Immune checkpoint inhibitors for progressive multifocal leukoencephalopathy: a new gold standard?

Journal of Neurology - Progressive multifocal leukoencephalopathy (PML) is a very rare and opportunistic encephalitis caused by JC polyomavirus that is linked to profound immunosuppression and is...     

Concurrent excitatory and inhibitory effects of high frequency stimulation: an oculomotor study

OBJECTIVE: To describe a reversible neurological condition resembling a crossed midbrain syndrome resulting from high frequency stimulation (HFS) in the midbrain. METHODS: Postoperative evaluation of quadripolar electrodes implanted in the area of the subthalamic nucleus of 25 patients with Parkinson's disease (PD) successfully treated by HFS. RESULTS: Four of the 25 patients experienced reversible acute diplopia, with dystonic posture and tremor in the contralateral upper limb when the white matter between the red nucleus and the substantia nigra was stimulated. The motor signs resembled those caused by lesions of the red nucleus. The ipsilateral resting eye position was "in and down" (three patients) or "in" (one patient). Enophthalmos was seen. Abduction was impaired and vertical eye movements were limited, but adduction was spared. The movements of the controlateral eye were normal. The ocular signs could be best explained by sustained hyperactivity of the extrinsic oculomotor nerve. Simultaneous tonic contraction of the superior rectus, the inferior rectus, and inferior oblique may cause the enophthalmos and partial limitation of upward and downward eye movements. Antagonist tonic contraction of the ipsilateral medial rectus severely impairs abduction. CONCLUSION: This crossed midbrain syndrome, possibly resulting from simultaneous activation of oculomotor nerve and lesion-like inhibition of the red nucleus suggests that high frequency stimulation has opposite effects on grey and white matter.     

Clinico-biological markers for the prognosis of status epilepticus in adults

Journal of Neurology - Prediction of mortality, functional outcome and recovery after status epilepticus (SE) is a challenge. Biological and clinical markers have been proposed to reflect the brain...     

Neuron Specific Enolase,S100-beta protein and progranulin as diagnostic biomarkers of status epilepticus

Journal of Neurology - Status epilepticus (SE) is a life-threatening prolonged epileptic seizure. A rapid diagnosis is fundamental to initiate antiepileptic treatment and to prevent the development...     

Cerebrospinal fluid and blood biomarkers of status epilepticus

Status epilepticus is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms that lead to abnormally prolonged seizures and require urgent administration of antiepileptic drugs. Refractory status epilepticus requires anesthetics drugs and may lead to brain injury with molecular and cellular alterations (eg, inflammation, and neuronal and astroglial injury) that could induce neurologic sequels and further development of epilepsy. Outcome scores based on demographic, clinical, and electroencephalography (EEG) condition are available, allowing prediction of the risk of mortality, but the severity of brain injury in survivors is poorly evaluated. New biomarkers are needed to predict with higher accuracy the outcome of patients admitted with status in an intensive care unit. Here, we summarize the findings of studies from patients and animal models of status epilepticus. Specific protein markers can be detected in the cerebrospinal fluid and the blood. One of the first described markers of neuronal death is the neuron-specific enolase. Gliosis resulting from inflammatory responses after status can be detected through the increase of S100-beta, or some cytokines, like the High Mobility Group Box 1. Other proteins, like progranulin may reflect the neuroprotective mechanisms resulting from the brain adaptation to excitotoxicity. These new biomarkers aim to prospectively identify the severity and development of disability, and subsequent epilepsy of patients with status. We discuss the advantages and disadvantages of each biomarker, by evaluating their brain specificity, stability in the fluids, and sensitivity to external interferences, such as hemolysis. Finally, we emphasize the need for further development and validation of such biomarkers in order to better assess patients with severe status epilepticus.     

Characterization of SARS-CoV-2 Evasion: Interferon Pathway and Therapeutic Options

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. SARS-CoV-2 is characterized by an important capacity to circumvent the innate immune response. The early interferon (IFN) response is necessary to establish a robust antiviral state. However, this response is weak and delayed in COVID-19 patients, along with massive pro-inflammatory cytokine production. This dysregulated innate immune response contributes to pathogenicity and in some individuals leads to a critical state. Characterizing the interplay between viral factors and host innate immunity is crucial to better understand how to manage the disease. Moreover, the constant emergence of new SARS-CoV-2 variants challenges the efficacy of existing vaccines. Thus, to control this virus and readjust the antiviral therapy currently used to treat COVID-19, studies should constantly be re-evaluated to further decipher the mechanisms leading to SARS-CoV-2 pathogenesis. Regarding the role of the IFN response in SARS-CoV-2 infection, in this review we summarize the mechanisms by which SARS-CoV-2 evades innate immune recognition. More specifically, we explain how this virus inhibits IFN signaling pathways (IFN-I/IFN-III) and controls interferon-stimulated gene (ISG) expression. We also discuss the development and use of IFNs and potential drugs controlling the innate immune response to SARS-CoV-2, helping to clear the infection.