Nervous System Overview

Central Nervous System (CNS) and Peripheral Nervous System (PNS)

• CNS: brain and spinal cord
• PNS: cranial nerves and spinal nerves
• PNS pathways divided into:
  • Ascending (afferent): carries sensory information towards CNS
  • Descending (efferent): motor neurons travel away from CNS to innervate effector organs

Neurons

• Electrically excitable cells
• Cellular components:
  • Microtubules: transport substances (like neurotransmitters)
  • Neurofibrils: structure support
  • Nissl substances: granules made of rough ER, responsible for protein synthesis
• Structural classification:
  • Unipolar, pseudounipolar, bipolar, multipolar (most common)
• Functional classification:
  • Sensory neurons: impulses from sensory receptors to CNS (afferent pathway)
  • Motor neurons: impulses from CNS to effector organs (efferent pathway)
  • Interneurons (associational neurons): transmit impulses between neurons (>99% of all neurons)

Neuroglia (Glial Cells)

• CNS: astrocytes, microglia, oligodendrocytes, ependymal cells
• PNS: Schwann cells
• Function: support and maintain neurons
• Types:
  • Astrocytes: fill spaces between neurons
  • Microglia: remove debris within CNS (brain macrophages)
  • Oligodendrocytes: form myelin in CNS
  • Ependymal cells: line CSF-filled cavities in CNS and create CSF

Chemical Synapses

• Signaling from one cell to the next occurs through release of neurotransmitters
• Presynaptic neuron: releases neurotransmitters into synaptic cleft
• Postsynaptic neuron: receives neurotransmitters through receptors

Neurotransmitters

• "The language that allows the action potential to cross the synaptic cleft"
• Types:
  • Acetylcholine: regulates muscle contraction, memory, and cognition
  • Norepinephrine: involved in attention, arousal, and stress response
  • Dopamine: involved in reward, motivation, and movement
  • Serotonin: regulates mood, appetite, and sleep
  • GABA (gamma-aminobutyric acid): main inhibitory neurotransmitter in CNS

Cerebrovascular Disease

• Refers to a group of conditions that affect blood flow and blood vessels in the brain
• Types:
  • Ischemic stroke: occurs when blood vessels become blocked or narrowed
  • Hemorrhagic stroke: occurs when blood vessels rupture

Ischemic Stroke

• Abrupt onset of focal or global neurologic impairment
• Types:
  • Transient ischemic attack (TIA): episode of neurologic dysfunction lasting < 1 hour
  • Thrombotic stroke: occurs when a blood clot forms in a blood vessel
  • Embolic stroke: occurs when a blood clot forms in another part of the body and travels to the brain
  • Lacunar stroke: occurs when small blood vessels in the brain are blocked
  • Hypoperfusion stroke: occurs when blood flow to the brain is reduced

Pathophysiology of Infarction

• Infarction occurs when occlusion leads to loss of blood supply and ischemia
• Ischemic core vs. penumbra: central core of irreversible ischemia/necrosis surrounded by zone of borderline ischemic tissue

Hemorrhagic Stroke

• Occurs when blood vessels rupture
• Types:
  • Intracerebral hemorrhage: occurs when a blood vessel in the brain ruptures
  • Subarachnoid hemorrhage: occurs when a blood vessel on the surface of the brain ruptures
  • Subdural hemorrhage: occurs when a blood vessel between the brain and skull ruptures

Stroke Syndromes

• Middle cerebral artery (MCA) stroke: occurs when the MCA is blocked
• Posterior circulation (vertebrobasilar) stroke: occurs when the posterior circulation is blocked

Demyelinating Disorders

• Leukodystrophies: inherited metabolic disorders that affect myelin formation or maintenance
• Myelinoclastic diseases: diseases that destroy normally formed myelin
• Types:
  • Multiple sclerosis (MS): an autoimmune disease that affects the CNS
  • Progressive multifocal leukoencephalopathy (PML): a rare and opportunistic infection
  • Central pontine myelinolysis (osmotic demyelination syndrome): caused by rapid correction of chronic hyponatremia### Central Pontine Myelinolysis
• Caused by rapid correction of chronic hyponatremia
• Astrocytes and oligodendrocytes die 24 hours after initial insult
• Symptoms: para or quadriparesis, behavioral disturbances, movement disorders, seizures, lethargy, confusion, and coma
• Prevention: slowly correct chronic hyponatremia to allow cells to adapt to osmotic changes

Alzheimer's Disease

• Neurodegenerative disease
• Most common cause of dementia
• Two pathologic hallmarks: extracellular beta-amyloid deposits (plaques) and intracellular neurofibrillary tangles
• Diagnosis: insidious onset and progressive course of cognitive decline
• Cardinal symptoms: memory impairment, executive functioning impairment, language deficits, visuospatial abnormalities, apathy, social disengagement, and irritability
• Treatment: cholinesterase inhibitors (e.g., donepezil, rivastigmine) to increase concentration of acetylcholine and slow progression of symptoms

Meninges and Cerebrospinal Fluid

• Epidural hematoma: bleeding between skull and dura
• Subdural hematoma: bleeding between dura and arachnoid
• Subarachnoid hemorrhage: bleeding between arachnoid and pia
• CSF: clear fluid produced by ependymal cells of the choroid plexus in the lateral, third, and fourth ventricles
• CSF flow: produced in ventricles, flows through foramina, and reabsorbed by arachnoid granulations
• Functions: exerts pressure, provides cushioning, and protects against trauma

Ventricular System

• CSF ends up in the superior sagittal sinus and is reabsorbed by arachnoid granulations
• Ventricular system: CSF produced in ventricles and flows through foramina
• Make up of CSF: pH ~ 7.3, glucose level 2/3 of plasma, and very little protein

Clinical Correlation - CSF Analysis

• Lumbar puncture: sample of CSF and measurement of intracranial pressure
• Abnormalities: bacteria, RBCs, WBCs, elevated glucose, and protein levels

Hydrocephalus

• Accumulation of excess CSF in the ventricular system
• Types: obstructive (blockage of CSF flow) and communicating (overproduction of CSF)
• Normal pressure hydrocephalus: adult syndrome of progressive dementia, gait disorders, and urinary incontinence
• Main treatment option: VP shunt

Traumatic Brain Injury

• Caused by external force
• Pathophysiology: primary brain injury (diffuse axonal injury, focal cerebral contusions, and intracranial hemorrhage) and secondary brain injury (free-radical injury, electrolyte imbalances, mitochondrial dysfunction, and inflammatory responses)
• Clinical manifestations: concussion, altered mental status, and memory loss
• Concussion: mild traumatic brain injury, temporary impairment of neurologic function

CNS Infections

• Meningitis: infection of the meninges
• Encephalitis: infection of the brain parenchyma
• Clinical manifestations: fever, neck stiffness, and altered mental status
• Treatment: empiric antibiotics and antivirals, and steroids to reduce inflammation

Basal Ganglia

• Group of subcortical nuclei responsible for motor control
• Functions: initiating voluntary motor movement and regulating movement
• Made up of the substantia nigra, caudate nucleus, and putamen

Movement Disorders

• Huntington's disease: rare autosomal dominant genetic disorder
• Clinical manifestations: dementia, psychiatric symptoms, and chorea movements
• Treatment: focused on symptom management

Parkinson's Disease

• Degenerative disorder of the substantia nigra
• Clinical manifestations: pill-rolling tremor, rigidity, shuffling gait, and bradykinesia
• Treatment: levodopa/carbidopa to replace dopamine

Amyotrophic Lateral Sclerosis (ALS)

• Progressive neurodegenerative disorder of upper and lower motor neurons
• Clinical manifestations: muscle atrophy, weakness, and paralysis
• Treatment: focused on symptom management

Peripheral Nervous System

• Direct extension of the central nervous system
• Components: autonomic nervous system and somatic nervous system
• Functions: monitors and reacts to external stimuli

Diabetic Peripheral Neuropathy

• Most common complication of diabetes
• Clinical manifestations: progressive loss of sensation, numbness, and pain
• Pathophysiology: distal symmetric polyneuropathy, ischemia, and buildup of advanced glycation end products

Guillain-Barré Syndrome

• Autoimmune destruction of the schwann cells surrounding peripheral nerves
• Clinical manifestations: symmetric, ascending weakness, and numbness
• Diagnosis: clinical diagnosis, EMG, and nerve studies
• Treatment: supportive care, pain control, and IVIG

Carpal Tunnel Syndrome

• Compression of the median nerve as it travels through the wrist
• Clinical manifestations: numbness, tingling, and pain in the hand and forearm
• Prevention: supportive care, and corticosteroid injections### Carpal Tunnel
• The carpal tunnel is formed by the transverse carpal ligament superiorly and the carpal bones inferiorly.
• The median nerve passes through the carpal tunnel along with nine flexor muscle tendons.
• The median nerve provides motor and sensory innervation to the hand.
• Compression of the median nerve leads to ischemia and mechanical disruption.

Innervation of the Hand

• The median nerve supplies the abductor pollicis brevis, the flexor pollicis brevis (superficial head), the opponens pollicis, and the first and second lumbricals.

Charcot-Marie-Tooth Disease (CMT)

• CMT is a group of hereditary disorders that cause peripheral neuropathy in both sensory and motor neurons.
• It is a “demyelinating” disorder of the peripheral nervous system.
• Over time, neurons degenerate leading to muscle weakness/atrophy.
• CMT affects longer nerves first, with symptoms typically beginning in the feet/lower legs and then the fingers, hands, and arms.
• High arched feet are a common feature due to muscular imbalance (from atrophy).
• Pathogenic variants in various genes lead to abnormalities in peripheral nerves or myelin.
• Thin or misfolded myelin sheaths and hypertrophic myelination are characteristic of CMT.
• Symptoms of CMT include hammertoe, foot drop, trips and falls due to gait disorders, and repeated ankle sprains.

Myasthenia Gravis

• Myasthenia Gravis is an autoimmune disorder of the neuromuscular junction that manifests as progressive skeletal muscle weakness and fatigability.
• The body makes autoantibodies to the acetylcholine receptor, reducing the number of available receptor sites.
• Repeated stimulation leads to progressive neuromuscular fatigue and depletion of acetylcholine in the nerve terminal.
• Clinical manifestations include generalized proximal limb weakness and fatigability with repeated activities, drooping of eyelids (ptosis), flattened smile, and difficulty breathing in severe cases.
• Treatment options include acetylcholinesterase inhibitors, immunosuppressants like corticosteroids, plasmapheresis, and IV immunoglobulin.