55Cobalt (Co) as a PET-tracer in stroke, compared with blood flow, oxygen metabolism, blood volume and gadolinium-MRI

Axonal degeneration plays an important role in the accumulation of disability in patients with multiple sclerosis (MS). Pathological studies have demonstrated axonal damage, particularly in areas of acute inflammation and demyelination, and in chronic lesions. Axonal loss and its progression, which is associated with neurological disability, has also been demonstrated by magnetic resonance imaging (MRI) studies. The mechanisms of axonal loss are uncertain, but may involve axonal degeneration secondary to demyelination, or damage to the axonal cytoskeleton. Inflammatory mediators, including cytokines and proteolytic enzymes may contribute to axonal damage, as may nitric oxide. Axonal destruction may also be due to immune attack directed at axonal components. The realisation that axonal degeneration is a fundamental component of MS that may occur early in the disease course should alter the approach to management and open avenues to a more targeted immunotherapy aimed at reducing the progression of disability.     

Capillary telangiectasis, angiographically occult vascular malformations. MRI symptomatology apropos of 7 cases

OBJECTIVE: Describe the MRI findings in capillary telangiectasias. MATERIALS AND METHODS: Between 1996 and 1999, we observed 9 cases of capillary telangiectasia in 7 patients explored 5 times for posterior fossa symptoms. In two cases capillary telangiectasia was a fortuitous discovery. All patients were explored by MRI with T1 sequences with and without gadolinium injections, turbo spin echo T2 coupled in 5 cases with a double echo gradient echo T2 sequence (TR: 970 ms, TE: 15 and 35 ms). Two patients also underwent vertebral angiography. RESULTS: The telangiectasia gave a low intensity signal on T1 sequences in 2 of the 9 cases and a discretely high intensity signal on T2 sequences in all cases. After gadolinium injection, 9 telangiectasias showed homogeneous or speckled enhancement. The echo-gradient T2 images showed a very low intensity signal in 7 out of 7 cases on the second echo. At the first echo, 4 capillary telangiectasias were undetectable. The two vertebral angiographies were normal and the follow-up MRI in 5 patients showed lesion stability. CONCLUSION: Pontile lesions with no mass effect showing enhancement after gadolinium injection and with or without a discrete T2 high intensity signal but with a frank echo-gradient T2 signal strongly suggest capillary telangiectasia.     

3-Nitropropionic acid induces a spectrum of Huntington's disease-like neuropathology in rat striatum

Systemic administration of the mitochondrial toxin 3-nitropropionic acid (3-NP) to rats results in selective striatal lesions and serves as an experimental model of Huntington's disease (HD). However, the effects of the 3-NP treatment are unpredictable and result in lesions of variable severity. The present study was aimed at further characterizing the variability of the striatal lesions induced by systemic administration of 3-NP using osmotic pumps. Hematoxylin-eosin (HE) and Nissl stains as well as immunohistochemical labelling of astrocytes and striatal neurones were performed to analyse the neurotoxic effects of 3-NP. In general, chronic systemic administration of 3-NP resulted in obvious bilateral striatal lesions, which ranged from mild to severe, together with a subtle, but detectable behavioural lesion. Severe type lesions showed marked neuronal loss and an increased expression of glial fibrillary acidic protein (GFAP) in astrocytes surrounding the lesion area, whereas in the core of the lesion GFAP-immunoreactivity was absent. The mild type lesion was characterized by a substantial loss of striatal neurones and an increased expression of GFAP-positive astrocytes throughout the lesion. In a number of 3-NP-treated animals, neither type of lesion was observed, although these animals demonstrated behavioural changes in the paw test compared to controls. In the striatum of these tested 3-NP-treated animals, compromised rk' neurones were detected, suggestive of subtle and early 3-NP-induced neuronal injury. Similar dark neurones were also detected in mild and severe lesions and were immunocytochemically characterized as gamma-aminobutyric acid (GABA) and substance P containing spiny neurones, which belong to the neuronal population that is affected in early HD. These results indicate that systemic administration of 3-NP to rats may result in a spectrum of striatal pathology of which the morphology of the mild type lesion resembles the characteristic HD neuropathology most closely.     

Biochemical features of mtDNA 14484 (ND6/M64V) point mutation associated with Leber's hereditary optic neuropathy

We report the effect on complex I function of the 14484 Leber's hereditary optic neuropathy (LHON) mutation affecting the ND6 subunit gene. The same gene was also reported to carry another mutation, at position 14459, associated with the LHON/dystonia phenotype that induces a reduction of complex I-specific activity and increases the sensitivity to the product decylubiquinol. Given the proximity of both mutations in the ND6 gene, we tested the specific activity of complex I and its sensitivity to myxothiazol and nonylbenzoquinol, both inhibitors at the ubiquinol product site, in platelet submitochondrial particles from nine 14484 homoplasmic individuals, 8 Italians with Caucasian mtDNA haplogroup J (adjunctive 4216 and 13708 mutations), and 1 Tunisian with an African mtDNA haplogroup. The specific activity of complex I was not affected by the 14484 mutation, but the sensitivity to both inhibitors was significantly increased compared with control subjects regardless of the presence of haplogroup J polymorphisms. Analysis of 70 different amino acid sequences of the ND6 subunit indicated that the 14484 mutation affects an amino acid belonging to its most conserved region, which shows local similarities with cytochrome b regions interacting with ubiquinone or ubiquinol in complex III. Our results suggest that both 14484 and 14459 mutations may affect amino acids forming the interaction site of ubiquinol product, and the 14484 mutation produces a biochemical defect resembling in part that already reported for the common 11778/ND4 LHON mutation.     

Community care for patients with Alzheimer's disease and non-demented elderly people: use and satisfaction with services and unmet needs in family caregivers

OBJECTIVE: This study measures and compares use of and satisfaction with medical and social services in addition to subjectively perceived needs of family supporters of patients with probable or possible Alzheimer's disease (AD) and family supporters of non-demented elderly people. Differences in judgement of services within the subpopulation of families of AD patients are also assessed by gender and burden level.METHODS: The main family supporters of 60 community-dwelling elderly (aged over 65) with Alzheimer's disease and of 60 age- and sex-matched controls were tested with a detailed questionnaire on use and satisfaction with services, any unmet needs and kinds of intervention perceived to be helpful.RESULTS: Supporters of elderly people with AD were significantly more involved in providing care than supporters of non-demented people. Judgement on the health, social relations and financial status of their families was significantly worse in AD supporters than in supporters of non-demented elderly people. Although the former made more use of available health and social services than the control population, they did appear to make little use of such services, not only because of lack of information but also for logistic reasons or because they would prefer a service with more specifically trained operators or more tailored intervention. AD family supporters would like to receive more information and support from their general practitioner, which confirms the importance of this figure in management of this pathology. They were less satisfied with the care provided than the control population, particularly those with a moderate-high burden. Irrespective of burden level, they also expressed a need for financial and psychological support and adequate intervention schemes, especially within the home. These should be provided by specially trained personnel and be tailored to specifically manage the individual patient's problems, especially in relation to behavioural disorders. This would help alleviate caregiver burden and allow patients to continue to be managed at home.     

Early onset cerebellar ataxia and preservation of tendon reflexes: clinical phenotypes associated with GAA trinucleotide repeat expanded and non-expanded genotypes

The aim of this study was to determine phenotypie characteristics of patients with early onset cerebellar ataxia (EOCA) with preserved tendon reflexes. The series comprises 25 patients, representing 10% of all ataxic patients who have been genetically studied in our laboratory since 1990. There were 11 males and 14 females. Fourteen patients were homozygous for the GAA expansion on chromosome 9q13 (group 1) and therefore a diagnosis of Friedreich's ataxia with retained reflexes (FARR) was given. The remaining 11 patients had two normal non-expanded alleles (group 2) and a working diagnosis of EOCA with retained reflexes (EOCARR) was established. Mean ages of onset were 13.7 +/- 5.9 years (3-25) for group 1 and 10.3 +/- 7.3 for group 2; the difference was not significant. Frequencies of symptoms and signs were also comparable for both groups the only significant differences being the higher frequency of nystagmus, cardiomyopathy and sensory neuropathy in group 1 patients. There was a tendency for FARR patients to have higher frequencies of hypopallesthesia in the lower limbs and skeletal deformities. In none of the cases diabetes mellitus was observed. We conclude that differentiation of FARR and EOCARR may be suspected by classical clinical and electrophysiological data and confirmed by analysis of the GAA repeat.     

Phenylalanine hydroxylation across the kidney in humans rapid communication

Phenylalanine hydroxylation across the kidney in humans. BACKGROUND: Although phenylalanine hydroxylase activity is detectable in in vitro renal tissue preparations, no data on in vivo phenylalanine hydroxylation across the human kidney, as well as on its possible contribution to whole-body hydroxylation, currently exist. METHODS: To this aim, we have measured whole-body, renal, and splanchnic phenylalanine hydroxylation to tyrosine, as well as phenylalanine and tyrosine rates of appearance (Ra) and disposal (Rd), in postabsorptive subjects by means of renal and splanchnic arteriovenous catheterization combined with phenylalanine and tyrosine isotope infusions. RESULTS: In the kidney, a relevant phenylalanine hydroxylation activity was detected (3.51 +/- 0.97 micromol/min x 1.73 m2 of body surface), whereas it was 2.48 +/- 1. 35 micromol/min x 1.73 m2 across the splanchnic area. These two sites together accounted for virtually the entire whole-body phenylalanine hydroxylation. Renal production of tyrosine from phenylalanine hydroxylation accounted for approximately 13% of whole-body tyrosine Ra, whereas renal total tyrosine Ra accounted for approximately 34% of whole-body tyrosine Ra. In the splanchnic area, these figures were approximately 9 and 40%, respectively. Hydroxylation accounted for approximately 70% of phenylalanine Rd in the kidney, as opposed to approximately 8% in the splanchnic area. CONCLUSIONS: These data indicate that hydroxylation represents the major route of phenylalanine disposal within the kidney. The kidney and the splanchnic bed together account for all of the whole-body phenylalanine hydroxylation. These data also provide a further explanation for the reduced tyrosine pools occurring in uremia.     

Tentorial dural arteriovenous fistula obliterated using the petrosal approach

BACKGROUND: Tentorial dural arteriovenous fistulas (AVFs) are uncommon lesions usually treated surgically using a subtemporal exposure with division of the tentorium. This exposure requires significant retraction of the temporal lobe and has the possibility of significant arterialized venous bleeding if a draining vein is accidentally cut during division of the tentorium. Skull base surgical techniques may provide alternate approaches for the surgical treatment of tentorial dural AVFs. METHODS: A tentorial dural arteriovenous fistula supplied by the tentorial artery and drained by the petrosal vein was exposed and obliterated using the petrosal (subtemporal-presigmoid) approach. RESULTS: The petrosal approach allowed the exposure and division of the superior petrosal sinus and tentorium with direct visualization of the supratentorial and the infratentorial compartments, avoiding accidental damage to the draining veins. The dural fistula was easily obliterated after its venous drainage was interrupted and the tentorial artery occluded. CONCLUSIONS: Tentorial dural AVFs can be safely treated with interruption of the venous drainage. The exposure can be enhanced with a petrosal approach, decreasing the possibility of uncontrolled bleeding during the procedure.     

Urinary interleukin-2 monitoring during prolonged bacillus Calmette-Guerin treatment: can it predict the optimal number of instillations?

PURPOSE: In patients with superficial bladder cancer treated with a first 6-week instillation course of bacillus Calmette-Guerin (BCG) the induction pattern of urinary interleukin (IL)-2 has been described, and the levels of urinary IL-2 were associated with the clinical response to BCG treatment. We evaluated urinary IL-2 kinetics in patients with recurrent superficial bladder tumor receiving a second or third 6-week BCG instillation course. To our knowledge there have been no studies of prolonged BCG treatment and urinary cytokine responses. MATERIALS AND METHODS: Urinary IL-2 was determined in 12 patients with superficial transitional cell carcinoma of the bladder receiving a complete (6-week) second or third BCG instillation course and in 3 patients receiving 3 BCG instillations during a maintenance schedule at month 3. Urinary IL-2 was determined with an enzyme-linked immunosorbent assay using an oligoclonal system. RESULTS: Of 12 patients 10 had a urinary IL-2 positive response during the subsequent BCG course and at week 1 urinary IL-2 was already increased. Comparing the urinary IL-2 kinetics observed during a second or third with a first course, urinary IL-2 tended to be higher during the first and lower during the last weeks. If the interval between subsequent courses was short (12 months or less) significantly higher urinary IL-2 levels at weeks 1 and 2, and a lower level at week 6 were observed. CONCLUSIONS: During a repeat BCG instillation course urinary IL-2 reached a maximum at an earlier week, especially if the interval between the subsequent courses was short. Since an association between urinary IL-2 levels and response to BCG treatment during an induction course has been observed, these immunological data argue in favor of a limited number of instillations during prolonged BCG therapy which could reduce side effects as well as costs.