Seizure Disorders and Alzheimer's Disease

Seizure Disorders

• Characterized by hyperexcitable and hypersynchronous activity with ion channel dysfunction
• There is an imbalance between excitatory (glutamate) and inhibitory (GABA) neurotransmitters
• Manifestations include loss of consciousness, tonic-clonic, absence, myoclonic, and atonic activity, or simple or complex partial seizures in specific brain regions
• Medication actions include increasing GABA to enhance neuronal inhibition, blocking Na+ channels to prevent excessive neuron firing
• Other medication actions include blocking Ca2+ channels to reduce excitatory neurotransmitter release, and reducing glutamate to limit neuronal excitability

Alzheimer's Disease

• Involves progressive neurodegeneration due to amyloid-beta plaques and tau protein tangles
• There is decreased acetylcholine (ACh) and glutamate dysfunction
• Common symptoms are memory loss, disorientation, confusion, behavioral changes, and severe cognitive decline
• Therapies include increasing acetylcholine (ACh) by preventing its breakdown to enhance cognition
• Therapies can regulate glutamate activity to prevent excitotoxicity and neuron death

Huntington's Disease

• This Autosomal dominant genetic disorder that features atrophy of the caudate nucleus and putamen
• There is decreased GABA and ACh, and elevated dopamine
• Typical signs are Chorea, cognitive decline, psychiatric symptoms, and progressive rigidity
• Treatments work to reduce excess dopamine to prevent involuntary movements (chorea)
• Treatments control psychiatric symptoms with antipsychotics (Haloperidol) for psychosis/agitation and SSRIs (Fluoxetine, Sertraline) for depression

Parkinson's Disease

• This disorder involves loss of dopaminergic neurons in the substantia nigra, and Lewy body accumulation
• There is decreased dopamine, and increased acetylcholine
• Classic motor issues are a resting tremor, bradykinesia, rigidity, postural instability, and a shuffling gait
• Therapies increase dopamine levels by replacing lost dopamine, stimulating dopamine receptors, and reducing dopamine breakdown by inhibiting MAO-B or COMT enzymes
• Other treatments reduce acetylcholine (ACh) to restore the dopamine-ACh balance to reduce tremors

Multiple Sclerosis (MS)

• MS is an autoimmune demyelination of CNS neurons, and formation of plaques
• There is no direct neurotransmitter involvement, but inflammation disrupts synaptic function
• Signs are vision problems, muscle weakness, spasticity, fatigue, and cognitive impairment
• Therapies suppress the immune system to reduce autoimmune attack on myelin
• Treatments reduce inflammation to manage acute flare-ups
• Aim to manage symptoms like muscle spasticity and fatigue

Amyotrophic Lateral Sclerosis (ALS)

• ALS includes degeneration of upper and lower motor neurons
• Glutamate excitotoxicity is a key factor
• Muscle weakness, fasciculations, progressive paralysis, cognition mostly spared are common
• Reduce glutamate toxicity to slow motor neuron degeneration
• Reduce oxidative stress to delay disease progression
• Support patient by managing muscle spasticity

CVA/Stroke

• This is either Ischemic which means a blocked blood flow, or Hemorrhagic which means a ruptured vessel
• Glutamate accumulation occurs
• Neurons suffer oxygen deprivation, ATP depletion, inflammation and cell death
• Break down clots in ischemic stroke with tPA (Tissue Plasminogen Activator, given within 3-4.5 hours)
• Prevent clots with Aspirin, Clopidogrel (antiplatelets), Warfarin (anticoagulant for atrial fibrillation)
• Lower blood pressure to manage hemorrhagic stroke
• Reduce Brain Swelling with Mannitol (osmotic diuretic)
• Prevent Seizures (Post-TBI Epilepsy) with Phenytoin (sodium channel blocker)
• Treat symptoms of Pain/Agitation with Opioids, Sedatives
• Respiratory support as disease progresses

Traumatic Brain Injury (TBI)

• Focal injuries like contusions, hematomas, and Diffuse Axonal Injury (Shearing of axons) can appear
• The neurotransmitters are not specified
• Can cause Coma, and persistent vegetative state
• Reduce Brain Swelling with Mannitol (osmotic diuretic)
• Prevent Seizures (Post-TBI Epilepsy) with Phenytoin (sodium channel blocker)
• Treat symptoms of Pain/Agitation with Opioids, Sedatives

Myasthenia Gravis

• This involves an autoimmune attack on acetylcholine receptors at the neuromuscular junction
• Impaired acetylcholine transmission is seen
• Can diagnose with Ptosis, diplopia, difficulty swallowing, muscle fatigue
• Increase Acetylcholine (ACh) at Neuromuscular Junction to Improves muscle function with acetylcholinesterase inhibitor
• Suppress Immune System to Reduce autoantibody attack on ACh receptors with Corticosteroids (immunosuppressants)
• Or with Plasmapheresis/IV Immunoglobulin (IVIG) that Removes harmful antibodies (used in myasthenic crisis)

Guillain-Barré Syndrome (GBS)

• GBS is an Autoimmune demyelination of PNS, triggered by infection
• The neurotransmitters are not specified
• Signs are Ascending muscle weakness, paralysis, and absent reflexes
• Suppress Immune Response preventing further nerve damage with IVIG (intravenous immunoglobulin) or Plasmapheresis (removes autoantibodies)
• Support Patient with Mechanical ventilation if respiratory muscles weaken
• Treat symptoms of with Pain management (Gabapentin, Pregabalin)