Enzyme Replacement Improves Ataxic Gait and Central Nervous System Histopathology in a Mouse Model of Metachromatic Leukodystrophy

Inherited deficiencies of lysosomal hydrolases cause lysosomal storage diseases (LSDs) that are characterized by a progressive multisystemic pathology and premature death. Repeated intravenous injection of the active counterpart of the deficient enzyme, a treatment strategy called enzyme replacement therapy (ERT), evolved as a clinical option for several LSDs without central nervous system (CNS) involvement. To assess the efficacy of long-term ERT in metachromatic leukodystrophy (MLD), an LSD with prevailing nervous system disease, we treated immunotolerant arylsulfatase A (ASA) knockout mice with 52 doses of either 4 or 50 mg/kg recombinant human ASA (rhASA). ERT was tolerated without side effects and improved disease manifestations in a dose-dependent manner. Dosing of 4 mg/kg diminished sulfatide storage in kidney and peripheral nervous system (PNS) but not the CNS, whereas treatment with 50 mg/kg was also effective in the CNS in reducing storage in brain and spinal cord by 34 and 45%, respectively. Histological analyses revealed regional differences in sulfatide clearance. While 70% less storage profiles were detectable, for example, in the hippocampal fimbria, the histopathology of the brain stem was unchanged. Both enzyme doses normalized the ataxic gait of ASA knockout mice, demonstrating prevention of nervous system dysfunctions that dominate early stages of MLD.     

Septicemia Caused by Tick-borne Bacterial Pathogen Candidatus Neoehrlichia mikurensis

We have repeatedly detected Candidatus Neoehrlichia mikurensis, a bacterium first described in Rattus norvegicus rats and Ixodes ovatus ticks in Japan in 2004 in the blood of a 61-year-old man with signs of septicemia by 16S rRNA and groEL gene PCR. After 6 weeks of therapy with doxycycline and rifampin, the patient recovered.     

Diagnosis and Laparoscopic Approach to Gallbladder Torsion and Cholelithiasis

Torsion of the gallbladder is common in elderly women. Different causes have been proposed for this rare condition. The presence of a long mesentery and loss of visceral fat are the main causes for the development of torsion. Patients present with a sudden, acute pain in the right upper quadrant, suggesting cholecystitis. Different imaging methods have shown particular findings, but the diagnosis is still complex. Today, just a few cases have been reported in the literature. The treatment for this condition consists of surgical detorsion and cholecystectomy. Gall-bladder torsion is a very rare entity and should be suspected when these clinical findings are present.