Isolated granulomatous angiitis with eosinophilia in the central nervous system

A 73-year-old man was admitted for epileptic seizures. Diffuse white matter lesions were observed in the bilateral occipital lobes, and the left occipital lobe biopsy showed eosinophils and giant cells in the walls of medium to small blood vessels, fibrinoid necrosis, occluded blood vessels, and glia degeneration. Allergic granulomatous angiitis was pathologically diagnosed. No eosinophilic granulomatosis with polyangiitis findings were observed in other organs, and isolated granulomatous angiitis with eosinophilia in the central nervous system was clinically diagnosed. Prednisolone combined with immunosuppressant therapies improved his symptoms markedly

Neuromyelitis optica spectrum disorders accompanying subarachnoid hemorrhage and reversible white matter lesions

A 48-year-old man was admitted to Tomakomai City Hospital, Tomakomai, Japan, because of intractable hiccups and nausea, and orthostatic hypotension. Brain magnetic resonance imaging findings showed a dorsal medullary lesion. Respiratory failure occurred, and he underwent tracheotomy and mechanical ventilation when magnetic resonance imaging showed subarachnoid hemorrhage in addition to enlarged medullary lesions. Serum anti-aquaporin-4 antibody was positive and the cerebrospinal fluid was bloody. We diagnosed meuromyelitis optica spectrum disorders complicating subarachnoid hemorrhage. He was treated with a steroid. Although extensive white matter lesions occurred transiently, the patient was discharged from the hospital when he became able to walk with the use of the walker on the 52nd day. We suggest that the subarachnoid hemorrhage and transient white matter lesions were associated with vascular damage associated with the meuromyelitis optica spectrum disorders

Combination of hypertonic saline and low-dose furosemide is an effective treatment for refractory congestive heart failure with hyponatremia

AbstractHyponatremia often associates with heart failure. Although severe salt restriction is generally recommended in heart failure treatment, it may promote hyponatremia which is a risk factor for increased morbidity and mortality in heart failure patients. Therefore, it is not yet clear whether correction of hyponatremia is an effective treatment in congestive heart failure with hyponatremia. We experienced a successful case of refractory congestive heart failure with hyponatremia treated with hypertonic saline and furosemide. A 45-year-old man, suffering from dilated cardiomyopathy, was admitted to our hospital for heart failure worsening with hyponatremia. We started diuretics therapy without correction of hyponatremia, but his clinical status of heart failure was not improved. Therefore, we additionally started to correct hyponatremia by continuous injection of hypertonic saline. The correction of hyponatremia increased urinary volume dramatically, and improved cardiac output and clinical status of heart failure. This case strongly suggests that combination of hypertonic saline and furosemide could enhance diuretic effect, and improve the clinical status of heart failure in congestive heart failure patients with hyponatremia.<Learning objective: Hyponatremia is a major problem associated with heart failure, but it is not yet clear whether correction of hyponatremia is an effective treatment in patients with congestive heart failure. We experienced a successful case of refractory congestive heart failure with hyponatremia treated with hypertonic saline and low dose furosemide. This case strongly suggests that aggressive correction of hyponatremia can be an effective treatment for refractory congestive heart failure with hyponatremia.

Inhibition of glycogen synthase kinase 3β during heart failure is protective

Glycogen synthase kinase (GSK)-3, a negative regulator of cardiac hypertrophy, is inactivated in failing hearts. To examine the histopathological and functional consequence of the persistent inhibition of GSK-3β in the heart in vivo, we generated transgenic mice with cardiac-specific overexpression of dominant negative GSK-3β (Tg-GSK-3β-DN) and tetracycline-regulatable wild-type GSK-3β. GSK-3β-DN significantly reduced the kinase activity of endogenous GSK-3β, inhibited phosphorylation of eukaryotic translation initiation factor 2Bε, and induced accumulation of β-catenin and myeloid cell leukemia-1, confirming that GSK-3β-DN acts as a dominant negative in vivo. Tg-GSK-3β-DN exhibited concentric hypertrophy at baseline, accompanied by upregulation of the α-myosin heavy chain gene and increases in cardiac function, as evidenced by a significantly greater Emax after dobutamine infusion and percentage of contraction in isolated cardiac myocytes, indicating that inhibition of GSK-3β induces well-compensated hypertrophy. Although transverse aortic constriction induced a similar increase in hypertrophy in both Tg-GSK-3β-DN and nontransgenic mice, Tg-GSK-3β-DN exhibited better left ventricular function and less fibrosis and apoptosis than nontransgenic mice. Induction of the GSK-3β transgene in tetracycline-regulatable wild-type GSK-3β mice induced left ventricular dysfunction and premature death, accompanied by increases in apoptosis and fibrosis. Overexpression of GSK-3β-DN in cardiac myocytes inhibited tumor necrosis factor-α–induced apoptosis, and the antiapoptotic effect of GSK-3β-DN was abrogated in the absence of myeloid cell leukemia-1. These results suggest that persistent inhibition of GSK-3β induces compensatory hypertrophy, inhibits apoptosis and fibrosis, and increases cardiac contractility and that the antiapoptotic effect of GSK-3β inhibition is mediated by myeloid cell leukemia-1. Thus, downregulation of GSK-3β during heart failure could be compensatory.Supported by United States Public Health Service grants HL 59139, HL67724, HL69020, AG23039, and AG28787; and American Heart Association Grant 0340123N. S.H. and H.T. were supported by Postdoctoral Fellowships from the American Heart Association Heritage Affiliate.Peer reviewe

Usefulness of C-11-methionine-positron emission tomography for the diagnosis of progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a subacute demyelinating disease of the brain caused by the JC virus that occurs mainly in immunocompromised patients. The prognosis is very poor. As the lesion looks like non- specific leukoencephalopathy, making a diagnosis at the early stage is very difficult. We report three PML cases in which there was a mismatch between C-11-methionine-positron emission tomography (MET-PET) uptake and F-18-fluorodeoxyglucose-positron emission tomography (FDG-PET) uptake. All three cases demonstrated the hyper-uptake of MET around the white matter lesions and hypo-uptake of FDG inside the lesions. We speculate that the infection had ended inside the white matter lesions of these patients, while JC virus infection was ongoing around the lesions, resulting in the increase of methionine metabolism, and the glucose metabolism was reduced or intermediate because inflammatory cells infiltrate PML lesions rarely. Two patients who were diagnosed and treated with mefloquine while the JC virus was at a low level in the cerebrospinal fluid are still alive. We suggest the usefulness of MET-PET for the early diagnosis of PML and early treatment with mefloquine