| Name | Giacomo |
| Surname | Lus |
| Institution | Università degli Studi della Campania Luigi Vanvitelli |
| giacomo.lus@unicampania.it | |
| Address | II Division of Neurology & Center fo Rare Diseases Department of Medical Surgical, Neurological, Metabolic Sciences, and Aging, University of Campania Luigi Vanvitelli, Edificio 10 Via Sergio Pansini, 580131 Naples, Italy |
To examine the effect of high-dose interferon (IFN)-beta1a [44 microg administered subcutaneously (sc) 3 times weekly (tiw)] on tumor necrosis factor-alpha (TNF-alpha) and insulin-like growth factor-1 (IGF-1) levels in patients with relapsing-remitting multiple sclerosis (RRMS), and any correlation with clinical and magnetic resonance imaging (MRI) data. Previously treatment-naive patients with RRMS and an Expanded Disability Status Scale score < or = 3.5 were enrolled. At baseline, monthly for the first 5 months, and then after 12 months of treatment with 44 microg sc tiw of IFN-beta1a, all patients underwent clinical examination, assessment of serum TNF-alpha and IGF-1 levels and baseline, 5th, and 12th months to MRI scanning. Mean TNF-alpha values decreased significantly from months 0 to 12 of the study (P = 0.003), but mean IGF-1 values showed a nonsignificant reduction (P = 0.265). Serum levels of TNF-alpha and IGF-1 were sometimes correlated throughout the study, but no significant interactions were observed between serum TNF-alpha or IGF-1 and clinical or MRI findings. A borderline significant trend toward higher basal TNF-alpha levels was found in patients who developed new T1 lesions at 12 months compared with those who did not (P = 0.057). Interferon-beta1a therapy may reduce serum TNF-alpha levels in patients with RRMS, without a clear correlation with disease activity.
A 26-year-old man presented at onset with the syndrome of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) and later with a phenotype for MELAS and myoclonic epilepsy and ragged red fiber disease (MELAS/MERRF).
Current treatments of relapsing-remitting multiple sclerosis (RRMS) with immunosuppressive or immunomodulatory drugs have been shown to modify the course of the disease in a significative number of patients. However, in many cases, the response to either interferon beta (IFN-beta) or azathioprine (AZA) treatments was not satisfactory and new therapeutic approaches are needed. We studied clinical and MRI efficacy, safety and tolerance of AZA and IFN-beta(1a) combined therapy in 23 patients with clinically definite RRMS, who had not previously been responsive to either monotherapies. Our cases were divided into three subgroups: 8 previously untreated patients (subgroup A) with at least 2 years of natural course of the disease, 8 patients (subgroup B) previously treated with AZA for 2 years and 7 patients (subgroup C) previously treated with IFN-beta(1a) for 2 years. The baseline Expanded Disability Status Scale (EDSS) ranged from 2 to 4 in all subgroups. All patients completed 2 years of combined treatment with a dose of AZA adjusted to reduce lymphocyte count down to 1,000 +/- 100/microl in association with IFN-beta(1a) at a dose of 6 MIU every other day. The mean number of relapses during the combined treatment period was significantly lower than that observed before combined therapy in all the three subgroups. Also, the mean Delta EDSS score was significantly lower during combined treatment than in monotherapy in subgroups B and C. Moreover, after 2 years of combined treatment, the number of new T(1) hypointense lesions, the number and volume of proton density/T(2) hyperintense lesions and the gadolinium enhancement of T(1) hypointense lesions were significantly lower than before combined treatment. After 2 years of treatment, this combination therapy appears to be safe and well tolerated and no serious side effects were reported. Despite some limitations of our study design, the information regarding efficacy, safety and tolerance of the association of AZA and IFN-beta is most encouraging.
The authors report an Italian family with autosomal-dominant Charcot-Marie-Tooth disease (CMT) in which there were giant axons in the sural nerve biopsy. Linkage to the known CMT2 loci (CMT2A, CMT2B, CMT2D, CMT2F) and mutations in the known CMT2 genes (Cx32, MPZ, NEFL), GAN, NEFM, and CMT1A duplication/HNPP deletion were excluded. This family with CMT and giant axons has a pathologic and genetic entity distinct from classic CMT.
Chorea-Acanthocytosis (CHAC) is an autosomal recessive disease characterized by neurodegeneration and acanthocytosis. Enhanced creatine kinase concentration is a constant feature of the condition. The mechanism underlying CHAC is unknown. However, acanthocytosis and enhanced creatine kinase suggest a protein defect that deranges the membrane-cytoskeleton interface in erythrocytes and muscle, thereby resulting in neurodegeneration. Acanthocytes have been correlated with structural and functional changes in membrane protein band 3--a ubiquitous anion transporter. Residue Gln-30 of band 3 serves as a membrane substrate for tissue transglutaminase (tTGase), which belongs to a class of intra- and extra-cellular Ca2+-dependent cross-linking enzymes found in most vertebrate tissues. In an attempt to cast light on the pathophysiology of CHAC, we used reverse-phase HPLC and immunohistochemistry to evaluate the role of tTGase in this disorder. We found increased amounts of tTGase-derived N(epsilon)-(-gamma-glutamyl)lysine isopeptide cross-links in erythrocytes and muscle from CHAC patients. Furthermore, immunohistochemistry demonstrated abnormal accumulation of tTGase products as well as proteinaceous bodies in CHAC muscles. These findings could explain the mechanisms underlying the increased blood levels of creatine kinase and acanthocytosis, which are the most consistent features of this neurodegenerative disease.
We report the case of a 64 year-old man with a clinical history suggesting a low thoracic-cord involvement, in which an unexpected vertebral osteoid osteoma was discovered. The patient underwent MRI of the thoraco-lumbar spine, which included sagittal and axial T1-weighted images, and sagittal double-echo T2-weighted images. Subsequently, CT scan was carried out with 2-mm-thick axial sections, aimed at T10 vertebra. Magnetic resonance imaging disclosed an extra-axial mass at T10 level. Computed tomography scan suggested an osteoid osteoma of the tenth thoracic vertebra, involving the lamina with marked sclerosis and prevalently endocanalar extension. Histology following surgical resection confirmed the diagnosis. In the reported case CT scan provided the correct pre-operative diagnosis of osteoid osteoma despite its unusual clinical--anamnestic presentation. Magnetic resonance imaging was useful in establishing the relationship of the neoplasm with the spinal cord.
To investigate whether unusual allele segregation might explain the dominant negative effect of the expanded allele for myotonic dystrophy on myotonin protein kinase mRNA metabolism, which is suggested to cause the disease, we determined the number of CTG repeats at the DM locus in the nonaffected alleles of 64 DM (dystrophia myotonia) patients. The relative distribution was then compared with the distributions obtained from alleles of the normal parents and normal siblings of DM patients. Comparison was also made with the allele distribution of normal subjects from the same geographic area. It appears that the CTG repeat number of the nonaffected allele in DM patients is not critical for the expression of the disease.
Shy-Drager syndrome is a very rare disease affecting the autonomic nervous system. Usefulness of beta-adrenergic chronic therapy has already been focused in these cases. Ambulatory blood pressure monitoring may help to study the cardiocirculatory adaptation in Shy-Drager syndrome patients.
Progressive rubella panencephalitis is a very rare slow virus disease of the nervous system. The authors present a case, concerning a young man, aged 20 years, died 11 months after the onset of the disease. The following peculiarities of the case are emphasized: 1) the clinical symptomatology and the evolution (myoclonus, lack of cerebellar impairment) could suggest the diagnosis of SSPE; 2) the EEG recordings showed epileptiform abnormalities, long latency diffuse periodic complexes and--during interferon therapy and simultaneously with a temporary clinical improvement--the appearance of short latency anterior periodic complexes.
The pathological changes in muscles biopsied from 2 brothers with rigid spine syndrome are reported. The findings ranged from marked fascicular atrophy and fibrosis to hypotrophy of small groups of fibres and vacuolation in most fibres. The presence of vacuoles and deposits of accumulated material seemed to be common to all the biopsies. These findings, compared with those reported in the literature, confirmed the histopathological heterogeneity of this syndrome but proposed also the hypothesis that similar elementary lesions of muscle fibres can account for the initiation of the pathological process, developing asynchronously in different muscles because of their different activity.