Reproducibility and effect of levodopa on dopamine transporter function measurements: a [18F]CFT PET study.

The objective of this article was to study the reproducibility and effect of levodopa on dopamine transporter function measurements using 2beta-carbomethoxy-3beta-(4-[18F]fluorophenyl)tropane ([18F]CFT) positron emission tomography (PET). Seven de novo patients with Parkinson's disease (PD) were studied twice, before and after three months of levodopa medication. Eight healthy volunteer subjects participated in the reproducibility study. The [18F]CFT PET scan was done twice with an interval of approximately 2.5 months. The regions of interest (anterior and posterior putamen, caudate nucleus, and cerebellum) were drawn on individual magnetic resonance imaging (MRI) images, matched with the PET images, and copied onto the PET images. The [18F]CFT uptake was calculated as the region-cerebellum:cerebellum ratio at 180 to 210 minutes. Three-month levodopa treatment in PD patients had no significant effect on [18F]CFT uptake in any striatal subregion between the two PET scans. In PD patients, the percent change from baseline was 4.1% in the anterior putamen, 1.9% in the posterior putamen, and 4.0% in the caudate nucleus. No significant differences in [18F]CFT uptake between the first and second PET scan in any striatal subregion occurred in healthy controls. The intraclass correlation, indicating the reproducibility of the PET scan within subjects, was 0.94 for the anterior putamen, 0.86 for the posterior putamen, and 0.91 for the caudate nucleus. The percent change from baseline was 4.0% in the anterior putamen, 1.1% in the posterior putamen, and 2.8% in the caudate nucleus. Long-term levodopa treatment in PD patients had no effect on the [18F]CFT uptake in the striatum and the test-retest reproducibility was very high. These findings confirm [18F]CFT as a suitable ligand to monitor progression of PD.

Central and peripheral nervous system dysfunction in the clinical variation of Salla disease.

OBJECTIVE: To evaluate the degree of possible peripheral nervous system (PNS) involvement in addition to CNS manifestations in Salla disease, a free sialic acid storage disorder leading to severe mental retardation with a wide clinical variation. BACKGROUND: Salla disease is a lysosomal storage disorder that affects the white matter of the CNS. MRI findings and recent 1H MRS study results provide evidence for delayed central myelination, but there is no previous evidence for PNS involvement in this disease. The gene coding for a presumptive sialic acid transport protein has recently been identified, and the first disease-causing mutations have been characterized. METHODS: Nerve conduction studies; evoked potentials to visual (VEP), brainstem auditory (BAEP), and somatosensory stimuli (SEP); and EEG were carried out on 22 patients (age range 2 months to 57 years) with biochemically and genetically confirmed Salla disease. Brain MRI were available on 14 patients. RESULTS: Nerve conduction studies revealed abnormalities in nearly half of the patients (10/21). The four severely disabled patients and the oldest patient had greatly reduced nerve conduction velocities and prolonged distal latencies compatible with demyelinating polyneuropathy. In addition, SEP was abnormal in the majority of the patients, but VEP and BAEP in only a few cases. PNS involvement was clearly associated with both the phenotypic severity and MRI findings. CONCLUSIONS: The results indicate that dysmyelination in Salla disease occurs not only in the CNS but also in the peripheral nervous system, contributing to the phenotypic variation, which can now be correlated with the molecular basis of the disease.

A new metabolite contributing to N-acetyl signal in 1H MRS of the brain in Salla disease.

OBJECTIVE: To determine whether N-acetylaspartate (NAA) is reduced in patients with Salla disease, a neurodegenerative disorder. BACKGROUND: 1H MRS allows the brain metabolism to be studied noninvasively in vivo. N-acetyl (NA) is composed primarily of NAA, which is regarded as a neuronal marker. The NA signal in 1H MRS is reduced in several neurodegenerative disorders. Increased NA signal has thus far only been found in Canavan's disease as a result of NAA accumulation in the brain tissue. In Salla disease, an autosomal recessive free sialic acid storage disorder, N-acetylneuraminic acid (NANA), accumulates in lysosomes of brain tissue. METHODS: The authors studied eight patients with Salla disease (age range, 6 to 44 years) and eight age-matched healthy volunteers using quantitative 1H MRS. The spectra were obtained from two selected 8-cm3 volumes of interest localized in the basal ganglia and in the parietal white matter using conventional 1.5-T MRI equipment. The spectral resonance lines of NA groups, creatine and phosphocreatine (Cr), and choline-containing compounds (Cho) were analyzed quantitatively. All MR images were evaluated to verify the state of myelination. RESULTS: 1H MRS from parietal white matter revealed 34% higher NA and 47% higher Cr concentrations, and a 35% lower Cho concentration in the patients with Salla disease compared with the age-matched control subjects. The patients had a 22% higher water content in their parietal white matter, whereas in the basal ganglia the water concentrations did not differ significantly. In the patients' basal ganglia the Cr concentration was 53% higher. CONCLUSIONS: NAA is considered to be a neuronal marker that, except for Canavan's disease, has been found or assumed to be either stable or reduced. However, in Salla disease the high NA signal may have a contribution from accumulated lysosomal NANA, which offsets the possible loss of NAA. The high Cr is in line with the increased glucose uptake found in our earlier 2-fluoro-2-deoxy-D-glucose-PET study, reflecting increased energy demand. It is worth noting that in a conventional 1H MRS ratio-based analysis these underlying abnormalities would have remained undetected. Our study thus emphasizes the importance of a quantitative assessment of metabolite concentrations in 1H MRS for detecting altered brain metabolism.

Radiotherapy treatment planning and long-term follow-up with [(11)C]methionine PET in patients with low-grade astrocytoma.

PURPOSE: To evaluate the feasibility of [(11)C]-methionine positron emission tomography (MET PET) in radiotherapy (RT) treatment planning and long-term follow-up in patients with low-grade glioma. PATIENTS: Thirteen patients with low-grade astrocytoma and 1 with anaplastic astrocytoma underwent sequential MET PET and magnetic resonance imaging (MRI) before and 3, 6, 12, and 21-39 months after RT, respectively. Ten patients were studied after initial debulking surgery or biopsy and 4 in the recurrence phase. METHODS: A total of 58 PET scans were performed. After transmission scanning, a median dose of 425 MBq of MET was injected intravenously and emission data was acquired 20 min after injection for 20 min. The uptake of MET in tumor area was measured as standardized uptake value (SUV) and tumor-to-contralateral brain SUV ratios were generated to assess irradiation effects on tumor metabolism. Functional imaging with PET was compared with concurrent MRI in designing the RT planning volumes and in assessment of response to RT during a median follow-up time of 33 months. RESULTS: In 12 patients (86%), tumor area was clearly discernible in the baseline PET study. In the remaining 2 patients with a suspected residual tumor in MRI, PET showed only a diffuse uptake of MET interpreted as negative in the original tumor area. In the dose planning of RT, MET PET was helpful in outlining the gross tumor volume in 3 of 11 cases (27%), whereas PET findings either coincided with MRI (46%) or were less distinctive (27%) in other cases. In quantitative evaluation, patients with a low tumor SUV initially had significantly better prognosis than those with a high SUV. Tumor-to-contralateral brain uptake ratios of MET discriminated well patients remaining clinically stable from those who have since relapsed or died of disease. CONCLUSION: Quantitative MET PET has prognostic value at the time of initial treatment planning of low-grade glioma. Some patients may benefit of RT volume definition with MET PET, which seems to disclose residual tumor better than MRI in selected cases. Stable or decreasing uptake of MET in tumor area after RT during follow-up seems to be a favorable sign.

Bone mineral density after allogeneic bone marrow transplantation.

Bone turnover markers and bone mineral density (BMD) were studied in 25 adult patients (14 females, 11 males) who had undergone allogeneic bone marrow transplantation (BMT). The interval from BMT to the first examination was at least 1 year (mean 3, range 1-10). Mean age of the patients at the time of first evaluation was 42 (range 19-54) years. Blood samples and urine collections for evaluation of biochemical factors reflecting skeletal turnover were performed together with the first BMD measurement. BMD was measured from the lumbar vertebrae (L2 to L4) with computed tomography and results were expressed as Z-scores. At the time of the first measurement five patients (20%) had Z-scores <-2.5 s.d. and 12 patients (48%) between -1 and -2.5 s.d. In 12 patients BMD assessments were repeated and it seemed that reduction in BMD had mostly occurred during and shortly after BMT and remained the same during follow-up. The cross-linked carboxyterminal telopeptide of type I collagen (ICTP) correlated negatively with BMD (r = -0.45, P = 0.045) as did bone-specific alkaline phosphatase (BAP; r = -0.64, P = 0.002). No correlation between BMD and time interval from diagnosis to BMT, conditioning regimen, corticosteroid use or hospital stay during transplantation was found. In conclusion, bone disease is common after BMT. Our findings demonstrate an increased collagen and bone turnover and a high risk of osteoporosis. BMD measurements must be repeated regularly and collagen markers such as ICTP and BAP can be beneficial in estimating the activity of bone disease.

Striatal D2 dopamine receptor binding characteristics in vivo in patients with alcohol dependence.

Striatal D2 dopamine receptor characteristics of nine male patients with alcohol dependence abstinent for 1-68 weeks and eight healthy male volunteers were studied in vivo with positron emission tomography. The selective D2 receptor ligand [11C]raclopride and equilibrium model was used for D2 receptor density (Bmax) and affinity (Kd) measurements. A trend for a decreased striatal D2 receptor density and for reduced D2 receptor affinity was observed in patients with alcohol dependence. These parameters were not statistically significantly different between alcoholics and controls, but the ratio between D2 receptor density and affinity (Bmax/Kd or the striatum/cerebellum ratio from the high specific activity scan) was highly significantly lower in alcoholics than that of controls. In conclusion, the low D2 dopamine receptor Bmax/Kd ratio (striatum/cerebellum ratio) indicates that specific aspects of striatal [11C]raclopride binding in vivo are deviant in alcoholics compared to controls. The result is compatible with a reduced avidity of striatal dopamine D2 receptors in alcoholics, which is in line with the idea that D2 dopaminergic mechanisms are involved in the biology of alcohol dependence in man.

Brain involvement in Salla disease.

BACKGROUND AND PURPOSE: Our purpose was to document the nature and progression of brain abnormalities in Salla disease, a lysosomal storage disorder, with MR imaging. METHODS: Fifteen patients aged 1 month to 43 years underwent 26 brain MR examinations. In 10 examinations, signal intensity was measured and compared with that of healthy volunteers of comparable ages. RESULTS: MR images of a 1-month-old asymptomatic child showed no pathology. In all other patients, abnormal signal intensity was found: on T2-weighted images, the cerebral white matter had a higher signal intensity than the gray matter, except in the internal capsules. In six patients, the white matter was homogeneous on all images. In four patients, the periventricular white matter showed a somewhat lower signal intensity; in five patients, a higher signal intensity. In the peripheral cerebral white matter, the measured signal intensity remained at a high level throughout life. No abnormalities were seen in the cerebellar white matter. Atrophic changes, if present, were relatively mild but were found even in the cerebellum and brain stem. The corpus callosum was always thin. CONCLUSION: In Salla disease, the cerebral myelination process is defective. In some patients, a centrifugally progressive destructive process is also seen in the cerebral white matter. Better myelination in seen in patients with milder clinical symptoms.

Proton spectroscopy in children with epilepsy and febrile convulsions.

An association between complex febrile convulsions and the development of hippocampal atrophy, which is characterized by neuron loss and gliosis, has been suggested but is still controversial. In proton magnetic resonance spectroscopy (1H-MRS) a reduction in N-acetylaspartate (NAA), a neuron marker, or in its ratio to other metabolites, that is, creatine and phospocreatine (Cr) and choline-containing compounds (Cho), is considered a sensitive method for detecting neuron loss. We performed 1H-MRS of mesial temporal regions, including hippocampi, in two different groups of children with epilepsy: in children with a history of complex febrile convulsions (CFCs) (n = 7; mean age 7.1 years) and in children without any history of CFCs, referred to herein as the non-CFC group (n = 6; mean age 7.6 years). Changes in the metabolite ratios were detected in 57% of children in the CFC group and in 67% of children in the non-CFC group. In both groups, NAA/(Cho + Cr), NAA/Cho, and NAA/Cr were significantly decreased ipsilaterally to the seizure focus when compared with the control group, but no significant differences were detected between the CFC and non-CFC groups. Also on the contralateral side, NAA/(Cho + Cr) and NAA/Cr were significantly decreased in both patient groups, but the differences were not significant between the CFC and non-CFC groups. Metabolite abnormalities in the mesial temporal region were detected in children with intractable epilepsy and in children whose epilepsy is well controlled by antiepileptic medication. The noninvasive 1H-MRS can be considered an additional diagnostic method to promote early detection of mesial temporal abnormalities that, in the light of this study, seem to be underdiagnosed in children with either temporal lobe epilepsy or other seizure types.

Temporal lobe pathology in epilepsy: proton magnetic resonance spectroscopy and positron emission tomography study.

Hippocampal atrophy characterized by neuronal loss is a common feature in intractable temporal lobe epilepsy in adults. In proton magnetic resonance spectroscopy, a reduction in N-acetylaspartate or in its ratio to other metabolites is considered a sensitive method for detecting neuronal loss. This noninvasive approach was used to study the temporal lobes, especially the hippocampal regions of children with partial epilepsy. In all cases, 2-[18F]fluoro-2-deoxy-D-glucose scans were studied to verify the extension of the hypometabolic area. Five children manifested temporal lobe epilepsy; in 2 of them, epilepsy was intractable. Both manifested temporal hypometabolism on positron emission tomography, hippocampal atrophy on magnetic resonance imaging, and significant reductions in the metabolite ratios on spectroscopy ipsilateral to the seizure focus, as verified by EEG. Three children with temporal lobe epilepsy had infrequent seizures. One of them had a reduction in metabolite ratios in the hippocampus and hippocampal atrophy on magnetic resonance imaging ipsilateral to the seizure focus. The results show that the value of proton spectroscopy lies not only in lateralizing hippocampal atrophy but also in detecting bilaterality and the extent of neuronal loss outside hippocampi. This noninvasive preoperative diagnostic method can be considered an additional technique to be used in conjunction with other imaging techniques for clinical assessment of children with intractable temporal lobe epilepsy.

CT examination of spinal tumours.

Forty-five patients with a spinal, intraspinal or paraspinal tumour were evaluated by computed tomography. All examinations revealed pathological findings. In 30 cases the extent of the tumour was determined at surgery and in only two cases was there a discrepancy from the CT findings. Twenty-nine patients also underwent conventional myelography, three of which were negative. In the estimation of the extent of extradural tumours or bone involvement, CT was superior to other methods, but the size and localization of intradural tumours were estimated equally well by CT and conventional myelography. In patients with an intramedullary lesion CT was necessary to distinguish a solid neoplasm from a cystic lesion. In CT examinations of intraspinal tumours, intrathecal contrast medium increased the amount of information obtained especially in the thoracic and cervical regions, but was not necessary if myelograms were available. Intravenous contrast medium helped in the evaluation of some intraspinal neoplasms but did not improve the delineation of the paraspinal components.

MRI and plain radiographics in acute frontal sinus infections.

Twenty-seven patients with acute frontal sinusitis, collected during a 4-month period, were examined with plain radiographics and MRI both at the time of diagnosis and one month later. Findings in the frontal and ethmoidal sinuses were recorded. Frontal sinus trephination was performed in 13 of the 27 cases. The study shows that MRI is as reliable as X-ray in diagnosing an acute paranasal sinus infection with clinical symptoms. Frontal sinusitis is not an isolated disease affecting only the frontal sinuses: Mucosal pathology can also be found widely in the ethmoidal cells, and this pathology seems to persist in many cases for weeks. MRI showed its capability in confirming these findings. MRI was not found to be an over-diagnosing method in registering the secretions and mucosal swelling during an acute paranasal sinus infection.

Adolescent disc degeneration--no headache association.

The objective of the study was to determine whether adolescents with headache have more disc degeneration in the cervical spine than headache-free controls. This study is part of a population-based follow-up study of adolescents with and without headache. At the age of 17 years, adolescents with headache at least three times a month (N = 47) and adolescents with no headache (N = 22) participated in a magnetic resonance imaging (MRI) study of the cervical spine. Of the 47 headache sufferers, 17 also had weekly neck pain and 30 had neck pain less than once a month. MRI scans were interpreted independently by three neuroradiologists. Disc degeneration was found in 67% of participants, with no difference between adolescents with and without headache. Most of the degenerative changes were located in the lower cervical spine. In adolescence, mild degenerative changes of the cervical spine are surprisingly common but do not contribute to headache.

Dorsal CSF space at CI-II level. Technique of cervical myelography.

The width of the dorsal CSF space at the CI-II lateral puncture site was measured, both in extension and in the neutral position of the head, in 60 patients undergoing cervical myelography. The sagittal diameter of the dorsal CSF space did not change in 22 patients, was larger in extension in 27 patients, and larger in the neutral position in 11 patients. In three patients with a large dorsal CSF space the change in diameter was more than 2 mm whereas in other patients the change was minimal. Lateral CI-II puncture may be performed safely both in extension and in the neutral position. Distribution of the contrast medium was more satisfactory if the head was extended.

Spinal epidural abscess: an unusual cause of sciatica.

A previously healthy patient was admitted to our hospital because of low back pain and sciatica. For 4 weeks preceding the admission, he had been treated with nonsteroidal antiinflammatory analgetics and bed rest with a clinical diagnosis of lumbar disc herniation. On admission, the patient was subfebrile but developed general symptoms of septic infection by the next day. Computed tomography and magnetic resonance imaging of the lumbar spine revealed a spinal epidural abscess and spondylodiscitis at the L5-S1 level. During an emergency laminotomy, gross pus in abundance was evacuated from the epidural space; microbiological cultures from the pus and blood yielded Staphylococcus aureus. The unique clinical presentation of our patient combined with merely indolent symptoms of infection delayed the correct diagnosis. We are not aware of any similar reports of patients with lower spinal epidural abscess whose primary presentation was sciatic pain.

Suppression of GH secretion in pituitary gigantism by continuous subcutaneous octreotide infusion in a pubertal boy.

We describe a 12-y-old boy with excessive growth hormone and prolactin secretion presumably due to diffuse somatotroph hyperplasia. Until mid-puberty, his growth rate was under reasonable control, with high-dose octreotide injections every 8 h combined with a dopamine agonist. As his growth velocity started to increase, the efficacy of continuous s.c. octreotide infusion on GH secretion was tested. Similar total daily doses (600 microg) of octreotide were administered either by incremental s.c. injections at 8 h intervals, or by continuous s.c. infusion, two-thirds of the amount during night-time to control the presumed high nocturnal growth hormone (GH) peaks of the pubertal growth spurt. An overnight GH profile showed inadequate suppression of GH levels by incremental injections, while continuous s.c. infusion efficiently brought down the GH secretion. Another somatostatin analogue, lanreotide as a single depot injection was not effective. A 6-mo trial on the s.c. infusion regimen significantly reduced growth hormone secretion (as judged by IGF-I and IGFBP3 concentrations), and normalized growth velocity overcoming the pubertal growth spurt. It also caused a decrease in the pituitary size in magnetic resonance images. We conclude that the efficacy of octreotide infusion in suppressing GH secretion is superior to incremental injections with the same dose.

Extrastriatal dopamine D(2) receptors in Parkinson's disease: a longitudinal study.

Most antiparkinsonian drugs are known to act through central dopamine D(2) receptor agonism. A previous longitudinal positron emission tomography (PET) study has indicated that, in the striatum of Parkinson's disease (PD) patients, dopamine D(2) receptor binding declines at a relatively fast annual rate of 2-4% (compared to the rate of <1%/year in healthy individuals). In the present study, the examination of longitudinal changes in D(2) receptors was extended to extrastriatal brain regions in PD. Eight early PD patients were examined twice with PET, approximately 3 years apart, using a high-affinity extrastriatal D(2)/D(3) receptor tracer, [(11)C]FLB 457. Both the MRI-referenced region-of-interest method and the voxel-based statistical analysis method were used independently in the analysis. Regional D(2)-like availabilities (binding potentials) in the left dorsolateral prefrontal cortex, the left temporal cortex and the left and right medial thalami were significantly decreased at the second examination by 20-37% (corresponding to an annual decline of 6-11%). Thus, the annual loss of extrastriatal D(2) availability in PD is up to three times faster than the rate previously reported in the putamen. Our longitudinal study shows first evidence concerning cortical D(2) receptor loss in the progression of PD, although it is not possible to distinguish between the effects of the therapy and the disease.