Polyneuropathy and monoclonal gammopathy of undetermined significance (MGUS); update of a clinical experience.

BACKGROUND AND PURPOSE: Polyneuropathies associated with monoclonal gammopathy of undetermined significance (MGUS) encompass a group of phenotypically and immunologically heterogeneous neuropathies. While the best characterized is that associated with anti-myelin glycoprotein (MAG) antibodies, there are phenotypical and immunological neuropathy variants that still lack a clear classification. We analyzed a significant number of patients, in order to better evaluate the distribution of neuropathy phenotypes and to look for some common characteristics. METHODS: Clinical, neurophysiological, and laboratory data from 87 consecutive MGUS patients with peripheral neuropathy were analyzed and compared among patient groups with different MGUS classes and autoantibody reactivity. RESULTS: Anti-MAG neuropathy cases account for the most homogeneous group with regard to clinical and neurophysiological findings. Patients with anti-gangliosides or sulfatide (GS) antibodies, despite a marked phenotype heterogeneity, still share several common features, including a younger age at diagnosis, a more severe disease, and a prompt and sustained response to both immunoglobulin and rituximab therapies, mostly requiring chronic administration of immune treatment. CONCLUSIONS: Although heterogeneous, MGUS-associated, anti-GS antibody positive neuropathies have important similar features possibly resulting from a similar biological background.

A case of Takotsubo syndrome during a multiple sclerosis brainstem relapse.

BACKGROUND: We report a case of a woman affected by relapsing remitting Multiple Sclerosis who developed acute left ventricular dysfunction in the context of a severe brainstem relapse, one month after an attempt of in-vitro fertilization. DISCUSSION: The characteristics of our case are consistent with the hypothesis of a possible causal association between an acute medulla oblongata lesion and the occurrence of Takotsubo cardiomyopathy. CONCLUSION: Our case adds to previous reports in this field and calls for awareness of this exceptional extra-neurological manifestation of MS. It seems also to confirm the possible association between MS relapses and ovarian stimulation.

Fragile X premutation with atypical symptoms at onset.

OBJECTIVE: To evaluate the presence of carriers of the fragile X premutation among male patients with sporadic ataxia without expansion into known spinocerebellar ataxia genes. DESIGN: Clinical and genetic examinations were performed on patients with sporadic pure ataxia and patients with ataxia associated with extracerebellar features such as pyramidal and extrapyramidal signs, dementia, or peripheral neuropathy. SETTING: University department of neurology. PATIENTS: One hundred forty-two Italian men with sporadic ataxia with onset at age 30 to 84 years. INTERVENTIONS: The CGG repeat size of the FMR1 gene was evaluated with fluorescent polymerase chain reaction. Premutated allele lengths were confirmed with Southern blot analysis. RESULTS: FMR1 premutation alleles with a repeat number greater than 55 were detected in 3 probands (2.1%) from a total of 142 male subjects initially referred to our university medical center for evaluation of sporadic ataxia. Two patients had typical fragile X syndrome with associated tremor or ataxia, and the third patient had spastic paraparesis without clear symptoms of cerebellar ataxia and without the common signs seen at magnetic resonance imaging. CONCLUSIONS: Genetic analysis of the FMR1 gene could provide a reliable diagnostic tool for the definitive diagnosis of late-onset ataxias. Additional studies are needed to clarify the importance of premutation screening in patients with movement disorders or other associated atypical features at onset, such as paraparesis.

Identification of new presenilin gene mutations in early-onset familial Alzheimer disease.

BACKGROUND: Mutations in the presenilin 1 (PS1) and presenilin 2 (PS2) genes, and more rarely in beta-amyloid precursor protein (betaAPP), underlie the pathogenesis of most cases of familial Alzheimer disease (FAD). OBJECTIVE: To screen the entire coding region of the PS1 and PS2 genes and exons 16 and 17 of the betaAPP to find pathogenetic mutations in FAD. Patients Patients with FAD were consecutively enrolled from among the outpatients from the neurology departments at the Universities of Florence and Parma and the Santa Maria Nuova Hospital in Reggio Emilia, Italy. DESIGN AND METHODS: Polymerase chain reaction-single-strand conformation polymorphism and DNA se-quencing were used to investigate the affected members of families with FAD. RESULTS: We identified a family carrying a novel Ser130Leu mutation in the PS2 gene. Moreover, we found 2 novel PS1 mutations: Cys92Ser in exon 4 in 2 unrelated families and Leu174Met in exon 6 in the PS1 gene. We also found a fourth Italian family with the betaAPP Val717Ile mutation. CONCLUSIONS: One novel PS2 mutation associated with highly penetrant but variable age at onset (35-85 years) and 2 novel PS1 missense mutations associated with early-onset Alzheimer disease at age 49 to 54 years have been identified in Italian families. Screening for new mutations in presenilin and betaAPP genes was beneficial in characterizing gene function in FAD.

A family with spinocerebellar ataxia type 8 expansion and vitamin E deficiency ataxia.

BACKGROUND: Ataxia with vitamin E deficiency is a recessive autosomal neurodegenerative disorder resembling the Friedreich ataxia phenotype but is due to mutations in the alpha-tocopherol transfer protein (TTPA) gene. In a recent article, we described a patient with ataxia carrying reduced serum vitamin E levels and showing CTA/CTG expansions of 320 triplet repeats in the SCA8 gene. OBJECTIVES: To perform a screening of the TTPA gene in the patient and to evaluate the effects of treatment with vitamin E on the patient's neurologic disturbances. PATIENT AND METHODS: We performed a single-strand conformation polymorphism and nucleotide sequence analysis of the 5 exons of the TTPA gene in the patient's family members. RESULTS: The results indicated the patient to be a compound heterozygote for 2 mutations (in exon 3), each transmitted by one of the 2 parents, yielding a nonfunctional protein. CONCLUSIONS: We describe for the first time, to our knowledge, a mutated form of the TTPA gene in a patient also carrying an expansion in the SCA8 gene. The lack of improvement in the patient's symptoms on supplementation with alpha-tocopherol suggests that the SCA8 mutations may act in the neurodegeneration process, worsening the neurologic signs caused by the vitamin E deficit, and it could be speculated that the co-occurrence of mutant alleles for 2 distinct loci may influence the clinical course of the disease.