[An outbreak of encephalopathy after eating autumn mushroom (Sugihiratake; Pleurocybella porrigens) in patients with renal failure: a clinical analysis of ten cases in Yamagata, Japan].

In September and October, 2004, an outbreak of encephalopathy of unknown etiology occurred in certain areas of Japan including Yamagata, Akita, and Niigata prefectures. These patients had a history of chronic renal failure, most of them had undergone hemodialysis, and also had a history of eating Sugihiratake (Pleurocybella porrigens), an autumn mushroom without known toxicity. Since clinical details of this type of encephalopathy remain unknown, we analyzed the clinical, radiological and electroencephalographic (EEG) features of ten cases of this encephalopathy in Yamagata prefecture. The summary of the present study is as follows: 1. Ten patients had chronic renal failure, and seven underwent hemodialysis. 2. Each patient had a history of eating Sugihiratake within 2-3 weeks of the onset of neurological symptoms. 3. The onset was subacute; the initial symptoms were tremor, dysarthria, and/or weakness of the extremities, which lasted an average of 4.5 days (ranging from 2 to 11 days), followed by severe consciousness disturbance and intractable seizures, resulting in status epilepticus in 5 patients. Myoclonus was also seen in 4 patients and Babinski reflex in 3. 4. Brain CT and MRI examinations were unremarkable in the early stages of the disease. Three to eight days after onset, however, conspicuous lesions appeared in the areas of the insula and basal ganglia in 6 patients. On MRI, these brain lesions were hyperintense on T2-weighted and FLAIR images, and hypointense on T1-weighted images. 5. EEG examination was performed in 6 patients, all of whom showed abnormal EEG findings. Periodic synchronous discharge (PSD) was seen in 2 patients, spike and wave complex in one patient, and non-specific slow waves in 3. 6. Prognosis was different from case to case. Three patients died at 13, 14, and 29 days after onset. Two patients still showed persistent disturbance of consciousness one month after onset. One patient showed parkinsonism after recovering from consciousness disturbance. Four patients recovered nearly completely around one month after onset In 3 of the 4 recovered patients, renal failure was not severe and they did not need to undergo hemodialysis. This suggests that the degree of renal failure is a key for the prognosis of this type of encephalopathy. The present study suggests that this endemic disease is a newly recognized clinical entity of encephalopathy.

A novel type of encephalopathy associated with mushroom Sugihiratake ingestion in patients with chronic kidney diseases.

BACKGROUND: The etiology of encephalopathy in uremic patients is multiple. We recently encountered a novel type of encephalopathy which occurred exclusively in patients with chronic kidney diseases after ingestion of a mushroom called Sugihiratake. While the exact etiology of this encephalopathy remained mysterious, we aimed to describe its clinical features. METHODS: A total of 32 patients with chronic kidney diseases who had presented with encephalopathy following ingestion of Sugihiratake were enrolled from seven prefectures in Japan., with 24 of the 32 patients undergoing regular hemodialysis. The patient's clinical data were from surveillance by The Japanese Society of Nephrology. RESULTS: There was a significant association between Sugihiratake ingestion and the occurrence of encephalopathy in 524 hemodialysis patients questioned for a recent ingestion of this mushroom (P= 0.0006). The latent asymptomatic period before the onset of symptoms varied from 1 to 31 days (mean 9.1 +/- 7.3) days. The patient's symptoms consisted of disturbed consciousness in 30 patients (93.8%), convulsions in 25 (78.1%), myoclonus in 15 (46.9%), dysarthria in ten (31.3%), ataxia in eight (25.0%), paresis or paralysis in seven (21.9%), and skin parasthesia in two patients (6.3%). Nine (27.2%) patients died, mostly due to respiratory failure. The other patients were either discharged or still in hospitals with various degrees of clinical improvement. CONCLUSION: Patients with chronic kidney diseases are at risk of having serious encephalopathy following Sugihiratake ingestion and must refrain from eating it. Physicians, in those parts of the world, where this mushroom harvesting is common, should be aware of this complication.

Effects of erythropoietin-gene electrotransfer in rats with adenine-induced renal failure.

BACKGROUND: We previously demonstrated that erythropoietin (Epo) expression increases in five-sixths nephrectomized rats, after muscle-targeted gene transfer by in vivo electroporation, using plasmid DNA expressing rat Epo (pCAGGS-Epo). Here, we apply this method to a rat model with severe anemia associated with chronic renal failure; these rats have hematocrit levels in the 30-35% range, similar to those in humans with end-stage renal disease. METHODS: Wistar rats were treated to produce adenine-induced uremia. The uremic rats were then treated with muscle-targeted gene transfer using pCAGGS-Epo. Some uremic rats died from chronic renal failure; one of these was dissected, and the kidneys were histologically examined. For the remaining rats, we measured body weight and blood pressure, and obtained blood samples regularly. RESULTS: The uremic rats showed severe anemia, with hematocrit levels at 32.6 +/- 3.3%. Epo-gene transfer increased Epo expression and serum Epo levels, and also increased the hematocrit levels to 64.5 +/- 4.8%. The dose of pCAGGS-Epo used in this study did not induce severe hypertension. CONCLUSIONS: Continuous Epo-gene expression improves the anemia associated with chronic renal failure, and without severe side effects. Our results support the potential use of gene electrotransfer for human gene therapy applications.

Serum cystatin C reliably detects renal dysfunction in patients with various renal diseases.

A clinical investigation was conducted to clarify the reliability and efficacy of serum cystatin C measurement for estimation of the glomerular filtration rate (GFR). Two hundred twelve patients with various renal diseases enrolled in the study. All patients were evaluated for 24-hour creatinine clearance (24 h C(Cr)) and the standard sodium thiosulfate clearance test (C(Thio)) within a week of blood sample collection. Serum cystatin C concentration was determined by a particle-enhanced immunonephelometry method. C(Thio) and 1/cystatin C, 24 h C(Cr), 1/beta2-microglobulin and 1/creatinine were well correlated. The correlation coefficients for C(Thio) obtained by 24 h C(Cr) and 1/cystatin C were comparable to each other (0.701 vs. 0.679). Receiver-operated characteristic (ROC) analysis revealed that 24 h C(Cr) showed the highest area under the curve when C(Thio) = 60 ml/min or C(Thio) = 100 ml/min were applied as the discrimination point. However, the ROC value obtained by cystatin C was slightly greater than 24 h C(Cr) when C(Thio) = 80 ml/min was used as the discrimination point. Patient age, gender, glucose tolerance, presence of proteinuria, systemic inflammation, lupus, or systemic use of steroids did not interfere in the relationship between C(Thio) and 1/cystatin C. In conclusion, serum cystatin C measurement is an excellent diagnostic test for detecting patients with subclinical renal dysfunction.