For Alzheimer’s Sufferers, Brain Inflammation Ignites a Neuron-Killing “Forest Fire”

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For decades researchers have focused their attacks against Alzheimer’s on two proteins, amyloid beta and tau. Their buildup in the brain often serves as a defining indicator of the disease. Get rid of the amyloid and tau, and patients should do better, the thinking goes.

But drug trial after drug trial has failed to improve patients’ memory, agitation and anxiety. One trial of a drug that removes amyloid even seemed to make some patients worse. The failures suggest researchers were missing something.

A series of observations and recently published research findings have hinted at a somewhat different path for progression of Alzheimer’s, offering new ways to attack a disease that robs memories and devastates the lives of 5.7 million Americans and their families……Continue reading….

By: Karen Weintraub

Source: For Alzheimer’s Sufferers, Brain Inflammation Ignites a Neuron-Killing “Forest Fire” | Scientific American

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Critics:

Encephalitis is inflammation of the brain. The severity can be variable with symptoms including reduction or alteration in consciousness, headachefeverconfusion, a stiff neck, and vomitingComplications may include seizureshallucinations, trouble speaking, memory problems, and problems with hearing.

Causes of encephalitis include viruses such as herpes simplex virus and rabies virus as well as bacteriafungi, or parasitesOther causes include autoimmune diseases and certain medications. In many cases the cause remains unknown. Risk factors include a weak immune system. Diagnosis is typically based on symptoms and supported by blood testsmedical imaging, and analysis of cerebrospinal fluid.

Certain types are preventable with vaccinesTreatment may include antiviral medications (such as acyclovir), anticonvulsants, and corticosteroids. Treatment generally takes place in hospital. Some people require artificial respiration. Once the immediate problem is under control, rehabilitation may be required. In 2015, encephalitis was estimated to have affected 4.3 million people and resulted in 150,000 deaths worldwide.

Adults with encephalitis present with acute onset of feverheadacheconfusion, and sometimes seizures. Younger children or infants may present with irritability, poor appetite and fever. Neurological examinations usually reveal a drowsy or confused person. Stiff neck, due to the irritation of the meninges covering the brain, indicates that the patient has either meningitis or meningoencephalitis.

Viral encephalitis can occur either as a direct effect of an acute infection, or as one of the sequelae of a latent infection. The majority of viral cases of encephalitis have an unknown cause; however, the most common identifiable cause of viral encephalitis is from herpes simplex infection. Other causes of acute viral encephalitis are rabies viruspoliovirus, and measles virus.

Additional possible viral causes are arboviral flavivirus (St. Louis encephalitisWest Nile virus), bunyavirus (La Crosse strain), arenavirus (lymphocytic choriomeningitis virus), reovirus (Colorado tick virus), and henipavirus infections. The Powassan virus is a rare cause of encephalitis. It can be caused by a bacterial infection, such as bacterial meningitis, or may be a complication of a current infectious disease such as syphilis (secondary encephalitis).

Certain parasitic or protozoal infestations, such as toxoplasmosismalaria, or primary amoebic meningoencephalitis, can also cause encephalitis in people with compromised immune systemsLyme disease or Bartonella henselae may also cause encephalitis. Other bacterial pathogens, like Mycoplasma and those causing rickettsial disease, cause inflammation of the meninges and consequently encephalitis. A non-infectious cause includes acute disseminated encephalitis which is demyelinated.

Limbic encephalitis refers to inflammatory disease confined to the limbic system of the brain.The clinical presentation often includes  disorientationdisinhibitionmemory lossseizures, and behavioral anomalies. MRI imaging reveals T2 hyperintensity in the structures of the medial temporal lobes, and in some cases, other limbic structures. Some cases of limbic encephalitis are of autoimmune origin.

An ideal drug to treat brain infection should be small, moderately lipophilic at pH of 7.4, low level of plasma protein binding, volume of distribution of litre per kg, does not have strong affinity towards binding with P-glycoprotein, or other efflux pumps on the surface of blood–brain barrier. Some drugs such as isoniazid, pyrazinamide, linezolid, metronidazole, fluconazole, and some fluoroquinolones have good penetration to blood brain barrier.

Treatment (which is based on supportive care) is as follows:

Pyrimethamine-based maintenance therapy is often used to treat toxoplasmic encephalitis (TE), which is caused by Toxoplasma gondii and can be life-threatening for people with weak immune systems. The use of highly active antiretroviral therapy (HAART), in conjunction with the established pyrimethamine-based maintenance therapy, decreases the chance of relapse in patients with HIV and TE from approximately 18% to 11%. 

This is a significant difference as relapse may impact the severity and prognosis of disease and result in an increase in healthcare expenditure.The effectiveness of intravenous immunoglobulin for the management of childhood encephalitis is unclear. Systematic reviews have been unable to draw firm conclusions because of a lack of randomised double-blind studies with sufficient numbers of patients and sufficient follow-up.

 There is the possibility of a benefit of intravenous immunoglobulin for some forms of childhood encephalitis on some indicators such as length of hospital stay, time to stop spasms, time to regain consciousness, and time to resolution of neuropathic symptoms and fever. Intravenous immunoglobulin for Japanese encephalitis appeared to have no benefit when compared..

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