pathophys2test3: CNS Infections, Seizures, Head Trauma & Movement Disorders ppt

Head Trauma

• Traumatic Brain Injury (TBI) is an alteration in brain function or evidence of brain pathology caused by external force
• Common mechanisms of TBI include direct impact, rapid acceleration/deceleration, penetrating injury, and blast waves
• The external mechanical forces are transferred to intracranial contents, causing damage to the brain, including focal contusions and hematomas, shearing of white matter tracts, and possible cerebral edema
• The injury can be focal or diffuse, depending on the mechanism of injury

TBI Pathophysiology: Primary Brain Injury

• Diffuse Axonal Injury is caused by shearing/tearing of neuronal axons due to shifting/rotation of the brain within the skull during trauma
• Seen in "coup contrecoup" injuries; abrupt deceleration causes the brain to collide with the skull
• Can be seen on neuroimaging as multiple small lesions within white matter tracts
• Focal Cerebral Contusions are the most common lesions, commonly seen in the basal frontal and temporal areas due to direct impact on basal skull surfaces in the setting of acceleration/deceleration injuries
• Intracranial hemorrhage can occur, including epidural hematomas, subdural hematomas, or subarachnoid hemorrhage

TBI Pathology: Secondary Brain Injury

• Cascade of molecular injury mechanisms that start at the time of injury and continue for hours to days
• Free-radical injury to cell membranes, electrolyte imbalances, mitochondrial dysfunction, inflammatory responses, apoptosis, and secondary ischemia from vasospasm lead to neuronal cell death and cerebral edema
• It is critical to avoid secondary brain insults after an initial TBI due to the cells being vulnerable to further damage

Concussion

• Mild traumatic brain injury (mTBI)
• Temporary impairment of neurologic function
• Memory loss, attention deficits, headache, altered mental status
• Neuronal dysfunction happens due to metabolic insults from the trauma rather than an actual structural abnormality
• Concussed cells become very vulnerable, and if a second concussion is sustained during this period, damage can be irreversible
• Hallmark symptoms are confusion and amnesia with or without loss of consciousness

Chronic Traumatic Encephalopathy

• Repetitive closed-head injuries, like in boxers, football players
• Progressive neurological disorder that often presents like dementia, can also have motor disorders

CNS Infections

Meningitis

• Infection of the meninges resulting in inflammation
• Can be viral, bacterial, or fungal

Bacterial Meningitis

• Virulence factors of a pathogen overcome host defense mechanisms
• Common pathogens include Group B streptococcus, Neisseria meningitidis, Streptococcus pneumoniae, H. influenza, and E. coli
• Invasion of bacteria into the meninges through the bloodstream or direct extension from local infection
• Clinical manifestations include fever, neck stiffness, and altered mental status
• Treatment includes empiric antibiotics, antivirals, and steroids to reduce inflammation

Neurodegenerative & Movement Disorders

Basal Ganglia

• Group of subcortical nuclei responsible primarily for motor control
• Made up of the substantia nigra, caudate nucleus, putamen, and others
• Functions include initiating voluntary motor movement, suppressing unwanted movement, and procedural learning
• Substantia Nigra contains dopamine and projects to the striatum

Movement Disorders

• Group of neurologic conditions that cause abnormal movements
• Can be either increased movements (spasms, tremors, etc.) or decreased/slow movement
• Can affect both voluntary and involuntary movements
• Common disorders include ataxia, chorea, dystonia, tremor, Huntington's disease, and Parkinson's disease

Huntington's Disease

• Rare autosomal dominant genetic disorder
• Clinical manifestations include dementia, psychiatric symptoms, chorea movements, and progressive neuronal degeneration
• Genetic mutation in Huntingtin (HTT) gene causes triplet repeat expansion of a particular DNA sequence responsible for coding for glutamine
• Accumulations of this abnormal protein lead to neuronal death/dysfunction as well as dysfunction of glutamate/dopamine signaling in the basal ganglia
• Treatment focuses on symptom management, usually aimed at trying to help suppress the abnormal chorea movements to improve quality of life

Parkinson's Disease

• Degenerative disorder of the substantia nigra
• Progressive degeneration of dopamine-producing neurons in the substantia nigra
• Symptoms include "pill-rolling" tremor at rest, rigidity, masked facies, shuffling gait, bradykinesia, and dementia in later stages
• Clinical correlation: Parkinson's treatment includes Levodopa/Carbidopa to increase dopamine levels in the brain

Amyotrophic Lateral Sclerosis (ALS)

• Progressive neurodegenerative disorder of upper and lower motor neurons
• Etiology is unknown, with some genetic susceptibility
• Sporadic form accounts for 90-95% of cases, and familial forms make up 5-10% of cases
• Pathophysiology includes motor neuron degeneration and death, cortical motor neuron death, spinal cord atrophy, and loss of large myelinated fibers in motor nerves
• Unfortunately, no cure exists, and it is always fatal, usually within five years of diagnosis