Friedreich's ataxia: clinical heterogeneity in two sisters.

Diagnostic evaluation of two sisters affected by ataxia, with similar age of onset, revealed a characteristic trinucleotide expansion in the Friedreich's ataxia (FRDA) locus and two different phenotypic presentations. At onset the elder sister had retained deep tendon reflexes (FARR), while the younger sister presented classic FRDA. The GAA expansion in the patients' alleles proved to be similar in both siblings, ruling out that age at onset and clinical heterogeneity could be due to different FRDA mutations. On the whole, clinical and genetic data on these patients confirmed that FARR is a variant phenotype of FRDA.

A rare case of paraneoplastic cerebellar degeneration discovered by whole-body F-18 FDG PET.

A rare case of paraneoplastic cerebellar degeneration (PCD) in a 36-year-old woman is reported. She developed hyposthenia of the inferior limbs, diplopia, and disequilibrium in July 2001. Routine blood tests, tumoral markers, brain MRI, evoked potentials, and cerebrospinal fluid (CSF) examination were substantially normal. The clinical syndrome rapidly worsened in the following 2 months; she was wheelchair-bound with marked limb ataxia. CSF showed an increase of the IgG index with oligoclonal bands; brain MRI remained negative. The patient's serum and CSF were analyzed to detect antineuronal antibodies; anti-Yo antibodies were found that is typical of PCD. No tumor was found until April 2003; repeated CT scan, ultrasound, and mammographic examinations were negative. A further worsening in clinical symptoms was observed with a complete loss of autonomy (Rankin score 5) despite the performance of immunosuppressive therapy. In April 2003, an F-18 FDG PET scan visualized an area of abnormal uptake in the upper outer quadrant of the left breast. Interestingly, brain F-18 FDG uptake was normal. Suspicious microcalcifications were found on a new mammography and malignant cells were disclosed at cytology. The patient was operated on and final histologic examination revealed an infiltrating ductal breast cancer. In the reported case, F-18 FDG PET played a crucial role in detecting the unknown primary tumor in a young patient with PCD.

Prevalence of inherited ataxias in the province of Padua, Italy.

Few population studies are available on epidemiological indexes of hereditary ataxias. An investigation on the prevalence rate of these movement disorders is in progress for the Veneto region, the main area of northeast Italy with a population of 4,490,586 inhabitants. The first results of this epidemiological survey concern the province of Padua, which numbers 845,203 residents (January 1, 2002). The prevalence rate of inherited ataxias has been estimated at 93.3 cases per million inhabitants. The most common types appeared to be the autosomal dominant forms, namely spinocerebellar ataxia type 1 and 2, with a prevalence of 24 per 1,000,000. In the same population, with a prevalence rate of 6 per 1,000,000, Friedreich's ataxia was defined as the prominent recessive autosomal form. There were very rare cases of ataxia telangiectasia, ataxia with vitamin E deficiency and cerebellar ataxia with congenital muscular dystrophy, a recently identified autosomal recessive disease.

Ataxia and congenital muscular dystrophy: the follow-up of a new specific phenotype.

Cerebellar hypoplasia may, at neuroimaging studies, be found in association with congenital muscular dystrophy (CMD), although it is an extremely rare occurrence. We here report on three CMD patients who underwent a longitudinal evaluation of clinical and neuroimaging features for a mean period of 18 years. Case 1, a 22-year-old woman, and cases 2 and 3, brothers aged 26 and 20 years, respectively, had presented a mild to moderate muscular weakness and increased serum creatine kinase (CK) levels since birth. All cases were diagnosed in the first years of life, with identification of evident dystrophic changes at muscle biopsy and moderate to severe cerebellar hypoplasia at brain computed tomography (CT) scan. Subsequently, all the patients underwent a second muscle biopsy, with immunostaining and immunoblot analysis, which showed normal values for merosin, dystrophin and dystrophin-related proteins. During the longitudinal study, the patients underwent repeated neurological and psychiatric examinations, serum CK controls, intellectual ability assessments and neuroimaging evaluations (CT and/or magnetic resonance imaging (MRI)). In all cases, these investigations indicated a mild to moderate deficit in the proximal muscles and a clear-cut cerebellar syndrome which, it was assumed, had been present since the first years. The patients also presented some intellectual difficulties, with an IQ of 0.69 in case 1, 0.83 in case 2 and 0.61 in case 3. The clinical course of all the patients was static, and all symptoms of the combined muscle and brain involvement persisted. Nor were any changes in the cerebellar hypoplasia observed at repeat MRIs. Findings obtained by us on the longitudinal study and a review of the literature indicate that cerebellar hypoplasia and merosin-positive CMD constitute a particular clinical phenotype, mainly characterized by an ataxic syndrome associated with a non-severe muscular involvement and a possible mild intellectual impairment.