO uptake in patients undergoing single photon emission computed tomography (SPECT) is presented. This method, based on particular elaboration techniques of sequential multiple acquisitions, provides a local index: cumulative transit time (CTT) related to all factors, other than blood flow, affecting 99mTc-HM-PAO uptake. Because a correct qualitative blood flow estimation is based on the uniformity of the above factors, the occurrence of a change of this index indicates a nonlinear relation between blood flow and 99mTc-HM-PAO uptake distributions. It was shown that although linearity between blood flow and 99mTc-HM-PAO uptake may be questionable, a qualitative assessment of blood flow was correct in 100% of ischemic patients. In nonischemic patients this percentage fell to 60%.

Intravenous 99mTc HM-PAO radionuclide angiography as an adjunct to SPECT assessment of cerebral disease.

An application of intravenous radionuclide angiography as an adjunct to SPECT with 99mTc HM-PAO is presented. From the angiographic sequence a two-dimensional parametric image is generated computing, pixel by pixel, the center of gravity (COG) of the local time curves. This index is independent of blood flow and reflects the relation between transmitted and extravasated activity. COG value, compared in two symmetrical regions analyzed for differences in flow by SPECT, may help to state whether a detected SPECT changed uptake is linearly related or not to the corresponding change of blood flow. All 23 ischemic patients taken into consideration had a similar backflux in symmetrical regions with conspicuous changed uptake. In 3 meningiomas and 2 arteriovenous angiomas it was possible to detect the occurrence of a changed backflux in the lesion suggesting a nonlinearity between blood flow and 99mTc HM-PAO uptake.

Single photon emission computed tomography with technetium-99m hexamethyl propylenamino oxime in the clinical assessment of cerebral ischemia. A preliminary evaluation.

94 subjects, 64 with cerebral ischemia of varying severity and outcome, and 30 controls were studied with technetium-99m hexamethyl propylenamino oxime single photon emission computed tomography in order to evaluate the suitability of this technique in the assessment of cerebral ischemia. Decreased uptake corresponding to the side of clinical symptomatology and/or to CT lesion was found in 93% of the patients with complete stroke and in 28% of the patients with transient ischemic attack. This procedure can be a useful tool in the routine examination of ischemic patients, although the mechanism underlying brain uptake is far from being completely understood and the possible quantitative evaluation of regional cerebral blood flow is worthy of further assessment.

[Computerized radionuclide angiography of brain tumors. Analysis of activity-time curves]. / Angioscintigrafia computerizzata nei tumori cerebrali. Analisi delle curve attività-tempo.

43 patients with a cerebral supratentorial tumor and an increased uptake at the static scan underwent intravenous radionuclide angiography with time-activity curve analysis. The increased uptake was evident during radionuclide angiography in about 50% of the cases, 16% during the upslope and 40% during the downslope of the curve. From these data it was concluded that increased uptake in tumours is determined rather than by an increased blood flow by the barrier disruption which may be operative in determining the increased uptake during the first pass in about 40% of the cases. In this case thy typical modification of the curve is characterized by a decreased falling rate of the downslope.

Evaluation of asymmetries of blood flow rate and of circulation time by intravenous radionuclide cerebral angiography in patients with ischemic completed stroke.

155 patients with ischemic completed stroke of varying severity and outcome have been evaluated by radionuclide cerebral angiography with analysis of regional time-activity curves. Two parameters have been evaluated: area under the upslope of the curve (Aup) reflecting regional blood flow rate and moment of the whole curve reflecting tracer circulation time (rABCT) Combination of these two methods ensured increased detection of perfusion asymmetries.