Mod 9

Key Neurological Terms

• Agnosia refers to issues in sensory information processing and recognition
• Akinesia refers to difficulty initiating movement
• Amnesia is memory loss; retrograde amnesia impacts remote memory, and posttraumatic amnesia follows a TBI
• Aphasia is a language processing deficit, classified by location (Wernicke's, Broca's) or fluency
  • Broca Aphasia (motor/expressive) causes slow, difficult, dysfluent, and agrammatic speech, though verbal comprehension is usually intact
  • Wernicke Aphasia (sensory/receptive) involves fluent but meaningless speech due to inability to understand language
  • Global Aphasia is the most severe form, impacting both motor and sensory abilities, reading, writing, and comprehension
• Apoptosis refers to programmed cell death
• Ataxia refers to lack of muscle coordination
• Athetosis refers to slow, writhing, involuntary movements
• Automatism is defined as unconscious behavior with complex, repetitive movements
• Bradykinesia refers to slowness of movement
• Chorea are jerky, involuntary movements
• Cognitive deficits are impairments in attention, memory, language, judgment, and decision-making
• Contusion refers to bruising of neural tissue, potentially causing swelling and functional loss
• Delirium (Acute Confusional State - ACS) involves transient or persistent awareness disorder with cognitive, emotional, perceptual, and consciousness changes, potentially being hyperactive, hypoactive, mixed, or terminal
• Dementia is acquired, progressive deterioration of cerebral functions impacting intellectual processes
• Demyelination refers to damage to the myelin nerve sheath, impairing neural transmission
• Dysarthria means unclear articulation due to cranial nerve or muscle damage
• Dysphagia refers to difficulty swallowing
• Dysphonia denotes difficulty producing speech sounds, often of laryngeal origin
• Dyskinesias refers to abnormal, involuntary movements and paroxysmal dyskinesias manifest as spasms
• Dystonia refers to sustained muscle contractions that lead to twisting, repetitive movements, or abnormal postures
• Excitotoxicity refers to neuronal damage or death from excessive excitatory neurotransmitters, like glutamate
• Fasciculations are brief, involuntary muscle twitching visible under the skin
• Glasgow Coma Scale (GCS) assesses consciousness level
• Hemiparesis refers to weakness on one side of the body
• Hemiplegia refers to paralysis on one side of the body
• Hyperkinesia refers to excessive, purposeless movement
• Hypokinesia refers to loss of associated movement
• Hypoxia refers to deficiency in oxygen reaching tissues
• Increased Intracranial Pressure (IICP) refers to elevated pressure within the skull
• Ischemia refers to insufficient brain blood flow, leading to oxygen and nutrient deprivation and potential infarction
• Locked-in syndrome (ventral pontine syndrome) involves complete voluntary muscle paralysis except for vertical gaze and upper eyelid movement, with intact cognition
• Meninges refers to protective membranes covering the brain and spinal cord and inflammation refers to meningitis
• Myoclonus refers to brief, sudden, involuntary muscle contractions
• Neurofibrillary Tangles are insoluble filaments of hyperphosphorylated tau protein, found in neurons in Alzheimer's disease
• Nuchal rigidity refers to neck stiffness
• Paresis refers to muscle weakness
• Parkinsonism refers to tremors, rigidity, bradykinesia, and postural instability
• Plaques (Amyloid/Senile) are extracellular deposits with aggregated amyloid-beta peptide, found in brain parenchyma in Alzheimer's, marking demyelination in Multiple Sclerosis
• Postictal state refers to altered consciousness after a seizure
• Seizure refers to sudden, uncontrolled brain electrical disturbance and epilepsy involves recurrent seizures
• Spasticity refers to increased muscle tone and stiffness, often with exaggerated reflexe
• Stereotypy refers to ritutalistic behavior, such as rocking, a complex repetitive movement
• Tremor refers to involuntary, rhythmic shaking; resting tremors occur when muscles are relaxed, decreasing with movement and are characteristic of Parkinson's disease
• Transient Ischemic Attack (TIA) is a brief neurological dysfunction from focal brain ischemia lasting less than 24 hours without acute infarction evidence
• Vascular malformation (e.g., Arteriovenous Malformation - AVM) refers to rare congenital vascular lesions

Neuron Physiology

• Neurons transmit electrical signals to axon terminals, where neurotransmitters are released affecting effector cells
• Neuron activity depends on excitatory and inhibitory input balance

Brain Region Anatomy and Function

• Basal ganglia are involved in movement initiation and regulation and receive input from the cerebral cortex via the thalamus, while degeneration characterizes Parkinson's disease
• Hippocampus impacts learning and declarative memory, with shrinkage seen in Alzheimer's disease
• Amygdala plays a role in emotion and memory
• Thalamus integrates and relays sensory and motor function, with the pulvinar nucleus affecting selective attention
• Hypothalamus regulates homeostasis and behavior, where dysfunction associates with cluster headaches
• Cerebellum affects coordination and balance, and when damaged, leads to ataxia
• Cerebral cortex mediates higher-level cognitive functions
  • Frontal lobe affects vigilance, detection, and working memory and damage to the inferior frontal gyrus affects Broca's area
  • Temporal lobe affects working memory and long-term storage, the superior temporal gyrus contains Wernicke's area, and medial temporal lobe damage (including the hippocampus) impacts declarative memory
  • Parietal lobe is involved in selective attention and contains sensory areas with damage causing agnosia, while the left angular gyrus links to Gerstmann syndrome
  • Occipital lobe contains the visual cortex for processing visual information
  • Motor cortex (Precentral gyrus) controls voluntary movement
  • Sensory cortex (Postcentral gyrus) processes sensory information
  • Association areas (temporal, parietal, occipital lobes) store long-term memories
  • Broca's area (inferior frontal gyrus) controls motor speech; damage can cause expressive aphasia
  • Wernicke's area (superior temporal gyrus) controls sensory speech and damage leads to receptive aphasia
• Brainstem connects the cerebrum and cerebellum to the spinal cord, consisting of the midbrain, pons, and medulla oblongata
  • Midbrain damage can lead to decerebrate posturing, the superior colliculus facilitates the "move" component of selective attention, and the midbrain tectum coordinates eye/body movement
  • Pons damage can lead to decerebrate posturing and a flaccid state, while injury at the base can cause locked-in syndrome
  • Medulla controls basic life functions
• Ventricles are cavities in the brain containing cerebrospinal fluid, which are enlarged in Alzheimer's and Huntington's diseases
• Striatum (Corpus striatum) contains the caudate nucleus and putamen and is part of the basal ganglia and is severely degenerated in Huntington's disease
• Substantia nigra is located in the midbrain and contains dopaminergic neurons projecting to the basal ganglia (nigrostriatal pathway), and the loss of these neurons characterizes Parkinson's disease

Neural Pathways and Structures

• Nigrostriatal pathway is a dopaminergic pathway between the substantia nigra and striatum, critical for motor control, and degeneration results in Parkinson's disease
• Axon is a nerve cell projection conducting electrical impulses away from the cell body, and axonal shearing can occur in TBIs
• Myelin sheath is a CNS lipid-rich substance produced by oligodendrocytes that insulates axons to increase action potential propagation speed, and degeneration marks multiple sclerosis
• Nodes of Ranvier are gaps in the myelin sheath with localized ion channels that enable saltatory conduction of action potentials in myelinated axons
• Neurotransmitters are chemical messengers that transmit signals across a synapse, where alterations in availability associates with delirium
  • Loss of acetylcholine associates with Alzheimer's disease
  • Dopamine is affected in Parkinson's disease
  • Glutamate excitotoxicity impacts ALS and autoimmune encephalitis
• Action potential is an electrical signal traveling along a neuron's axons and myelin increases its propagation speed
• Neuromuscular junction (NMJ) is the synapse between a motor neuron and muscle fiber, where dysfunction characterizes myasthenia gravis and is impacted in ALS

Protective CNS Structures

• Blood-brain barrier (BBB) protects the brain from toxins, pathogens, hormones, and ionic fluctuations, where damage occurs in TBIs, Alzheimer's, meningitis, and encephalitis
• Meninges are membrane layers (dura, arachnoid, pia mater) that stabilize the brain and spinal cord, and inflammation marks meningitis
• Cerebrospinal fluid (CSF) circulates within ventricles and the subarachnoid space to physically, chemically protect the brain and spinal cord to diagnose disorders while obstruction leads to hydrocephalus
• Brain blood supply comes from vertebral and internal carotid arteries
  • Occlusion/rupture leads to cerebrovascular accidents (strokes)
  • The middle cerebral artery impacts aphasia

Pathophysiology of Some Diseases/Disorders

• Traumatic Brain Injury (TBI) is caused by an external mechanical force
  • Primary injury involves direct damage like lacerations, fractures, contusions, and hemorrhages (epidural, subdural, intracerebral, subarachnoid) upon impact
  • Secondary injury evolves over time from systemic processes and intracerebral processes that cause cellular ones such as a neurotransmitter release, failure of cell ion pumps and mitochondria, BBB disruption, and cell death
  • Diffuse axonal injury (DAI) involves widespread shearing/stretching via acceleration/deceleration forces
  • Alterations include altered consciousness, cognitive/sensory-motor deficits, and behavioral changes
  • Mild TBI (concussion) presents with headache, dizziness, and fatigue
  • Moderate-severe TBIs lead to more significant impairments
• Spinal Cord Injury (SCI) is caused by mechanical trauma
  • Primary injury involves tissue destruction that results in cord concussion, contusion, laceration, or transection and function loss below the injury level
  • Secondary injury includes blood supply damage and ischemia
  • Characteristics of SCI include motor/sensory loss below the injury level, where complete transection results in complete loss, while incomplete injuries have variable presentations
• Degenerative Spine Disorders' specific pathophysiology is not detailed
• Seizure disorders can be caused by epilepsy
  • Possible causes are genetic, structural, metabolic, immune, or unknown
  • Seizures are a sudden, transient disruption resulting from abnormal excessive and synchronous neuronal firing that are often treated with medications
  • Result in alterations of behavior, motor function, sensation, or consciousness and can be described as recurrent unprovoked seizures
• Cerebrovascular Disorders (CVD) or Cerebrovascular Accidents (CVA) or Stroke are often caused by pathologic processes in blood vessels
  • Result in ischemia or hemorrhage
  • Ischemic strokes (87%) are caused by vessel occlusion or hypoperfusion and creates an ischemic cascade leading to neuronal damage
  • Hemorrhagic strokes (13%) are caused by vessel rupture, in the form of an intracerebral hemorrhage or subarachnoid hemorrhage, leading to ischemia, edema, and increased pressure with secondary injury from inflammation, oxidative stress, and excitotoxicity
  • Stroke characteristics are a sudden onset of focal deficits such as slurred speech, difficulty swallowing, limb weakness or paralysis, hemiparesis, hemisensory loss, visual impairment, dizziness, severe headache, and aphasia
• Primary Headache Syndromes include migraines, cluster headaches, and tension-type headaches
  • Migraines are multifaceted, triggered by genetics and estrogen withdrawal
    • Caused by cortical spreading depression (CSD) that initiates a cascade involving the trigeminal vascular system
    • Resulting in vasodilation, inflammation, and pain receptor sensitization
    • Results in episodic or chronic headaches lasting for 4 to 72 hours with unilateral location, pulsating quality, moderate-severe pain, aggravation by activity, nausea, vomiting, photophobia, and phonophobia with/without aura
  • Cluster headaches are caused by hypothalamic dysfunction in the trigeminovascular system with autonomic reflexes
    • Activation results in vasoactive peptides, neuroinflammation, sympathetic underactivity, and parasympathetic activation
    • Results in severe unilateral pain in the trigeminal distribution with ipsilateral autonomic manifestations like tearing, ptosis, nasal congestion, with cyclical patterns
  • Tension-type headaches (TTH) can be caused by peripheral mechanisms.
    • Myofascial factors cause pericranial muscle tenderness that can induce central sensitization with increased central excitability/decreased pain inhibition
    • Results in mild-moderate bilateral headaches, often described as pressure, not aggravated by routine activity, and usually presented without nausea, vomiting, photophobia, or phonophobia
• Infections and Inflammation of the Central Nervous System include Meningitis, Encephalitis, Brain or Spinal Cord Abscess, and Neurologic Complications due to HIV
  • Meningitis is caused by organisms (bacteria, viruses, fungi, parasites, or toxins) that enter the CNS via the bloodstream or direct invasion
    • Bacterial meningitis recruits neutrophils to cause inflammation and increased pressure, potentially causing cerebral ischemia and infarction
    • The resulting characteristics are fever, headache, neck stiffness (nuchal rigidity), photophobia, mental state alteration, and focal dysfunction with possible tachycardia, chills, Kernig/Brudzinski signs, seizures, vomiting, and rash (meningococcal)
  • Encephalitis is caused by viruses such as Herpes simplex or West Nile virus, as well as autoimmunity or post-infection, via entry through the bloodstream, olfactory bulb, or peripheral nerves
    • Results in inflammation, cell degeneration, edema, necrosis, and increased pressure, as well as autoimmune antibodies against neural cell surface/intracellular antigens
    • Characteristics are fever, headache, nausea, stiff neck, confusion, behavioral changes, seizures, deficits, and movement disorders
  • Brain or spinal cord abscesses can be caused by organisms via direct extension from sinusitis/mastoiditis, along veins, or via infective emboli
    • Results in pus and inflamed tissue, increasing mass effect, pressure, and deficits
    • Characteristics depend on the abscess location/size
  • HIV-related complications are often caused by immunosuppression
    • HIV infects microglia/macrophages in the CNS for nerve cell degeneration and brain atrophy, increasing the risk of opportunistic infections and tumors
    • Characteristics include cognitive impairment, motor deficits, and sensory abnormalities, dependent on the specific complication
• Peripheral nervous system disorders (neuropathies) can be due to diabetes, trauma, infections, toxins, and genetic disorders
  • Damage to peripheral nerves from the cause can result in demyelination, axonal degeneration, or nerve compression
  • Characteristics include weakness, numbness, pain, and autonomic dysfunction in the extremities
• Central nervous system tumors (brain/spinal cord tumors)
  • Possible causes are abnormal cell growth or metastatic growth.
  • Result in neurological deficits, increased pressure, and disrupted function
  • Can cause headaches, seizures, deficits, changes, and personality changes
• Disorders of Awareness include delirium and dementia
  • Delirium is caused by a disruption of widely distributed neural networks due to toxins, inflammation, metabolic derangement, ischemia, hypoxia, and medications
    • Results in direct destruction and indirect effects of toxins, inflammation, and chemicals, with theories of neuronal aging, neuroinflammation, oxidative stress, and dysregulation
    • The defining characteristics are acute onset, fluctuating course, and alterations in attention, cognition, emotion, perception, and consciousness, manifesting in various states
  • Dementia is caused by neuron degeneration, compression of brain tissue, atherosclerosis of cerebral vessels, brain trauma, genetic predisposition, and CNS infections, for which Alzheimer's disease is the most common cause
    • Multiple mechanisms are the cause such as degeneration, compression, atherosclerosis, and trauma, with varying initial symptoms and progression
    • Neurodegenerative diseases like AD involve beta-amyloid plaques
    • Lewy body dementia involves alpha-synuclein inclusions
    • Vascular dementia can results from cerebrovascular disease and brain infarcts or a loss of cholinergic neurons
    • Characteristics include the progressive decline in orientation, memory, language, judgment, and decision-making with behavior changes and varying symptoms
• Aphasia is typically cause by cerebrovascular accidents
  • Broca area in the frontal lobe and Wernicke area in the temporal lobe has damage and disruption
  • Difficulty producing spoken or written language (Broca aphasia) and impaired comprehension of written or spoken language (Wernicke aphasia) is characterized

Common Diseases and Disorders

• Agnosia is caused by injured specific association areas to integrate sensory information
  • Results in the inability to recognize the specific stimuli
• Locked-in syndrome is caused by injuries at the base of the pons from basilar artery occlusion
  • Resulting in a disruption where patients are paralyzed in voluntary muscles except for the eyes while consciences stays completely intact
  • Can often communicate with eye-blinks and movements
• Parkinson's disease affects the dopaminergic neurons and creates instability between dopamine and acetylcholine
  • The characteristics can results in muscle tremors, rigidity, bradykinesia, and immobility
• Huntington's disease is caused by a genetic mutation in the gene that can damage striatum
  • Results in a progressive motor (chorea, athetosis, ballism, rigidity, dystonia, bradykinesia), cognitive decline, and psychiatric and behavioral disturbances
• Amyotrophic Lateral Sclerosis may have an unknown cause, but the risk factors include age, sex and familial factors
  • Results in motor paralysis and speech impairment
• Multiple Sclerosis is a chronic autoimmune disease where T and B cells attack the brain and cause inflammation of the brain
• This demyelination leads to impaired gait, pain, incontinence, brainstem and cerebellum syndrome and optic neuritis
• Guillain-Barre syndrome is caused by an immunologic reaction that involves damages peripheral nerve and infections
  • Results in muscle weakness starting in the legs and ascending to the face
• Myasthenia gravis is caused by an autoimmune disorder
  • Results can include muscle weakness that commonly effects swallowing, facial and eye muscles