Gabriella Zara

The Total Neuropathy Score as an assessment tool for grading the course of chemotherapy-induced peripheral neurotoxicity: comparison with the National Cancer Institute-Common Toxicity Scale

Abstract  Chemotherapy‐induced peripheral neurotoxicity (CIPN) is a major side effect of several antineoplastic drugs. However, despite its clinical importance, there is no agreement as to the best way to assess the severity and changes in CIPN. We have previously demonstrated a correlation between the severity of CIPN, assessed using the Total Neuropathy Score (TNS) or its reduced versions, and several common toxicity scales. In this study, we investigated two series of patients (total number = 173) who were evaluated at baseline and during chemotherapy with the TNS (n= 122) or the TNSc (the TNS version based exclusively on the clinical evaluation of the patients, n= 51) and with the National Cancer Institute‐Common Toxicity Criteria (NCI‐CTC) 2.0, with the aim of comparing the sensitivity to the changes in CIPN severity. In both series, the TNS and the TNSc had a significant correlation with the NCI‐CTC in scoring the severity of CIPN, confirming the results of previous studies. Moreover, both the TNS and the TNSc showed a higher sensitivity to CIPN changes. We, therefore, propose the TNSc as a reliable method for assessing not only the severity but also the changes in CIPN.

Neurological complications of celiac disease and autoimmune mechanisms: A prospective study

Humoral immune mechanisms may have a role in the neurological complications of celiac disease (CD). We assessed 71 CD patients for neurologic manifestations and presence of serum antibodies to neural antigens. Sixteen patients (22.5%) were found to have neurological deficits including headache, depression, entrapment syndromes, peripheral neuropathy, and epilepsy. Antibody reactivity to neural antigens was detected in 30/71 (42.2%) patients. There was no clear correlation between anti-neural reactivity and neurologic dysfunction. Follow-up of 62 patients did not reveal change in electrophysiology or antibodies, regardless of diet. However, in 2 patients with neuropathy, symptoms improved or worsened depending on the diet.

Thalidomide neurotoxicity Prospective study in patients with lupus erythematosus

The authors prospectively followed 14 patients treated with thalidomide for cutaneous lupus erythematosus (CLE), in order to evaluate the occurrence of peripheral neuropathy (PN) and to assess whether PN correlates with thalidomide dose. The patients were followed for up to 24 months with neurologic and electrophysiologic evaluations. Seven patients (50%) developed sensory axonal PN. The median time free from PN was 14 months. PN occurred after 10 months in the majority of patients. No correlations were found between thalidomide cumulative dose and occurrence of PN (Mann-Whitney U test; p > 0.16).

Non-neural phenotype of spinal and bulbar muscular atrophy: results from a large cohort of Italian patients

Objective To carry out a deep characterisation of the main androgen-responsive tissues involved in spinal and bulbar muscular atrophy (SBMA). Methods 73 consecutive Italian patients underwent a full clinical protocol including biochemical and hormonal analyses, genitourinary examination, bone metabolism and densitometry, cardiological evaluation and muscle pathology. Results Creatine kinase levels were slightly to markedly elevated in almost all cases (68 of the 73; 94%). 30 (41%) patients had fasting glucose above the reference limit, and many patients had total cholesterol (40; 54.7%), low-density lipoproteins cholesterol (29; 39.7%) and triglyceride (35; 48%) levels above the recommended values. Although testosterone, luteinising hormone and follicle-stimulating hormone values were generally normal, in one-third of cases we calculated an increased Androgen Sensitivity Index reflecting the presence of androgen resistance in these patients. According to the International Prostate Symptom Score (IPSS), 7/70 (10%) patients reported severe lower urinal tract symptoms (IPSS score >19), and 21/73 (30%) patients were moderately symptomatic (IPSS score from 8 to 19). In addition, 3 patients were carriers of an indwelling bladder catheter. Videourodynamic evaluation indicated that 4 of the 7 patients reporting severe urinary symptoms had an overt prostate-unrelated bladder outlet obstruction. Dual-energy X-ray absorptiometry scan data were consistent with low bone mass in 25/61 (41%) patients. Low bone mass was more frequent at the femoral than at the lumbar level. Skeletal muscle biopsy was carried out in 20 patients and myogenic changes in addition to the neurogenic atrophy were mostly observed. Conclusions Our study provides evidence of a wide non-neural clinical phenotype in SBMA, suggesting the need for comprehensive multidisciplinary protocols for these patients.

Neurological complications of celiac disease and autoimmune mechanisms: preliminary data of a prospective study in adult patients.

Abstract: Antibodies to gangliosides and Purkinje cells have been reported in patients with celiac disease (CD) with neuropathy and ataxia, respectively. Whether these antibodies are pathogenic is not clear. The response of neurological symptoms and antibody titers to a gluten‐free diet is still controversial. The objective of our study was to assess whether neurological manifestations in CD patients correlate with antibody titers and a gluten‐free diet.Thirty‐five CD patients (9 males, 26 females, mean age 37.1 ± 12.6 yrs) were followed prospectively. At initial evaluation, 23 were on a gluten‐free diet, 12 were not. At recruitment and during follow‐up, patients underwent neurological and electrophysiological evaluation. IgG, IgM, and IgA anti‐ganglioside antibodies were assayed by ELISA; anti‐neuronal antibodies were assessed by immunohistochemistry and Western blot. Four patients, all males, had electrophysiological evidence of neuropathy; three had been on a gluten‐free diet for several months, and one was newly diagnosed. One had reduced tendon reflexes; another complained of distal paresthesias. With regard to anti‐ganglioside antibodies, three patients had a moderate increase in antibodies without symptoms or signs of neuropathy. No patients had ataxia or cerebellar dysfunction, although in four patients reactivity to neuronal antigens was found. In 17 patients, an electrophysiological follow‐up (mean duration of follow‐up, 9 months) showed no changes. In conclusion, the preliminary results of this prospective study indicate that neuropathy, usually subclinical, may accompany CD. Antibody titers do not seem to correlate with neurological symptoms/signs or diet. Ongoing follow‐up will help confirm these data and clarify the role, if any, of antibodies in neurological involvement in CD.

Natural history of upper motor neuron-dominant ALS

Abstract A new amyotrophic lateral sclerosis (ALS) category named ‘UMN-dominant ALS’ and defined as ‘due predominantly to UMN signs but with minor electromyogram (EMG) denervation or LMN signs on examination’ has been proposed. The clinical and laboratory features of 20 patients with UMN-dominant ALS are described here, their disease course is analysed longitudinally according to their disability progression, and all these parameters are compared with those of typical ALS patients. Ten women and 10 men diagnosed with UMN-dominant ALS were evaluated. Their mean age at disease onset was 58.6 years. At the most recent evaluation, after a mean disease duration of 7.7 years, all patients progressed to a tetrapyramidal syndrome with pseudobulbar features of varying degree. No patient had respiratory problems. Cognitive impairment was observed in eight patients. The differences in disease progression between the UMN-dominant ALS and typical ALS patients proved significant (p <0.02) both with regard to the total ALSFRS-R score at six months and to each single region subscore at 12 months. Our findings suggest that there is both a different pattern of disability and longer survival in UMN-dominant ALS compared to classic ALS patients.

Case of sensory ataxic ganglionopathy-myelopathy in copper deficiency

Spinal cord involvement associated with severe copper deficiency has been reported in the last 8 years. Copper deficiency may produce an ataxic myelopathy. Clinical and neuroimaging findings are similar to the subacute combined degeneration seen in patients with vitamin B12 deficiency. Macrocytic, normocytic and microcytic anemia, leukopenia and, in severe cases, pancytopenia are well known hematologic manifestations. The most patients with copper deficiency myelopathy had unrecognized carency. Some authors suggested that early recognition and copper supplementation may prevent neurologic deterioration but clinical findings do not improve. We present a patient with copper deficiency, dorsal root ganglions and cervical dorsal columns involvement. Clinical status and neuroimaging improved after copper replacement therapy. Sensory neurons of dorsal root ganglia may be the most sensitive nervous pathway. In this case the early copper treatment allowed to improve neurologic lesions and to prevent further involvements.

Thalidomide and sensory neurotoxicity: a neurophysiological study

Beckground: Recent studies confirmed a high incidence of sensory axonal neuropathy in patients treated with different doses of thalidomide. The studys aims were to measure variations in sural nerve sensory action potential (SAP) amplitude in patients with refractory cutaneous lupus erythematosus (CLE) treated with thalidomide and use these findings to identify the neurotoxic potential of thalidomide and the recovery capacity of sensory fibres after discontinuation of treatment. Patients and methods: Clinical and electrophysiological data in 12 female patients with CLE during treatment with thalidomide and up to 47 months after discontinuation of treatment were analysed. Sural nerve SAP amplitude reduction ⩾40% was the criteria for discontinuing therapy. Results: During treatment, 11 patients showed a reduction in sural nerve SAP amplitude compared to baseline values (9 with a reduction ⩾50% and 2 <50%). One patient showed no changes in SAP amplitude. Five patients complained of paresthesias and leg cramps. After thalidomide treatment, sural SAP amplitude recovered in 3 patients. At detection of reduction in sural nerve SAP amplitude, the median thalidomide cumulative dose was 21.4 g. The threshold neurotoxic dosage is lower than previously reported. Conclusions: Sural nerve SAP amplitude reduction is a reliable and sensitive marker of degeneration and recovery of sensory fibres. This electrophysiological parameter provides information about subclinical neurotoxic potential of thalidomide but is not helpful in predicting the appearance of sensory symptoms.

PERIPHERAL NEUROTOXICITY OF PEGYLATED INTERFERON ALPHA: A PROSPECTIVE STUDY IN PATIENTS WITH HCV

OBJECTIVE To assess whether pegylated interferon alpha (PEG-IFNalpha) may induce peripheral neuropathy or antibodies to peripheral nerve antigens in patients with hepatitis C virus (HCV) infection. METHODS We studied 52 patients with HCV (38 men, 14 women; mean age 44.6 +/- 10.6 years) treated with IFNalpha. Before therapy (T(0)), patients underwent quantitative viral RNA determination, HCV genotype analysis, and neurologic and electrophysiologic evaluation. At the end (T(1)) and after therapy (T(2)), patients were neurologically and electrophysiologically re-evaluated. Antibodies to gangliosides and sulfatides were assayed by ELISA at T(0) and T(1). Twenty-three patients with HCV with comparable age, viral load, and genotype, not treated with IFNalpha, were studied as controls. RESULTS Seven patients (six in IFNalpha, one control) had peripheral neuropathy at recruitment. No significant differences in the electrophysiologic measures were detected between T(0) and T(1) (repeated-measures analysis of variance [ANOVA]) in any of the 52 patients or in those with neuropathy at T(0). No changes were found at T(2), independent of the viral response to treatment. Two patients, one with neuropathy, had antiganglioside antibodies at recruitment. Two patients, one not treated with IFNalpha, developed low antibody titers during follow-up, without symptoms or signs of neuropathy. CONCLUSIONS Pegylated interferon alpha therapy was not associated with the occurrence (or worsening) of peripheral neuropathy or antibodies to peripheral nerve antigens in patients with hepatitis C virus.

Anti-ganglioside antibodies in children with coeliac disease: correlation with gluten-free diet and neurological complications.

Background : Emerging evidence points to humoural mechanisms in neurological complications of coeliac disease. Immunoglobulin G anti‐ganglioside antibodies have been reported in coeliac disease patients with neuropathy, suggesting an immune response to peripheral nerve antigens. No data are so far available on anti‐ganglioside antibodies in coeliac disease children or on antibody modifications after gluten‐free diet.