Seasonal ataxia: A case report of a disappearing disease

Introduction

Seasonal ataxia is a clinical syndrome of acute cerebellar ataxia which follows ingestion of roasted larvae of Anaphe venata Butler, an alternative protein source consumed in western Nigeria. It was first reported in the 1950s in western Nigeria when it caused a wave of epidemics. This is the first case report of this condition in the literature since 1993.

Case report

We present the case of a 35 year old woman from western Nigeria who was admitted in October 2012 with acute onset of gait instability and bilateral hand tremors, preceded by several episodes of vomiting. She had ingested a meal containing roasted larvae of the African silkworm, 2 hours before the onset of vomiting.

Conclusion

Seasonal ataxia is an important differential diagnosis of acute cerebellar ataxia among the indigenous ethnic population of western Nigeria.It is non-fatal and treatable, with complete resolution of symptoms usually following thiamine therapy.     

Hepatitis B virus X stimulates redox signaling through activation of ataxia telangiectasia mutated kinase

Hepatitis B virus X (HBX) protein plays a crucial role in carcinogenesis, but its mechanism is unclear. The involvement of ataxia telangiectasia mutated (ATM) kinase in the enhanced redox system was investigated by examining the phosphorylation level of ATM in HBX gene-transfected cells and in transgenic mice following redox system manipulation by treatment with hydrogen peroxide (H₂O₂) or antioxidant. Western blotting and immunostaining showed that phospho-ATM was significantly increased by HBX both in vitro (3.2-fold; p<0.05) and in vivo (4-fold; p<0.05), and this effect was abrogated by antioxidant treatment. The level of PKC-δ in HBX-expressing cells was increased 3.5-fold compared to controls. Nuclear localized NF-E2-related factor 2 (Nrf2) was increased in HBX-expressing cells exposed to H₂O₂, but remained at lower levels after the treatment with rottlerin, KU55933, or caffeine. The levels of anti-oxidant molecules were increased in HBX expressing cells and in transgenic mice, indicating that HBX stimulates the Nrf2-mediated redox system. The levels of intracellular reactive oxygen species (ROS) were significantly increased in HBX-expressing cells treated with hydrogen peroxide in the presence of ATM inhibitor KU55933 or caffeine. Treatment of HBX-expressing cells with KU55933 or caffeine before the exposure to H₂O₂ increased the ratio of cell apoptosis to 33 ± 4% (p<0.05) and 22 ± 4% (p<0.05), respectively. Collectively, HBX stimulates the ATM-mediated PKC-δ/Nrf2 pathway, and maintains the enhanced activity of the redox system. Therefore, manipulating ATM kinase activity might be a useful strategy for treating HBX-induced carcinogenesis.     

Molecular epidemiology of spinocerebellar ataxias in Cuba: Insights into SCA2 founder effect in Holguin

The objective of this study was to determine the prevalence of hereditary ataxias in Cuba, with a special focus on the clinical and molecular features of SCA2. Clinical assessments were performed by neurological examinations and application of the SARA scale. Molecular analyses of genes SCA1–3, SCA6, SCA17 and DRPLA identified 753 patients with SCA and 7173 asymptomatic relatives, belonging to 200 unrelated families. 86.79% of all SCA patients were affected with SCA2. In the Holguin province, the average population prevalence of SCA2 is 40.18 × 10⁵ inhabitants, with the remarkable figure of 141.66 × 10⁵ in the Baguanos municipality. The high prevalence of the SCA2 mutation in Holguin reflects most likely a founder effect. The stabilization of the prevalence along time suggests the existence of premutated chromosomes with pure CAG, acting as reservoir for further expansions. CAG repeat length correlated inversely with age at onset, accounting for 80% of the variability. Genetic anticipation was observed in the 80% of transmissions. Repeat instability was greater in paternal transmissions whereas CAG expansions without anticipation was observed in 10.97% suggesting the effect of CAA interruptions in the CAG segment, which decrease the toxicity of the abnormal ataxin-2, and/or other protective factors.     

The chromosome 16q‐linked autosomal dominant cerebellar ataxia (16q‐ADCA): A newly identified degenerative ataxia in Japan showing peculiar morphological changes of the Purkinje cell

The chromosome 16q22.1‐linked autosomal‐dominant cerebellar ataxia (16q‐ADCA) is a form of spinocerebellar ataxia (SCA) common in Japan. It is clinically characterized by late‐onset purely cerebellar ataxia. The neuropathologic hallmark of 16q‐ADCA is degeneration of Purkinje cells accompanied by an eosinophilic structure which we named “halo‐like amorphous materials”. By immunohistochemistry and electron microscopy, the structure has been so far found to contain two components: the somatic sprouts from the Purkinje cells and presynaptic terminals of unknown origin. As far as we are aware, this peculiar morphological change of Purkinje cells has not been previously described. Further investigations may disclose unique pathological processes in SCA.     

头项针治疗中风共济失调疗效评定及对血管内皮生长因子的影响

目的观察头项针治疗中风共济失调的临床疗效及对血清血管内皮生长因子(VEGF)表达的影响。方法将中风共济失调患者42例随机分为2组,治疗过程中各脱落1例。治疗组20例以头项针为手段治疗,每日1次;对照组20例用传统针刺治疗,每日1次。2组均连续针刺5日,休息2日,10次为1个疗程,2个疗程后统计疗效。并采用酶联免疫吸附双抗体夹心法(ELISA)定量测定治疗前(发病72 h内),发病第7日、第14日血清VEGF的含量的变化。结果治疗组愈显率85%,总有效率100%,对照组愈显率30%,总有效率75%,2组比较差异均有统计学意义(P<0.01,P<0.05)。治疗组在第7日和第14日的VEGF表达均高于对照组(P<0.01)。结论头项针治疗中风共济失调疗效确切,其作用可能与VEGF的表达有关。     

Late onset ataxia phenotype in dentatorubro-pallidoluysian atrophy (DRPLA)

We clinically and genetically studied three patients in a family with dentatorubro-pallidoluysian atrophy (DRPLA). The proband patient had 58/24 CAG repeat alleles of the DRPLA gene (normal ≤ 34 repeats). Cerebellar ataxia first developed in the 6–7^th decades and was the predominant feature for more than 10 years in all three, after which two of them manifested dementia and choreiform movements in the advanced stage. Atrophy of the cerebellum and brain stem an CT or MRI had suggested dominant spinocerebellar ataxia as a diagnosis in their ataxia-predominant stage, with a diagnosis of DRPLA being impossible based on the clinical findings alone. Our experience implies that DRPLA must be taken into account in the differential diagnosis of late onset ataxic disorders, since it can easily be overlooked. Received: 2 April 2001, Received in revised form: 23 July 2001, Accepted: 21 August 2001     

Analysis of SCA8 and SCA12 loci in 134 Italian ataxic patients negative for SCA1–3, 6 and 7 CAG expansions

Spinocerebellar ataxias (SCA) are a heterogeneous group of neurodegenerative disorders, six of which are caused by expansion of a polyglutamine-coding CAG repeats (SCA1- 3, 6, 7 and 17). In addition, expansions of a CAG triplet in the 5' region of a gene and a CTG triplet in an antisense RNA have been demonstrated in the SCA12 and SCA8 genes respectively. Our series of 134 ataxic patients (22 familial and 112 sporadic, tested negative for SCAI–3, 6, 7) was investigated for the presence of triplet expansions in the SCA8 and SCA12 genes. No SCA12 expansion was identified. A moderate SCA8 expansion (85–97 repeats) was found in two unrelated families with slowly progressive cerebellar ataxia. The frequency of SCA8 expansion accounts for ∼4.3 % of the whole pool of our ataxia families (2 out of 46), while none of the 127 controls screened carried > 35 CTG+CTA repeats. Our data suggest a possible pathogenetic role of this mutation, which at present is still controversial, and confirm the rarity of the SCA12 expansion in Italian patients. Received: 30 March 2001, Received in revised form: 20 November 2001, Accepted: 15 January 2002     

Near infrared muscle spectroscopy in patients with Friedreich's ataxia

Friedreich's ataxia is a progressive neurodegenerative disorder of the afferent cerebellar pathways associated with mitochondrial dysfunction at the cellular level. We have used noninvasive continuous near infrared muscle spectroscopy (NIRS) to investigate the delivery and utilization of oxygen in response to exercise in this disorder. Patients performed an incremental treadmill walking protocol in which levels of muscle deoxygenation or oxygenation were continuously measured in the medial calf muscle. The kinetics of recovery from exercise-induced deoxygenation, called the half-time of recovery (t(1/2)) were determined. The t(1/2) was prolonged in patients with Friedreich's ataxia compared with controls, and the degree of prolongation correlated with the length of the shorter GAA repeat, a genetic measure that correlates with the age of onset of disease. The t(1/2) also correlated inversely with patient age and with the maximum treadmill speed attained. Several patients also displayed features consistent with inadequate oxygen utilization by muscle. These results suggest that NIRS may be an effective tool for monitoring the biochemical and functional features of Friedreich's ataxia in parallel.