Cryptococcal meningoencephalitis: time for action.

Cryptococcal meningoencephalitis was first described over a century ago. This fungal infection is preventable and treatable yet continues to be associated with excessive morbidity and mortality. The largest burden of disease resides in people living with HIV in low-income and middle-income countries. In this group, mortality with the best antifungal induction regimen (7 days of amphotericin B deoxycholate [1·0 mg/kg per day] and flucytosine [100·0 mg/kg per day]) in a clinical trial setting was 24% at 10 weeks. The world is now at an inflection point in terms of recognition, research, and action to address the burden of morbidity and mortality from cryptococcal meningoencephalitis. However, the scope of interventional programmes needs to increase, with particular attention to implementation science that is specific to individual countries. This Review summarises causes of excessive mortality, interventions with proven survival benefit, and gaps in knowledge and practice that contribute to the ongoing high death toll from cryptococcal meningoencephalitis. TRANSLATIONS: For the Vietnamese and Chichewa translations of the abstract see Supplementary Materials section.

Vitamin D deficiency decreases survival of bacterial meningoencephalitis in mice.

BACKGROUND: Meningoencephalitis caused by Escherichia coli is associated with high rates of mortality and risk of neurological sequelae in newborns and infants and in older or immunocompromised adults. A high prevalence of neurological disorders has been observed in geriatric populations at risk of hypovitaminosis D. METHODS: In vivo, we studied the effects of vitamin D3 on survival and the host's immune response in experimental bacterial meningoencephalitis in mice after intracerebral E. coli infection. To produce different systemic vitamin D3 concentrations, mice received a low, standard, or high dietary vitamin D3 supplementation. Bacterial titers in blood, spleen, and brain homogenates were determined. Leukocyte infiltration was assessed by histological scores, and tissue cytokine or chemokine concentrations were measured. RESULTS: Mice fed a diet with low vitamin D3 concentration died earlier than control animals after intracerebral infection. Vitamin D deficiency did not inhibit leukocyte recruitment into the subarachnoid space and did not lead to an increased density of bacteria in blood, spleen, or brain homogenates. The release of proinflammatory interleukin (IL)-6 was decreased and the release of anti-inflammatory IL-10 was increased in mice fed a diet with high vitamin D3 supplementation. CONCLUSION: Our observations suggest a detrimental role of vitamin D deficiency in bacterial central nervous system infections. Vitamin D may exert immune regulatory functions.

Therapeutic plasma exchange for malignant refractory status epilepticus: a case report.

BACKGROUND: Refractory status epilepticus is a prolongation of status epilepticus despite anticonvulsant therapy with two or three medications in proper doses; it is defined as malignant status epilepticus if it takes weeks or months. Intravenous immunoglobulin, high-dose steroids, magnesium infusion, pyridoxine, hypothermia, ketogenic diet, electroconvulsive therapy, and surgical therapy are the other treatment options for status epilepticus. PATIENT: Our 5-year-old male patient was hospitalized at our pediatric intensive care unit because of status epilepticus secondary to meningoencephalitis. No response could be obtained with many medical and nonmedical therapies in our patient, who developed malignant status epilepticus with unknown etiology. Therapeutic plasma exchange was applied as convulsions continued. RESULT: Ours is the first child for whom therapeutic plasma exchange was successfully applied because of malignant refractory status epilepticus secondary to meningoencephalitis. CONCLUSION: Therapeutic plasma exchange may be a treatment option for children with refractory status epilepticus following presumed meningoencephalitis.

Erythrina abyssinica prevents meningoencephalitis in chronic Trypanosoma brucei brucei mouse model.

Human African trypanosomiasis is prevalent in Sub-sahara African countries that lie between 14° North and 29° south of the equator. Sixty million people are at risk of infection. Trypanosoma brucei gambesience occurs in West and Central Africa while Trypanosoma brucei rhodesience occurs in East and Southern Africa. The neurological stage of the disease is characterized by neuroinflammation. About 10% of patients treated with the recommended drug, melarsoprol develop post treatment reactive encephalopathy, which is fatal in 50% of these patients, thus melarsoprol is fatal in 5% of all treated patients. This study was aimed at establishing the potential activity of Erythrina abyssinica in reducing neuroinflammation following infection with Trypanosoma brucei brucei. Swiss white mice were divided into ten groups, two control groups and eight infected groups. Infected mice received either methanol or water extract of Erythrina abyssinica at 12.5, 25, 50 or 100 mg/kg body weight. Parasite counts were monitored in peripheral circulation from the third day post infection up to the end of the study. Brains were processed for histology, immunohistochemistry scanning and transmission electron microscopy. Following infection, trypanosomes were observed in circulation 3 days post-infection, with the parasitaemia occurring in waves. In the cerebrum, typical brain pathology of chronic trypanosomiasis was reproduced. This was exhibited as astrocytosis, perivascular cuffing and infiltration of inflammatory cells into the neuropil. However, mice treated with Erythrina abyssinica water extract exhibited significant reduction in perivascular cuffing, lymphocytic infiltration and astrocytosis in the cerebrum. The methanol extract did not have a significant difference compared to the non-treated group. This study provides evidence of anti-inflammatory properties of Erythrina abyssinica and may support its wide use as a medicinal plant by various communities in Kenya.

Angiostrongylus cantonensis: apoptosis of inflammatory cells induced by treatment with mebendazole or/and interleukin 12 in mice.

Angiostrongylus cantonensis is the major cause of human eosinophilic meningoencephalitis. ICR mice were infected orally with 35 infective larvae and sacrificed at 4-14 days, 25 days or 32 days post infection (dpi) for pathological and immunocytochemical examinations. In the non-treated group, no apoptosis signal was found in the meninges or parenchyma of the brains (4-14 dpi). Only a few apoptotic cells were noticed at 25 dpi (3%) and 32 dpi (10%). In the groups, the animals were given a single dose of mebendazole (20 mg/kg, per os at various times) or injections of interleukin 12 (IL-12) (10 ng/daily, intraperitoneally), all the animals were sacrificed at 14 dpi; the number of apoptotic cells was increased (17-21%). In the group that received a single dose of mebendazole (4 dpi) in combination with IL-12 injections (4-13 dpi), mild meningitis was observed, and most of the infiltrated inflammatory cells were in the apoptotic program (55%). Taken together, apoptosis of the inflammatory cells (most were eosinophils) could be induced when the infected mice were treated with mebendazole or/and IL-12.

[Acute onset of tuberculous meningoencephalitis presenting with symmetric linear lesions in the bilateral thalamus: a case report].

A 18-year-old woman was admitted to our hospital because of high fever and headache. Nuchal stiffness was present, and a CSF examination showed lymphocyte-domonant pleocytosis and a decreased level of glucose. Although antibiotics, aciclovir and an antimycotic drug were administered, disturbance of consciousness, involuntary movements, and pyramidal tract signs appeared. Soon after the medications were changed to antituberculous medicines, the meningoencephalitis started to subside, and was finally cured. Judging from the clinical findings, the CSF findings, the effectiveness of antituberculous medicines, an elevated ADA level in CSF, and positive conversion in tuberculin tests, the final diagnosis was made as tuberculous meningoencephalitis. At the severest stage of the disease, a brain MRI showed symmetric, linear lesions without the effect of Gd-enhancement in the bilateral thalamus, which thereafter disappeared along with the healing of the illness. From all these things, we conclude that thalamic and other parenchymal lesions should be kept in mind in case of acute tuberculous meningoencephalitis.

Comparative efficacies of antibiotics in a rat model of meningoencephalitis due to Listeria monocytogenes.

The antibacterial activities of amoxicillin-gentamicin, trovafloxacin, trimethoprim-sulfamethoxazole (TMP-SMX) and the combination of trovafloxacin with TMP-SMX were compared in a model of meningoencephalitis due to Listeria monocytogenes in infant rats. At 22 h after intracisternal infection, the cerebrospinal fluid was cultured to document meningitis, and the treatment was started. Treatment was instituted for 48 h, and efficacy was evaluated 24 h after administration of the last dose. All tested treatment regimens exhibited significant activities in brain, liver, and blood compared to infected rats receiving saline (P < 0.001). In the brain, amoxicillin plus gentamicin was more active than all of the other regimens, and trovafloxacin was more active than TMP-SMX (bacterial titers of 4.1 +/- 0.5 log10 CFU/ml for amoxicillin-gentamicin, 5.0 +/- 0.4 log10 CFU/ml for trovafloxacin, and 5.8 +/- 0.5 log10 CFU/ml for TMP-SMX; P < 0.05). In liver, amoxicillin-gentamicin and trovafloxacin were similarly active (2.8 +/- 0.8 and 2.7 +/- 0.8 log10 CFU/ml, respectively) but more active than TMP-SMX (4.4 +/- 0. 6 log10 CFU/ml; P < 0.05). The combination of trovafloxacin with TMP-SMX did not alter the antibacterial effect in the brain, but it did reduce the effect of trovafloxacin in the liver. Amoxicillin-gentamicin was the most active therapy in this study, but the activity of trovafloxacin suggests that further studies with this drug for the treatment of Listeria infections may be warranted.

An autopsied case of acute lymphocytic meningoencephalitis with a long clinical course: special reference to CT, MR, SPECT and neuropathological findings.

This report describes the clinico-pathological features of acute lymphocytic meningoencephalitis (ALME) of a patient with a long clinical course of 24 months. The patient rapidly developed a confusional state, occasionally with stupor, various involuntary movements and generalized convulsions followed by fever and headache at the age of 29. Clinical symptoms, except fever and convulsions, had not distinctly improved throughout the clinical course, and cortical atrophy on CT and MR gradually progressed. SPECT revealed a low blood perfusion in the cerebral cortices. Neuropathologically, inflammatory findings were very mild, but nerve cells degenerated prominently. From these clinicopathological findings, it is suggested that chronic degenerative changes followed an acute inflammatory phase.

Fahr's syndrome: local inflammatory factors in the pathogenesis of calcification.

Three cases of Fahr's syndrome are described. All patients had disturbances of calcium metabolism and had had a meningoencephalitis in childhood. It is suggested that gliovascular changes, induced by cerebral inflammation, can later facilitate the occurrence of calcification of the striopallidodentate system when abnormality of calcium metabolism develops.

[Development and practical use of new experimental models of the various forms of herpetic infection]. / Razrabotka i prakticheskoe ispol'zovanie novykh éksperimental'nykh modelei raznykh form gerpeticheskoi infektsii.

New experimental models of neurological herpes in cotton rats and genital herpes in male guinea pigs have been developed which are more adequate to the corresponding human diseases, and models of ophthalmic herpes in rabbits and guinea pigs have been improved. These models may be used for screening and evaluation of the effectiveness of drugs for herpes. A high activity against herpes of bromovinyldeoxyuridine and acyclovir has been verified, a marked therapeutic effect of Soviet monophosphates ara-A, ara-C, and original silur preparation in some forms of herpes infection has been demonstrated.

Granulomatous encephalitis, intracranial arteritis, and mycotic aneurysm due to a free-living ameba.

Primary amebic meningoencephalitis and granulomatous amebic encephalitis are well recognized clinicopathological entities caused by free-living amebas. Associated arteritis and "mycotic aneurysms" with infiltration of intracranial arteries by lymphocytes, amebic trophozoites and cysts have not been previously reported. A 26-month-old girl had a 3-week history of encephalitis, characterized, initially, by vomiting and low-grade fever. Subsequently, she developed ataxia, generalized weakness, lethargy, and esotropia. The first CSF showed 490 RBC/microliters, 705 WBC/microliters with 90% mononuclears. Her pupils reacted briskly to light. Moderate nuchal rigidity, nystagmus, fixed downward gaze, anisocoria, bilateral 6th nerve palsy, left arm monoparesis and left Babinski were present. CAT scan revealed slight symmetrical dilatation of anterior horns of lateral ventricles and an area of abnormal enhancement above the 3rd ventricle. She died 14 days after admission, 5 weeks after onset of symptoms. The brain showed focal necrotizing encephalopathy, involving thalami, cerebellum, brain stem, and cervical and upper thoracic spinal cord. Numerous free-living amebic trophozoites and cysts were present within a chronic granulomatous encephalitis. There were trombosis of basilar, posterior cerebral, and vertebral arteries with profuse chronic panarteritis, fibrinoid necrosis, and mycotic aneurysms.