Acute cerebellar ataxia: a rare Toscana Virus (TOSV) meningoencephalitis complication.

Purpose: Arbovirosis, viral infection transmitted by arthropods, is a widespread health problem. In Italy, as well for all Mediterranean basin, from late spring to the end of summer, Toscana Virus (TOSV), a sandfly borne virus, accounts for the majority of aseptic meningitis/meningoencephalitis cases. TOSV meningitis/meningoencephalitis has usually a self-extinguishing benign course. Our aim is to report a case of a young healthy women diagnosed with Toscana Virus meningoencephalitis with a complicated clinical course.Materials and methods/results: Case report of a 33-years old woman, admitted to the Infectious Diseases Unit at Careggi General Hospital (Florence-Italy), with a diagnosis of Toscana Virus meningoencephalitis. Seventy-two hours after the admission, she developed typical symptoms, as impaired legs coordination, slurred speech, stumbling and dysmetria, of acute cerebellar ataxia (ACA). Urgent neurological assessment was provided performing an electroencephalography study followed by a brain and brainstem magnetic resonance imaging. In the meanwhile, bilateral nystagmus arised. Through neurologist consultation ACA clinical diagnosis was then made and intravenous steroid therapy was administered with prompt symptoms resolution. The patient was finally discharged at day 10 since the ACA onset in good clinical conditions.Conclusions: To raise awareness among physicians about possible neurological complications during Toscana Virus meningoencephalitis.

Virus Infections on Prion Diseased Mice Exacerbate Inflammatory Microglial Response.

We investigated possible interaction between an arbovirus infection and the ME7 induced mice prion disease. C57BL/6, females, 6-week-old, were submitted to a bilateral intrahippocampal injection of ME7 prion strain (ME7) or normal brain homogenate (NBH). After injections, animals were organized into two groups: NBH (n = 26) and ME7 (n = 29). At 15th week after injections (wpi), animals were challenged intranasally with a suspension of Piry arbovirus 0.001% or with NBH. Behavioral changes in ME7 animals appeared in burrowing activity at 14 wpi. Hyperactivity on open field test, errors on rod bridge, and time reduction in inverted screen were detected at 15th, 19th, and 20th wpi respectively. Burrowing was more sensitive to earlier hippocampus dysfunction. However, Piry-infection did not significantly affect the already ongoing burrowing decline in the ME7-treated mice. After behavioral tests, brains were processed for IBA1, protease-resistant form of PrP, and Piry virus antigens. Although virus infection in isolation did not change the number of microglia in CA1, virus infection in prion diseased mice (at 17th wpi) induced changes in number and morphology of microglia in a laminar-dependent way. We suggest that virus infection exacerbates microglial inflammatory response to a greater degree in prion-infected mice, and this is not necessarily correlated with hippocampal-dependent behavioral deficits.

Encephalitic Arboviruses: Emergence, Clinical Presentation, and Neuropathogenesis.

Arboviruses are arthropod-borne viruses that exhibit worldwide distribution, contributing to systemic and neurologic infections in a variety of geographical locations. Arboviruses are transmitted to vertebral hosts during blood feedings by mosquitoes, ticks, biting flies, mites, and nits. While the majority of arboviral infections do not lead to neuroinvasive forms of disease, they are among the most severe infectious risks to the health of the human central nervous system. The neurologic diseases caused by arboviruses include meningitis, encephalitis, myelitis, encephalomyelitis, neuritis, and myositis in which virus- and immune-mediated injury may lead to severe, persisting neurologic deficits or death. Here we will review the major families of emerging arboviruses that cause neurologic infections, their neuropathogenesis and host neuroimmunologic responses, and current strategies for treatment and prevention of neurologic infections they cause.

Continuous myocloni and tonic spasms in a 2-month-old infant with enterovirus 71 brain stem encephalitis.

Brain stem encephalitis is a cardinal presentation of central nervous system involvement in enterovirus 71 infection, and manifests as myoclonus, ataxia, tremor, and autonomic dysfunction. A 2-month-old infant with enterovirus 71 brain stem encephalitis demonstrated continuous myocloni and tonic spasms. On admission, the patient's myoclonus, which mainly involved the shoulders and the arms, was considerably worse during wakefulness and occurred once or twice a minute. Several hours after admission, the myoclonic jerks steadily worsened, appeared ceaselessly every 1 to 2 seconds, and were intermixed with tonic spasms of all four extremities accompanied by crying. Video electroencephalography revealed a normal background without epileptiform discharges and no ictal electroencephalographic changes during the myoclonic jerks and tonic spasms. Complete remission was achieved without complications after completion of a 3-day immunoglobulin therapy. This case suggests that the brain stem may be a major origin site for not only myoclonus but also tonic spasm.

Medical and molecular perspectives into a forgotten epidemic: encephalitis lethargica, viruses, and high-throughput sequencing.

The emergence of encephalitis lethargica (EL), an acute-onset polioencephalitis of unknown etiology as an epidemic in the years 1917-1925 is still unexplainable today. Questioned by the first descriptor of EL himself, Constantin von Economo, there has been much debate shrouding a possible role of the "Spanish" H1N1 influenza A pandemic virus in the development of EL. Previous molecular studies employing conventional PCR for the detection of influenza A virus RNA in archived human brain samples from patients who died of acute EL were negative. However, the clinical and laboratory characteristics of EL and its epidemiology are consistent with an infectious disease, and recently a possible enterovirus cause was investigated. With the rapid development of high-throughput sequencing, new information about a possible viral etiology can be obtained if sufficient specimens for analysis were still available today. Here, we discuss the implications of these technologies for the investigation of a possible infectious cause of EL from archived material, as well as a prospectus for future work for acquiring viral nucleic acids from these sources.

Encephalitis lethargica in 5 South African children.

The clinical features and cognitive outcome in 5 South African childhood cases of sporadic encephalitis lethargica seen between 2002 and 2006 are discussed. All children presented with an acute encephalopathic illness complicated by sleep disturbance, extrapyramidal and neuropsychiatric symptoms. Diagnosis was based on shared clinical features with other cases described in the literature and exclusion of known infective, biochemical and metabolic causes of acute childhood encephalopathy. The negative findings on neuro-imaging in all cases strongly supported the diagnosis. All children survived but 3 cases became learning disabled and all required cognitive rehabilitation after recovery. The cases demonstrate that encephalitis lethargica does indeed occur among South African children. The condition should be considered in any previously well child that presents with an acute encephalopathic illness with prominent extrapyramidal and neuropsychiatric symptoms and negative infectious, biochemical, autoimmune, metabolic and radiologic investigations. Recognition is important as it allows counseling of parents regarding the protracted course but generally favorable outcome of the condition.

Murray Valley encephalitis in an adult traveller complicated by long-term flaccid paralysis: case report and review of the literature.

Murray Valley encephalitis (MVE) virus, a mosquito-borne flavivirus, is the most common cause of viral encephalitis in the tropical 'Top End' of northern Australia. Clinical encephalitis due to MVE virus has a mortality rate of approximately 30%, with a similar proportion of patients being left with significant neurological deficits. We report the case of a 25-year-old man from the UK who acquired MVE while travelling through northern Australia. He required prolonged admission to the Intensive Care Unit and several years later remains partly ventilator-dependent, with flaccid quadriparesis. To our knowledge, this is the first reported case of MVE virus-induced flaccid paralysis in an adult in northern Australia, although it is well described in children. Paralysis was thought to be due to anterior horn cell involvement in the spinal cord and extensive bilateral thalamic destruction, both of which are well recognised complications of infection with MVE virus. Cases of flaccid paralysis with similar pathology have been described following infection with the related flavivirus Japanese encephalitis virus as well as more recently with West Nile virus. Our case highlights the potential severity of flavivirus-induced encephalitis and the importance of avoiding mosquito bites while travelling through endemic areas.

Fiebre del nilo del oeste (west nile fever): una nueva amenaza de los viejos continentes / West Nile fever : a new threat of old continents

La Fiebre del nilo del oeste (WNF) ha sido conocido en los viejos continentes, desde hace 70 años. El virus fue aislado en Uganda por primera vez en 1937. Brotes de esta enfermedad han ocurrido en Israel desde 1950 involucrando a más del 60 por ciento de la población. Han ocurrido brotes también en el sur de Europa y Asia. La infección fue documentada por primera vez en el hemisferio occidental en ocasión de un brote de encefalitis en New York; siendo documentada serológicamente en 236 de 290 pacientes con síntomas agudos. ¿Qué interés y relación tiene esta antigua infección viral con los países latinoamericanos? Se demostró que este virus es transmitido entre aves salvajes por los mosquitos culex. Y los pájaros migratorios podrían fácilmente distribuir esta infección a Honduras. Durante los meses de verano, puede encontrarse el vector, culex pipiens en Honduras, lo mismo que los mosquitos aedes y anopheles que han sido asociados con WNF. Más aún, las características clínicas son muy similares a nuestras epidemias actuales de dengue. El virus fue documentado en Norteamérica, y las condiciones son apropiadas para su diseminación en el hemisferio Occidental. Es el propósito principal de este artículo, por lo tanto, brindar una actualización en este y otros aspectos del WNF al médico latinoaméricano

PET study and neuropsychological assessment of a long-lasting post-encephalitic parkinsonism.

A 76-year old woman was affected by lethargic encephalitis in 1918, at the age of 3 months. Long-term clinical follow-up with late neuropsychological evaluation revealed post-encephalitic parkinsonism, which worsened very slowly and was improved by levodopa. Obsessive and compulsive disorders (OCD) were associated to nosophobia. Neuropsychological evaluation showed mild visuocontructional memory deficit, which was isolated. 18 Fluoro-Dopa PET demonstrated a severe bilateral and symmetrical reduction in fluoro-dopa uptake, which was more marked in the putamen than in the caudate. Thus, the pattern of dopaminergic denervation was similar to the one observed in idiopathic Parkinson's disease.

Atypical affective disorder with episodic dyscontrol: a case of von Economo's disease (encephalitis lethargica).

The case is described of a patient with atypical affective disorder, episodic behavioural dyscontrol and parkinsonism resulting from presumed encephalitis lethargica. EEG abnormalities were found which were compatible with a post-encephalitic state and suggestive of epileptiform complications. Poor or deleterious response to neuroleptics, sleep disorder, and parkinsonism are features that may allow recognition of this illness in a psychiatric setting.

[A case of brain infarction associated with viral encephalitis: MRI and pathological findings].

A 10-year-old girl had an infarction in the left brain during an acute viral meningoencephalitis. She initially showed seizure, unconsciousness and fever, and right hemiplegia gradually developed. She died at the 48th day of disease from respiratory disturbance and renal failure. Cranial MRI during the acute phase of the disease, when there was no clinical sign of right hemiplegia, showed a high intensity lesion in the left parietal and occipital areas on T-2 weight image. Autopsy disclosed the findings suggesting viral encephalitis, including multiple focal necrosis, perivascular round cell infiltration, proliferation of glial cells and spongy degeneration with some intranuclear inclusion bodies, and infarction in the left hemisphere. These findings suggest that T-2 high intensity lesion on MRI reflected infarction.