[Show abstract][Hide abstract] ABSTRACT: The SCA17 clinical phenotype includes characteristics associated with cerebellar and cortical atrophy such as ataxia, dementia, epilepsy, chorea and parkinsonian features. Here we describe the case of a 38-year-old male presenting with ataxia, cognitive impairment and seizures, who was found to carry 43 repeats on one allele of the TATA-binding protein (TBP) gene. Therefore, genetic analysis of TBP gene triplets was performed on the patient's entire family, identifying three asymptomatic carriers of the same allele. A neuroradiological phenotype appeared to segregate with this allele, suggesting that it may play at least a contributory role in the determination of SCA17.
[Show abstract][Hide abstract] ABSTRACT: One hundred forty-one adult patients treated for no less than 6 months with standard daily doses of the commonest antiepileptic drugs (AEDs) were recruited in five Italian centers and submitted to intensive clinical and electrophysiologic investigation to assess the effects of AEDs on peripheral nerves. Eighty percent of the patients were receiving monotherapy. Carbamazepine (CBZ) was the most common AED (51 cases), followed by phenytoin (PHT) (46), phenobarbital (PB) (42), and valproate (VPA) (25). Fifty-three percent of the patients had one or more symptoms of polyneuropathy (paresthesias being the most common complaint). The neurologic examination was abnormal in 32%. Electrophysiologic findings in two or more separate nerves were abnormal in 77 patients (54.6%); of these, 27 (19.1%) had abnormal neurologic findings and 21 (14.9%) also had symptoms of polyneuropathy. Sensory functions were most frequently impaired. Sural nerve biopsy was performed in 4 patients receiving monotherapy with CBZ, PHT, PB, and VPA. Except in patients receiving VPA (in whom no morphologic abnormalities were detected), mild predominantly axonal damage with secondary myelin changes was noted. A correlation was noted between polyneuropathy, age of the patient and, to a lesser extent, receipt of two or more AEDs.RéSUMéCent-quarante et un patients adultes traités pendant au moins 6 mois avec des doses quotidiennes habituelles des médicaments antiépileptiques (MAE) courants ont été recrutés dans 5 centres italiens et ont bénéficié d'investigations cliniques et électrophysiologiques intensives afin d'évaluer l'effet des MAE sur les nerfs périphériques. Quatre-vingt pour cent des cas étaient traités par monothérapie. La carbamézépine (CBZ) était le médicament le plus prescit (51 cas), suivie par la phénytoïne (PHT) (46 cas), le phénobarbital (PB) (42 cas), et le valproate (VPA) (25 cas). Cinquante-trois pour cent des patients présentaient un ou plusieurs symptômes de polyneuropathie, les paresthésies étant les plus fréquemment signalées. L'exarnen neurologique était anormal dans 32% des cas. Les constatations électrophysiologiques au niveau de 2 ou plus tronc nerveux étaient anormales dans 77 cas (54, 6%); 27 de ceux-ci (10, 1%) présentaient des anomalies à l'examen neurologique, et 21 (14, 9%) présentaient également des symptômes de polyneuropathie. Les fonctions sensitives étaient le plus souvent touchées. Une biopsie du nerf sural a été réaliste chez 4 patients traités en rnonothéraie par CBZ, PHT, PB, et VPA. A l'exception des patients sous VPA (chez lesquels aucune anomalie rnorphologique n'a été mise en évidence), les lésions modérées, prédominant au niveau des axones, avec des modifications secondaires de la myéline, ont été constatées. Une corrélation a été constatée entre l'existcnce d'une polyneuropathie, l'âge du patient, et, à un moindre degré, I traitement par 2 MAE ou plus.ZUSAMMENFASSUNG141 erwachsene Patienten, die mehr als einen Monat mit einer Standard-Dosis der üblichen Antiepileptika behandelt wurden, wurden in fünf verschiedenen Zentren einer intensiven klinischen und elektrophysiologischen Untersuchung unterzogen. Die Nebenwirkungen der Antiepileptika auf die peripheren Nerven sollte untersucht werden. 80% der Patienten erhielten eine Monotherapie. Am häufigsten wurde Carbamazepin gegeben (51 Fälle), gefolgt von Phenytoin (46), Phenobarbital (42) und Valproat (25). 53% der Patienten boten mehr als ein Symptom der Polyneuropathie (am häufigsten waren die Klagen über Parästhesien). Auffällige neurologische Zeichen fanden sich in 32% der Fälle. Bei 77 Patienten zeigte sich ein elektrophysiologisch pathologischer Befund an zwei oder mehreren untersuchten Nerven (54, 6%). Von ihnen hatten 27 auffällige neurologische Befunde und 21 Zeichen einer Polyneuropathie. Die sensorischen Funktionen waren am häufigsten herabgesetzt. Eine N.suralis-Biopsie wurde bei 4 Patienten unter Monotherapie rnit CBZ, PHT, PB und VPA durchgeführt. Es fanden sich hauptsächlich Axonchäden rnit sekundären Myelinveränderungen-nur der Patient unter VPA zeigte keine morphologischen Auffälligkeiten. Das Auftreten der Polyneuropathie korrelierte am ehesten rnit dem Alter des Patienten und in geringerem Maβe mit der Einnahme von 2 oder mehreren Antiepileptika.
[Show abstract][Hide abstract] ABSTRACT: The authors describe a case of primary progressive multifocal leukoencephalopathy (pPML). Unlike previous similar reports, our patient underwent up-to-date and extensive in vivo and post-mortem investigations that established beyond doubt the competence of his immune system and the absence of underlying predisposing disorders. The various implications of this case, both clinical and related to the possible pathogenetic mechanisms of JC virus infection, are discussed.
[Show abstract][Hide abstract] ABSTRACT: We investigated the possible use of clinical signs of chemotherapy-induced peripheral neurotoxicity (CIPN) or of nerve growth factor (NGF) circulating levels to predict the final outcome of CIPN.
Sixty-two women affected by locally advanced squamous cervical carcinoma treated with TP (paclitaxel 175 mg/m2 over a 3 h infusion plus cisplatin 75 mg/m2) or TIP (TP plus ifosphamide 5 mg/m2) were examined and scored according to the Total Neuropathy Score (TNS), before and during chemotherapy.
A correlation with the final severity of CIPN was observed with vibration perception and deep tendon reflex evaluation, while pin sensibility, strength, and autonomic symptoms and signs were not informative. A highly significant correlation existed between the decrease in circulating levels of NGF and the severity of CIPN (r = -0.579; P < 0.001; 95% confidence limits -0.702 to -0.423). However, circulating levels of NGF were not effective as predictors of the final neurological outcome of each patient.
Our study indicates that a precise clinical evaluation of the peripheral nervous system of patients treated with platinum and taxane combination polychemotherapy not only gives reliable information regarding the course of CIPN, but also can be used to predict the final neurological outcome of the treatment.
Annals of Oncology 09/2004; 15(9):1439-42. · 6.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated the possible use of individual Total Neuropathy Scale (TNS) items to predict the neurological outcome in patients undergoing cisplatin and paclitaxel combination chemotherapy in a series of thirty-four women divided, according to the worst TNS score reached during the period of observation, into three groups, i.e. with a score <5 (n = 14), >5 but <10 (n = 5) or >10 (n = 15). At the visit performed before the onset of the worst neuropathy signs, 14 out of the 15 patients with the worst TNS had a change of 2 or more points in the sum of the semiquantitative vibration score (tuning fork) plus the DTR examination. In 12 of them the change was due to both vibration perception and DTR impairment. A change in the combined score was observed also in 7 out of the 14 patients with the better neurological outcome, but none of them had any change in the vibration perception. Early disappearance of DTR in the lower limbs (i.e. both ankle and patellar reflexes bilaterally) was observed in 7 out of the 15 patients with a worst outcome, while only 1 patient in the better outcome group had this clinical sign. The results of the VDT score obtained with a vibrameter did not improve the accuracy of the neurological assessment. Our study indicates that the accurate clinical evaluation of the patients treated with platinum and taxane combination polychemotherapy can be used to predict the final neurological outcome of the treatment.
Journal of the Peripheral Nervous System 05/2004; 9(2):105 - 105. · 2.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The authors compared clinically based neurotoxicity scales with the Total Neuropathy Scale, with the aim of improving the grading of the severity of chemotherapy-induced peripheral neuropathy (CIPN). The severity of CIPN was evaluated in a series of 60 women treated with cisplatin- and paclitaxel-based chemotherapy. A reduced version of TNS (TNSr) was also compared. The authors concluded that the TNS and TNSr can be used to assess the severity of CIPN effectively, and the results of this evaluation can be reliably correlated with the oncologic grading of sensory peripheral neurotoxicity.
[Show abstract][Hide abstract] ABSTRACT: Hematopoietic toxicity of high-dose carboplatin (HD-CBDCA) chemotherapy can be managed effectively with autologous blood cell support, but no conclusive data are available on its neuro- and ototoxicity.
We determined the neuro- and ototoxicity of HD-CBDCA in 10 patients affected by advanced ovarian cancer. HD-CBDCA was delivered as 24-hour continuous infusion or as 5-day schedules. Each patient underwent an extended clinical and instrumental neurological and otological evaluation before, during and after treatment.
After HD-CBDCA only 1 patient had a clinically-evident peripheral neuropathy, while 3 additional patients had only distal paresthesias. Neurophysiological examination evidenced mild, although diffuse, sensory nerve impairment. Motor nerve impairment was also occasionally observed. All the sensory and motor pathological changes had a favorable course during the follow-up period. Ototoxicity was more severe than neurotoxicity and, in one case it was dose-limiting and audiologic impairment tended to remain constant also in the follow-up period.
HD-CBDCA treatment can be tolerated by most of the patients, but careful monitoring of neuro- and, especially, ototoxicity should be planned.
Anticancer research 01/1998; 18(5B):3797-802. · 1.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cisplatin sensory neuropathy is not equally severe in all patients and may progress even after drug withdrawal. A major goal in cisplatin chemotherapy would be the identification of early predictors of an unfavorable neurological outcome in order to adjust the schedules of administration. The final neurological outcome of 63 women treated with the same schedule of cisplatin (CDDP) was compared with the general demographic and oncological parameters and with the baseline neurological results. No definite association could be drawn between any of the parameters evaluated and peripheral neuropathy. Further studies are needed to investigate the individual factors which are at the basis of the remarkable variability of this severe side effect of CDDP.
International Journal of Oncology 08/1997; 11(2):365-70. · 2.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In recent years several authors have described a close correlation between circulating antineuronal antibodies of different types and the occurrence of paraneoplastic neurological syndromes. Because this has not been widely accepted, we screened 300 serum samples from 181 ovarian cancer patients for the presence of circulating antineuronal antibodies by immunofluorescence. The findings were confirmed by immunoblotting. In 11 patients circulating antineuronal antibodies were detected. In 4 patients they were classified as anti-Yo and in 7 as anti-Ri, titres ranging from 1:400 to 1: 204,800. All the patients underwent thorough neurological and neurophysiological investigations, with special regard to paraneoplastic syndrome. None of them had symptoms pointing to a paraneoplastic neurological syndrome, although patients were followed up to 2 years after the first examination. Thus the frequency of circulating antineuronal antibodies in ovarian cancer patients is higher than the frequency of paraneoplastic syndromes, and antibody positivity does not necessarily lead to the appearance of a neurological paraneoplastic syndrome.
Journal of Neurology 03/1997; 244(2):85-9. · 3.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare the neurotoxicity and ototoxicity of combination cisplatin plus paclitaxel versus cisplatin plus cyclophosphamide using extensive clinical and instrumental evaluation.
Forty-six of 51 consecutive patients affected by-epithelial ovarian cancer seen in our institution between October 1994 and August 1995 entered the study. After randomization, they were assigned to receive cisplatin 75 mg/m2 every 3 weeks associated with cyclophosphamide 750 mg/m2 (CC group, n = 22) or paclitaxel 175 mg/m2 over a 3-hour infusion (CP group, n = 24). Treatment was repeated six times in 43 patients and nine times in 25. Before treatment and after three, six, and nine courses of chemotherapy, patients underwent clinical and instrumental neurologic and otologic examinations.
Mild sensory impairment was evident even after only three courses of both treatments and signs and symptoms were more severe at the end of treatment. On clinical grounds only, it was possible to demonstrate after six and nine courses a difference between CC and CP treatment, due to the involvement in some CP patients of pain and thermal sensory modalities. However, the overall severity of the neuropathy was similar. Audiometric parameters demonstrated a more negative outcome after treatment in CC compared with CP patients. However, the different severity of the involvement was closely correlated to this initial difference in audiologic performance.
Up to nine courses of chemotherapy, the CC and CP schedules are similar in terms of severity of neurotoxicity and ototoxicity when patients are evaluated during and immediately after treatment. With the doses used in our study, these toxicities are not dose-limiting. Our results suggest that most of the toxic effects observed during the treatment were due to cisplatin.
Journal of Clinical Oncology 02/1997; 15(1):199-206. · 17.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Several drugs have been proposed for chemoprevention from cisplatin (CDDP)-induced neurotoxicity. For the purpose of this study the effectiveness of reduced glutathione (GSH) during CDDP-based first-line treatment was evaluated in a series of 54 patients affected by epithelial ovarian cancer. Neurotoxicity was assessed by clinical examination, vibrametry and neurophysiology before, during and after chemotherapy. First of all, it is noteworthy that GSH cotreatment did not impair CDDP antineoplastic effectiveness. Non-neurological side effects were similar in the two groups, with the exclusion of oliguria which occured more frequently in CDDP alone-treated patients. From a neurological point of view, the comparison between CDDP alone and CDDP+GSH treated groups at the end of treatment (CDDP total dose 500–675 mg m−2) constantly evidenced a trend toward less severe neurotoxicity after cotreatment with all methods. Although neuroprotection was not complete, these findings are in agreement with previous preclinical and clinical data and further support the view that chemoprevention with GSH should be considered in CDDP-treated patients.
International Journal of Gynecological Cancer 08/1996; 6(5):415 - 419. · 1.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Taxol is a new anticancer drug that acts as a tubulin polymeration enhancer. Its major toxicities are myelosuppression, hypersensitivity, and mucositis, but it also induces peripheral nerve damage. The use of taxol has recently been proposed for platinum-resistant cancers, but in these cases there is a possibility of cumulative toxicity in the peripheral nervous system.
Twenty-two patients affected by a relapse of cisplatin-treated ovarian cancer were examined clinically and neurophysiologically to determine the evolution of taxol-induced peripheral somatic and autonomic neurotoxicity and the possible cumulative effect of a combination of taxol and cisplatin. Each patient was examined before, during, and after taxol treatment (using a dose of 135 or 175 mg/m2 in 3 hours every 3 weeks).
No patients were excluded from the study because of unacceptable toxicities of any kind. The serial examinations demonstrated that taxol induced onset of (or worsening of preexisting) neuropathic symptoms and signs in almost all the patients. The features were those of a distal, symmetrical, sensory polyneuropathy due to an axonopathy. Motor nerves and the autonomic nervous system were unaffected. Taxol neurotoxicity appeared early in the course of the treatment (i.e., after three courses) and was not severely disabling. In most cases after the early onset of peripheral neuropathy, stabilization of this side effect occurred.
Considering the low doses of taxol used in this study, the sensory nerve damage was unexpectedly severe. It appears that a cumulative, but not dose-limiting, neurotoxic effect occurs using taxol in patients previously treated with cisplatin.
Cancer 04/1995; 75(5):1141-50. · 4.90 Impact Factor