esn- neurocognitive disorders

• Neurocognitive Disorders include Delirium and Major and Mild Neurocognitive Disorder (NCD).
• Neurocognitive Disorders are primarily cognitive disorders that represent decline and are not developmental.
• Underlying brain pathology is a characteristic of Neurocognitive Disorders.
• Dementia typically refers to degenerative disease in the elderly.
• The category of Dementia is expanded by DSM to include diseases of younger individuals such as HIV, traumatic brain injury.
• Major Neurocognitive Disorder (NCD) is characterized by Significant Cognitive Decline that interferes with independence and is not due to delirium or other mental disorder.
• There was no long term reduction in disability (up to 5 years follow up).
• The immune response is the most frequent target of attempted therapy in MS.
• Long term effects of IFNß are partial, with not all patients responding, and some experiencing adverse effects related to immune system complications (opportunistic infections, etc).
• Unlike grey matter, white matter exhibits a reasonable capacity for regeneration.
• The exact cause of inflammatory processes in MS remains unknown, and while the general inflammatory profile in MS bears similarities with other CNS inflammatory diseases (e.g viral encephalomyelitis), only MS manifests primarily white matter damage.
• The primary pathological hallmark of multiple sclerosis (MS) is demyelination with associated inflammatory infiltrate and glial scarring.
• A randomized placebo controlled blinded Phase III study using IFNß1b administered subcutaneously was conducted on 372 patients with relapse-remitting MS, with the primary end point being the annual relapse rate.
• Lymphocytes move across the blood-brain barrier (BBB) into the CNS through the 4-integrin surface receptor.
• T-cell, B-cell and macrophage vascular infiltration in MS is believed to be in response to autoimmunity against common myelin antigens.
• Interferon acts by limiting the spread of an immune response via surface receptors on cells.
• The study showed a 34% reduction in annual relapse rate with a 58% reduction in active lesion rate per year (MRI).
• The active immune phase is an early event in MS lesion pathology, hence the relatively limited efficacy in progressive forms of disease.
• MS is characterized by diffuse inflammatory markers throughout the brain and spinal cord that are particularly concentrated at demyelinated plaques.
• In the inflammatory stage of MS, T cells, B cells and antigen-presenting cells (APCs), including macrophages, enter the central nervous system (CNS), where they secrete cytokines that damage the oligodendroglial cells.
• Interferonß (IFNß) is the most commonly prescribed therapeutic for relapse-remitting MS.
• Early on it was recognized that IFN was deficient in the CSF of MS patients, leading to formulation of a putative therapy.
• This step is impeded by antibodies specific for 4-integrin or by interferon- (IFN -).
• Mild Neurocognitive Disorder (NCD) is characterized by Moderate Cognitive Decline that does not interfere with independence and is not due to delirium or other mental disorder.
• Cognition is defined psychometrically.
• Mild Neurocognitive Disorder (NCD) is diagnosed when cognitive testing is 1-2 standard deviations (SD) below the norm, between the 3rd and 16th percentiles.
• Severity (level of disability) in neurocognitive disorders can be mild, where instrumental ADLs are preserved, or moderate to severe, where basic ADLs are affected.
• Psychosis, mood, and agitation can occur without being clinically significant.
• Types of neurocognitive disorders include Delirium, Major and Mild Neurocognitive Disorder (NCD), and Major Neurocognitive Disorder.
• Differential diagnosis of Delirium includes Major Neurocognitive Disorder, Delirium due to a General Medical Condition, Substance Intoxication Delirium, Substance Withdrawal Delirium, Delirium due to Multiple Etiologies, and Delirium NOS.
• Delirium diagnostic criteria include key features of rapid and abrupt onset of impaired attention and lack of awareness of environment, and a change in at least one cognitive domain such as recent memory, orientation, or language.
• NCD due to Alzheimer’s disease, Vascular disease, Traumatic Brain Injury, Lewy body disease, and several others.
• Delirium differs from other NCDs in that it has a rapid onset in hours to days, is linked to a medical condition, substance intoxication/withdrawal, medications, and other causes, and may resolve completely.
• Major Neurocognitive Disorder (NCD) is diagnosed when cognitive testing is below 2 SD or 3rd percentile.
• Mild and Major Neurocognitive Disorders exist on a continuum.
• Cognitive domains specified in DSM-5 include Complex attention, Executive function, Learning & memory, Language, Perceptual-motor, and Social cognition.
• Tay Sachs HexA is a cause of Tay Sachs Disease (TSD).
• Metachromatic leukodystrophy (MLD) is caused by a toxic gain of function caused by loss of function of a lysosomal enzyme, specifically Arasulfatase A (ARSA).
• Krabbe GalC is a cause of Krabbe Disease (KD).
• Symptoms of MLD include progressive motor and cognitive decline with evidence of diffuse symmetric myelin abnormalities as seen by MRI.