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1.
J Neuroimmune Pharmacol ; 7(3): 665-72, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22585413

ABSTRACT

The risk of progressive multifocal leukoencephalopathy (PML) in patients treated with natalizumab for multiple sclerosis (MS) is a serious concern. The presence of anti-JC virus antibodies is a risk factor for PML development, but 2.5 % of the patients result falsely-negative, while the prognostic relevance of testing JCV-DNA in biological fluids of treated patients is debated. Aim of this work was to evaluate the utility of testing JCV-DNA, together with anti-JCV antibodies, in biological samples of treated patients as a tool for PML risk stratification. 126 subjects from 5 MS Centers in Italy were included in the study. We performed a cross-sectional study in 63 patients testing JCV-DNA in blood, peripheral blood cells and urine. We longitudinally assessed the presence of JCV-DNA in a cohort of 33 subjects, one of which developed PML. We could test retrospectively serum samples from another PML case occurred during natalizumab therapy. Anti-JCV antibodies and urinary JCV-DNA were both tested in 73 patients. No changes in JCV-DNA status occurred during natalizumab treatment. The subject who developed PML in the longitudinal cohort had detectable JCV-DNA in urine at all time-points while serum or blood from both PML patients were always negative before the onset of disease and, in one case, after. Four subjects with JCV-DNA in urine and undetectable anti-JCV antibodies were retested for anti-JCV antibodies and three out of four resulted positive. In conclusion, testing JCV-DNA in urine is complementary to testing anti-JCV antibodies in identifying patients at risk of PML.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , DNA, Viral/urine , JC Virus/metabolism , Leukoencephalopathy, Progressive Multifocal/diagnosis , Leukoencephalopathy, Progressive Multifocal/urine , Adult , Biomarkers/urine , Cross-Sectional Studies , Diagnostic Tests, Routine , Female , Humans , Leukoencephalopathy, Progressive Multifocal/drug therapy , Longitudinal Studies , Male , Middle Aged , Natalizumab , Retrospective Studies , Risk Factors , Young Adult
2.
Neurol Sci ; 31 Suppl 3: 299-302, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20544247

ABSTRACT

To evaluate the efficacy and safety of natalizumab in patients with active relapsing-remitting multiple sclerosis (MS). We included 285 MS patients receiving natalizumab. Clinical, neuroradiological and safety data were registered every 6 months. Neutralizing antibodies (NABs) were tested after 6 months of treatment. After 1 year, the annualized relapse rate decreased to 0.26, with a significant reduction compared to the previous year (2.13). At 24 months the proportion of "relapse free" patients was 78% while that of "MRI free" patients was 69%. Considering clinical and MRI cumulative activity, "disease free" patients were 63% at 24 months. A total of 18 patients showed NABs positivity. We reported 34 cases of treatment interruptions. In conclusion, our data confirm the remarkable efficacy of natalizumab in a group of patients with higher disease activity than that of pivotal studies.


Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Product Surveillance, Postmarketing/trends , Adult , Cohort Studies , Drug Hypersensitivity/etiology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Multiple Sclerosis, Relapsing-Remitting/physiopathology , Natalizumab , Treatment Outcome , Young Adult
3.
J Neurol Neurosurg Psychiatry ; 80(4): 440-3, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19289482

ABSTRACT

BACKGROUND: Hereditary spastic paraparesis (HPS) linked to mutations in the spastin gene (SPG4) is considered to be a pure form of spastic hereditary paraparesis. However, in this disease also other signs of central nervous system involvement are frequently found. METHODS: Clinical, genetical and neuroradiological investigations were carried out in a large family with autosomal dominant spastic paraparesis and in a sporadic case with spastic paraparesis. RESULTS: Additional clinical and molecular data are provided, studying other members of the same pedigree, as already described, with a five-base deletion in exon 9 of the SPG4 gene (1215-1219delTATAA) whose members show MRI anomalies that fall within the Dandy-Walker continuum. Furthermore, an unrelated female patient with hypoplasia of the cerebellar vermis is indicated, carrying a de novo previously reported mutation of the SPG4 gene (c.1741C>T p.R581X). CONCLUSIONS: Spastin may play an important role in the development of the central nervous system and in particular in the development of the structures of posterior fossa.


Subject(s)
Adenosine Triphosphatases/genetics , Cranial Fossa, Posterior/abnormalities , Cranial Fossa, Posterior/pathology , Spastic Paraplegia, Hereditary/genetics , Spastic Paraplegia, Hereditary/pathology , Adolescent , Adult , Aged , Child , Child, Preschool , Codon/genetics , Cognition/physiology , Dandy-Walker Syndrome/genetics , Dandy-Walker Syndrome/pathology , Electroencephalography , Electromyography , Exons/genetics , Female , Humans , Infant , Intellectual Disability/etiology , Intellectual Disability/genetics , Magnetic Resonance Imaging , Male , Middle Aged , Mutation , Neuropsychological Tests , Pedigree , Spastic Paraplegia, Hereditary/psychology , Spastin , Young Adult
4.
G Chir ; 29(11-12): 493-5, 2008.
Article in Italian | MEDLINE | ID: mdl-19068187

ABSTRACT

A case of bilateral testicular lymphoma with involvement of skin and oropharynx was described. After a review of literature, the Authors underline the clinical features focusing the diagnostic approaches and the therapeutics options.


Subject(s)
Lymphoma , Neoplasms, Multiple Primary , Testicular Neoplasms , Humans , Lymphoma/diagnosis , Lymphoma/surgery , Male , Middle Aged , Neoplasms, Multiple Primary/diagnosis , Neoplasms, Multiple Primary/surgery , Testicular Neoplasms/diagnosis , Testicular Neoplasms/surgery
5.
Br J Surg ; 95(11): 1339-43, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18844269

ABSTRACT

BACKGROUND: Thrombosed external haemorrhoids are one of the most frequent anorectal emergencies. They are associated with swelling and intense pain. Internal sphincter hypertonicity plays a role in the aetiology of the pain. This study evaluated the efficacy and safety of an intrasphincteric injection of botulinum toxin for pain relief in patients with thrombosed external haemorrhoids. METHODS: Thirty patients with thrombosed external haemorrhoids who refused surgical operation were randomized into two groups. Patients received an intrasphincteric injection of either 0.6 ml saline or 0.6 ml of a solution containing 30 units botulinum toxin. Anorectal manometry was performed before treatment and 5 days afterwards. RESULTS: After 5 days of treatment, the maximum resting pressure fell in both groups, but was significantly lower in the botulinum toxin group (P = 0.004). Pain intensity was significantly reduced within 24 h of botulinum toxin treatment (P < 0.001), but only after 1 week in the placebo group (P = 0.019). CONCLUSION: A single injection of botulinum toxin into the anal sphincter seems to be effective in rapidly controlling the pain associated with thrombosed external haemorrhoids, and could represent an effective conservative treatment for this condition. REGISTRATION NUMBER: NCT00717782 (http://www.clinicaltrials.gov).


Subject(s)
Botulinum Toxins, Type A/administration & dosage , Hemorrhoids/drug therapy , Neuromuscular Agents/administration & dosage , Pain/drug therapy , Thrombosis/drug therapy , Adult , Anal Canal , Analgesics/therapeutic use , Female , Hemorrhoids/complications , Humans , Injections, Intralesional , Male , Pain/etiology , Pain Measurement , Severity of Illness Index , Thrombosis/etiology , Treatment Outcome
6.
Neurology ; 61(10): 1446-8, 2003 Nov 25.
Article in English | MEDLINE | ID: mdl-14638977

ABSTRACT

We recently reported a paradoxical facilitatory effect of 1 Hz repetitive TMS (rTMS) on the primary visual cortex in migraine possibly due to the failure of inhibitory circuits, unable to be upregulated by low frequency rTMS. To investigate if inhibitory circuit dysfunction extends beyond striate cortex in migraine with aura, we studied the effects of 1 Hz rTMS over the right extrastriate cortex on perception of illusory contours in these patients. Low-frequency rTMS enhanced activity of extrastriate cortex in migraineurs, speeding up reaction times on illusory contour perception. This finding supports the view of a failure of inhibitory circuits also involving the extrastriate cortex in migraine with aura.


Subject(s)
Magnetics , Migraine Disorders/physiopathology , Visual Cortex/physiopathology , Adult , Female , Humans , Kinetics , Male , Neural Inhibition , Photic Stimulation , Visual Perception
7.
Acta Neurol Scand ; 108(5): 323-6, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14616301

ABSTRACT

OBJECTIVES: Previous papers have mainly demonstrated the presence and the frequency of cognitive impairment in patients suffering from relapsing-remitting multiple sclerosis. The purpose of this study was to investigate subjects with the relapsing-remitting form of the disease and mild clinical disability (EDSS < or = 3.5), so as to quantify this deficit when the illness does not yet interfere with daily living and the ability to work. METHODS: Fifty patients and 50 healthy controls were submitted to a wide neuropsychological battery, including Wechsler Memory Scale I- (WMS), Benton Visual Retention Test D- (BVRT), Raven Coloured Progressive Matrices (RCPM), Kohs' test (KT), Judgement of Lines Orientation H- (JLO), Facial Recognition (FR) and Aachner Aphasie Test (AAT). They also underwent Clinical Depression Scale (CDQ) and State-Trait Anxiety Inventory (STAI). RESULTS: The results show the presence of significant memory impairment on both WMS (P = 0.000) and BVRT (P = 0.000) in patients compared with controls. Patients were also impaired in abstract reasoning and problem-solving deficit (KT P = 0.003; RCPM P = 0.000) and in FR (P = 0.019). Cognitive decline correlated with illness duration (r = 0.761), but was independent of EDSS (r = 0.085). CONCLUSION: Cognitive decline was present even when physical disability was not yet severe, but it was mild and did not limit patients' ability to work. The cognitive impairment outlined was of the subcortical type and correlated with illness duration. This study emphasizes the importance of cognitive examination in clinical practice. It is suggested that a complete neurological examination include tests on memory and abstract reasoning.


Subject(s)
Cognition Disorders/diagnosis , Multiple Sclerosis, Relapsing-Remitting/complications , Adult , Cognition Disorders/etiology , Female , Humans , Male , Memory Disorders/diagnosis , Memory Disorders/etiology , Neuropsychological Tests , Severity of Illness Index , Task Performance and Analysis
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