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Gerstmann-Straussler-Scheinker syndrome (GSS) is an exceedingly rare prion disease. There are only 3 case reports of GSS in China. Here we report the first GSS family in southern China. A 47-year-old female complained of unsteady gait and dysarthria. Seven other individuals presented similar symptoms in 3 generations of her family, and all died 4-6 years after onset. To detect causative mutations, we employed a gene analysis panel of hereditary diseases. This revealed a P102L mutation in the prion protein gene (PRNP) gene, which is commonly found in GSS featuring cerebellar ataxia. However, GSS is an uncommon cause of hereditary cerebellar ataxia that might be overlooked because many neurologists are unfamiliar with it. To avoid misdiagnosis in the patients with hereditary cerebellar ataxia, GSS should be taken into account if other causes are absent, especially in patients that have accompanying psychiatric symptoms and a short survival time.

It would be useful to identify additional postmortem markers of Purkinje cell loss in essential tremor (ET). In hereditary cerebellar ataxia, Purkinje cell loss has been reported to result in a secondary increase in the density of the remaining cell populations in the cerebellar molecular layer. However, this phenomenon has not been studied in ET. We quantified cerebellar molecular layer cellular density in 15 ET cases, 15 controls, and 7 spinocerebellar ataxia (SCA) cases (2:2:1 ratio).A standard neocerebellar tissue block was stained with Luxol fast blue HematoxylinEosin. Within 5 selected fields, cell soma (e.g., stellate, basket, and glial cell bodies) were counted. Cellular density was the number of cells/cm(2).The Purkinje cell count differed across the three groups (p 0.001), with the highest counts in controls, intermediate counts in ET cases and lowest counts in SCA cases. ET cases and controls had similar molecular layer cellular density (p = 0.79) but SCA cases had higher values than both groups (p 0.01). A robust inverse correlation between Purkinje cell count and molecular layer cellular density (i.e., brains with more Purkinje cell loss had higher molecular layer cellular density), observed in SCA and controls (r = -0.55, p = 0.008), was not observed in ET cases.Although Purkinje cell counts were reduced in ET cases compared to controls, an increase in molecular layer cellular density was not evident in ET. The increase in molecular layer cellular density, observed in SCA cases, may require a more marked loss of PCs than occurs in ET.

Розглядається клінічний випадок спадкової мозочкової атаксії, труднощі при діагностиці даного захворювання.

A family has been studied in which four sibs were affected with an adult-onset form of cerebellar ataxia and deafness. The ataxia and hearing loss have been slowly progressive over a 10 year follow-up period, and no other neurological signs have developed in the interim. This variety of hereditary ataxia, which appears to be a distinct autosomal recessive entity, is compared and contrasted with other genetic types, compiled in tabular form. It is emphasized that closer attention to other symptoms, either in the central nervous system or elsewhere, might have considerable use in the differential diagnosis of these conditions and thus provide for more effective genetic counselling.

The cerebellum is an essential part of the neural network involved in adapting goal-directed arm movements. This adaptation might rely on two distinct signals: a sensory prediction error or a motor correction. Sensory prediction errors occur when an initial motor command is generated but the predicted sensory consequences do not match the observed values. In some tasks, these sensory errors are monitored and result in on-line corrective motor output as the movement progresses. Here we asked whether cerebellum-dependent adaptation of reaching relies on sensory or on-line motor corrections. Healthy controls and people with hereditary cerebellar ataxia reached during a visuomotor perturbation in two conditions: “shooting” movements without on-line corrections and “pointing” movements that allowed for on-line corrections. Sensory (i.e., visual) errors were available in both conditions. Results showed that the addition of motor corrections did not influence adaptation in control subjects, suggesting that only sensory errors were needed for learning. Cerebellar subjects were comparably impaired in both adaptation conditions relative to controls, despite abnormal and inconsistent on-line motor correction. Specifically, poor on-line motor corrections were unrelated to cerebellar subjects' adaptation deficit (i.e., adaptation did not worsen), further suggesting that only sensory prediction errors influence this process. Therefore adaptation to visuomotor perturbations depends on the cerebellum and is driven by the mismatch between predicted and actual sensory outcome of motor commands.

The authors review the most important contributions of Pierre Marie to the elucidation and description of several neurological diseases, such as Charcot-Marie-Tooth’s disease and hereditary cerebellar ataxia, as well as his contributions to Internal Medicine, including his pioneering studies on acromegaly, ankylosing spondylitis, and hypertrophic pulmonary osteoarthropathy. His works led to incontestable advances in the medical sciences that transcended his time. Os autores revisaram as mais importantes contribuições de Pierre Marie para a elucidação e a descrição de várias doenças neurológicas, tais como a doença de Charcot-Marie-Tooth e a ataxia cerebelar hereditária, bem como na medicina interna, incluindo os seus estudos pioneiros na acromegalia, espondilite anquilosante e osteo-artropatia hipertrófica pulmonar. Os seus trabalhos promoveram uma crescimento incontestável das ciências médicas que transcenderam o seu tempo.

We read with interest the Article by Silvia Romano and colleagues, describing a novel and potentially important application of riluzole in patients with spinocerebellar ataxia or Friedreich’s ataxia. The investigators noted that riluzole significantly improved ataxia at 3 months and 12 months. This improvement was assessed as at least a one-point reduction in the Scale for Assessment and Rating of Ataxia (SARA), a rating scale with summed scores of up to a maximum of 40 points in the domains of gait, kinetics, and speech. A posthoc analysis showed improvement in the patients’ quality of life (on the SF-36 scale). In absence of an ideal biomarker for ataxia, Romano and colleagues predefined a one-point reduction in the SARA score as a cutoff for improvement in ataxia. The chosen cutoff suggests that the smallest difference in any of the three SARA domains would represent an improvement in ataxia. We challenge this assumption. First, any selected cutoff should exceed the effects of interobserver and intraobserver variability. Because of the inclusion of heterogeneous patients in Romano and colleagues’ trial, a high variation in SARA scores (2·0–29·5) would induce an increase in the margin of error. Thus, although we noted high interobserver and intraobserver agreements on SARA scores (intraclass correlation coefficient of 0·91–0·98 and 0·96–0·98, respectively), the investigators’ chosen cutoff is highly likely to refer to the margin of error. Second, as indicated by Durr, potentially confounding effects on SARA scores should be taken into account, especially for the comparison of two small and heterogeneous treatment groups. In previous reports, we have shown that SARA scores are not only aff ected by ataxia, but also by age of the child (in terms of observer variability and absolute scores), and by muscle force (in Friedreich’s ataxia). Although we are interested in the potentially positive eff ect of riluzole treatment, the interpretation of the SARA score outcomes are open to question. Until biomarkers for ataxia progression are available, consideration of the SARA construct is important to prevent overinterpretation. The Childhood Ataxia and Cerebellar Group of the European Pediatric Neurology Society (CACG-EPNS), is now doing a SARA validation study in children to provide increased uniformity for the interpretation of longitudinal ataxia trajectories, from childhood to adulthood.

We investigated how humans with hereditary cerebellar degeneration [spinocerebellar ataxia (SCA) type 6 and 8, n = 9] and age- and sex-matched healthy controls ( n = 9) adapted goal-directed arm movements to an unknown external force field. We tested whether learning could be generalized to untrained regions in the workspace, an aspect central to the idea of an internal model, and if any learning could be retained. After removal of the force field, SCA patients showed little or no learning-related aftereffects indicating that repeated force-field exposure never led to successful force compensation. In contrast, healthy control subjects quickly adapted their movements to the new force field. The difference in force adaptation was significant for movements to targets that required both the shoulder and elbow joint ( P < 0.001). Moreover, the generalization of learned movements to targets outside the learned workspace was prevented by the cerebellar degeneration ( P < 0.01). Retention of force adaptation was significantly lower in SCA patients ( P = 0.003). The severity of ataxia in SCA patients correlated negatively with the extent of learning ( r = –0.84, P = 0.004). Our findings imply that progressive loss of cerebellar function gradually impairs force adaptation. The failure to generalize learning suggests that cerebellar degeneration prevents the formation of an internal representation of the limb dynamics.

Background: Gluten sensitivity (GS) is a spectrum of disorders with diverse manifestations. Recent evidence suggests that ataxia may be the only manifestation of GS and that it may be one of the causes of sporadic ataxia. Aim: To investigate the prevalence of gluten ataxia among patients with ataxia in China. Materials and Methods: Serum levels of anti-gliadin, anti-transglutaminase 2 (TG2), and anti-transglutaminase 6 (TG6) antibodies measured in 125 patients with ataxia (100 patients with sporadic ataxia and 25 patients with hereditary ataxia) and 51 healthy controls by enzyme-linked immunosorbent assay (ELISA). Results: The serum concentrations of anti-gliadin, anti-TG2 IgG, IgA, and TG6-IgG antibodies were elevated in ataxia patients, but the increase was not statistically significant. However, TG6-IgA serum levels were significantly higher in sporadic ataxia as compared to those in healthy controls (P < 0.05). Conclusions: These results provide evidence that sporadic ataxia in a subgroup of patients may be due to gluten ataxia in mainland China. Measurement of serum anti-TG6 antibodies along with anti-TG2 and anti-gliadin antibodies may be useful for diagnosing gluten ataxia.

Five families with at least three generations of members affected with autosomal dominant spinocerebellar ataxia (SCA) were studied. HLA typing was carried out and the coded HLA haplotypes were used to calculate the likelihood of linkage using the LIPED computer program. The combined lod scores from these five families does not, by itself, support linkage. Negative lod scores were observed in all five families, however, when pooled with the previously published data significant lod scores were obtained [Z = 3.343 (theta = 0.20) and +4.286 (theta = 0.30)]. In four families, affected members had clinical features consistent with autosomal dominant cerebellar ataxia (ADCA) type I while in the fifth, ADCA type II was suggested. Clinical heterogeneity within ADCA raises doubts about the significance of summed lod scores. In view of the previous reports probably two genetically heterogeneous types of ADCA exist -- HLA linked and nonlinked.

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