Ozone autohemotherapy induces long-term cerebral metabolic changes in multiple sclerosis patients.

Ozone autohemotherapy is an emerging therapeutic technique that is gaining increasing importance in treating neurological disorders. A validated and standard methodology to assess the effect of such therapy on brain metabolism and circulation is however still lacking. We used a near-infrared spectroscopy (NIRS) system to monitor the cerebral metabolism and a transcranial Doppler (TCD) to monitor the blood flow velocity in the middle cerebral arteries. Fifty-four subjects (32 neurological patients and 22 controls) were tested before, during, and after ozone autohemotherapy. We monitored the concentration changes in the level of oxygenated and deoxygenated haemoglobin, and in the level of the Cytochrome-c-oxidase (CYT-c). As a primary endpoint of the work, we showed the changes in the brain metabolism and circulation of the entire population. The concentration of oxygenated haemoglobin increased after the reinjection of the ozoned blood and remained higher than the beginning for another 1.5 hours. The concentration of the deoxygenated haemoglobin decreased during the therapy and the CYT-c concentration markedly increased about 1 hour after the reinjection. No significant changes were observed on the blood flow velocity. As secondary endpoint, we compared the NIRS metabolic pattern of 20 remitting-relapsing multiple sclerosis (MS) patients against 20 controls. We showed that by using only 7 NIRS variables it was possible to characterize the metabolic brain pattern of the two groups of subjects. The MS subjects showed a marked increase of the CYT-c activity and concentration about 40 minutes after the end of the autohemotherapy, possibly revealing a reduction of the chronic oxidative stress level typical of MS sufferers. From a technical point of view, this preliminary study showed that NIRS could be useful to show the effects of ozone autohemotherapy at cerebral level, in a long-term monitoring. The clinical result of this study is the quantitative measurement of the CYT-c level changes in MS induced by ozone autohemotherapy.

Time and time-frequency analysis of near-infrared signals for the assessment of ozone autohemotherapy long-term effects in multiple sclerosis.

Ozone autohemotherapy is an emerging therapeutic technique that is gaining increasing importance in treating neurological disorders. A validated and standard methodology to assess the effect of such therapy on brain metabolism and circulation is however still lacking. We used a near-infrared spectroscopy system (NIRS) to monitor the cerebral oxygenation of 9 subjects: 4 remitting-relapsing multiple sclerosis (MS) sufferers and 5 controls. Subjects were tested before, during, and after ozone autohemotherapy. We monitored the concentration changes in the level of oxygenated and deoxygenated haemoglobin, and in the level of the Cytochrome-c-oxidase (CYT-c). From the time and time-frequency analysis of the NIRS signals we extracted 128 variables, which were used to characterize the metabolic brain pattern during the therapy. We showed that by using only 7 NIRS variables out of 128 it is possible to characterize the metabolic brain pattern of the two groups of subjects. The MS subjects showed a marked increase of the CYT-c activity and concentration about 40 minutes after the end of the autohemotherapy, possibly revealing a reduction of the chronic oxidative stress level typical of MS sufferers. From a technical point of view, this preliminary study showed that NIRS could be useful to show the effects of ozone autohemotherapy at cerebral level, in a long term monitoring. The clinical result of this study is the quantitative measurement of the CYT-c level changes in MS induced by ozone autohemotherapy.

CALSFOAM-completed automated local statistics based first order absolute moment" for carotid wall recognition, segmentation and IMT measurement: validation and benchmarking on a 300 patient database.

AIM: In this work we present a novel methodology (called CALSFOAM) for the automated segmentation of ultrasound carotid images and intima-media thickness (IMT) measurement. CALSFOAM was developed in order to overcome limitations of a previously developed snake-based technique. METHODS: CALSFOAM consists of two stages: Stage-I is an automatic recognition of the carotid artery system in an image frame and Stage-II is a combination of segmentation and IMT measurement sub-system. Stage-I is performed by using local statistics and by automatically tracing the profile of the distal adventitia. Stage-II takes the traced adventitia boundary and builds an ROI for distal wall segmentation that uses a first order absolute moment (FOAM) technique. CALSFOAM was benchmarked against our previous snake based technique and validated on a 300-image multi-institutional dataset. RESULTS: CALSFOAM's lumen-intima (LI) segmentation error was 0.049±0.039 mm, the media-adventitia (MA) error was 0.088±0.054 mm; the IMT measurement bias was 0.125±0.103 mm. To reduce CALSFOAM error, we adopted a GREEDY approach for fusing the boundaries from the two techniques and obtained LI and MA errors equal to 0.02±0.014 mm, 0.023±0.013 mm, and an IMT bias of 0.074±0.068 mm. CONCLUSION: Even though CALSFOAM's performance was lower than snake-based segmentation techniques, it helped in avoiding possible inaccuracies of snakes and its parameter sensitivities. The very accurate performance obtained by the GREEDY approach demonstrated that the two techniques could be considered as complementary.

Ultrasonography and MR Imaging in Progressive Supranuclear Palsy.

Progressive supranuclear palsy (PSP) also known as Steele, Richardson and Olszewski disorder (1-4) is a neurodegenerative brain disease that has no known cause, treatment or cure. PSP has no known geographical, occupational or racial preference and affects brain cells that control walking, balance, mobility, vision, speech and swallowing. Symptoms begin on average in the early 60s, but may start as early as in the 40s: a good history and physical examination support the clinical diagnosis and latency of each feature makes us suspect a probable PSP, an atypical Parkinsonism. The diagnosis of a large number of cases of PSP is missed or delayed: 75% of the patients are never clinically diagnosed by neurologist and in most cases the median interval between onset and diagnosis is three years. Notwithstanding such differences in clinical presentation, there remains an overlap in symptoms making the differential diagnosis between such neurodegenerative disorders challenging. A few imaging techniques developed to evaluate brain anatomy and function are used extensively to improve the diagnostic accuracy of different forms of Parkinsonism. Non-invasive and safe methods can now document brain structures. Transcranial sonography (TCS) is a very low cost tool to assess the basal ganglia and mesencephalic echogenicity (5,6). Conventional magnetic resonance imaging (MRI) is a valuable tool to exclude secondary Parkinsonism. Our purpose is to define characteristic objectively measured imaging markers that point out normal biological processes, and pathogenic processes in PSP. Such markers should be sufficiently sensitive and specific to show the underlying biological disease and the pharmacological responses to therapy.

Follow-up of residual shunt after patent foramen ovale closure.

OBJECTIVES: Transesophageal echocardiography (TEE) is usually recommended in the evaluation of the patent foramen ovale (PFO). Our goal is to confirm the efficacy of contrast-enhanced transcranial Doppler (ce-TCD) in detecting residual significant right-to-left shunts (RLS) after PFO percutaneous closure. MATERIALS AND METHODS: Sixty-eight patients with a previous transient ischemic attack, stroke and a large PFO were investigated for residual RLS after percutaneous closure. RESULTS: Assuming TEE as the gold standard, the sensitivity and negative predictive value of ce-TCD was 100%, whereas the specificity was 75.8% and the positive predictive value was 28%. CONCLUSIONS: ce-TCD appears to be the preferable technique to identify subjects with significant residual shunts after percutaneous closure of a PFO. In follow-up, if ce-TCD is negative, no further examination may be necessary; whereas if ce-TCD shows a residual shunt, it is advisable to perform a TEE investigation.

Why do we need NIRS in migraine?

Migraine patients may present altered values of the parameters related to their cerebral circulation. The non-invasive assessment of the autoregulation of such patients can be helpful in investigating the causes of migraine. We developed a joint analysis protocol based on transcranial Doppler (TCD) and near-infrared spectroscopy (NIRS) for assessing cerebral autoregulation. We tested 30 healthy subjects and 30 patients suffering from migraine without aura. We measured the baseline values of cerebral blood flow velocity (CBFV) in the middle cerebral arteries and the concentration of oxygenated (oxy-Hb) and reduced (deoxy-Hb) haemoglobin in brain tissue. Afterwards, the subjects performed a breath-holding (BH) task. In baseline conditions, we did not find significant difference between the CBFVs of healthy subjects and of migraineurs, even though the latter group showed a greater dispersion of the velocities (healthy: 70.6+/-6.8 cm/s; migraine: 71.5+/-14.4 cm/s). Strong differences in the CBFV were observable during the BH task: migraineurs showed a smaller BH index than controls (0.83+/-0.55% vs. 1.29+/-0.71%; p<0.005) and a reduced increase of the oxy-Hb (migraineurs: 0.033+/-0.019 micromol/l/s; healthy: 0.055+/-0.037 micromol/l/s; p<0.01). Also, we found a different haemoglobin balancing during the BH phase between migraineurs and controls, revealing that migraineurs do not show a marked vasodilation as functional response to the CO(2) increase. We propose this joint analysis protocol to assess cerebral autoregulation of migraine patients, and suggest NIRS as a low-cost, easy, reliable and fast technique to deeply investigate cerebral coupling deregulations.

Transcranial Doppler for monitoring the cerebral blood flow dynamics: normal ranges in the Italian female population.

AIM: This study was aimed at recording, by means of a transcranial Doppler (TCD) device, the values of blood flow velocities (BFV) in the middle cerebral artery (MCA) in physiological conditions, in a population of healthy women in various ages of their life, in order to establish normative data in an Italian female population. METHODS: Our sample consisted of 100 healthy women (mean age 38 +/-15.14 years, range 12-78) that underwent an investigation of the intracranial circulation by means of TCD. Patients were subdivided into 4 age groups: less than 20 years; 20-34 years; 35-50 years; more than 50 years. RESULTS: No statistically significant differences were present between the mean BFV in the left and right MCAs of the subjects considered as a unique population (left MCA 68.06+/-9.22 cm/s; right MCA 66.71+/-8.79 cm/s). The BFVs tended to significantly decrease with the increasing of age. In fact, they were so distributed: left MCA 82.55+/-6.85 cm/s and right MCA 80.27+/-4.13 cm/s in the younger group; left MCA 72.15+/-6.37 cm/s and right MCA 70.68+/-6.79 cm/s in women aged 20-34; left MCA 63.85+/-7.08 cm/s and right MCA 63.06+/-7.29 cm/s in women aged 35-50; left MCA 60.67+/-6.85 cm/s and right MCA 59.10+/-5.36 cm/s in the last group. CONCLUSIONS: The present study defined a normal age-related range of variations in MCA BFVs, useful for future comparisons in studies involving pathological female subjects.

Two episodes of ifosfamide-related neurotoxicity in the same patient following different schedules and doses of the drug. A case report.

We report the first case of recurrent ifosfamide-related neurotoxicity in the same patient following two distinct administrations of the drug at different doses and schedules and with a long interval between the two episodes. Remarkably, the first event was characterized by confusion and hallucinations, while the second, 29 months later, was characterized by partial and generalized seizures. Between the two episodes the patient had received high-dose cyclophosphamide, an oxazophoshorine agent closely related to ifosfamide, without any neurological side effects. We briefly discuss the diagnosis and management of ifosfamide-related encephalopathy.

[Evoked potentials and headache]. / Potenziali evocati e cefalea.

The multiform clinical varieties of idiopathic headache still represent an unclearly defined nosological entity; what is more, there is still no definitive etiopathogenetic and clinical classification which is unanimously supported by specialists in this sector. Moreover, given that the physiopathological mechanism which triggers off the various forms of headache is still not completely clear, yet it is obvious that research is focused on the identification of a test which is valid in terms of clinical diagnosis but at the same time can contribute towards neurophysiological examination. In order for a test to be of practical use also in terms of neurophysiological research, as well as being diagnostic, it should be able to examine the patient's neurosensory function, offering advantages in clinical terms, and contribute to clarifying the role of neurotransmitters in pain genesis. The test must also be non-invasive, offer comparable results, be repeatable after short intervals and be well tolerated by children. These represent the fundamental characteristics of a test which is applicable to the heterogeneous population of headache sufferers. In this context evoked potentials (EPs), using various forms of sensorial stimulus, appear to represent the ideal test; by exploring the well known and anatomically well defined neuronal systems at various levels of the CNS, they also help to explore the neurotransmitter function of the former, providing further information regarding the genesis of the crisis. A review of the literature examined in the present study showed the validity of the tests both in discriminating the various clinical forms of headache and supplying important information regarding the neurotransmitter-related genesis of the chain of nervous and vascular alterations leading to cephalic pain.

Effect of lipid-lowering treatment on progression of atherosclerotic lesions--a duplex ultrasonographic investigation.

The Prevenzione Aterosclerosi Studio Torino (P.A.S.T.) was a prospective, randomized trial testing the effect on carotid and femoral atherosclerotic lesions of lipid-lowering therapy, as assessed by duplex scanning (DS) technique, in 85 patients (12 women, 73 men), forty-five to fifty-five years old, with ischemic heart disease (IHD), and randomly assigned to a hypolipidemic diet or diet + 250 mg acipimox (a nicotinic acid compound) two to three times/day. Forty-one patients, without inclusion criteria, were compared with the randomized groups as a reference population. All three groups were submitted to DS and to hematic monitoring of lipid levels at the beginning and at the end of the study. During three years of treatment, there was a significant reduction (-6.5%) in total plasma cholesterol in the diet + drug group (P = 0.04) and a simultaneous elevation of high-density lipoprotein cholesterol, significant in the treatment groups (respectively, +15% P = 0.02 in the diet and +16% P = 0.016 in the diet + drug group). Every group showed a trend toward the increasing number of lesions in all explored areas and toward the progression in size of the already existing ones. Whereas in the initial DS the prevalence of lesions was significantly lower in the nonrandomized group in every site, at the end of the study the total number of lesions did not differ among groups, and there was a significant increase of plaques in carotid area in the nonrandomized group in comparison with the treatment groups. The final number of stable plaques was greater in the treatment groups as compared with the nonrandomized group (P = 0.01 diet vs nonrandomized, P = 0.03 diet + drug vs nonrandomized). In conclusion, lipid-lowering treatment, with diet and with diet + drug, was useful in slowing the natural progression of atherosclerosis; particularly, it reduced the development of new lesions in the carotid and femoral arteries and increased the stability of the already existing ones. In these patients, diet was equivalent to diet + drug in regard to progression of lesions. The most favorable results in the treatment groups seem to correlate with high-density lipoprotein cholesterol, significantly increased in comparison with the nonrandomized group.

Cerebral blood flow and volume in symptom-free migraineurs: a SPECT study.

Both CBF and CBV were evaluated by gamma-camera SPECT in 14 patients with classic migraine, all studied while symptom-free. Nuclear data were correlated with CT and MRI. A decreased regional CBF was observed in 13 of the 14 patients. The decreased perfusion was localized in the frontal lobe in 6 patients, the temporal lobe in one, the parietal lobe in 11 and the occipital lobe in 5 patients. The parieto-occipital cortex was involved more often than the frontal cortex; the association of hypoperfusion with parieto-occipital cortex was quite high. The right parieto-occipital regions were affected more often than the left ones. Regional CBV was increased in 8 patients. There was good topographical concordance between decreased CBF and increased CBV, but the increase of CBV was in general more evident at the periphery of the hypoperfusion. It is of interest that the only patient with a normal CBF study had a pathological CBV study. Apparently, CBF derangements are very common in symptom-free patients with classic migraine, a CBF decrease being often accompanied by a CBV increase. In these patients both CT and MRI have a lower diagnostic yield than SPECT.

[Comparison between Doppler CW and Duplex-Scanning in the assessment of silent peripheral vascular lesions in a population of ischemic heart disease patients]. / Confronto tra Doppler CW e Duplex-Scanning nella valutazione delle lesioni vascolari periferiche silenti in una popolazione con cardiopatia ischemica.

A recent ultrasound technique, Duplex Scanning (D-S), endowed with significant sensitivity, specificity and accuracy has been used to screen atherosclerotic disease in subjects at risk. Within the context of a transverse investigation aimed at identifying the multi-district nature of atherosclerotic plaques, the sensitivity and specificity values and the concordance index of Doppler C.W. (D-CW) have been checked using the D-S in carotid districts as a reference test in 205 patients suffering from ischaemic cardiopathy, asymptomatic for carotid vasculopathy, aged between 45 and 55. 170 patients had the D-CW and the D-S in 340 carotid vessels. D-CW revealed atherosclerotic changes in 122 carotids (prevalence 36%) while the D-S in 119 districts (prevalence 35%) revealed plaques greater than simple thickening, of which 89 (26%) with stenosis less than 30% and 30 (9%) with stenosis greater than 30%. Of the latter, 25 were greater than 60% and 5 less than 60%: one of them provoked a stenosis greater than 75%, the limit beyond which the change becomes haemodynamically significant. D-CW showed 46% sensitivity, a specificity of 70% and a concordance percentage of 59% with respect to D-S. D-CW sensitivity proved apparently low as did the concordance percentage between C-CW and D-S. However, considering that the lesions encountered were prevalently all haemodynamically non-significant, these values may become acceptable.(ABSTRACT TRUNCATED AT 250 WORDS)

[Chemodectoma of the pterygo-maxillary fossa]. / Chemodectoma della fossa pterigo-mascellare.

Cervicocephalic chemodectomas are rare non-chromaffin paraganglionic tumours, most often originating in the carotid body or the jugular ganglion. Their main features are a reluctance to invade adjacent tissue and the absence of general clinical signs. Since they are histologically quite varied they may at times be difficult to recognise. A chemodectoma of a hitherto unreported type is described. Encountered in the pterygo-maxillary fossa it was identified by computerised axial tomography and angiography.