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R Tortelli,
M Ruggieri,
R Cortese,
E D'Errico,
R Capozzo,
A Leo,
M Mastrapasqua,
S Zoccolella,
R Leante, P Livrea,
G Logroscino,
I L Simone
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ABSTRACT: BACKGROUND: To date there are no biomarkers with proven reliability as measure of disease burden in amyotrophic lateral sclerosis (ALS). The aim of our study is to assess the neurofilament light chain (NFL) in cerebrospinal fluid (CSF) samples as a measure of disease activity and progression in ALS. METHODS: Thirty-seven consecutive patients with ALS, 25 with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and 21 with other neurodegenerative diseases (OND) were evaluated. CSF NFL levels were assayed by two-site solid-phase sandwich ELISA. In patients with ALS, neurological status was assessed by revised ALS Functional Rating Scale (ALSFRS-r) and Medical Research Council (MRC), and the progression of the disease was evaluated using the 'diagnostic delay' and the 'progression rate'. RESULTS: Cerebrospinal fluid NFL levels were higher in ALS cases than in controls (P < 0.0001). Using the Receiver Operating Curve (ROC) analysis, an optimal NFL cut-off of 1981 ng/l discriminated between patients with ALS and neurological controls, with a sensitivity of 78.4% and specificity of 72.5%. Multivariate logistic regression confirmed the association between CSF NFL levels and the presence of ALS (age and sex adjusted odds ratio for ALS 8.9; 95% CI 3.1-25.8; P < 0.0001). In ALS, CSF NFL negatively correlated with the diagnostic delay (P < 0.0001) and the ALSFRS-r (P = 0.014) and positively with the progression rate (P < 0.0001). CONCLUSIONS: High CSF NFL levels were found in patients with ALS, reflecting the burden of neurodegeneration. The significant relation between CSF NFL levels and disease progression suggests that NFL may be a useful marker of disease activity and progression in ALS.
European Journal of Neurology 06/2012; · 3.69 Impact Factor
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ABSTRACT: Belief and expectation are part of placebo effect. Migraine patients are characterized by a dysfunctional modulation of pain processing, though a clear placebo effect emerges in clinical trials. The aim of the study was to evaluate the effect of visual and verbal suggestion on subjective pain sensation and cortical responses evoked by CO2 painful laser stimuli in migraine without aura patients vs healthy controls. Twenty-six patients were recorded during the inter-ictal phase and compared to 26 sex and age-matched controls. The right hand and the right supraorbital zone were stimulated during a not conditioned and a conditioned task, where laser stimuli were delivered after a verbal and visual cues of decreased (D), increased (I) or basal (B) intensity, which was left unmodified during the entire task. In control subjects pain rating changed, according to the announced intensity, while in migraine patients the basal hyper-algesia remained unmodified. The N1 and N2 amplitudes tended to change coherently with the stimulus cue in controls, while an opposite paradoxical increase in decreasing condition emerged in migraine. The P2 amplitude modulation was also reduced in migraine, differently from controls. The altered pattern of pain rating and N2 amplitude modulation concurred with frequency of migraine, disability and allodynia. In controls suggestion influenced cortical pain processing and subjective pain rating, while in migraine a peculiar pattern of cortical activation contrasted external cues in order to maintain the basal hyper-algesia. This scarce influence of induced suggestion on pain experience seemed to characterize patients with more severe migraine and central sensitization.
CNS & neurological disorders drug targets 04/2012; 11(2):110-26. · 3.57 Impact Factor
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C Tortorella,
M Ruggieri,
E Di Monte,
E Ceci,
P Iaffaldano,
V Direnzo,
M Mastrapasqua,
A Frigeri,
M P Amato,
B Hakiki,
A Ghezzi,
A Lugaresi,
G De Luca,
F Patti,
E D'Amico,
P Sola,
A M Simone,
M Svelto, P Livrea,
M Trojano
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ABSTRACT: The identification of biomarkers able to improve the differential diagnosis between multiple sclerosis (MS) and neuromyelitis optica (NMO) is challenging because of a different prognosis and response to treatment. Growing evidence indicates that brain and CSF N-acetyl aspartate (NAA) concentration is a useful marker for characterising different phases of axonal pathology in demyelinating diseases, and preliminary studies suggest that increased serum NAA levels may be a telltale sign of acute neuronal damage or defective NAA metabolism in oligodendrocytes.
To evaluate whether serum and CSF NAA concentration differs in patients with MS and NMO.
Observational, multicentre, prospective, cross sectional study.
Serum samples were collected from 48 relapsing-remitting MS, 32 NMO and 76 age matched healthy controls. Coeval CSF samples were available for all MS and for 8/32 NMO patients. NAA was measured in serum and CSF by liquid chromatography-mass spectrometry.
MS patients showed higher serum and CSF NAA levels than NMO patients, and higher serum NAA levels than healthy controls (p<0.001). High serum NAA values, exceeding the 95th percentile of serum NAA values in healthy controls, were found in 100% of patients with MS and in no patient with NMO. No differences in serum NAA levels were found between NMO and healthy controls. In MS, serum and CSF NAA levels correlated with disability score.
Determination of serum and CSF NAA levels may represent a suitable tool in the diagnostic laboratory workup to differentiate MS and NMO.
Journal of neurology, neurosurgery, and psychiatry 05/2011; 82(12):1355-9. · 4.87 Impact Factor
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ABSTRACT: The aim of the present study was to evaluate pain perception and evoked responses by laser stimuli (LEPs) in mild not demented Huntington's Disease (HD) patients. Twenty-eight HD patients and 30 control subjects were selected. LEPs were obtained by four scalp electrodes, (Fz, Cz, referred to the nasion; T3, T4, referred to Fz), stimulating the dorsum of both hands. All patients were also evaluated by somatosensory evoked potentials (SEPs) by median nerve stimulation. Only 3 patients referred pain of arthralgic type. Laser pain perception was similar between HD patients and controls. An abnormal N2, P2 and N1 latency increase was evident in the majority of HD patients. LEPs features were similar between patients taking and not taking neuroleptics. The N2 and P2 latencies, showed a negative correlation with functional score and Mini Mental State Examination, and a positive correlation with the severity of hyperkinetic movements. A delay in nociceptive input processing emerged in HD, concurring with the main features of the disease, in absence of clinical evidence of abnormalities in pain perception. The dysfunction of pain signals transmission in HD may induce sub-clinical changes of sensory functions, which may probably interfere with sensory-motor integration and contribute to functional impairment.
Acta neurologica Belgica 03/2011; 111(1):33-40. · 0.54 Impact Factor
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F. Roselli,
Nm Pisciotta,
Ms Aniello,
A. Gigante,
Mf De Caro,
E. Ferrannini,
B. Tartaglione,
A. Niccoli-Asabella,
G Defazio, P Livrea,
G Rubini
Movement Disorders 10/2010; 25(14):2478. · 4.51 Impact Factor
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M Trojano,
F Pellegrini,
D Paolicelli,
A Fuiani,
G B Zimatore,
C Tortorella,
I L Simone,
F Patti,
A Ghezzi,
V Zipoli, [......],
E Millefiorini,
M Clerico,
G Lus,
M Vianello,
C Avolio,
P Cavalla,
V Lepore, P Livrea,
G Comi,
M P Amato
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ABSTRACT: Recent findings support greater efficacy of early vs. delayed interferon beta (IFNbeta) treatment in patients with a first clinical event suggestive of multiple sclerosis (MS). We aimed to evaluate the effectiveness of early IFNbeta treatment in definite relapsing-remitting MS (RRMS) and to assess the optimal time to initiate IFNbeta treatment with regard to the greatest benefits on disability progression.
A cohort of 2,570 IFNbeta-treated RRMS patients was prospectively followed for up to 7 years in 15 Italian MS Centers. A Cox proportional hazards regression model adjusted for propensity score (PS) quintiles was used to assess differences between groups of patients with early vs. delayed IFNbeta treatment on risk of reaching a 1-point progression in the Expanded Disability Status Scale (EDSS) score, and the EDSS 4.0 and 6.0 milestones. A set of PS-adjusted Cox hazards regression models were calculated according to different times of treatment initiation (within 1 year up to within 5 years from disease onset). A sensitivity analysis was performed to assess the robustness of findings.
The lowest hazard ratios (HRs) for the three PS quintiles-adjusted models were obtained by a cutoff of treatment initiation within 1 year from disease onset. Early treatment significantly reduced the risk of reaching a 1-point progression in EDSS score (HR = 0.63; 95% CI = 0.48-0.85; p < 0.002), and the EDSS 4.0 milestone (HR = 0.56; 95% CI = 0.36-0.90; p = 0.015). Sensitivity analysis showed the bound of significance for unmeasured confounders.
Greater benefits on disability progression may be obtained by an early IFNbeta treatment in RRMS.
Annals of Neurology 10/2009; 66(4):513-20. · 11.09 Impact Factor
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M Trojano,
F Pellegrini,
D Paolicelli,
A Fuiani,
G B Zimatore,
C Tortorella,
I L Simone,
F Patti,
A Ghezzi,
E Portaccio, [......],
M Vianello,
C Avolio,
P Cavalla,
P Iaffaldano,
V Direnzo,
M D'Onghia,
V Lepore, P Livrea,
G Comi,
M P Amato
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ABSTRACT: There are a few and conflicting results from randomised controlled trials (RCTs) pertaining to the influence of gender in response to currently used disease modifying drugs in Multiple Sclerosis (MS). Observational studies may be especially valuable for answering effectiveness questions in subgroups not studied in RCTs.
To conduct a post-marketing analysis aimed to evaluate the gender effect on Interferon beta (IFNbeta) treatment response in a cohort of relapsing (RR) MS patients.
A cohort of 2570 IFNbeta-treated RRMS was prospectively followed for up to 7 years in 15 Italian MS Centers. Cox proportional hazards regression models were used to assess gender differences for risk of reaching 1st relapse and risk of progression by 1 point on Expanded Disability Status Scale (EDSS) score. Gender effects were also explored by a propensity score (PS) matching algorithm, and a tree-growing technique.
The multivariate Cox Regression analyses showed that male patients had a significant (p=0.0097) lower risk for 1st relapse and a trend (p=0.0897) for a higher risk to reach 1 point EDSS progression than females. The PS matched multivariate Cox Regression confirmed these results. The RECPAM analysis showed that male sex conferred a significant reduction in the risk for 1st relapse (HR=0.86; 95% CI=0.76-0.98; p=0.0226) in the subgroup with a low pre-treatment number of bouts, and a significant increase in the risk for 1 point EDSS progression (HR=1.33; 95% CI: 1.00-1.76; p<0.05) in the subgroup with a delayed treatment, but a still young age at the start of treatment.
The results of this exploratory analysis seem to suggest that male patients do not respond to IFNbeta treatment in the same way of females.
Journal of the neurological sciences 08/2009; 286(1-2):109-13. · 2.32 Impact Factor
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U Nocentini,
G Tedeschi,
R Migliaccio,
D Dinacci,
L Lavorgna,
S Bonavita,
V Bresciamorra,
G Comanducci,
G Coniglio, P Livrea, [......],
F Patti,
A Quattrone,
G Salemi,
G Savettieri,
I L Simone,
P Valentino,
M Zappia,
V Bonavita,
M Musicco,
C Caltagirone
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ABSTRACT: Multiple sclerosis (MS) patients are often emotionally disturbed. We investigated anger in these patients in relation to demographic, clinical, and mood characteristics.
About 195 cognitively unimpaired MS patients (150 relapsing-remitting and 45 progressive) were evaluated with the State Trait Anger Expression Inventory, the Chicago Multiscale Depression Inventory, and the State Trait Anxiety Inventory. The patients' anger score distribution was compared with that of the normal Italian population. Correlation coefficients among scale scores were calculated and mean anger scores were compared across different groups of patients by analysis of variance.
Of the five different aspects of anger, levels of withheld and controlled Anger were respectively higher and lower than what is expected in the normal population. Although anger was correlated with anxiety and depression, it was largely independent from these mood conditions. Mean anger severity scores were not strongly influenced by individual demographic characteristics and were not higher in more severe patients.
The presence of an altered pattern of anger, unrelated to the clinical severity of MS, suggests that anger is not an emotional reaction to disease stress. An alteration of anger mechanisms might be a direct consequence of the demyelination of the connections among the amygdale, the basal ganglia and the medial prefrontal cortex.
European Journal of Neurology 07/2009; 16(12):1312-7. · 3.69 Impact Factor
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D Martino,
M Muglia,
G Abbruzzese,
A Berardelli,
P Girlanda,
M Liguori, P Livrea,
A Quattrone,
F Roselli,
T Sprovieri,
E M Valente,
G Defazio
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ABSTRACT: Adult-onset dystonia may be related, amongst other factors, to abnormal neuronal plasticity in cortical and subcortical structures. Brain-derived neurotrophic factor is a major modulator of synaptic efficiency and neuronal plasticity. Recent works documented that a single nucleotide polymorphism (SNP) of the BDNF gene, the Val66Met SNP, modulates short-term plastic changes within motor cortical circuits. In this study we aimed at exploring the effect of this SNP upon the risk of developing common forms of primary adult-onset dystonia.
We explored the influence of the Val66Met SNP of the BDNF gene on the risk of cranial and cervical dystonia in a cohort of 156 Italian patients and 170 age- and gender-matched healthy control subjects drawn from the same population.
The presence of the rare Met allele was not significantly associated with the diagnosis of dystonia (age- and gender-adjusted odds ratios of 1.22, P = 0.38). The study had a >90% power to detect a 50% change in the risk of developing cranial-cervical dystonia associated with the presence of the Met allele. Moreover, there was no relationship between Val66Met SNP and age at dystonia onset or type of dystonia.
Our data do not support the common variant Val66Met of the BDNF gene as an etiologic factor shared by the various forms of primary adult-onset dystonia.
European Journal of Neurology 05/2009; 16(8):949-52. · 3.69 Impact Factor
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G Tedeschi,
D Dinacci,
M Comerci,
L Lavorgna,
G Savettieri,
A Quattrone, P Livrea,
F Patti,
V Brescia Morra,
G Servillo, [......],
A Bellacosa,
P Valentino,
M Quarantelli,
A Brunetti,
G Salemi,
M D'Amelio,
I Simone,
M Salvatore,
V Bonavita,
B Alfano
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ABSTRACT: To investigate in a large cohort of patients with multiple sclerosis (MS), lesion load and atrophy evolution, and the relationship between clinical and magnetic resonance imaging (MRI) correlates of disease progression.
Two hundred and sixty-seven patients with MS were studied at baseline and two years later using the same MRI protocol. Abnormal white matter fraction, normal appearing white matter fraction, global white matter fraction, gray matter fraction and whole brain fraction, T2-hyperintense, and T1-hypointense lesions were measured at both time points.
The majority of patients were clinically stable, whereas MRI-derived brain tissue fractions were significantly different after 2 years. The correlation between MRI data at baseline and their variation during the follow-up showed that lower basal gray matter atrophy was significantly related with higher progression of gray matter atrophy during follow-up. The correlation between MRI parameters and disease duration showed that gray matter atrophy rate decreased with increasing disease duration, whereas the rate of white matter atrophy had a constant pattern. Lower basal gray matter atrophy was associated with increased probability of developing gray matter atrophy at follow-up, whereas gray matter atrophy progression over 2 years and new T2 lesion load were risk factors for whole brain atrophy progression.
In MS, brain atrophy occurs even after a relatively short period of time and in patients with limited progression of disability. Short-term brain atrophy progression rates differ across tissue compartments, as gray matter atrophy results more pronounced than white matter atrophy and appears to be a early phenomenon in the MS-related disease progression.
Multiple Sclerosis 12/2008; 15(2):204-11. · 4.26 Impact Factor
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ABSTRACT: Fibromyalgia syndrome (FMS) is a chronic pain condition of unknown aetiology characterized by diffuse pain and tenderness at tender points. The aim of the study was to assess the prevalence and clinical features of FMS in the different forms of primary headaches, in a tertiary headache centre. Primary headache patients (n = 217) were selected and submitted to the Total Tenderness Score, anxiety and depression scales, Migraine Disability Assessment, allodynia questionnaire, Short Form 36 Health Survey and the Medical Outcomes Study-Sleep Scale. In patients with FMS, the Multidimensional Assessment of Fatigue, the Pain Visual Analog Scale, the Manual Tender Point Survey and the Fibromyalgia Impact Questionnaire were employed. FMS was present in 36.4% of patients and prevailed significantly in tension-type headache and in patients with higher headache frequency. Headache frequency, pericranial muscle tenderness, anxiety and sleep inadequacy were especially associated with FMS comorbidity. In the FMS patients, fatigue and pain at tender points were significantly correlated with headache frequency. FMS seems increasingly prevalent with increased headache frequency, for the facilitation of central sensitization phenomena favoured by anxiety and sleep disturbances.
Cephalalgia 12/2008; 29(4):453-64. · 3.43 Impact Factor
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G Defazio,
D Martino,
G Abbruzzese,
P Girlanda,
M Tinazzi,
G Fabbrini,
C Colosimo,
M S Aniello,
L Avanzino,
M Buccafusca,
G Majorana,
C Trompetto, P Livrea,
A Berardelli
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ABSTRACT: Prior coffee and smoking habits were investigated in a multicentre case control study involving 166 patients presenting with primary late onset blepharospasm (BSP), 228 hospital control patients with primary hemifacial spasm and 187 population control subjects from five Italian centres. Information on age at disease onset, smoking and coffee drinking status at the reference age and average number of cups of coffee drunk/cigarettes smoked per day reached high and similar test-retest reproducibility in case and control patients. Unadjusted logistic regression analysis yielded a significant inverse association of prior coffee drinking and cigarette smoking with case status for the control groups. After adjustment for age, sex, referral centre, disease duration, years of schooling and ever coffee drinking/cigarette smoking, as appropriate, the smoking estimate lacked significance whereas the association of coffee intake and BSP did not (cases vs hospital control patients: OR 0.37 (95% CI 0.20 to 0.67); cases vs population control subjects: OR 0.44 (95% CI 0.23 to 0.85)). The strength of the inverse association between BSP and coffee intake tended to increase with the average number of cups drunk per day. There was a significant correlation between age of BSP onset and number of cups per day (adjusted regression coefficient 1.73; p = 0.001) whereas no correlation was found with number of packs of cigarettes per day. Coffee drinking may be inversely associated with the development of primary BSP and this association may partly depend on the amount consumed.
Journal of neurology, neurosurgery, and psychiatry 09/2007; 78(8):877-9. · 4.87 Impact Factor
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ABSTRACT: The aim of this study was to test the function of the diffuse noxious inhibitory control system (DNIC) in chronic and episodic migraine, exploring the blink reflex (BR) modifications induced by topical application of capsaicin on the hand. We evaluated 11 migraine without aura (MA) and nine chronic migraine (CM) patients during the not symptomatic phase; they were compared with 14 non-headache subjects (N). The BR was elicited by weak electrical stimuli delivered to the right supraorbital nerve; it was obtained 10 min and 20 min after the application of 1 ml of 3% capsaicin in a cream base (Teofarma) on the skin of the dorsum of the right hand, and 60 min after capsaicin removal. The subjective pain sensation induced by capsaicin was significantly increased in CM with respect to both MA patients and normal subjects; the R2 area was increased in CM patients during capsaicin application, with respect to controls and MA patients, who did not exhibit any reflex alterations. These results may suggest a failure of DNIC and a disturbed control of the trigeminal reflex at the central level, linked with migraine frequency.
Cephalalgia 09/2007; 27(8):881-90. · 3.43 Impact Factor
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P Nazzaro,
V Lucivero,
G Schirosi,
D Di Noia,
M Sancilio,
M Petruzzellis,
M P Prontera,
A Tinelli, P Livrea,
A M Pirrelli,
F Federico
High Blood Pressure & Cardiovascular Prevention 09/2007; 14(3):145.
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ABSTRACT: Recent evidence from neuropsychologic and neuroimaging studies suggests that central nervous system involvement in amyotrophic lateral sclerosis (ALS) extends beyond motor neurons. Our purpose was to obtain measures of global and regional atrophy in nondemented patients with ALS to assess subtle structural brain changes.
MR images, acquired from 16 patients and 9 healthy subjects (HS), were processed by using the Structural Imaging Evaluation of Normalized Atrophy (SIENA) software to estimate whole-brain atrophy measures and the voxel-based morphometry (VBM) method to highlight the selective volumetric decrease of single cerebral areas. In addition, each subject underwent a neuropsychologic examination.
In patients with ALS, brain parenchymal fraction was slightly lower compared with HS (P = .012), and seemed to be related to the presence of cognitive impairment. Patients showed a gray matter volume decrease in several frontal and temporal areas bilaterally (P < .001 uncorrected) compared with HS, with a slight prevalence in the right hemisphere. No volume reduction in primary motor cortices of patients was detected. Performances on Symbol Digit Modalities Test were significantly worse in patients compared with HS (P = .025).
The presence of mild whole-brain volume loss and regional frontotemporal atrophy in patients with ALS could explain the presence of cognitive impairment and confirms the idea of ALS as a degenerative brain disease not confined to motor system.
American Journal of Neuroradiology 02/2007; 28(2):255-9. · 2.93 Impact Factor
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XXXVII Congress Italian Society of Neurology, Bari-Italy; 10/2006
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ABSTRACT: The Multiple Sclerosis Database Network (MSDN) is the first Italian multiple sclerosis (MS) registry. The preliminary results on the MSDN cohort demonstrated that the risk of disability progression, in a sample of 2090 MS patients, was reduced by about four- to five-fold in patients exposed to IFNbeta for more than 4 years compared with patients exposed for up to 2 years. More recent results showed, in a subset of 1170 relapsing-remitting MS patients, of whom 918 were treated with IFNbeta and 252 were untreated, that IFNbeta-treated patients had a differential reduction in EDSS score change of -0.055 for each year of follow-up in comparison with the untreated group. These results provide significant information on the effectiveness of IFNbeta treatment on long-term disability progression in MS.
Neurological Sciences 10/2006; 27 Suppl 5:S358-61. · 1.32 Impact Factor
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S Bonavita,
D Dinacci,
L Lavorgna,
G Savettieri,
A Quattrone, P Livrea,
V Bresciamorra,
G Orefice,
M Paciello,
G Coniglio,
A Di Costanzo,
P Valentino,
F Patti,
G Salemi,
I Simone,
G Tedeschi
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ABSTRACT: This follow-up study assessed the 2-year clinical and magnetic resonance imaging (MRI) outcomes of patients with multiple sclerosis (MS) originally enrolled in an MRI study conducted at eight centres in south Italy (the South Italy Mobile MRI Project). Of the 597 MS patients recruited at baseline, 391 returned for the follow-up study. Of these, 363 provided 2-year clinical and MRI follow-up data, and 215 were still undergoing treatment with one of four interferon beta regimens: Avonex, 30 mcg intramuscularly once weekly; Betaferon, 250 mcg subcutaneously (sc) every other day; Rebif 22 mcg sc three times weekly (tiw; Rebif 22); or Rebif 44 mcg sc tiw (Rebif 44). Over the 2-year follow-up period, patients receiving the higher dose of Rebif were more likely to remain free from relapses [odds ratio (OR) = 2.23] and from developing both new T2 (OR = 0.15) and new T1 black hole lesions (OR = 0.22), when compared with patients in the Avonex group. Despite some limitations in the trial design, the results from this follow-up study provide helpful clinical and MRI data on the efficacy of interferon beta regimens in MS patients treated in the clinical setting.
Neurological Sciences 10/2006; 27 Suppl 5:S365-8. · 1.32 Impact Factor
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ABSTRACT: Previous family studies provided evidence that blepharospasm (BSP) can aggregate in families but did not give accurate and reliable information on the characteristics and degree of familial clustering.
To evaluate the proportion of familial and non-familial BSP cases, the clinical expression of dystonia within families, the inheritance pattern, and the extent of penetrance.
The study was based on the examination of the first degree relatives of 56 probands with primary BSP.
The 56 families produced a potential population of 436 first degree relatives of whom 296 were alive and 233 were examined. The proportion of index patients with at least one first degree relative affected by BSP, or adult onset dystonia other than BSP, was 27%. There was a remarkable degree of phenotypic variability of dystonia within families. Similar segregation ratios were calculated for probands' siblings and children. Under the assumption of autosomal dominant transmission of adult onset dystonia, penetrance was about 20%.
The findings of this family study are relevant for accurately counselling the families of patients with BSP and may help identify the most appropriate study design to explore genetic susceptibility in BSP.
Journal of Neurology Neurosurgery & Psychiatry 03/2006; 77(2):252-4. · 4.76 Impact Factor
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ABSTRACT: Apoptotic deletion of autoreactive T-cells is defective in patients with multiple sclerosis (MS). Glatiramer acetate (GA) treatment seems to restore apoptosis of detrimental T-cells. We analyzed the mitochondria membrane pro- (Bax) and anti-apoptotic (Bcl- 2) and cytosolic pro-apoptotic (Cyt-c, APAF-1) proteins expression in peripheral lymphocytes from relapsing-remitting (RR) MS patients during GA treatment. Blood samples were collected from 8 healthy controls (HCs) and from 8 RR MS patients prior to and every three months during the 9 months of GA treatment. Peripheral blood mononuclear cells (PBMNCs) Bcl-2, Bax, Cyt-c and APAF-1 were quantified by western blot followed by densitometric scanning and Bax/Bcl-2, cytosolic Cyt-c/Bcl-2 and APAF-1/Bcl-2 ratios were calculated. T-cells were in vitro tested for oxygen consumption by a respirometric analysis. Bax/Bcl-2, cytosolic Cyt-c/Bcl-2 and APAF-1/Bcl-2 ratios in untreated MS patients were significantly (p < 0.05) lower than in HCs. Bax/Bcl-2 ratio increased (p = 0.03) and Cyt-c/Bcl-2 ratio showed a trend to increase during the 9 months of GA treatment in MS patients. A reduction of 58% and 59% in oxygen consumption by PBMNCs was evident after GA treatment in vitro or when GA treated patients' cells were compared with those from HCs, respectively. Our findings suggest that GA exerts a regulatory effect on peripheral T lymphocytes through pro-apoptosis mechanisms involving mitochondria and cytosolic proteins.
Journal of Neurology 02/2006; 253(2):231-6. · 3.47 Impact Factor
