V. Lucivero

Localised 1H-MR spectroscopy for metabolic characterisation of diffuse and focal brain lesions in patients infected with HIV

OBJECTIVES To evaluate the role of proton MR spectroscopy (1H-MRS) in detecting metabolic changes in diffuse or focal lesions in the brain of patients infected with HIV. METHODS Sixty HIV seropositive patients (25 with HIV related encephalopathies, 20 with toxoplasmosis, eight with progressive multifocal leukoencephalopathies (PMLs), and seven with lymphomas) and 22 HIV seronegative neurological controls were examined with a combined MRI and1H-MRS technique using a Siemens 1.5 Tesla Magnetom. Spectra (Spin Echo sequence, TE 135 ms) were acquired by single voxel, localised on focal lesions in toxoplasmosis, PML, lymphomas, and HIV encephalopathies and on the centrum semiovale of neurological controls. Choline (Cho), creatine (Cr), N-acetyl aspartate (NAA), lactate, and lipids were evaluated in each spectrum and NAA/Cr, NAA/Cho, and Cho/Cr ratios were calculated. RESULTS A significant decrease in NAA/Cr and NAA/Cho ratios were found in all HIV diagnostic groups in comparison with neurological controls (p<0.003), suggesting neuronal or axonal damage independent of brain lesion aetiology. However, the NAA/Cr ratio was significantly lower in PML and lymphomas than in HIV encephalopathies (p<0.02) and toxoplasmosis (p<0.05). HIV encephalopathies, lymphomas, and toxoplasmosis showed a significant increase in the Cho/Cr ratio in comparison with neurological controls (p<0.03) without between group differences. The presence of a lipid signal was more frequent in lymphomas (71%) than in other HIV groups (Fisher’s test, p=0.00003). The presence of mobile lipid resonance together with a high Cho/Cr ratio in lymphomas may be related to an increased membrane synthesis and turnover in tumour cells. A lactate signal (marker of inflammatory reaction), was found in all but one patient with PML lesions (75%), but had a lower incidence in the other HIV diagnostic groups (Fisher’s test, p=0.00024). CONCLUSION 1H-MRS shows a high sensitivity in detecting brain involvement in HIV related diseases, but a poor specificity in differential diagnosis of HIV brain lesions. Nevertheless, the homogeneous metabolic pattern that characterises PML suggests the usefulness of 1H-MRS as an adjunct to MRI in differentiating CNS white matter lesions, such as HIV encephalopathies, from PML.

Proton magnetic resonance spectroscopy in Parkinson's disease and progressive supranuclear palsy.

OBJECTIVES: Proton magnetic resonance spectroscopy (1H-MRS) localised to the lentiform nucleus, was carried out in eight patients with idiopathic Parkinsons disease and five patients with progressive supranuclear palsy. The aim of the study was to assess the concentration of N-acetyl-aspartate (NAA), creatine and phosphocreatine (Cr), and choline containing compounds (Cho) in the putamen and globus pallidus of these patients. METHODS: Peak ratios obtained from patients were compared with those from nine healthy age matched controls. RESULTS: NAA/Cho and NAA/Cr ratios were reduced significantly in patients with progressive supranuclear palsy. CONCLUSION: These results suggest an NAA deficit, due to neuronal loss, in the lentiform nucleus of these patients. 1H-MRS is a non-invasive technique that can provide useful information concerning striatal neuronal loss in the basal ganglia of patients with parkinsonian syndromes.

Different roles of matrix metalloproteinases-2 and -9 after human ischaemic stroke

Accumulating data suggest that matrix metalloproteinases (MMPs), in particular MMP-2 and MMP-9, are deleterious after acute ischaemic stroke. A beneficial effect of MMPs in the repairing phases of cerebral ischaemia has also been proposed. This study investigated the relationship between MMP-2 and MMP-9 and stroke subtypes, clinical recovery and haemorrhagic transformation (HT). We measured MMP-9 and MMP-2 plasma levels in 29 patients with ischaemic stroke at days one and seven. MMP-2 levels increased only in lacunar strokes, whilst MMP-9 increased only in patients with more severe stroke. Basal MMP-2 levels were higher in patients with stable or recovering symptoms whilst MMP-9 values at day seven were correlated with worse clinical outcome. No differences related to the presence of HT were found. This study sustains a different behaviour of MMPs after ischaemic stroke. MMP-2 seems to be expressed early and related to better outcome, whilst MMP-9 seems to be late and related to more severe stroke.

Metabolic Changes in Neuronal Migration Disorders: Evaluation by Combined MRI and Proton MR Spectroscopy

Summary: Purpose: To assess the role of 1H‐magnetic resonance spectroscopy (MRS) in detecting biochemical abnormalities in neuronal migration disorders (NMDs).

Axonal damage in multiple sclerosis plaques: a combined magnetic resonance imaging and 1H-magnetic resonance spectroscopy study

The purpose of this study was to compare magnetic resonance imaging (MRI) features and proton MR spectroscopy (1H-MRS) patterns of multiple sclerosis (MS) plaques in order to define the metabolic substrate in different lesion subtypes. Combined MRI and single-voxel 1H-MRS investigation was performed in 54 MS patients (47 relapsing remitting (RR) and seven secondary progressive (SP)). Sixty-seven MS lesions were selected. Thirty-seven lesions were Gadolinium (Gd) enhancing (nine isointense and 28 hypointense on pre-contrast T(1)-weighted scans) and 30 Gd unenhancing (six isointense and 24 hypointense on pre- and post-contrast T(1)-weighted scans). Choline (Cho), creatine (Cr), N-acetyl aspartate (NAA) and lactate were evaluated in 1H spectra acquired from MS plaques and from normal white matter (NWM) of 22 neurological controls. MS lesions of RR patients were characterized by a significant increase of Cho/Cr and decrease of NAA/Cr and NAA/Cho ratios. No significant metabolite changes were found in lesions of SP patients. Gd enhancing plaques showed lactate signal with higher frequency (37.8%) than Gd unenhancing plaques (16.7%) (p=0.04). A significant increase of Cho/Cr was found in Gd enhancing lesions when compared to controls (p<0.01), and to Gd unenhancing lesions (p<0.05). In particular, there was evidence of a significant increase of Cho/Cr in pre-contrast T(1) hypointense Gd enhancing lesions (p<0.01 vs. controls). The Gd unenhancing lesions (p<0.01), in particular the T(1) hypointense group (p<0.05), showed a significant decrease of NAA/Cr only when compared to controls. These data confirm that in vivo MRS indicates key pathological features of MS plaques. The increased Cho/Cr ratio found in Gd-enhancing plaques, in particular in the T(1) hypointense lesions, may reflect increased membrane cell turnover. The T(1) hypointense Gd unenhancing plaques better reflect axonal damage, as suggested by the decrease of NAA/Cr. Nevertheless, the lack of statistical differences in NAA/Cr between plaque subgroups suggests that axonal impairment might occur even in the early stages.

Usefulness of proton magnetic resonance spectroscopy in differentiating parkinsonian syndromes

Abstract Proton magnetic resonance spectroscopy (1H-MRS) was performed in patients with a clinical diagnosis of idiopathic Parkinsons disease (IPD), multiple system atrophy (MSA) or progressive supranuclear palsy (PSP) in order to assess metabolic differences between the three groups of patients. Single-volume 1H-MRS, localized to the lentiform nucleus, was carried out in 19 IPD patients, 14 MSA patients, 11 PSP patients and 12 age-matched healthy subjects. The signals of N-acetylaspartate (NAA), choline-containing compounds (Cho) and creatine-phosphocreatine (Cr) were evaluated as peak area ratios. The NAA/Cho peak ratio was significantly reduced in MSA and in PSP patients compared to IPD patients and to controls. The NAA/Cr peak ratio was significantly reduced in MSA, in PSP and in IPD patients compared to controls, but only in MSA compared to IPD patients. The NAA reduction in the basal ganglia of MSA and PSP patients may reflect a neuronal loss or damage. Single-volume 1H-MRS may be a useful tool in differentiating MSA and PSP from IPD patients.

Prognostic significance of metabolic changes detected by proton magnetic resonance spectroscopy in ischaemic stroke.

Proton magnetic resonance spectroscopy has proved to be useful for monitoring a number of metabolites in cerebral infarction. Combined magnetic resonance imaging and spectroscopy investigations were carried out in 14 patients with a recent ischaemic stroke (< 1 week); follow-up examinations were performed from day 28 to day 252 after stroke. The aim of this study was to assess the correlation between the changes ofN-acetyl-aspartate, choline, creatine-phosphocreatine, lactate and clinical evolution measured by the Scandinavian Neurological Scale (SNS). Initially the lactate magnetic resonance signal was present in all patients and the other metabolite contents were significantly reduced (P < 0.001; unpairedt-test) as compared with those on the contralateral side. Spearmans rank correlation test showed a positive correlation between the initial reduction ofN-acetyl-aspartate content and the SNS (P < 0.05), and between the finalN-acetyl-aspartate content and the SNS (P < 0.001). Our results suggest that serial examination in stroke patients may provide further prognostic information and encourage controlled clinical studies.

Ischaemic stroke in progressive systemic sclerosis

Abstract.Progressive systemic sclerosis (PSS) or scleroderma is a multisystem disease affecting the skin, lungs, myocardium, kidneys and gastrointestinal tract. Primary involvement of cerebral arteries in PSS has been reported but is very rare. A 61–year–old woman suffering from scleroderma for six years was hospitalised for two subsequent episodes of transient acute dysarthria and left hemiparesis. After five hours from the first onset of symptoms, she was submitted to brain magnetic resonance (MR) protocol that showed a right subinsular ischaemic lesion and whole right middle cerebral artery (MCA) territory hypoperfusion. Intracranial and epiaortic MR angiography reported a focal stenosis in the M2 portion of MCA. She was immediately treated with i.v. high dose steroids and oral acetylsalicylic acid. At one–month follow up, MR findings were confirmed. We have documented a cerebral infarct in a PSS patient. In our opinion, the ischaemic stroke was caused by a localised autoimmune angiopathy.

Proton magnetic resonance spectroscopy in primary blepharospasm

Single-volume proton magnetic resonance spectroscopy, localized to basal ganglia, was carried out in 10 patients with primary blepharospasm (PB) to assess the levels of N-acetyl aspartate (NAA), creatine-phosphocreatine, and choline-containing compounds. NAA was reduced significantly in patients compared with control subjects. This result suggests a striatal neuronal loss in PB.

Posterior spinal artery infarct due to patent foramen ovale: a case report.

Study Design. Case report. Objective. To report the first case of posterior spinal artery (PSA) infarct due to patent foramen ovale (PFO). Summary of Background Data. Infarct in the territories of PSA are very rare: till now 38 cases are reported in the literature. Moreover only 1 case of spinal cord infarction was attributed to paradoxical embolism through PFO, but in the anterior spinal artery territory. Methods. A 60-year-old woman was hospitalized for sudden numbness of the right leg. Neurologic examination revealed right leg mild paresis and loss of proprioception and dysesthesia at T11. Spine-MRI showed T5–T7 posterolateral cord ischemia. Transesophageal echocardiography disclosed a PFO with severe right-left shunt confirmed by transcranial Doppler. Results. During the hospitalization she was treated with oral-500 mg ticlopidine, because of a mild allergic reaction to acetylsalicylic acid. No steroids were administrated. Physiotherapy was performed daily. Motor and urinary symptoms disappeared in 20 days. At 1-month clinical follow-up only suspended dysesthesia on the right side was present. At 3 months follow-up spine-MRI showed no signal abnormalities within the spinal cord but the patient still complained of dysesthesia. The therapy was changed to oral 75 mg clopidogrel, cause of leucopoenia. At 1-year follow-up dysesthesia was still present, but less complaining and no recurrence and adverse effect due to clopidogrel therapy were reported. Conclusion. This report describe a case of acute nontraumatic myelopathy. At 4 days after onset, PSA infarct was diagnosed on the basis of neurologic findings and MR images. After extensive diagnostic work-up, we were able to identify only PFO, so it was the first case of PSA due to probable paradoxical embolism. The patient was treated with antiplatelet therapy with good recovery and no recurrence at 1-year follow-up.